European Journal of Clinical Investigation最新文献

{"title":"Current investigation of carcinoembryonic antigen cell adhesion molecule (CEACAM) biology summary of the 32nd CEA symposium: 20–23 September 2024. Würzburg, Germany","authors":"James M. Fleckenstein, Sonia M. Najjar, Wolfgang Zimmermann, Christof R. Hauck, Quynh Nguyen, Raquel Mejias-Luque, Asima Bhattacharyya, Alex J. McCarthy, Arup Sarkar, Maciej Kujawski, Anastasia Konieva, Fadi Elyateem, Irina Kube-Golovin, Gunther Wennemuth, Robert Kammerer, Keith M. Skubitz, John E. Shively, Kenneth J. Dery, Gabriela Dveksler, Lisa Götz, Florian Kleefeldt, Süleyman Ergün","doi":"10.1111/eci.14355","DOIUrl":"10.1111/eci.14355","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827954","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":"The influence of hypoxia-mediated CEACAM6 upregulation on epithelial cell and macrophage response in the context of gastric cancer","authors":"Indrajit Poirah,&nbsp;Debashish Chakraborty,&nbsp;Pragyesh Dixit,&nbsp;Supriya Samal,&nbsp;Smaran Banerjee,&nbsp;Tathagata Mukherjee,&nbsp;Subhasis Chattopadhyay,&nbsp;Gautam Nath,&nbsp;Asima Bhattacharyya","doi":"10.1111/eci.14352","DOIUrl":"10.1111/eci.14352","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The hypoxic microenvironment is a key component of the gastric tumour niche. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is upregulated in gastric cancer and is considered a novel biomarker for the disease. However, no prior studies have elaborated on the status of CEACAM6 and its role in the hypoxic gastric cancer niche.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this short study, we evaluated the effect of hypoxia in modulating CEACAM6 level in gastric cancer cells (GCCs) through western blotting and determined the effect of CEACAM6 upregulation on gastric cancer progression through clonogenicity, cell proliferation and migration assays. The wound-healing ability of GCCs was downregulated by siRNA-mediated <i>CEACAM6</i> silencing. Human gastric cancer biopsy samples were examined by immunofluorescence microscopy to assess the level of a hypoxia marker HIF1α and CEACAM6. The effect of empty vector or <i>CEACAM6-</i>expression on peripheral blood-derived mononuclear cell (PBMC)-derived macrophage polarization under normoxia or hypoxia was studied by incubating macrophages in conditioned medium collected from GCC cultures. Macrophage polarization status was observed using flow cytometry and fluorescence microscopy. Reactive oxygen species (ROS) generation by macrophages was evaluated using fluorescence microscopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified that hypoxia promoted CEACAM6 in GCCs, and these cells acquired increased proliferative potential and migration ability. Moreover, the cell culture supernatant from hypoxia-exposed CEACAM6-overexpressing cells promoted an M2-like macrophage population and discouraged the M1 phenotype.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study established that hypoxia increased CEACAM6 which promoted gastric cancer progression by influencing GCC proliferation and motility as well as macrophage polarization.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827977","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":"Reciprocity between the regulation of the expression and functions of CEACAM","authors":"Sonia M. Najjar,&nbsp;M. Paula Macedo","doi":"10.1111/eci.14362","DOIUrl":"10.1111/eci.14362","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827962","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":"The role of CEACAMs in neutrophil function","authors":"Keith M. Skubitz","doi":"10.1111/eci.14349","DOIUrl":"10.1111/eci.14349","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In addition to the long-known antibacterial actions of neutrophils, neutrophils are recognized to have a variety of other effects and are functionally diverse. Neutrophils can either stimulate or inhibit B cells and T cells, regulate NK development and activity, augment or direct the resolution of inflammation, act as myeloid-derived suppressor cells, modulate tumour growth and metastasis and trigger autoimmune diseases. CEACAMs 1, 3, 6 and 8 are expressed on human neutrophils.