European Journal of Clinical Investigation最新文献

{"title":"Educational level, clinical outcomes and quality of care in a Swiss cohort of patients with acute coronary syndromes.","authors":"Maëlle Achard, Cédric Follonier, Evelyne Fournier, David Carballo, Mattia Branca, Dik Heg, David Nanchen, Lorenz Räber, Roland Klingenberg, Stephan Windecker, Thomas F Lüscher, Christian M Matter, Nicolas Rodondi, François Mach, Baris Gencer","doi":"10.1111/eci.70097","DOIUrl":"https://doi.org/10.1111/eci.70097","url":null,"abstract":"<p><strong>Background: </strong>Despite universal coverage, inequities persist in acute coronary syndrome (ACS) care. This study examines how educational levels impact the quality and outcomes of health care.</p><p><strong>Methods: </strong>A cohort of ACS patients hospitalized in five Swiss university hospitals was categorized into four educational levels (EL) with EL1 defined as lower than vocational school and EL4 as a university degree. The use of medical therapies, achievement of preventive targets and risk of clinical events were evaluated across ELs at baseline (N = 6040), 1-year (N = 5756) and 5-years (N = 2253) and presented with adjusted marginal odds ratios (mOR), average marginal effect (AME) and hazard ratios (HRs).</p><p><strong>Results: </strong>Among 6040 patients, the mean age was 63 years, and 81% were male. Participants with lower EL had a greater burden of cardiovascular risk factors at baseline. Compared with EL4 participants EL1 participants had lower adherence to cardiac rehabilitation (mOR = .6 [95% CI .5-.8], AME = -10%) and were less likely to be followed by a cardiologist (mOR .6 [95% CI .5-.8], AME = -6%). Use of medical therapies did neither differ across EL at discharge nor during follow-up. At 1 year, smoking cessation (mOR = .7 [95% CI .5-.9], AME = -10%) and weight reduction ≥5% among overweight or obese participants (mOR = .7 [95% CI .5-.9], AME = -6%) were less frequent in individuals with EL1 compared with EL4. At long term, achievement of LDL-C <1.8 mmol/L (<70 mg/dL) (mOR = .6 [95% CI .4-.9], AME = -9%) was less frequent in individuals with EL1 compared with EL4. Lower EL was associated with an increased risk of major acute coronary event (MACE) at short- (aHR = 1.4 [95% CI 1.0-2.0] for EL1 vs. EL4) and long term (aHR = 1.3 [95% CI 1.0-1.6] for EL1 vs. EL4) and all-cause death at long term (aHR = 1.6 [95% CI 1.1-2.2] for EL1 vs. EL4).</p><p><strong>Conclusion: </strong>In Switzerland, disparities in ACS care and outcomes remain across EL, emphasising the need for tailored interventions to reduce inequities.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70097"},"PeriodicalIF":3.6,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729043","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":"Ketone bodies and cancer risk in the general population: The prevention of renal and vascular end-stage disease (PREVEND) study","authors":"Li Luo,&nbsp;Martine G. E. Knol,&nbsp;Lyanne M. Kieneker,&nbsp;Bert van der Vegt,&nbsp;Stephan J. L. Bakker,&nbsp;Eke G. Gruppen,&nbsp;Rudolf A. de Boer,&nbsp;Joseph Pierre Aboumsallem,&nbsp;Margery A. Connelly,&nbsp;Robin P. F. Dullaart,&nbsp;Ron T. Gansevoort","doi":"10.1111/eci.70100","DOIUrl":"https://doi.org/10.1111/eci.70100","url":null,"abstract":"&lt;p&gt;Ketone bodies (KBs) comprise acetoacetate (AcAc), acetone and β-hydroxybutyrate (β-OHB). In the state of limited glucose supply, KBs are produced from fatty acids in the liver and transported to the extrahepatic cells as an alternative source of energy. Research interest in the association between KBs and cancer is growing, largely because a ketogenic diet has been reported to have the potential to delay cancer development by starving proliferating tumour cells, which highly depend on aerobic glycolysis and thus cannot use KBs that are produced during fasting as an alternative source of energy (i.e., the Warburg effect).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Conversely, metabolomic studies have shown that higher KBs, as a sign of metabolic dysregulation, are associated with cancer development and progression.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; One possible reason for these conflicting findings between KB levels and cancer incidence may be the lack of adjustment for important confounders.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Another possible explanation can be differences in study populations of cancer patients versus the general population, as the effects of KBs on cancer may function through unique pathways subject to a specific pathophysiological context. For example, the effect of KBs in sensitising cancer cells to radiotherapy only applies to cancer patients, not to healthy individuals. Of note, available cohort studies on the association between KBs and cancer in the general population are scarce yet important, as KBs have been suggested to be promising markers to screen for cancer.