European Journal of Clinical Investigation最新文献

{"title":"The potential of artificial intelligence in clinical trials","authors":"Rahul Aggarwal,&nbsp;Deepak L. Bhatt","doi":"10.1111/eci.70182","DOIUrl":"10.1111/eci.70182","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Clinical trials are an important part of evidence generation in medicine but remain burdened by escalating costs, inefficiencies and manual processes. Artificial intelligence (AI) has emerged as a promising approach to address these limitations by improving efficiency across the trial lifecycle.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this review, we examine emerging applications of AI across the clinical trial lifecycle. We highlight key examples demonstrating feasibility and potential impact.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AI-based approaches show promise in optimizing trial design, improving recruitment, streamlining conduct and enhancing data interpretation. Despite the potential of AI in trials, challenges persist, including data quality, regulatory and privacy concerns, as well as infrastructure issues. Ethical use will require strong governance frameworks emphasizing transparency and human oversight. The success of these technologies will depend on their continuous validation and monitoring of these technologies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>With appropriate validation, monitoring and governance, AI could enable a more efficient, cost-saving and effective clinical trial landscape that accelerates discovery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12949343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147316884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EXPRESSION OF CONCERN: COVID-19 re-infection","authors":"","doi":"10.1111/eci.70186","DOIUrl":"10.1111/eci.70186","url":null,"abstract":"<p><b>EXPRESSION OF CONCERN</b>: P. Brouqui, P. Colson, C. Melenotte, L. Houhamdi, M. Bedotto, C. Devaux, P. Gautret, M. Million, P. Parola, D. Stoupan, B. La Scola, J.-C. Lagier, and D. Raoult, “COVID-19 Re-Infection,” <i>European Journal of Clinical Investigation</i> 51, no. 5 (2021): e13537. https://doi.org/10.1111/eci.13537</p><p>This Expression of Concern is for the above article, published online on 6 March 2021 in Wiley Online Library (wiley onlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Fabrizio Montecucco; the European Society for Clinical Investigation; and John Wiley &amp; Sons Ltd. The Expression of Concern has been agreed due to questions raised about the study's adherence to French legal and ethical requirements for research involving human subjects. The investigation into these concerns is ongoing. Therefore, the journal has decided to issue an Expression of Concern to inform and alert readers.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 3","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147283268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical considerations for the use of vericiguat in older patients with heart failure and reduced ejection fraction","authors":"Francesco Castelletti,&nbsp;Elena Bianco,&nbsp;Giulia Fabro,&nbsp;Eleonora Nicolini,&nbsp;Francesco Dentali,&nbsp;Luca Liberale,&nbsp;Flavio Tangianu,&nbsp;Aldo Bonaventura","doi":"10.1111/eci.70173","DOIUrl":"10.1111/eci.70173","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Worsening heart failure (WHF) is a red flag in the natural history of heart failure (HF) that negatively impacts the prognosis. Urgent improvements in the management of WHF, especially among HF with reduced ejection fraction (HFrEF) patients, are needed to reduce morbidity and mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Vericiguat is an oral soluble guanylate cyclase (sGC) stimulator that was able to reduce the composite of HF hospitalization or cardiovascular (CV) death in the VICTORIA trial and is now recommended with a IIb indication by HF guidelines of different societies. Accordingly, several observational studies confirmed the positive findings observed in the trial. Since the population with HFrEF includes a large number of older patients with multiple comorbidities and different degrees of frailty, implementation and up-titration of guideline-directed medical treatments (GDMTs) could be challenging due to a higher odd of side effects. To this end, vericiguat possesses many advantages: once daily administration, good tolerance, limited side effects (e.g. hypotension), no need for routine laboratory testing or therapeutic drug monitoring. This makes vericiguat a good candidate for older, frail patients in order to increase patient compliance and limit drug discontinuation caused by side effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although commonly named as the fifth pillar of GDMTs, vericiguat should be considered as soon as possible among those patients with HFrEF and a WHF episode. However, the recently published VICTOR trial has investigated the effect of vericiguat in HFrEF patients who did not experience a recent WHF and did not demonstrate a reduction in the composite outcome of HF hospitalization or CV death, while providing beneficial effects on CV and all-cause mortality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146226048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise-induced immune response in breast cancer patients during prehabilitation, neoadjuvant or adjuvant treatment: A systematic review and meta-analysis","authors":"Simone Ubaghs,&nbsp;Kenza Mostaqim,&nbsp;Astrid Lahousse,&nbsp;Ishtiaq Ahmed,&nbsp;Andrea Polli,&nbsp;Christel Fontaine,&nbsp;Lore Dams,&nbsp;Yanthe Buntinx,&nbsp;Jolien Hendrix,&nbsp;Joeri Aerts,&nbsp;Eva