Paediatric adrenocortical tumours (pACT) are rare endocrine neoplasms characterised by marked biological heterogeneity and variable clinical behaviour. Current risk stratification relies largely on histopathology and clinical staging, which incompletely capture underlying tumour biology. We aimed to define proteome-based subtypes of pACT and evaluate their biological, clinical, and therapeutic relevance.

In this retrospective cohort study, we performed mass spectrometry-based proteomic profiling of 83 pACT and adjacent non-tumour adrenal tissues. Differential abundance analysis, pathway enrichment, consensus clustering, survival analyses, and clinicopathological correlations were performed. A minimal protein classifier was derived using forward feature selection and leave-one-out cross-validation. Cluster-specific therapeutic vulnerabilities were assessed using a curated druggability framework.

Tumours displayed profound proteomic differences compared with adjacent non-tumour adrenal cortex, characterised by activation of cholesterol biosynthesis, steroidogenic, MYC, mTORC1, and cell-cycle programs and suppression of extracellular matrix, adhesion, and immune-related pathways. Unsupervised clustering identified four proteome-defined tumour states that only partially overlapped with histopathological diagnosis. These subtypes differed significantly in endocrine phenotype, vascular invasion, Ki67 index, necrosis, and overall survival (log-rank p = 0.00036). Distinct biological programs included stromal-immune-enriched, mitochondrial steroidogenic, IGF/mTOR-driven anabolic, and highly proliferative chromatin-remodelled states. A five-protein classifier (DAAM2, CIP2A, TSC2, PALS2, and P3H1) reproduced cluster assignments with 92.8% leave-one-out cross-validation accuracy. Cluster-specific analyses identified distinct therapeutic target landscapes, including IGF-axis and epigenetic vulnerabilities.

Proteomic profiling defines biologically and clinically distinct pACT subtypes that provide prognostic information beyond histopathology. This framework enables proteome-based stratification, identifies candidate therapeutic vulnerabilities, and can be approximated by a five-protein classifier.

German Childhood Cancer Foundation, Mitteldeutsche Kinderkrebsforschung, European Union's EU4Health Programme, Max Planck Society, Onassis Foundation, and Joachim Herz Stiftung.

Breast cancer is the second most common malignant neoplasm among women worldwide. Computed tomography (CT) plays an important role in diagnosis, staging, follow-up, and metastatic assessment. This study aimed to evaluate the role of chest CT in patients with breast neoplasms at a public hospital and to compare dosimetric parameters with Diagnostic Reference Levels (DRLs), based on CTDI_vol and dose-length product (DLP). Related malignancies (ovarian and cervical) were included for preliminary analysis. A retrospective study of 334 elective outpatient chest CT examinations performed in 2025 was conducted. All patients were female, with a mean age of 59.04 ± 12.57 years, and most (65.40%) were within the recommended screening age range (50-74 years), while 15.19% were aged 40-49 years. DICOM data were obtained from two 64-slice CT scanners: Philips Incisive (CT A) and Canon Aquilion (CT B). CTDIvol and DLP values for CT A were stratified by clinical indication. Percentile analysis (P25-P75) showed lower CTDI_vol values for CT A (4.06-5.82 mGy) compared with CT B (4.99-8.83 mGy), while DLP values were higher in CT A (146.97-201.45 mGy cm) than in CT B (94.51-201.49 mGy cm). Median CTDI_vol values were 4.70 and 7.65 mGy, and DLP values were 169.42 and 141.36 mGy cm for CT A and CT B, respectively. The P75 values remained below international DRLs for adult chest CT and CT for radiotherapy planning. These findings highlight the importance of continuous dosimetric assessment to optimize CT protocols and ensure radiation protection in patients undergoing treatment.