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Taking these considerations together, we aimed to examine whether and how KBs are associated with cancer incidence in a prospective population-based cohort study with extensive adjustment for confounders.&lt;/p&gt;&lt;p&gt;For this study, we analysed data from 6079 subjects in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, a prospective, population-based cohort.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Total KBs (AcAc, β-OHB and acetone) were measured by the plasma-based NMR method. The primary outcome was the incidence of overall cancer. Secondary outcomes were the incidence of urinary tract, lung and colorectal cancer. Cox regression models were performed to calculate hazard ratios (HRs, 95% CIs), crude and adjusted. Details of the methods are provided in the (Tables S1 and S2, Figure S1).&lt;/p&gt;&lt;p&gt;While our study found no association between KBs and cancer development, several studies suggested potential protective effects of KBs on cancer. Notably, most of these studies suggesting the antitumour effects of increasing KBs were conducted in the context of a ketogenic diet designed specifically for cancer patients.&lt;span&gt;&lt;sup&gt;7, 8&lt;/sup&gt;&lt;/span&gt; One reason why the direction of the association between KBs and cancer is different between our findings and these studies may be that the beneficial effects of KBs on cancer are unique for patients with prevalent cancer ","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057901","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":"Advances in regenerative cardiology: Stem cells versus bioartificial tissues.","authors":"Jenyfer María Fuentes-Mendoza, Juan Muñoz-Moreno, Marcio Concepción-Zavaleta, Luis Concepción-Urteaga, José Paz-Ibarra, Roger Gonzales-Valdivieso, Fernanda Ginebra Castillo-Velásquez, Angie Sofía Burgos-Castillo, Regina Garza-Boullosa, Vanesa Daniela Núñez-Pérez","doi":"10.1111/eci.70101","DOIUrl":"https://doi.org/10.1111/eci.70101","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular disease (CVD) remains the leading cause of mortality worldwide. The human myocardium has a limited regenerative capacity, prompting the development of innovative strategies to restore cardiac function. Stem cells (SCs) and bioartificial tissues (BATs) have emerged as promising tools in regenerative cardiology for myocardial repair and functional recovery.</p><p><strong>Methods: </strong>This review analyzes current preclinical and clinical research focused on SC- and BAT-based therapies for CR. Literature was identified through comprehensive database searches. Studies evaluating cardiomyocyte differentiation, integration into host tissue, vascularisation and electromechanical properties were selected. Emphasis was placed on therapeutic potential, safety and translational challenges.</p><p><strong>Results: </strong>SCs, including embryonic and mesenchymal stem cells, demonstrated potential to differentiate into cardiomyocyte-like cells and contribute to myocardial restoration. When combined with biomaterial scaffolds or decellularized matrices, SCs showed improved survival, structural support, and functional integration. BATs, such as engineered heart tissue, replicated native myocardial architecture and supported synchronized contraction. Despite these advances, concerns persist regarding immunogenicity, arrhythmias, and long-term efficacy. Technical hurdles in large-scale production and personalised application remain unresolved.</p><p><strong>Conclusions: </strong>SC- and BAT-based therapies offer innovative avenues for repairing damaged myocardium. Their application could revolutionise treatment strategies for heart failure and post-infarction remodelling. However, clinical translation requires addressing immune compatibility, arrhythmic risk and manufacturing limitations. Interdisciplinary collaboration and regulatory standardisation are essential for their future clinical adoption.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70101"},"PeriodicalIF":4.