Huysmans,&nbsp;Jo Nijs","doi":"10.1111/eci.70176","DOIUrl":"10.1111/eci.70176","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Adjuvant and neoadjuvant treatment for breast cancer (BC) such as chemotherapy and radiotherapy can lead to immune system impairment. Exercise is hypothesized to mitigate these effects by modulating immune responses and reducing chronic inflammation. This review aims to summarize the existing evidence on the impact of physical exercise on inflammatory markers and cellular immune function in patients with BC during prehabilitation, adjuvant or neoadjuvant treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic literature search was conducted in PubMed, Web of Science, Scopus and Embase to identify randomized controlled trials investigating exercise interventions in individuals with BC undergoing medical treatment. The included studies assessed outcomes on markers of immune function and inflammation. Subgroup analyses were undertaken for type of training, supervision, risk of bias, timing, duration and intensity of intervention and sample size.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty randomized controlled trials, including 1109 participants, were included in this review. Based on the available evidence, no significant influence of exercise on the determined immune factors and markers of inflammation could be confirmed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These meta-analyses suggest that exercise does not significantly alter immune function or markers of inflammation in BC patients during prehabilitation, adjuvant or neoadjuvant treatment. As no negative effect was observed, exercise appears to be safe and should be recommended to patients during cancer treatment because of its beneficial effects on quality of life, fatigue, cancer-related pain and survival.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146194415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased levels of serum surfactant protein D are associated with cardiovascular disease incidence in the Spanish adult population: [email protected] study","authors":"Wasima Oualla-Bachiri,&nbsp;Ana Lago-Sampedro,&nbsp;Eva García-Escobar,&nbsp;Cristina Maldonado-Araque,&nbsp;Elías Delgado,&nbsp;Felipe J. Chaves,&nbsp;Luis Castaño,&nbsp;Alfonso Calle-Pascual,&nbsp;Josep Franch-Nadal,&nbsp;Gabriel Olveira,&nbsp;Gemma Rojo-Martínez,&nbsp;Viyey Doulatram-Gamgaram,&nbsp;Sergio Valdés","doi":"10.1111/eci.70179","DOIUrl":"10.1111/eci.70179","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Cardiovascular disease (CVD) remains the leading cause of mortality. New biomarkers are needed to improve CVD risk prediction. Several studies have reported associations between surfactant protein D (SP-D), an innate immune system component, and CVD; however, general population studies remain scarce. The main aim of this study was to investigate the association between SP-D and CVD events incidence in the Spanish general adult population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Socio-demographic, lifestyle (including smoking status) and clinical data from 1707 participants of the [email protected] cohort without previous CVD events were collected and analysed. CVD events (including both morbidity and mortality) were reported at baseline and after 7.5 years of follow-up. SP-D serum levels were measured by ELISA and categorized in quartiles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SP-D categories are associated with CVD events incidence, independently from other strong risk factors such as cardiovascular risk scores (SCORE2 and SCORE2-OP), BMI, hs-CRP, or eGFR. Although SP-D has been linked to smoking, SP-D categories predicted CVD events incidence even among non-smokers. The addition of SP-D to multivariate models improved performance in the assessment, predicting 83% of the events with a specificity of 74% and a sensitivity of 84% in the overall population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SP-D may be considered as a promising biomarker of CVD events in combination with other well established factors in clinical practice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12892829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146156580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond glycemic control: How incretins are changing the cardiovascular trajectories of diabetes and obesity","authors":"Angelo Avogaro","doi":"10.1111/eci.70184","DOIUrl":"10.1111/eci.70184","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetes mellitus is a leading global health concern. The parallel rise in obesity has exacerbated this burden, with projections suggesting over half of the adult population will be overweight or obese by 2050. Incretin-based therapies have emerged as cornerstone treatments for type 2 diabetes (T2DM), offering glycemic control alongside promising cardiovascular and renal benefits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This review consolidates current evidence regarding the cardiovascular effects of incretin-based medications. GLP-1 receptor agonists (GLP-1RAs) have demonstrated protective effects in preclinical models. Clinical trials show modest but consistent reductions in major adverse cardiovascular events (MACE), with additional renal benefits. Conversely, DPP-4 inhibitors display cardiovascular neutrality. Real-world studies largely support the superiority of GLP-1RAs over other glucose-lowering agents (e.g. DPP-4 inhibitors, insulin) in reducing MACE, though their benefits in heart failure (HF) with reduced ejection fraction remain limited. Recent trials in patients with obesity-related HFpEF demonstrate that GLP-1RAs and