European Journal of Clinical Investigation最新文献

{"title":"The Triglyceride-Glucose (TyG) Index and Incident Diabetes and Cardiovascular Events in People Living With HIV-1 Infection. A 14-Year Observational Cohort Study","authors":"Daniele Pastori,&nbsp;Gianluca Gazzaniga,&nbsp;Tommaso Brogi,&nbsp;Marco Rivano Capparuccia,&nbsp;Caterina Fimiani,&nbsp;Claudio Mastroianni,&nbsp;Ivano Mezzaroma","doi":"10.1111/eci.70258","DOIUrl":"10.1111/eci.70258","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>People living with HIV (PWH) are at increased risk for metabolic and cardiovascular diseases. However, there is no structured prevention strategy for these subjects. The triglyceride-glucose (TyG) index has shown predictive value for Type 2 diabetes mellitus (T2DM) and cardiovascular events (CVEs) in the general population, but its utility in PWH remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective study including 477 PWH without baseline T2DM. TyG index was calculated as follows: ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. ROC analysis was used to identify the optimal TyG threshold for T2DM, and logistic regression analysis was used to evaluate the association with T2DM. The association between TyG index and CVEs was investigated using Kaplan–Meier survival analysis and Cox proportional hazards regression models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>477 PWH were included. Median age was 38 years and 26% were women. During a median follow-up of 14.2 years, 38 participants developed T2DM and 45 experienced CVEs. The TyG index demonstrated fair discrimination for incident T2DM (AUC: 0.675, 95% CI 0.591–0.759), with an optimal threshold of 4.78. Participants with TyG ≥ 4.78 had a higher risk of developing T2DM (aOR 2.86, 95% CI 1.35–6.12). PWH in the highest TyG tertile had also higher risk for CVEs compared with those in the lowest tertile (aHR 3.31, 95% CI 1.10–9.97).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In PWH, a higher TyG index was independently associated with an increased risk of both T2DM and CVEs over long-term follow-up. The TyG index represents a practical, low-cost tool for early metabolic risk stratification in this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873533","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":"Ethical Considerations on Artificial Intelligence, Health and Health Care. All That Glisters Is Not Gold","authors":"Piero Portincasa,&nbsp;Mohamad Khalil,&nbsp;Pierfrancesco Novielli,&nbsp;Sabina Tangaro","doi":"10.1111/eci.70254","DOIUrl":"10.1111/eci.70254","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Artificial intelligence (AI) is transforming global health care through innovations in deep learning, generative models and agentic AI systems. Traditional reductionist approaches to complex pathophysiological pathways fail to capture the true complexity of disease, motivating the adoption of network medicine (NM), which models biological systems as dynamic, interconnected networks. When combined with AI, NM enables integration of multiomic data and better characterizes disease mechanisms to guide precision therapies. Nevertheless, the rapid diffusion of AI in health care also raises profound ethical, regulatory and social challenges, since only a small fraction of AI tools have achieved routine clinical use, often due to limited generalizability, opaque algorithms and workflow incompatibility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Key strategies in this scenario are explainable AI (XAI) and counterfactual reasoning, which enhance transparency, accountability and fairness. These methods allow clinicians and regulators to interpret model decisions, identify biases and ensure human oversight in high-stakes contexts. Ethical frameworks such as the European Commission's Assessment List for Trustworthy AI (ALTAI) operationalize these goals through auditable requirements spanning transparency, fairness, privacy and societal well-being.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Yet, challenges persist, including algorithmic bias, data inequity and variable regulatory standards across regions. Machine learning and generative AI hold significant promise for improving diagnostics, drug discovery and population health, but their deployment must be guided by fairness, transparency and human rights principles. Indeed, inadequate governance risks can impact the already existing health inequalities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>For these reasons, the convergence of AI, NM and telemedicine requires a co-evolutionary model which must be rooted in ethical design, rigorous validation and equitable global implementation. Only by aligning technical innovation with sound ethical frameworks and explainability standards will AI become a highly transformative yet trustworthy force in the field of precision and public health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873520","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":"Pragmatic Clinical Trials in Internal Medicine: Design Principles and Context-Specific Implementation","authors":"Carmine Zoccali,&nbsp;Giovanni