European Journal of Clinical Investigation最新文献

{"title":"Reciprocity between the regulation of the expression and functions of CEACAM","authors":"Sonia M. Najjar, 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}

{"title":"Subtyping strokes using blood-based protein biomarkers: A high-throughput proteomics and machine learning approach","authors":"Shubham Misra,&nbsp;Praveen Singh,&nbsp;Shantanu Sengupta,&nbsp;Manoj Kushwaha,&nbsp;Zuhaibur Rahman,&nbsp;Divya Bhalla,&nbsp;Pumanshi Talwar,&nbsp;Manabesh Nath,&nbsp;Rahul Chakraborty,&nbsp;Pradeep Kumar,&nbsp;Amit Kumar,&nbsp;Praveen Aggarwal,&nbsp;Achal K. Srivastava,&nbsp;Awadh K. Pandit,&nbsp;Dheeraj Mohania,&nbsp;Kameshwar Prasad,&nbsp;Nishant K. Mishra,&nbsp;Deepti Vibha","doi":"10.1111/eci.14372","DOIUrl":"10.1111/eci.14372","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Rapid diagnosis of stroke and its subtypes is critical in early stages. We aimed to discover and validate blood-based protein biomarkers to differentiate ischemic stroke (IS) from intracerebral haemorrhage (ICH) using high-throughput proteomics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We collected serum samples within 24 h from acute stroke (IS &amp; ICH) and mimics patients. In the discovery phase, SWATH-MS proteomics identified differentially expressed proteins, which were validated using targeted proteomics in the validation phase. We conducted interaction network and pathway analyses using Cytoscape 3.10.0. We determined cut-off points using the Youden Index. We developed three prediction models using multivariable logistic regression analyses. We assessed the model performance using statistical tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 20 IS and 20 ICH in the discovery phase and 150 IS, 150 ICH, and six stroke mimics in the validation phase. We quantified 375 proteins using SWATH-MS. Between IS and ICH, we discovered 20 differentially expressed proteins. In the validation phase, the combined prediction model including three biomarkers: GFAP (aOR 0.04; 95%CI .02–.11), MMP-9 (aOR .09; .03–.28), APO-C1 (aOR 5.76; 2.66–12.47) and clinical variables independently differentiated IS from ICH (accuracy: 92%, negative predictive value: 94%). Adding biomarkers to clinical variables improved discrimination by 26% (<i>p</i> &lt; .001). Additionally, nine biomarkers differentiated IS from ICH within 6 h, while three biomarkers differentiated IS from mimics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study demonstrated that GFAP, MMP-9 and APO-C1 biomarkers independently differentiated IS from ICH within 24 h and significantly improved the discrimination ability of prediction models. Temporal profiling of these biomarkers in the acute phase of stroke is warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 4","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799862","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":"Risk of cardiovascular disease in elderly subjects with obesity and liver fibrosis and the potential benefit of statin treatment","authors":"Willy B. Theel,&nbsp;Vivian D. de Jong,&nbsp;Manuel Castro Cabezas,&nbsp;Diederick E. Grobbee,&nbsp;Johan W. Jukema,&nbsp;Stella Trompet","doi":"10.1111/eci.14368","DOIUrl":"10.1111/eci.14368","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Liver fibrosis progression is influenced by older age and cardiometabolic risk factors such as obesity and is associated with an increased risk of cardiovascular events. While statins may protect against cardiovascular complications, their effects in elderly individuals with obesity and liver fibrosis are unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) database was used to evaluate the effect of pravastatin on major adverse cardiovascular events in an elderly population (&gt;70 years). Subjects were categorized by BMI: lean (&lt;25 kg/m²), overweight (25–29.9 kg/m²) and obese (≥30 kg/m²). Liver fibrosis was assessed using the FIB-4 index: low risk (&lt;2.0), intermediate risk (2.0–2.66) and high risk (≥2.67). Time-to-event data were analysed using the Cox proportional hazards model, adjusted for confounders and compared the placebo and pravastatin groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 5.804 subjects were included. In the placebo group, the highest risk group (high FIB-4 and obesity) had a significantly higher hazard ratio for (non-)fatal stroke (HR 2.74; 95% CI 1.19–6.29) compared to the low FIB-4, lean BMI group. This risk disappeared in the same pravastatin group. Pravastatin did not affect other cardiovascular endpoints. All-cause mortality was significantly higher in subjects with lean weight and high FIB-4 on placebo (HR 1.88; 95% CI 1.14–3.11), but not on pravastatin (HR .58; 95% CI .28–1.20).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Elderly individuals with obesity and liver fibrosis are at higher risk for (non-)fatal stroke, which is reduced with pravastatin. Pravastatin also potentially lowers all-cause mortality in subjects with lean weight and liver fibrosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14368","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784757","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}