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689683","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":"High-density lipoproteins alleviate the endotoxin burden in patients with peritonitis and sepsis: The LIPS study.","authors":"Maxime Nguyen, Marvin Alvarez, Vivien Berthoud, Gaetan Pallot, Sohel Abagri, Damien Leleu, Jean-Paul Pais-De-Barros, Pablo Ortega-Deballon, Pierre-Grégoire Guinot, David Masson, Thomas Gautier, Belaid Bouhemad","doi":"10.1111/eci.70099","DOIUrl":"https://doi.org/10.1111/eci.70099","url":null,"abstract":"<p><strong>Background: </strong>The high-density lipoprotein (HDL) and the phospholipid transfer protein (PLTP) have been demonstrated to enhance endotoxin elimination and inactivation in animal models of sepsis. This study aimed to confirm such a role in patients presenting with abdominal sepsis undergoing emergent surgery and explore the relationships between HDL, PLTP and the lipopolysaccharide (LPS) burden (mass and activity).</p><p><strong>Methods: </strong>Patients operated for abdominal sepsis were prospectively included in the study. Blood samples were obtained before surgery, at the end of the operation (H0), 4 h (H4) and 24 h (H24) later. Peritoneal fluid was also sampled. HDL cholesterol, LDL cholesterol, PLTP activity, LPS mass and activity were measured.</p><p><strong>Results: </strong>Twenty-seven patients were included. At H0, LPS mass was mostly measured in the lipoprotein fractions (46% [23; 58] in HDL and 36% [29; 54] in LDL). Overall, LPS mass and LPS activity did not decrease in the 24 h following admission to the ICU. Both HDLc concentrations and PLTP activity were associated with increased H4-LPS elimination (drop in LPS concentration, -3% [-26;10] vs. 29% [13;52], p < 0.01 and -2% [-15;10] vs. 20% [8:52], p = 0.03, respectively). Increased H4-LPS elimination was associated with reduced inflammation (plasma cytokine concentration) and mortality. High HDL cholesterol was associated with reduced mortality but not with inflammation.</p><p><strong>Conclusion: </strong>Our data support the role of HDL and PLTP in the elimination of LPS during human peritonitis with sepsis. Increased H4-LPS elimination was associated with reduced inflammation and lower mortality.</p><p><strong>Clinicaltrials: </strong>gov: NCT04126577.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70099"},"PeriodicalIF":4.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667476","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":"Branched-chain amino acids and all-cause mortality in patients with liver cirrhosis, and the onset of diabetes in liver transplant recipients.","authors":"Yakun Li, Mateo Chvatal-Medina, Maria Camila Trillos-Almanza, Margery A Connelly, Han Moshage, Stephan J L Bakker, Vincent E de Meijer, Hans Blokzijl, Robin P F Dullaart","doi":"10.1111/eci.70096","DOIUrl":"https://doi.org/10.1111/eci.70096","url":null,"abstract":"<p><strong>Background and aims: </strong>Branched-chain amino acids (BCAA) have gained increasing recognition for their role in liver disease. This study investigated plasma BCAA alterations in patients with cirrhosis and liver transplant recipients (LTRs) and examined their associations with all-cause mortality and new-onset type 2 diabetes in LTRs.</p><p><strong>Methods: </strong>Plasma BCAA concentrations were measured using nuclear magnetic resonance spectroscopy in 129 patients with cirrhosis and 367 LTRs from the TransplantLines cohort study (NCT03272841), and compared with 4834 participants from the population-based PREVEND cohort. Kaplan-Meier survival analysis and Cox regression analysis were performed.</p><p><strong>Results: </strong>Total BCAA levels were significantly lower in patients with cirrhosis and LTRs than in PREVEND participants (p < .001). While total BCAA levels increased post-transplant, they remained lower than those in PREVEND (p < .001). The highest total BCAA tertile was associated with better survival versus the lowest BCAA tertile in patients with cirrhosis (log-rank p = .002). In Cox regression analysis adjusted for relevant co-variates, higher total BCAA levels were also associated with reduced mortality in patients with cirrhosis (HR .19 [95% CI: .04-.86], p = .031). In LTRs, the highest total BCAA tertile conferred a higher probability of new-onset diabetes (log-rank p = .004) but was not linked to mortality (log-rank p = .65). After adjusting for age, sex, and immunosuppressant use, the highest tertile of total BCAA levels remained independently associated with new-onset diabetes in LTRs (HR 1.42 [95% CI: 1.10-1.82], p = .006).</p><p><strong>Conclusions: </strong>Total BCAA levels increase after liver transplantation. In patients with cirrhosis, higher total BCAA levels are associated with reduced all-cause mortality. Although this association is not evident in LTRs, higher total BCAA levels are strongly linked to an increased risk of new-onset type 2 diabetes, warranting further investigation.