Tripepi","doi":"10.1111/eci.70252","DOIUrl":"https://doi.org/10.1111/eci.70252","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pragmatic clinical trials (PCTs) evaluate interventions under routine care conditions, prioritizing external validity and decision relevance over tightly controlled efficacy. Internal medicine, characterized by multimorbidity, polypharmacy, and heterogeneous care pathways, is a prime field for PCTs embedded in real-world practice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This narrative review synthesizes methodological developments in pragmatic trial design with a focus on internal medicine. Key domains include eligibility criteria, recruitment and randomization strategies, intervention and comparator definition, outcome measurement using routinely collected data, and integration within learning health systems, alongside ethical and regulatory considerations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PCTs may use broad eligibility criteria and recruitment processes aligned with local care pathways to enrol patients who resemble those for whom the treatment decision arises in practice. EHR-supported screening can facilitate this process in some health systems but is not a prerequisiteRandomization often occurs at the cluster level or at the point of care, minimizing disruption of workflows. Interventions typically compare accepted care strategies delivered via usual clinicians with flexible implementation. Outcomes emphasize patient- and system-relevant endpoints (e.g., hospitalizations, major events, quality of life) ascertained primarily from EHRs, claims, registries, and patient-reported systems. Embedding trials within health systems enables automated data capture, scalable implementation, and continuous learning but raises challenges in data quality, consent models, privacy, and equitable inclusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Pragmatic trials offer a powerful approach to generate decision-relevant evidence for internal medicine by aligning design features with real-world practice and existing data infrastructures. Their successful conduct requires close collaboration among clinicians, methodologists, data scientists, and health system leaders, with careful attention to ethics, governance, and health equity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 9","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807709","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":"Temporal Trends in Multimorbidity Patterns in Patients With Atrial Fibrillation—A Nationwide Cohort Study","authors":"Sanni Reinilä,&nbsp;Niklas Kiuru,&nbsp;Ville Langén,&nbsp;Jussi Jaakkola,&nbsp;Olli Halminen,&nbsp;Jukka Putaala,&nbsp;Ossi Lehtonen,&nbsp;Pirjo Mustonen,&nbsp;Jari Haukka,&nbsp;Miika Linna,&nbsp;Juha Hartikainen,&nbsp;K. E. Juhani Airaksinen,&nbsp;Mika Lehto,&nbsp;Gregory Y. H. Lip,&nbsp;Konsta Teppo","doi":"10.1111/eci.70253","DOIUrl":"https://doi.org/10.1111/eci.70253","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The prevalence of both atrial fibrillation (AF) and multimorbidity is increasing with population aging. However, reliable and comprehensive data on temporal trends in multimorbidity among patients with AF are lacking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The nationwide Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) cohort study includes all patients with incident AF between 2009 and 2018. Data on comorbidities were obtained from national healthcare, reimbursement and prescription registers using a fixed 5-year look-back period. A previously established comorbidity categorisation was applied to characterise multimorbidity burden. Temporal trends in the prevalence of common comorbidities and in the number of distinct diagnosis groups at the time of new-onset AF were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 85% of 196,536 individuals with new onset AF had diagnoses from ≥ 2 comorbidity groups and 28% from ≥ 6 comorbidity groups. Mean number of different groups increased from 3.9 to 4.2 between 2009 and 2018. Although adjustment for age attenuated the association, the increase in multimorbidity over time remained significant after adjustment for age and sex. Multimorbidity was more common in women than in men (4.2 vs. 3.9) and increased with age. Hypertensive diseases, obesity and other metabolic diseases, diabetes and other cardiovascular diseases were most prevalent. The prevalence of ischaemic heart disease and other diseases of the heart and pulmonary circulation declined during the study period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Multimorbidity is highly prevalent and increasing among patients with AF, highlighting the importance of a holistic management approach.