Optimizing antibiotic duration for pediatric community-acquired pneumonia (CAP) may reduce treatment burden and support antimicrobial stewardship. Although recent randomized trials and evidence syntheses have reported similar clinical outcomes with shorter antibiotic courses, the effect of treatment duration on adherence-an especially relevant consideration in children-has received comparatively limited systematic evaluation. We therefore aimed to compare treatment effectiveness, medication adherence, and antibiotic-related adverse events between short-course and conventional-duration antibiotic therapy for non-severe CAP in immunocompetent children. PubMed, Cochrane Library, Scopus, ClinicalTrials.gov, and WHO Global Index Medicus were sought through April 25, 2025. Only randomized clinical trials that included immunocompetent children < 18 years with non-severe CAP and compared short-course (≤ 5 days) with longer therapy (> 5 days) were considered. Data extraction and risk of bias (ROB 2) assessment were performed by two independent reviewers. Summary data were extracted by published reports. The principal outcomes were treatment effectiveness, assessed through treatment failure and relapse according to the definitions prespecified by each trial, and medication non-adherence to the active (non-placebo) study drug. Antibiotic-related adverse events were assessed as a secondary outcome. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Two hundred thirty studies were originally screened, after removal of duplicates and 10 trials (n = 8970) met inclusion criteria. No significant differences were found in treatment failure [RR = 1.07 (95% CI, 0.93-1.24), I² = 3%] or relapse [RR = 1.04 (95% CI, 0.72-1.49), I² = 0%]. Shorter regimens markedly reduced non-adherence [RR = 0.35 (95% CI, 0.24-0.50), I² = 54%], the most consistent and clinically meaningful difference. Adverse events were comparable [RR = 0.71 (95% CI, 0.36-1.40), I² = 81%].

 Short-course therapy was not associated with significantly different treatment failure or relapse rates compared with longer regimens and was associated with substantially lower non-adherence. These findings support shorter antibiotic courses as a reasonable treatment option for non-severe pediatric CAP, while acknowledging that the present meta-analysis was not designed to formally establish non-inferiority or equivalence.

• Short-course antibiotic therapy may achieve similar clinical outcomes to conventional longer courses in children with non-severe community-acquired pneumonia. • Medication adherence remains an important challenge in pediatric antibiotic therapy.

• This meta-analysis found no significant difference in treatment failure or relapse between short- and long-course therapy. • Short-course therapy was associated with substantially lower non-adherence, highlighting an important practical advantage of shorter regimens.

To evaluate the association between bronchopulmonary dysplasia (BPD) severity and post-discharge growth during the first year of corrected age in very preterm infants, including recovery from established growth failure at hospital discharge. This retrospective cohort included 1,106 infants born before 32 weeks' gestation, classified using the Jensen BPD definition as no BPD (n = 768), mild (n = 142), moderate (n = 154), or severe BPD (n = 42). Weight, length, and head circumference z-scores were assessed from birth to 12 months corrected age. Longitudinal growth trajectories and time to recovery from discharge growth failure were evaluated using adjusted models. Increasing BPD severity was associated with progressively poorer anthropometric outcomes at discharge and 12 months (all p < 0.001). At 12 months, severe BPD remained independently associated with lower weight (β - 0.596, 95% CI - 1.134 to - 0.057; p = 0.030), length (β - 0.800, 95% CI - 1.443 to - 0.156; p = 0.015), and head circumference (β - 1.177, 95% CI - 2.001 to - 0.353; p = 0.005) z-scores. Among infants with growth failure at discharge, severe BPD was associated with slower recovery of weight (HR 0.40, 95% CI 0.19-0.81; p = 0.011), length (HR 0.25, 95% CI 0.14-0.48; p < 0.001), and head circumference (HR 0.23, 95% CI 0.08-0.72; p = 0.012). Median recovery was not reached for any anthropometric domain in severe BPD; corresponding 12-month recovery probabilities were 41.3%, 42.6%, and 30.1%, respectively. Conclusion: Severe BPD was independently associated with persistent impairment in weight, length, and head circumference and substantially delayed recovery from established growth failure during infancy. These findings support structured longitudinal growth monitoring and targeted nutritional follow-up after discharge.

To assess whether lung ultrasound surface wave elastography (LUSWE), a non-invasive measure of lung stiffness, correlates with pulmonary function and high-resolution CT (HRCT) patterns in suspected interstitial lung disease (ILD). We hypothesised that LUSWE-derived lung stiffness would be associated with functional impairment and radiological ILD patterns.

Prospective, single-centre pilot study conducted in a tertiary referral ILD unit in Barcelona, Spain.

68 consecutive patients (41 men and 27 women) with suspected ILD were enrolled between June 2020 and February 2024 and completed LUSWE assessment at diagnosis under clinically stable conditions. Final diagnoses comprised sarcoidosis, idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, fibrosing ILD, connective tissue disease-related ILD, other ILD and absence of pulmonary disease.