dual GIP/GLP-1 agonists significantly improve symptoms, functional status, and reduce HF events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>While incretin therapies represent a transformative advancement in cardiometabolic care, challenges remain—including gastrointestinal side effects, adherence issues, lean mass loss and cost. As next-generation agents (e.g. triple agonists) advance, lifestyle interventions remain essential for durable, management of diabetes, obesity and associated cardiovascular conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can ammonia scavenging treat MASLD? Evaluating the evidence for L-ornithine L-aspartate—A systematic review","authors":"Abdulrahman Ismaiel,&nbsp;Vera Ciornolutchii,&nbsp;Stefan-Lucian Popa,&nbsp;Dan L. Dumitrascu","doi":"10.1111/eci.70185","DOIUrl":"10.1111/eci.70185","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Introduction&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;While hyperammonemia is traditionally associated with decompensated cirrhosis, emerging evidence suggests that disturbances in nitrogen homeostasis contribute to disease progression in earlier stages of steatohepatitis and fibrosis. L-ornithine L-aspartate (LOLA), an established ammonia scavenger, targets key pathophysiological mechanisms shared by metabolic dysfunction-associated steatotic liver disease (MASLD), including oxidative stress, mitochondrial dysfunction and hepatic stellate cell activation. This systematic review synthesizes current experimental and clinical research to evaluate the potential therapeutic role of LOLA in MASLD.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A systematic search of PubMed, Embase and SCOPUS was conducted up to December 1, 2025, following PRISMA 2020 guidelines. Eligible studies included experimental (in vivo/in vitro) and clinical trials evaluating the effects of LOLA or L-aspartate on hepatic steatosis, inflammation, or fibrosis in the context of MASLD. Data extraction and quality assessment were performed independently by two reviewers using appropriate tools for animal and human studies.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Nineteen studies were included, comprising 10 experimental pre-clinical models (9 in vivo animal studies and 1 in vitro study) and 9 clinical studies involving approximately 1671 participants. Experimental studies consistently demonstrated that LOLA intervention ameliorates hepatic steatosis, inflammation and collagen deposition. Identified molecular mechanisms included the activation of the LKB1-AMPK axis, restoration of mitochondrial bioenergetics and modulation of the gut-liver-muscle axis. In clinical studies, results from three randomized controlled trials (RCTs) indicated significant improvements in liver enzymes (ALT, AST) and lipid profiles, with reductions in hepatic steatosis. Evidence from six observational and open-label studies corroborated these biochemical improvements and further demonstrated significant reductions in blood ammonia levels, improved intrahepatic microcirculation and reduced liver stiffness and patient-reported fatigue. However, clinical evidence remains limited by study heterogeneity and a lack of large-scale randomized trials using specific MASLD criteria.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Preclinical evidence suggests that LOLA exerts pleiotropic hepatoprotective effects in MASLD by targeting hyperammonemia-induced fibrosis and metabolic dysregulation. While growing clinical data indi","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12882027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving end-of-life care in the cardiac intensive care unit: Navigating the challenge of timing palliative care intervention","authors":"Simona Giubilato,&nbsp;Roberta Della Bona,&nbsp;Alessia Gambaro,&nbsp;Carlotta Sorini-Dini,&nbsp;Serafina Valente,&nbsp;Giovanna Geraci,&nbsp;Carmine Riccio,&nbsp;Andrea Di Lenarda,&nbsp;Michele Massimo Gulizia,&nbsp;Massimo Grimaldi,&nbsp;Roberta Rossini,&nbsp;Fabrizio Oliva,&nbsp;Nicola Gasparetto,&nbsp;Alice Sacco","doi":"10.1111/eci.70174","DOIUrl":"10.1111/eci.70174","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Integrating end-of-life (EoL) care in cardiac intensive care units (CICUs) is particularly complex because it requires a shift from a purely curative approach to one that emphasizes symptom management, emotional and spiritual support and patient-centered care. Moreover, this transition is challenging due to the need to balance life-sustaining treatments with the goals of comfort and dignity. The concept of EoL care varies across countries and is influenced by cultural, ethical and legal factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This narrative review examines palliative and EoL care in critically ill cardiac patients, including those with advanced heart failure, cardiogenic shock and other acute or chronic cardiac conditions, with a focus on models of care, multidisciplinary team involvement, ethical challenges and barriers to implementation in the CICU setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Key candidates for palliative care (PC) in heart disease include patients with advanced heart failure, cardiogenic shock and other acute or chronic cardiac conditions; however, its implementation remains limited compared to other disciplines, such as oncology. In EoL care, multidisciplinary teams, including cardiologists, nurses, PC specialists and social workers, play a crucial role in providing holistic care. Effective communication with patients and their families is essential for aligning treatment with individual values and goals. Ethical dilemmas, such as the withdrawal of life-sustaining treatments and the deactivation of implanted cardiac devices, require compassionate and transparent decision-making. Unlike previous reviews, this work specifically highlights the timing of palliative care integration as the main factor influencing patient outcomes and family experience.