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 8","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785025","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":"MicroRNA and Inflammatory Biomarker Signatures Associated With Neurological Outcome After Out-Of-Hospital Cardiac Arrest: The MiRacle Study","authors":"Francisco Rafael Jiménez-Trinidad,&nbsp;Eva Moreno-Monterde,&nbsp;Carlos Roca-Guerrero,&nbsp;Oriol de Diego,&nbsp;Teresa López-Sobrino,&nbsp;Marc Izquierdo-Ribas,&nbsp;Pedro Cepas-Guillén,&nbsp;José María Moreno-Coca,&nbsp;Erwin Bechtold,&nbsp;Vanessa Hervas,&nbsp;Silvia Pérez-Ortega,&nbsp;Lidia Sabater,&nbsp;Ana Isabel Tercero,&nbsp;Carles Gaig,&nbsp;Josep Brugada,&nbsp;Ana García-Álvarez,&nbsp;Xavier Freixa,&nbsp;Ana Paula Dantas,&nbsp;Rut Andrea","doi":"10.1111/eci.70251","DOIUrl":"https://doi.org/10.1111/eci.70251","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Early neuroprognostication in Out-of-Hospital Cardiac Arrest (OHCA) remains challenging due to the lack of reliable biomarkers. Circulating microRNAs have emerged as potential indicators of inflammation and brain injury (HIBI). This study aimed to evaluate whether in silico-predicted microRNAs could discriminate neurological outcomes early in OHCA patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Consecutive OHCA patients admitted to the Acute Cardiac Care Unit with available cryopreserved blood samples were analysed. Neurological outcome was classified into favourable (Cerebral Performance Category (CPC) 1–2) and unfavourable (CPC 3–5). Blood samples at 0, 24, 72 h after hospital admission were collected. An in silico-derived network of inflammation-HIBI-related microRNA was generated and validated in all patients at the three time-points.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 100 patients were included (59.7 ± 12.5 years, 19% women). 53% had unfavourable neurological outcomes. Eleven candidate microRNAs were identified, showing differential time-dependent expression within 72 h. The earlier and most predictive microRNAs for unfavourable neurological outcome were miR-1-3p (AUC 0.637) and miR-124-3p (AUC 0.606) at 0 h, miR-21-5p (AUC 0.614) and miR-499a-5p (AUC 0.645) at 24 h. The miR-499-5p maintained the best AUC across all time-points. A multiparametric model achieved an AUC of 0.690. A pro-inflammatory environment, characterised by C-Reactive Protein (CRP) and neutrophil-to-lymphocyte ratio, showed distinct temporal expression patterns regarding neurological outcome. Neuroinflammatory miR-let-7a-5p, miR-23a-3p and miR-146a-5p were significantly overexpressed in the unfavourable group and correlated positively with CRP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In silico derived inflammatory and HIBI-related microRNAs showed time-dependent expression patterns that may distinguish neurological outcomes within 72 h after OHCA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 8","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70251","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783932","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":"Contemporary Management of Aortic Stenosis: Timing of Intervention and Lifetime Valve Management","authors":"Ottavia Cozzi,&nbsp;Thomas Pilgrim","doi":"10.1111/eci.70245","DOIUrl":"https://doi.org/10.1111/eci.70245","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Calcific aortic stenosis (AS) is the most relevant valvular heart disease in aging populations and remains both underdiagnosed and undertreated. Screening studies reveal a high prevalence of unrecognized disease, while up to 40% of patients with symptomatic severe AS do not undergo valve intervention, resulting in poor survival. No pharmacologic therapy has yet altered disease progression, although targeted approaches such as lipoprotein(a) inhibition are under investigation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This paper provides a comprehensive perspective review of the evolving epidemiology, timing of intervention, and long-term management of aortic stenosis, drawing on randomized trials and contemporary clinical data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Randomized trials have challenged the traditional watchful waiting strategy in asymptomatic severe AS, showing that early aortic valve replacement (AVR) reduces cardiovascular events, though survival benefit depends on patient selection and timing. Moderate AS is increasingly recognized as a high-risk condition, prompting ongoing trials evaluating earlier intervention. As transcatheter aortic valve implantation (TAVI) expands to younger, lower-risk patients, long-term issues—including conduction disturbances, paravalvular leak, cerebrovascular events, valve hemodynamics and durability, and redo feasibility—become central to care. Contemporary data suggest comparable mid-term durability between TAVI and surgery, but lifetime management planning is essential.