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70096"},"PeriodicalIF":4.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599838","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":"Higher afamin concentrations are associated with higher fatty liver indices: Population-based KORA F4/FF4 study.","authors":"Corinna Niersmann, Anna Zhu, Haifa Maalmi, Xinting Cai, Jana Nano, Wolfgang Rathmann, Wolfgang Koenig, Toshinari Takamura, Barbara Kollerits, Hans Dieplinger, Annette Peters, Michael Roden, Florian Kronenberg, Barbara Thorand, Christian Herder","doi":"10.1111/eci.70095","DOIUrl":"https://doi.org/10.1111/eci.70095","url":null,"abstract":"<p><strong>Background: </strong>Previous studies suggest that afamin is associated with steatotic liver diseases (SLD). However, the exact role of afamin in SLD development and fibrogenesis remains unclear. Potential modifying effects of sex and glucose tolerance status have also not been examined. Therefore, we investigated the associations of afamin with steatotic liver diseases and fibrosis defined by non-invasive tests and assessed for possible effect modifications.</p><p><strong>Methods: </strong>This study included 3080 participants from the population-based KORA F4/FF4 cohort. Cross-sectional and prospective associations (follow-up time 6.5 years) between afamin and NAFLD liver fat score (NAFLD LFS), hepatic steatosis index, fatty liver index and the fibrosis-4 index were assessed using multiple linear regression models. Models were adjusted for age, sex, body mass index, smoking status, alcohol consumption, physical activity, metabolic parameters, medication and subclinical inflammation.</p><p><strong>Results: </strong>In the cross-sectional analysis, afamin concentrations were positively associated with NAFLD LFS (β = .32; 95% CI .27-.37), hepatic steatosis index (β = .33; 95% CI .26-.39) and fatty liver index (β = 1.78; 95% CI 1.47-2.08) (all p < .001), but not with fibrosis-4 index. In the prospective analysis, higher afamin levels were associated with a higher increase only in NAFLD LFS (p < .001). Cross-sectional and prospective associations between afamin and NAFLD LFS were more pronounced in men than in women (p_interaction < .001 and .022; respectively). Cross-sectional associations between afamin and NAFLD LFS were also stronger in individuals with prediabetes or diabetes compared to those with normal glucose tolerance (p_interaction < .001).</p><p><strong>Conclusion: </strong>Higher afamin concentrations are positively associated with NAFLD LFS with potential effect modification by sex and glucose tolerance status.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70095"},"PeriodicalIF":4.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590794","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":"First-line diagnostic tests to intercept primary heart involvement in systemic sclerosis: Clinical associations from the SPRING-SIR registry.","authors":"Antonio Tonutti, Francesca Motta, Rossella De Angelis, Edoardo Cipolletta, Clodoveo Ferri, Gianluigi Bajocchi, Silvia Bellando-Randone, Cosimo Bruni, Martina Orlandi, Giovanni Zanframundo, Rosario Foti, Giovanna Cuomo, Alarico Ariani, Edoardo Rosato, Gemma Lepri, Francesco Girelli, Elisabetta Zanatta, Silvia Laura Bosello, Ilaria Cavazzana, Francesca Ingegnoli, Fabio Cacciapaglia, Giuseppe Murdaca, Giuseppina Abignano, Giorgio Pettiti, Alessandra Della Rossa, Maurizio Caminiti, Anna Maria Iuliano, Giovanni Ciano, Lorenzo Beretta, Gianluca Bagnato, Ennio Lubrano, Ilenia De Andres, Luca Idolazzi, Marta Saracco, Cecilia Agnes, Corrado Campochiaro, Marco Fornaro, Federica Lumetti, Amelia Spinella, Luca Magnani, Giacomo De Luca, Veronica Codullo, Elisa Visalli, Carlo Iandoli, Antonietta Gigante, Greta Pellegrino, Erika Pigatto, Maria Grazia Lazzaroni, Enrico De Lorenzis, Gianna Mennillo, Marco Di Battista, Giuseppa Pagano-Mariano, Federica Furini, Licia Vultaggio, Simone Parisi, Clara Lisa Peroni, Gerolamo Bianchi, Enrico Fusaro, Gian Domenico Sebastiani, Marcello Govoni, Salvatore D'Angelo, Franco Cozzi, Franco Franceschini, Serena Guiducci, Lorenzo Dagna, Andrea Doria, Dilia Giuggioli, Valeria Riccieri, Carlo Salvarani, Florenzo Iannone, Marco Matucci-Cerinic, Carlo Selmi, Maria De Santis","doi":"10.1111/eci.70094","DOIUrl":"https://doi.org/10.1111/eci.70094","url":null,"abstract":"<p><strong>Introduction: </strong>Primary heart involvement (pHI) is an overlooked and poorly characterised complication of systemic sclerosis (SSc), associated with the risk of heart failure, arrhythmia and death. Despite consensus definition by the World Scleroderma Foundation/Heart Failure Association (WSF/HFA), diagnostic criteria and risk factors remain poorly elucidated.