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A literature review was performed on the role of CEACAMs in neutrophil function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CEACAMs 1, 6 and 8 can be upregulated from intracellular stores, while CEACAM3, an opsonin-independent phagocytic receptor, is constitutively expressed. CEACAM1 has an intracellular ITIM motif and an ITSM motif, and CEACAM3 has an ITAM-like motif; CEACAMs 6 and 8 are glycosylphosphatidylinositol-linked. CEACAM8 can also be released in a soluble form. These CEACAMs can interact with multiple other host CEACAMs as well as other molecules on bacteria, fungi and host cells, both transmitting and receiving signals. Known CEACAM-binding pathogens bind the CFG face of the N domain which is also important in CEACAM-CEACAM binding, although the ABDE face also appears to be involved in higher-order oligomers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Understanding the exact role of each individual CEACAM in human neutrophils is complicated by the fact that the neutrophil CEACAMs can interact with multiple ligands. The data demonstrates some of the many roles of CEACAMs in neutrophil function and the extensive role of the neutrophil in human biology beyond its classical role as a short-lived phagocyte.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827978","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":"CEACAM1 in vascular homeostasis and inflammation","authors":"Lisa Götz,&nbsp;Uwe Rueckschloss,&nbsp;Süleyman Ergün,&nbsp;Florian Kleefeldt","doi":"10.1111/eci.14345","DOIUrl":"10.1111/eci.14345","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The glycoprotein Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1), also known as CD66a, is a member of the immunoglobulin superfamily. It is expressed in a variety of tissues including epithelial, immune, as well as endothelial cells, and is crucial to diverse physiological and pathological mechanisms. This review aims to provide a comprehensive understanding of CEACAM1's multifaceted roles in vascular biology and inflammatory processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Directed literature research was conducted using databases, such as PubMed, and relevant studies were categorized based on the physiological effects of CEACAM1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CEACAM1 plays a pivotal role in vascular homeostasis, particularly influencing the formation, maturation, and aging of blood vessels, as well as the endothelial barrier function. It supports endothelium-dependent vasodilation and nitric oxide formation, thus promoting vascular integrity and regulating blood pressure. Additionally, CEACAM1 is of emerging importance to vascular inflammation and its potential clinical consequences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CEACAM1 is a crucial regulator of vascular homeostasis and inflammation with significant implications for cardiovascular health. Despite the lack of understanding of tissue-specific modulation and isoform-dependent mechanisms, CEACAM1 could be a promising therapeutic target for the prevention of cardiovascular disease in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827952","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":"Insights into circulating CEACAM1 in insulin clearance and disease progression: Evidence from the Portuguese PREVADIAB2 study","authors":"Rita S. Patarrão,&nbsp;Maria João Meneses,&nbsp;Hilda E. Ghadieh,&nbsp;Laura Herrera,&nbsp;Sérgio Duarte,&nbsp;Rogério T. Ribeiro,&nbsp;João F. Raposo,&nbsp;Verena Schmitt,&nbsp;Bernhard B. Singer,&nbsp;Amalia Gastaldelli,&nbsp;Carlos Penha-Gonçalves,&nbsp;Sonia M. Najjar,&nbsp;M. Paula Macedo","doi":"10.1111/eci.14344","DOIUrl":"10.1111/eci.14344","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Type 2 diabetes (T2DM) and obesity are characterized by altered insulin metabolism and action. Reduced hepatic insulin clearance is increasingly recognized as a key contributor to hyperinsulinemia and insulin resistance. CEACAM1 promotes hepatic insulin clearance, and its loss in hepatocytes is associated with reduced insulin clearance in mice and men. This study examines whether CEACAM1 circulating levels reflect compromised insulin metabolism and resistance in the PREVADIAB2 cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 1019 individuals from the PREVADIAB2 cohort were evaluated for diabetes by 75 g-OGTT and classified according to WHO 2019 criteria. CEACAM1 circulating levels were measured by ELISA, and insulin metabolism parameters were calculated. Hierarchical clustering of insulin metabolic indices and CEACAM1 levels was performed. Statistical significance was assessed using Kruskal–Wallis and Wilcoxon–Mann–Whitney tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BMI, insulin resistance (HOMA-IR), and hepatic steatosis progressively increased with disease severity. Insulin secretion rose and its clearance declined in parallel to circulating CEACAM1 levels in prediabetes and T2DM, indicating compensatory hyperinsulinemia. Hierarchical metabolic clustering identified four clusters with distinct patterns and further showed that insulin clearance positively correlated with circulating CEACAM1, especially in individuals with normoglycemia, lower obesity and hepatic steatosis. This suggests that circulating CEACAM1 can reflect the status of hepatic insulin clearance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrates a progressive increase in insulin resistance and hyperinsulinemia in parallel to elevated BMI and hepatic steatosis prevalence, accompanied by declining circulating CEACAM1 levels. Cluster analysis further linked reduced insulin clearance to lower circulating CEACAM1 levels, suggesting its potential usefulness as a biomarker for metabolic disease progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827958","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":"Mechanism and function of CEACAM1 splice isoforms","authors":"Kenneth J. Dery,&nbsp;Sonia M. Najjar,&nbsp;Nicole Beauchemin,&nbsp;John E. Shively,&nbsp;Jerzy W. Kupiec-Weglinski","doi":"10.1111/eci.14350","DOIUrl":"10.1111/eci.14350","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alternative splicing is a fundamental mechanism in the post-transcriptional regulation of genes. The multifunctional transmembrane glycoprotein receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) undergoes extensive alternative splicing to allow for tunable functions in cell signalling, adhesion and modulation of immune and metabolic responses. Splice isoforms that differ in their ectodomain and short or long cytoplasmic tail (CEACAM1-S/CEACAM1-L) have distinct functional roles. The mechanisms that regulate CEACAM1 RNA splicing remain elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This narrative review summarizes the current knowledge of the mechanism and function of CEACAM1 splice isoforms. Historical perspectives address the biological significance of the glycosylated Ig domains, the variable exon 7, and phosphorylation events that dictate its signal transduction pathways. The use of small antisense molecules to target mis-spliced variable exon 7 is discussed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The Ig variable-like N domain mediates cell adhesion and immune checkpoint inhibitory functions. Gly and Tyr residues in the transmembrane (TM) domain are essential for dimerization. Calmodulin, Calcium/Calmodulin-dependent protein kinase II delta (CamK2D), Actin and Annexin A2 are binding partners of CEACAM1-S. Homology studies of the muCEACAM1-S and huCEACAM1-S TM predict differences in their signal transduction pathways. Hypoxia-inducible factor 1-α (HIF-1-α) induces alternative splicing to produce CEACAM1-S under limited oxygen conditions. Antisense small molecules directed to exon 7 may correct faulty expression of the short and long cytoplasmic tail splicing isoforms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>More pre-clinical and clinical studies are needed to elucidate the precise mechanisms by which CEACAM1 RNA splicing may be exploited to develop targeted interventions towards novel therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827960","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":"Regulation of lipid storage and inflammation in the liver by CEACAM1","authors":"Sonia M. Najjar,&nbsp;John E. Shively","doi":"10.1111/eci.14338","DOIUrl":"10.1111/eci.14338","url":null,"abstract":"<p>This review focuses on a special aspect of hepatic lipid storage and inflammation that occurs during nutritional excess in obesity. Mounting evidence supports that prolonged excess fatty acid (FA) uptake in the liver is strongly associated with hepatic lipid storage and inflammation and that the two processes are closely linked by a homeostatic mechanism. There is also strong evidence that bacterial lipids may enter the gut by a common mechanism with lipid absorption and that there is a set point to determine when their uptake triggers an inflammatory response in the liver. In fact, the progression from high uptake of FAs in the liver resulting in Metabolic dysfunction-associated steatotic liver disease (MASLD) to the development of the more serious Metabolic