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Optimal care of aortic stenosis requires earlier diagnosis, optimized procedural strategies, and a lifetime-oriented approach to management, supported by continued investigation into pharmacologic therapy and the timing of intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 8","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70245","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753892","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":"Oral Stepdown Therapy for Gram-Negative Bloodstream Infections: A Systematic Review and Meta-Analysis","authors":"Lorenzo Onorato,&nbsp;Ilaria De Luca,&nbsp;Marika Ferrante,&nbsp;Giuseppe Ricciardiello,&nbsp;Caterina Monari,&nbsp;Nicola Coppola","doi":"10.1111/eci.70244","DOIUrl":"https://doi.org/10.1111/eci.70244","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Early oral step-down has been proposed as a strategy to optimize antimicrobial use in Gram-negative bloodstream infections (BSIs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a systematic review and meta-analysis of full-text studies published in English and indexed in MEDLINE and EMBASE up to April 2025. Randomized controlled trials (RCTs) and observational studies including patients with Gram-negative BSIs managed either with oral step-down within 5 days of IV therapy or with continued IV therapy were eligible. Risk of bias was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle–Ottawa Scale for observational studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 4120 screened records, 13 studies (3 RCTs and 10 cohort studies) including 10,000 patients met the inclusion criteria; 5016 of enrolled patients (52%) switched to oral therapy, mainly to fluoroquinolones (2992, 59.6%). A lower all-cause mortality was observed in patients receiving oral step-down (RR: 0.39, 95% CI: 0.16–0.93; <i>p</i> = 0.034). When stratifying studies according to timing of the switch to oral therapy, no significant difference in mortality was observed in studies with a median switch time ≤ 3 days (<i>p</i> = 0.29). Conversely, studies with a median switch time &gt; 3 days showed a lower mortality rate in the oral step-down group, approaching statistical significance (<i>p</i> = 0.051). No significant differences were found between treatment groups in terms of clinical failure (<i>p</i> = 0.28). Microbiological failure was significantly less frequent among patients receiving oral step-down therapy (RR = 0.69, 95% CI: 0.49–0.97; <i>p</i> = 0.032), while adverse event rates were comparable (<i>p</i> = 0.52). However, sensitivity analyses limited to propensity score–adjusted data demostrated no significant differences in mortality (<i>p</i> = 0.32) or microbiological failure (<i>p</i> = 0.076).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Oral step-down therapy for Gram-negative BSIs appears to be a valuable alternative to prolonged IV treatment, potentially reducing IV exposure, complications and healthcare costs without compromising clinical or microbiological outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>PROSPERO registration number: CRD420251056335</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 8","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753891","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":"Evaluation of Liver Grafts During Machine Perfusion at 20°C via Metabolization of 13C-Methacetin","authors":"Charlotte von Horn,&nbsp;Laura Malkus,&nbsp;Derya Berger,&nbsp;Stefanie Bertram,&nbsp;Thomas Minor","doi":"10.1111/eci.70250","DOIUrl":"https://doi.org/10.1111/eci.70250","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Evaluative measures, helping to decide whether a marginal graft can be used for transplantation or rather be discarded are of utmost importance but yet basically underdeveloped. Recent technical developments allow for the isolated detection of 13C-labelled carbon dioxide in the oxygenator exhaust of an isolated perfused organ. By adding a 13C-labelled tracer, its metabolism can be monitored by measuring the increase in 13C carbon in the exhaust air. Here we evaluated the potential of the technique to evaluate pig livers during machine perfusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Porcine livers (six per group) were subjected to 5, 20 or 45 min of warm ischemia and cold stored overnight. Evaluative machine perfusion was done with MPS at 20°C for 2 h. After injection of 13C-methacetin as a tracer, ¹³CO₂ as metabolic end-product can be quantified by high precision laser-based spectroscopy in the gas outflow of the oxygenator.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The ¹³CO₂ test showed clear differences between all three groups, and provided superior discriminative potential when compared to conventional parameters (e.g., flow, transaminases, lactate). ROC curve analysis for discrimination between 5 and 20 min of warm ischemia revealed an area under the curve of 0.916 while comparison of 20 and 45 min of warm ischemia results in an area under the curve of 1.0 (<i>p</i> &lt; 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Thus, the 13C turnover test appears to have the potential of an objective, quantitative and valuable adjunct in the toolbox for pre-transplant evaluation of questionable liver grafts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 8","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753801","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":"Differential Effects of Tafamidis on Cardiac Remodelling in Transthyretin Amyloid Cardiomyopathy: Evidence From Contemporary Imaging Data","authors":"Tameem Quader,&nbsp;Krisha Patel,&nbsp;James Sindone,&nbsp;Shaun Khanna,&nbsp;Aditya Bhat,&nbsp;Henry Chen,&nbsp;Gary Gan,&nbsp;Nitesh Nerlekar,&nbsp;Suzanne Eshoo,&nbsp;Nicole Bart,&nbsp;Liza Thomas,&nbsp;Andrew Sindone","doi":"10.1111/eci.70246","DOIUrl":"10.1111/eci.70246","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Tafamidis