</p><p><strong>Methods: </strong>Out of 1922 patients in the Italian national SPRING registry, we excluded those with potentially confounding conditions according to WSF/HFA, and those with incomplete ECG or echocardiographic assessment, resulting in 600 subjects with clearly defined parameters to intercept SSc-pHI. Cross-sectional and longitudinal analyses were performed to identify factors associated with pHI.</p><p><strong>Results: </strong>ECG and/or echocardiographic signs of SSc-pHI were identified in 25% of patients at enrollment and were associated with older age (OR 1.04; 95% CI 1.02-1.06), diffuse cutaneous SSc (OR 1.85; 95% CI 1.05-3.26) and intestinal symptoms (OR 1.79; 95% CI 1.03-3.08). Diastolic dysfunction (62%) and conduction disturbances (34%) were the most frequent phenotypes, while diffuse hypokinesia with reduced ejection fraction was the least common (3%). During follow-up, new-onset signs of pHI were observed in an additional 25% of patients, particularly in those with skeletal muscle involvement (HR 2.83; 95% CI 1.01-7.73).</p><p><strong>Conclusions: </strong>pHI is a severe complication potentially affecting one-quarter of patients with SSc. Early detection is crucial, particularly in those with diffuse skin fibrosis, muscular involvement and intestinal manifestations.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70094"},"PeriodicalIF":4.4,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559601","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":"Elevated factor VIIa-antithrombin complexes are associated with stroke or cardiovascular death in patients with atrial fibrillation.","authors":"Elżbieta Szczygieł-Pilut, Michał Błaż, Elżbieta Pociask, Elżbieta Paszek, Anetta Undas","doi":"10.1111/eci.70091","DOIUrl":"https://doi.org/10.1111/eci.70091","url":null,"abstract":"<p><strong>Background: </strong>Atrial fibrillation (AF) is associated with a prothrombotic state. We investigated whether factor VIIa-antithrombin (FVIIa-AT) complexes, a marker of tissue factor (TF) exposure, are associated with thromboembolic events in AF.</p><p><strong>Methods: </strong>In 224 nonvalvular AF patients (66% men, median age 69 years, median CHA₂DS₂VASc score 4), 71% on direct oral anticoagulants, we measured FVIIa-AT complexes, along with endogenous thrombin potential (ETP), von Willebrand factor (VWF) and 8-isoprostane, reflecting oxidative stress. During a median follow-up of 53 [interquartile range, IQR 47-57] months, we recorded a composite endpoint: ischemic stroke, systemic thromboembolism or cardiovascular (CV) death.</p><p><strong>Results: </strong>FVIIa-AT complexes (median 145 [IQR 125-170] pM) were higher in patients with permanent AF (p < .001), vascular disease (p = .02), previous stroke (p < .001) and smoking (p = .006) as compared with patients without these comorbidities. FVIIa-AT correlated with NT-proBNP (r = .15, p = .022) and ETP (r = .25, p < .001). During follow-up, the composite endpoint was recorded in 30 patients (13.4%, 3.0% per year) including 20 with ischemic stroke (8.9%, 2.0% per year, respectively). Patients with the composite endpoint had 29.2% higher baseline FVIIa-AT complexes compared with the remainder. Patients with FVIIa-AT complexes in the top quartile (>170 pM) had an increased risk of the composite endpoint (HR 12.0, 95% CI 5.2-28.0, p < .0001). FVIIa-AT complexes, along with VWF, remained independently associated with the composite endpoint.</p><p><strong>Conclusions: </strong>This study is the first to show that high plasma FVIIa-AT complexes are independently associated with thromboembolic events or CV death in AF, suggesting the need for more potent anticoagulation to suppress the residual TF-mediated coagulation.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70091"},"PeriodicalIF":4.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324889","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":"Incretin system and glucagon secretion in patients with chronic pancreatitis.","authors":"Gea Ciccarelli, Gianfranco Di Giuseppe, Giulia Gliozzo, Laura Soldovieri, Giuseppe Quero, Enrico Celestino Nista, Michela Brunetti, Francesca Cinti, Sara Sofia De Lucia, Bolette Hartmann, Andrea Mari, Antonio Gasbarrini, Sergio Alfieri, Alfredo Pontecorvi, Jens Juul Holst, Andrea Giaccari, Teresa Mezza","doi":"10.1111/eci.70093","DOIUrl":"https://doi.org/10.1111/eci.70093","url":null,"abstract":"<p><strong>Background: </strong>Diabetes of the exocrine pancreas (DEP) is an underdiagnosed form of diabetes, prevalently caused by acute and chronic pancreatitis (CP). The contribution of incretin system dysfunction and the role of glucagon levels in the pathogenesis of DEP remain unclear. The aim of our study is to assess the secretion of glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and glucagon, along with the incretin effect, in individuals with and without CP. By comparing these parameters within the same glucose tolerance class, we seek to elucidate specific hormonal alterations that characterize DEP.