The primary outcome was the association between LUSWE velocity and pulmonary function parameters, specifically forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO). Secondary outcomes included associations with HRCT radiological patterns, fibrosing vs non-fibrosing ILD, usual interstitial pneumonia (UIP)/probable UIP vs other HRCT patterns and quantitative HRCT-derived fibrosis extent.

LUSWE velocity did not significantly correlate with FVC (r=0.23, 95% CI -0.01 to 0.45; p=0.07) or DLCO (r=0.13, 95% CI -0.12 to 0.36; p=0.31). No significant differences in LUSWE velocity were observed across HRCT patterns (Kruskal-Wallis χ²=1.2018; p=0.8778). Exploratory point-by-point analyses showed one significant association between the R2 point and FVC (r=0.33; p=0.0068), but this did not remain significant after correction for multiple comparisons (adjusted p=0.137). LUSWE distributions were similar between fibrosing and non-fibrosing ILD groups (3.35 (IQR 2.87-4.16) vs 3.55 (IQR 2.98-4.17) m/s; p=0.526) and between UIP/probable UIP and other HRCT patterns (3.36 (IQR 2.89-4.21) vs 3.59 (IQR 2.86-4.15) m/s; p=0.876). Quantitative HRCT analyses also showed weak, non-significant correlations between hemithorax-level fibrosis extent and corresponding LUSWE values.

In this heterogeneous cohort of patients evaluated at diagnosis for suspected ILD, LUSWE was not meaningfully associated with pulmonary function impairment, HRCT patterns or quantitative fibrosis extent. Larger multicentre studies using standardised acquisition protocols and focused on well-defined fibrosing ILD populations with predominant subpleural involvement are needed.

Bronchiectasis (BE) is a heterogeneous lung disease characterised by chronic neutrophilic inflammation. A "vicious vortex" develops through the interactions between neutrophilic inflammation, infection and impaired mucociliary clearance, leading to progressive structural lung damage and worsening lung function. As part of this neutrophilic inflammation, neutrophil serine proteases (NSPs) overwhelm their natural inhibitors, with high NSP levels being associated with pulmonary exacerbations in people with BE. NSPs, activated by dipeptidyl peptidase 1 (DPP1) during neutrophil maturation in the bone marrow, are released from neutrophils at sites of inflammation. Pharmacological inhibition of DPP1 is a compelling approach to reduce neutrophilic inflammation in BE. Three DPP1 inhibitors have had favourable results in clinical studies for BE, namely brensocatib, florensocatib and verducatib, with recent approval of brensocatib, a first-in-class DPP1 inhibitor, in the US and Europe, providing a promising treatment option for people with BE. Many questions about DPP1 inhibition remain, including long-term efficacy and safety, and efficacy in people with cystic fibrosis, primary COPD and immunodeficiencies, who were generally excluded from prior large studies. Despite the availability of cystic fibrosis transmembrane conductance regulator modulator therapy, many people with cystic fibrosis continue to have pulmonary exacerbations. The inclusion of a broad population with a range of aetiologies is key in the development of DPP1 inhibitors to support access to treatment for all those who could benefit. This review explores the current DPP1 inhibition landscape, discussing the clinical studies to date for these three novel DPP1 inhibitors and the evolution of DPP1 studies in BE.

While culturing the opportunistic pathogen Pseudomonas aeruginosa in standard bacterial culture media has provided fundamental insights into its pathological properties such as virulence and antibiotic resistance, growing evidence suggests that these conditions fail to accurately reflect the in vivo bacterial physiology. In the lungs of people living with cystic fibrosis (pwCF), where P. aeruginosa is a major contributor to the disease process, bacteria reside within a complex physicochemical environment that drives their behaviour. Until recently, efforts to evaluate how well laboratory models mimic these in vivo conditions were hampered by limited data on the physiology of P. aeruginosa during chronic cystic fibrosis (CF) lung infections. However, several omics-based studies have now successfully characterised P. aeruginosa from human CF sputum, revealing unique adaptation patterns associated within this niche. This data enables evaluating the physiological relevance of in vitro and in vivo model systems, hereby highlighting the usefulness (and limitations) of models that mimic aspects of the physicochemical in vivo environment for studying P. aeruginosa infections in CF. In this review, we summarise a range of models of P. aeruginosa infection, including artificial sputum medium, air-liquid interface cell culture, ex vivo pig lung and mouse models, that have been evaluated for their physiological resemblance using omics-based approaches. We also address the current lack of proteomic and metabolomic validation approaches and outline key considerations and future directions to guide the continued refinement of experimental model systems.