dysfunction-associated steatohepatitis (MASH) depends on the degree of inflammation and its progression from an acute to a chronic state. Thus, MASLD/MASH implicates both excess fatty acids and progressive inflammation in the aetiology of liver disease. We start the discussion by introduction of CD36, a major player in FA and lipopolysaccharide (LPS) uptake in the duodenum, liver and adipose tissue. We will then introduce CEACAM1, a major player in the regulation of hepatic de novo lipogenesis and the inflammatory response in the liver, and its dual association with CD36 in enterocytes and hepatocytes. We conclude that CEACAM1 and CD36 together regulate lipid droplet formation and inflammation in the liver.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827973","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":"The emerging role of Fusobacteria in carcinogenesis","authors":"Raisha J. Gibbs,&nbsp;Adam C. Chambers,&nbsp;Darryl J. Hill","doi":"10.1111/eci.14353","DOIUrl":"10.1111/eci.14353","url":null,"abstract":"<p>The <i>Fusobacterium</i> genus comprises Gram-negative, obligate anaerobic bacteria that typically reside in the periodontium of the oral cavity, gastrointestinal tract, and female genital tract. The association of Fusobacterial spp. with colorectal tumours is widely accepted, with further evidence that this pathogen may also be implicated in the development of other malignancies. Fusobacterial spp. influence malignant cell behaviours and the tumour microenvironment in various ways, which can be related to the multiple surface adhesins expressed. These adhesins include Fap2 (fibroblast-activated protein 2), CpbF (CEACAM binding protein of <i>Fusobacteria</i>), FadA (<i>Fusobacterium</i> adhesin A) and FomA (Fusobacterial outer membrane protein A). This review outlines the influence of <i>Fusobacteria</i> in promoting cancer initiation and progression, impacts of therapeutic outcomes and discusses potential therapeutic interventions where appropriate.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827975","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":"Residual risk prediction in anticoagulated patients with atrial fibrillation using machine learning: A report from the GLORIA-AF registry phase II/III","authors":"Yang Liu,&nbsp;Yang Chen,&nbsp;Ivan Olier,&nbsp;Sandra Ortega-Martorell,&nbsp;Bi Huang,&nbsp;Hironori Ishiguchi,&nbsp;Ho Man Lam,&nbsp;Kui Hong,&nbsp;Menno V. Huisman,&nbsp;Gregory Y. H. Lip,&nbsp;the GLORIA-AF Investigators","doi":"10.1111/eci.14371","DOIUrl":"10.1111/eci.14371","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although oral anticoagulation decreases the risk of thromboembolism in patients with atrial fibrillation (AF), a residual risk of thrombotic events still exists. This study aimed to construct machine learning (ML) models to predict the residual risk in these patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with newly diagnosed non-valvular AF were collected from the Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry. To predict the residual risk of the composite outcome of thrombotic events (defined as ischemic stroke, systemic embolism, transient ischemic attack and myocardial infarction), we constructed four prediction models using the logistic regression (LR), random forest, light gradient boosting machine and extreme gradient boosting machine ML algorithms. Performance was mainly evaluated by area under the receiver-operating characteristic curve (AUC), g-means and F1 scores. Feature importance was evaluated by SHapley Additive exPlanations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>15,829 AF patients (70.33 ± 9.94 years old, 55% male) taking oral anticoagulation were included in our study, and 641 (4.0%) had residual risk, sustaining thrombotic events. In the test set, LR had the best performance with higher AUC trend of 0.712. RF has highest g-means of 0.295 and F1 score of 0.249. This was superior when compared with the CHA₂DS₂-VA score (AUC 0.698) and 2MACE score (AUC 0.696). Age, history of TE or MI, OAC discontinuation, eGFR and sex were identified as the top five factors associated with residual risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ML algorithms can improve the prediction of residual risk of anticoagulated AF patients compared to clinical risk factor-based scores.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14371","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806498","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}