</p><p><strong>Methods: </strong>To pursue this aim, we conducted a cross-sectional study on 32 patients with chronic pancreatitis (wCP) and 60 patients without chronic pancreatitis (w/oCP), who were administered an oral glucose tolerance test, a hyperglycemic clamp and a mixed meal test with measurement of glucose, insulin, C-peptide, GLP-1, GIP and glucagon.</p><p><strong>Results: </strong>The comparison between individuals wCP and w/oCP showed worse beta-cell function and lower incretin effect for the former, but incretin and glucagon levels were similar. Diabetes prevalence was higher in the group wCP than in the group w/oCP (56% vs. 33%). Thus, to evaluate the differences determined by CP, we found it necessary to stratify individuals according to glucose tolerance class. After stratification, we found that both groups had similar beta-cell function, incretin effect and incretin and glucagon secretion.</p><p><strong>Conclusions: </strong>Therefore, incretin and glucagon levels and the incretin effect varied according to glucose tolerance, not the presence or absence of CP. Similar defects in incretin secretion and effects are responsible for diabetes development in individuals wCP and w/oCP.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70093"},"PeriodicalIF":4.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324890","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":"Enhanced mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) from young children with overweight/obesity and insulin resistance.","authors":"Eugenia Carvalho, Reid D Landes, Matthew Cotter, Leanna M Delhey, Elisabet Børsheim, Shannon Rose","doi":"10.1111/eci.70090","DOIUrl":"10.1111/eci.70090","url":null,"abstract":"<p><strong>Background: </strong>Studies implicating dysfunctional mitochondrial respiration in metabolic tissues in the development of insulin resistance in obesity have only included adults. Peripheral blood mononuclear cells (PBMCs) and platelets have been found to reflect systemic mitochondrial fitness and bioenergetic health. We sought to identify bioenergetic differences in PBMCs and platelets from children with obesity and insulin resistance and determine associations with whole-body metabolism and/or biomarkers of metabolic health and inflammation.</p><p><strong>Methods: </strong>We stratified prepubertal children (ages 5-10 years) into three groups: normal weight insulin sensitive (N-IS; n = 20), overweight/obese insulin sensitive (O-IS; n = 28) and overweight/obese insulin resistant (O-IR; n = 17). We measured oxygen consumption rate and proton efflux rate in PBMCs and platelets. We estimated whole-body resting metabolic rate by bioimpedance and dietary fatty acid oxidation by oral deuterated palmitate and quantifying recovery of D₂O in urine. We used ANOVA for comparisons among groups and Spearman correlations for associations between circulating cell bioenergetics and whole-body metabolism and biomarkers.</p><p><strong>Results: </strong>O-IS and O-IR PBMCs exhibited increased maximal mitochondrial respiration and spare respiratory capacity compared to N-IS. Bioenergetics shifted towards glycolysis in O-IS PBMCs as compared to both N-IS and O-IR PBMCs. In platelets, glycolysis and ATP production rates were decreased in O-IR compared to O-IS children. PBMC respiration positively correlated with BMIz, HOMA-IR and fasting glucose and insulin, but negatively correlated with inflammatory cytokines. Dietary fatty acid oxidation was higher in O-IS compared to N-IS children and positively correlated with PBMC spare respiratory capacity. Resting metabolic rate correlated positively with several parameters of PBMC mitochondrial respiration.</p><p><strong>Conclusions: </strong>PBMCs from young children with overweight/obesity exhibit adaptations to the metabolic stressors associated with insulin resistance, and PBMC metabolism correlates well with whole-body metabolism.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70090"},"PeriodicalIF":3.6,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12327403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316188","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}