Despite advances in colorectal cancer (CRC) treatment, outcomes in advanced disease remain poor. Current therapies mainly target the epithelial compartment of the tumor, yet increasing evidence highlights the tumor microenvironment (TME), particularly the tumor stroma, as a prognostic and potentially predictive factor. This narrative review summarizes current evidence on stromal features as biomarkers and therapeutic targets in CRC. These stromal markers, such as fibroblast-associated protein (FAP), are associated with adverse outcomes, underscoring their clinical relevance. However, therapies directly targeting these stromal components have largely failed to improve survival as single agents. Combination strategies, stromal modulation integrated with established treatments, appear more promising. However, to date, stromal targeting remains challenging and has not led to standard-of-care treatment options. This highlights the need for more effective agents, the rational design of combination strategies, and improved patient selection. Combining stroma modulators with standard therapy, guided by stromal biomarkers, may enhance efficacy and help overcome the TME-induced resistance.
Paediatric oncology relies heavily on medical imaging for diagnosis, treatment planning, and longitudinal disease monitoring. Yet the field faces unique challenges, including a limited number of patients, diverse anatomy, motion artefacts, and a global shortage of subspecialised radiologists. These constraints can compromise diagnostic accuracy, prolong workflows, and increase the risk of errors, highlighting a critical need for innovative solutions. Artificial intelligence (AI) has emerged as a transformative tool capable of enhancing the entire imaging pipeline. From acquisition to reporting, AI-driven methods show potential to improve image quality, correct motion artefacts, harmonise multicentre datasets, and accelerate scans while reducing radiation exposure. Deep learning models and radiomics have been shown capable of precise tumour segmentation, early lesion detection, and classification, while integration with clinical and molecular data supports individualised staging, prognosis, and therapeutic decision-making. Beyond analysis, natural language processing and large language models can streamline report generation and clinical documentation, potentially enabling more efficient communication and workflow optimisation. Despite these advances, paediatric applications remain constrained by small, heterogeneous datasets, limited paediatric-specific models, and challenges in generalisability, explainability, and regulatory approval. Strategies such as model generalisation across new datasets, the development of retrainable generic models, privacy-preserving training, and synthetic data generation can help overcome these barriers, thereby improving model robustness and promoting equity in care. By augmenting rather than replacing radiologists, AI holds the potential to transform paediatric oncology imaging, improving diagnostic precision, workflow efficiency, and enhancing access to high-quality care. Continued collaboration between clinicians, data scientists, and regulatory bodies will be essential to realise this promise safely and effectively.
Children are extremely vulnerable to climate-related environmental impacts and air pollution due to both biological and behavioral factors. Despite the emerging evidence of the increasing effects of climate change on the world and on children’s health, policies to drive change and halt the effects are lacking. Climate change is causing Europe to heat up faster than other continents. Here, we assessed the evidence-based effects of climate change and air pollution on child health in Europe. A scoping review was performed to map the impact of climate-related exposures on the health of children in Europe. A literature search was conducted in three bibliographic databases (PubMed, Embase.com, and Cochrane Database of Systematic Reviews/Cochrane Central Register of Controlled Trials), for studies published between January 1, 2014, and November 11, 2024. Studies were included if they met the following criteria: original studies performed in Europe, addressing climate-related exposures (i.e., the effects of air pollution, heat stress and/or wildfires) on clinical outcomes in neonates, infants, and children (<18 years). The literature search generated a total of 3838 unique articles; upon screening, 73 articles were included in this scoping review. Most studies were conducted in South and West Europe. Climate-related exposures were linked to negative neonatal outcomes, increased risk of respiratory and allergic disease, adverse neurological development, and a higher incidence of metabolic conditions in children. Most studies assessed the impact of air pollution (mainly particulate matter with a diameter smaller than 2.5 micrometers PM2.5 and PM10 exposure); few studies assessed other climate-related outcomes such as heat stress or wildfires. Conclusion: Climate change is an active driver of pediatric morbidity in Europe, posing urgent respiratory, neurological, and perinatal risks amplified by social inequality. Protecting future generations demands a paradigm shift in healthcare that moves beyond treating acute symptoms to addressing upstream environmental drivers, including the integration of environmental exposure data into clinical practice.
Pruritus is a common and distressing symptom among dialysis patients, yet its underlying mechanisms remain incompletely understood. Most previous research has focused on systemic inflammatory markers, while little is known about local skin alterations contributing to pruritus. This study aimed to characterize skin biomarker profiles in dialysis patients with pruritus, in comparison with dialysis patients without pruritus and healthy controls, and to explore differences between pruritic and non-pruritic skin sites. In this multi-center cross-sectional exploratory study, stratum corneum samples were obtained using the tape-stripping method from 91 participants (67 dialysis patients and 24 healthy controls). Biomarkers were quantified, and adjusted linear and logistic (mixed) models were used to assess group differences and skin site variations. Dialysis patients with pruritus exhibited a significantly elevated IL-1RA/IL-1α ratio and reduced IL-18 levels compared to non-pruritic patients. There was also a strong indication of concomitant increases in IL-1RA and IFN-β in pruritic skin. Across all dialysis patients, IL-8, CCL17, and CXCL10 levels were significantly lower than in healthy controls, independent of pruritus status. Dialysis patients with pruritus demonstrate distinct alterations in skin immune profiles suggestive of localized inflammation and potential involvement of the opioid pathway. These findings provide new insights into the inflammatory mechanisms underlying pruritus in this population and may inform the development of targeted, personalized therapies.
The 11th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 20-21, 2025. The Summit provided a multidisciplinary forum to review and discuss recent outcome trials investigating emerging pharmacological therapies targeting diseases of the cardiovascular-kidney-metabolic (CKM) continuum. This report highlights the unique developments of 2025 discussed during the Summit, including the first head-to-head CVOT (SURPASS-CVOT), the growing evidence base for combination therapies across the disease spectrum, new insights into the inflammatory component of the CKM syndrome, and relevant policy developments. The first part of this report summarizes pioneering clinical trials addressing combination therapy with finerenone and empagliflozin (CONFIDENCE), the oral glucagon-like peptide-1 (GLP-1) receptor agonists orforglipron (ATTAIN-1), and the aldosterone synthase inhibitor (ASI) baxdrostat (BaxHTN). The second part presents recent guideline and policy developments discussed by experts in endocrinology, diabetology, cardiology, nephrology, hepatology, and general practice. In addition, advances in medical technology, particularly in continuous glucose and ketone monitoring, are highlighted, as well as emerging therapies for diseases of the CKM continuum. These include pharmacological agents for a broad spectrum of metabolic disorders such as metabolic liver disease and type 1 Diabetes (T1D) alongside emphasis on the importance of early detection and innovative treatment strategies. The 12th Cardiovascular Outcome Trial Summit will be held virtually on 19-20 November 2026 (http://www.cvot.org).