Drug overdose remains an urgent public health concern as it is a leading cause of fatal injury in the United States, with approximately 90% being attributed to opioid-induced respiratory depression from synthetic opioids. This statistic is primarily driven by the rise in the use of fentanyl, a potent synthetic opioid and its increased use in combination with stimulant drugs. The rise in the combined use of opioids and stimulants raises questions about pharmacological and physiological interactions, and its implication for the treatment of their addictive consequences and of overdoses. Though opioid-related fatalities are due to respiratory depression and stimulant fatalities predominantly from cardiac disruption, co-use creates interactions that remain under studied. Similarly, how medications designed to treat opioid use disorder impact respiration has been mostly neglected. Here, we review preclinical and clinical studies on the effects of opioids and stimulants on respiration, focusing on brainstem respiratory nuclei, and explore implications for advancing prevention and treatment strategies for drug-related overdose.

The COVID-19 pandemic led to the rapid integration of telemedicine into health care delivery. As a result, the ability to effectively collaborate in interprofessional virtual teams became a necessity, as did the development of educational opportunities designed to equip health care students with these skills. Currently, there is a lack of dedicated tools to assess learners' ability and readiness to function as a well-coordinated virtual medical team.

The primary objective of this study was to conduct a psychometric assessment and validation of measures evaluating graduate-level health professions learners' experience and familiarity within virtual interprofessional settings. The secondary objective was to integrate these 2 validated subscales into a comprehensive survey tool for use in interprofessional education course evaluation, spanning domains including demographics, telehealth knowledge and skills, understanding interprofessional roles, communication, and teamwork.

An interprofessional expert panel reviewed an initial item pool of 126 questions compiled from adaptations of previously validated instruments and newly developed items. Five experts with experience in interprofessional education and telehealth competencies independently rated each item, and the highest-ranked items were selected for distribution to graduate health professions students at Stony Brook University. The survey was administered during mandatory in-class instruction across the School of Medicine, School of Nursing, School of Health Professions, and School of Social Welfare between November 2023 and June 2024. Participation was voluntary, and responses were anonymous. Item reduction focused on the 33 experience items and 8 familiarity items using interitem correlations, the Cronbach α, item-to-total correlations, and exploratory factor analysis (EFA); confirmatory factor analysis was not conducted.

A total of 520 responses were obtained. After excluding records without any response to questions 9 or 10 and duplicate submissions, 393 records were included in the analysis. The final survey was reduced from 51 to 32 items, including 5 demographic items, 3 telehealth knowledge items, 17 retained experience items, and 5 retained familiarity items. For the experience domain, EFA identified 17 items loading onto 3 factors, accounting for 69.81%, 13.00%, and 9.58% of the variance. Internal consistency remained high, with the Cronbach α decreasing from 0.94 to 0.90. For the familiarity domain, EFA supported a refined 5-item structure, with the Cronbach α decreasing from 0.94 to 0.91.

This EFA-based validation study provides preliminary psychometric support for 2 subscales assessing graduate health professions learners' experience and familiarity within virtual interprofessional settings. Additional validation work is needed before broader claims can be made regarding the full survey's ability to evaluate educational outcomes or clinical impact.

Pott's puffy tumour (PPT) is a rare complication of frontal sinusitis involving subperiosteal abscess and frontal bone osteomyelitis, often leading to serious intracranial sequelae. We report a case of a man in his 50s who presented with progressive, painless forehead swelling despite multiple antibiotic courses. Imaging confirmed bilateral subperiosteal collections and a right-sided epidural empyema. Initial management included broad-spectrum antibiotics, endoscopic sinus surgery and external drainage. Due to persistent collections, a second-stage osteoplastic approach was performed, resulting in complete resolution. Cultures were sterile, possibly due to early antibiotic administration. The patient completed 6 weeks of parenteral antibiotics and remained symptom-free at the 8-month follow-up. This case highlights the importance of early recognition, imaging and surgical management of PPT to prevent complications. An individualised, combined endoscopic and external approach may be essential in advanced presentations.