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Timely integration of palliative care in the CICU remains a major challenge. Significant gaps persist in training, resource allocation and quality indicators for palliative and EoL care. Addressing these shortcomings through enhanced education, standardized protocols and rigorous research is essential to ensure the effective delivery of PC in the CICU setting.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a pathological feed-forward loop linking succinate, HIF1α signalling and vascular remodelling in abdominal aortic aneurysm","authors":"S. Griepke,&nbsp;G. L. Tripodi,&nbsp;K. L. Kristensen,&nbsp;J. Hansen,&nbsp;P. S. Jensen,&nbsp;L. M. Rasmussen,&nbsp;J. S. Lindholt,&nbsp;D. F. J. Ketelhuth","doi":"10.1111/eci.70170","DOIUrl":"10.1111/eci.70170","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Succinate is a metabolite with roles beyond energy production, including regulation of metabolic pathways, signalling and protein modifications. Abdominal aortic aneurysm (AAA) is a disease characterized by deleterious remodelling of the aortic wall, increasing the risk of rupture and sudden death. Although succinate has been linked to vascular diseases, its regulation within the aorta and potential involvement in AAA remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims and Results</h3>\u0000 \u0000 <p>In this study, we combined analyses of human plasma and aortic tissue with cell culture experiments to help understand the role of succinate in AAA pathogenesis. Analysis of plasma samples from 461 AAA patients and 189 age-matched controls (67–72 years) from the ‘Viborg Vascular Screening Trial’ showed significantly increased succinate levels in AAA individuals, approximately 28% higher than in controls. Logistic regression adjusted for cardiovascular risk factors confirmed a strong association (OR = 4.56; 95% CI: 2.57–8.09, highest vs. lowest tertile). Analysis of tissue homogenates confirmed elevated succinate levels in AAA compared to control aortic tissue. Transcriptomic analyses of public AAA datasets indicated that succinate accumulation may result from downregulation of the succinate dehydrogenase complex and upregulation of the gamma-aminobutyric acid shunt pathway, particularly in vascular smooth muscle cells (VSMCs). In cultures, we showed that dedifferentiation increases succinate production, while succinate treatment, in turn, promotes VSMC dedifferentiation in a process involving HIF1α.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study proposes succinate as a driver of AAA through a feed-forward loop involving HIF1α signalling and VSMC phenotypic switching. Our work identifies the succinate–HIF1α axis as a promising therapeutic target to disrupt key pathological processes underlying AAA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146085209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing urine-derived stem cells: Cryopreservation validation and sex-specific metabolism","authors":"Gonçalo José Martins Afonso,&nbsp;Carla Cavaleiro,&nbsp;Sofia Marlene Nunes,&nbsp;Francisco Pereira,&nbsp;Paulo Jorge Oliveira,&nbsp;Jorge Valero,&nbsp;Sandra Isabel Mota,&nbsp;Elisabete Ferreiro","doi":"10.1111/eci.70172","DOIUrl":"10.1111/eci.70172","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Urine-derived stem cells (UDSC) are an emerging, non-invasive source of human stem cells combining easy collection, broad accessibility and high patient compliance with multilineage differentiation capacity. However, key gaps remain in UDSC research, particularly in understanding sex-related differences and the lack of a validated cryopreservation protocol, a critical aspect for primary cells, given their variability in colony formation, proliferation rates and experimental timing. To address these limitations, this study aimed to establish, for the first time, a reliable protocol for UDSC cryopreservation and to explore potential sex-related differences, with a specific focus on glycolysis and mitochondrial respiration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>UDSC were isolated from urine samples of healthy donors (aged 27–50, 4 males and 4 females), cultured in 1:1 DMEM:KSFM supplemented with 10% fetal bovine serum and cryopreserved at passages 2–4 using the same medium with the sole addition of 5% dimethyl sulfoxide. Cells were evaluated for viability, apoptosis/necrosis, metabolic profile and multilineage differentiation potential. Comparisons were performed based on donor sex, as well as before and after cryopreservation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Male- and female-derived UDSC displayed no significant differences in viability and cell death or metabolic profile. Moreover, supervised and unsupervised machine learning methods were unable to discriminate between the two groups, allowing for pooled data analysis and improved statistical power. Similarly, fresh and cryopreserved UDSC displayed comparable viability, metabolic activity and multilineage differentiation relative to fresh cells, with no detectable differences in computational analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings support UDSC adoption for biobanking, disease modelling and regenerative medicine.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12834848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}