is the only approved disease-modifying therapy for transthyretin amyloid cardiomyopathy (ATTR-CM) in Australia. Although its clinical efficacy is established, its effects on cardiac remodelling assessed by contemporary multimodality imaging remain incompletely defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MEDLINE, Embase and Cochrane databases were systematically searched from 2000 to 2025. Observational studies evaluating tafamidis-treated versus untreated/control patients that reported serial TTE, CMR or bone-tracer scintigraphy measurements were eligible. Change-from-baseline values were used to derive measures. Outcomes were pooled as standardised mean differences (SMDs) with 95% confidence intervals using random-effects modelling. A two-sided <i>p</i> &lt; 0.05 was considered statistically significant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Over a mean follow-up of 16 months, tafamidis was associated with significant improvements in left atrial reservoir strain (LASr) (SMD +0.58, 95% CI +0.27 to +0.89; <i>p</i> &lt; 0.001; <i>I</i>² = 0) on TTE and right ventricular ejection fraction (RVEF) (SMD +0.51, 95% CI +0.16 to +0.86; <i>p</i> = 0.004; <i>I</i>² = 0) on CMR. A reduction in left atrial volume index (LAVi) was observed (SMD –0.24, 95% CI –0.46 to −0.02; <i>p</i> = 0.034; <i>I</i>² = 0) on TTE. No consistent effects were seen for LV parameters including LVEF, LV-GLS, LV mass index, wall thickness, diastolic indices, pulmonary pressures, tissue characterisation markers (native T1, ECV), or H/CL ratio, despite trends toward benefit in some.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Tafamidis demonstrates selective remodelling effects in ATTR-CM, with the most benefits noted in left atrial function and RV systolic performance, rather than LV structural or functional parameters. Imaging parameters such as LASr, LAVi, and RVEF may serve as sensitive endpoints of therapeutic response in future clinical trials, offering mechanistic insights beyond conventional LV metrics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Study Registration</h3>\u0000 \u0000 <p>PROSPERO CRD420251145891.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 8","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711097","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":"Acute Myocarditis: From Pathophysiology to Risk-Stratified Management—A Clinical Review","authors":"Michele Golino,&nbsp;Marco Giuseppe Del Buono,&nbsp;Michele Marchetta,&nbsp;Nicola Potere,&nbsp;Aldo Bonaventura,&nbsp;Alessandra Vecchiè,&nbsp;Danilo Malandrino,&nbsp;Giacomo Emmi,&nbsp;Jordana Kron,&nbsp;Antonio Abbate","doi":"10.1111/eci.70247","DOIUrl":"10.1111/eci.70247","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Acute myocarditis is an inflammatory disease of the myocardium with an annual incidence of 4–14 per 100,000 individuals, predominantly affecting young adults. Its clinical features are frequently nonspecific, mimicking acute coronary syndrome, which makes early recognition and management challenging. The disease results from infectious (predominantly viral) and noninfectious triggers, including autoimmune disorders, immune checkpoint inhibitors and mRNA vaccines. Pathophysiology involves a dysregulated interplay between innate immunity and adaptive immunity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Clinical Features and Diagnosis</h3>\u0000 \u0000 <p>Presentation is typically dominated by chest pain, with dyspnea and syncope reported less frequently. Cardiac magnetic resonance (CMR), with the 2018 updated Lake Louise criteria, has become the cornerstone of noninvasive diagnosis, whereas endomyocardial biopsy (EMB), in experienced centres, remains the gold standard for histological characterization and guiding immunosuppressive therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Outcomes and Management</h3>\u0000 \u0000 <p>Uncomplicated myocarditis usually resolves spontaneously. However, approximately 25% of patients with myocarditis have left ventricular systolic dysfunction, ventricular arrhythmias or acute heart failure. Mortality ranges from 1% to 7%, depending on presentation, aetiology and specific populations. Treatment centers on guideline-directed heart failure therapy, with immunosuppression reserved for complicated presentations and virus-negative, autoimmune or histologically specific subtypes. Mechanical circulatory support is critical in fulminant cases, where mortality is high.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This clinical review synthesizes recent guideline updates and emerging trial data, primarily from literature published in the past 10 years, to support a phenotype-driven approach to acute myocarditis, in which management is guided by clinical severity, suspected aetiology, selective use of CMR and EMB and targeted therapy. Ongoing trials investigating corticosteroids, targeted biologics and novel therapies may further refine personalized immunomodulatory strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 8","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701154","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}