European Journal of Clinical Investigation最新文献

{"title":"Risk of cardiovascular disease in elderly subjects with obesity and liver fibrosis and the potential benefit of statin treatment.","authors":"Willy B Theel, Vivian D de Jong, Manuel Castro Cabezas, Diederick E Grobbee, Johan W Jukema, Stella Trompet","doi":"10.1111/eci.14368","DOIUrl":"https://doi.org/10.1111/eci.14368","url":null,"abstract":"<p><strong>Background: </strong>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><p><strong>Method: </strong>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 (>70 years). Subjects were categorized by BMI: lean (<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 (<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><p><strong>Results: </strong>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><p><strong>Conclusion: </strong>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>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14368"},"PeriodicalIF":4.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of oncologic diseases on outcome in patients with severe isolated tricuspid regurgitation.","authors":"Varius Dannenberg, Flora Zschocke, Kseniya Halavina, Katharina Mascherbauer, Gregor Heitzinger, Matthias Koschutnik, Carolina Donà, Christian Nitsche, Andreas A Kammerlander, Georg Spinka, Max-Paul Winter, Philipp E Bartko, Christian Hengstenberg, Jutta Bergler-Klein, Georg Goliasch, Matthias Schneider-Reigbert","doi":"10.1111/eci.14367","DOIUrl":"https://doi.org/10.1111/eci.14367","url":null,"abstract":"<p><strong>Background: </strong>Severe tricuspid regurgitation (TR) is associated with high morbidity and mortality. Isolated TR, defined as TR without overt heart disease, is typical and offers limited cardiac treatment options other than interventional repair or replacement. Survival history of cancer or active cancer treatment may lead to an unnecessary delay of TR treatment.</p><p><strong>Methods: </strong>We included all patients diagnosed with severe TR at the Medical University of Vienna between 2003 and 2016 who had normal left ventricular function and no other valvular lesions. Outcome analysis was performed on cancer type, status and the number of organs affected by cancer.</p><p><strong>Results: </strong>A total of 973 patients were included. 182 (19%) patients had cancer, 52 were active and 130 had a history of cancer at the time of TR diagnosis. Oncologic patients were divided into subgroups of gastrointestinal, skin, glands, gynaecological, breast, urogenital, lung and other cancers. Ten-year mortality of patients with cancer was higher than those without cancer (p < 0.001). Multivariate analysis adjusting for age did not reveal significantly higher mortality in patients with a history of cancer compared to patients without cancer (p = 0.59). Patients with lung, active, or multi-organ cancer showed the highest mortality.</p><p><strong>Conclusions: </strong>Mortality in patients with severe isolated TR is high and increased by active or multi-organ cancer but not by a history of cancer. These patients should be discussed in interdisciplinary cardio-oncology teams to avoid delaying life-saving treatment of TR and cancer.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14367"},"PeriodicalIF":4.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767381","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":"Carcinoembryonic antigen-related cell adhesion molecule 1 in cancer: Blessing or curse?","authors":"Lisa Götz, Uwe Rueckschloss, Sonia M Najjar, Süleyman Ergün, Florian Kleefeldt","doi":"10.1111/eci.14337","DOIUrl":"10.1111/eci.14337","url":null,"abstract":"<p><p>The Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1, also CD66a), a transmembrane glycoprotein of the immunoglobulin superfamily, is a pivotal mediator of various physiological and pathological processes, including oncologic disorders. However, its precise role in tumorigenicity is contradictory discussed by several clinical studies. This review aims to elucidate the clinical significance of CEACAM1 in different cancer entities focusing on tumour formation, progression and metastasis as well as on CEACAM1-mediated treatment resistance. Furthermore, we discuss the contribution of CEACAM1 to cancer immunity and modulation of the inflammatory microenvironment and finally provide a comprehensive review of treatment regimens targeting this molecule.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14337"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497506","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":"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":"https://doi.org/10.1111/eci.14355","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 Suppl 2 ","pages":"e14355"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","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":"Evolution of CEACAM pathogen decoy receptors in primates.","authors":"Wolfgang Zimmermann, Robert Kammerer","doi":"10.1111/eci.14356","DOIUrl":"10.1111/eci.14356","url":null,"abstract":"<p><strong>Background: </strong>CEACAM1 in leukocytes controls cell activation during inflammation. This and its expression in epithelial cells led to frequent independent appropriation of CEACAM1 as receptor by pathogens in humans and other species to gain host access and to downregulate its immune response. As a countermeasure, decoy receptors with CEACAM1-like pathogen-binding domains evolved. The granulocyte-specific human CEACAM3 endocytic receptor diverts CEACAM1-binding pathogens to neutrophils for internalization and destruction. The role of the glycosylphosphatidylinositol-anchored CEACAM5 and CEACAM6 which can also bind CEACAM1-targeting pathogens in humans is less clear.</p><p><strong>Methods: </strong>We analyzed the selection of CEACAMs to avoid pathogen binding and to maintain similarity between pathogen receptors and decoy receptors in 148 primate species.</p><p><strong>Results: </strong>Notably, functional CEACAM3 genes were not found in gibbons and New World monkeys. Interestingly, CEACAM6 in these primates exhibits similar high ratios of rates of nonsynonymous and synonymous substitution (dN/dS) in their pathogen-binding N domain exons as found for CEACAM1. High dN/dS ratios are indicative of selection for diversification typically seen in pathogen receptors. Human CEACAM6 is expressed on granulocytes and epithelial cells. Therefore, CEACAM6 could substitute for the missing endocytic receptor CEACAM3. In nearly all investigated primate groups also N exons of the epithelially expressed CEACAM5 exhibit selection for diversification. In African populations, five high-frequency polymorphisms are observed in the pathogen-binding region of CEACAM5 (I80V, V83A, I100T, I112V, I113T) with 3-4 polymorphisms combined in the same individual. These polymorphisms correspond to CEACAM1 pathogen-binding domain sequences.</p><p><strong>Conclusion: </strong>The glycosylphosphatidylinositol-anchored CEACAM5 and CEACAM6 are under selection to maintain similarity to the pathogen receptor CEACAM1 in most primate species, indicating a function as decoy receptors.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 Suppl 2 ","pages":"e14356"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827956","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 influence of hypoxia-mediated CEACAM6 upregulation on epithelial cell and macrophage response in the context of gastric cancer.","authors":"Indrajit Poirah, Debashish Chakraborty, Pragyesh Dixit, Supriya Samal, Smaran Banerjee, Tathagata Mukherjee, Subhasis Chattopadhyay, Gautam Nath, Asima Bhattacharyya","doi":"10.1111/eci.14352","DOIUrl":"10.1111/eci.14352","url":null,"abstract":"<p><strong>Background: </strong>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><p><strong>Methods: </strong>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 CEACAM6 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 CEACAM6-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><p><strong>Results: </strong>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><p><strong>Conclusion: </strong>This study established that hypoxia increased CEACAM6 which promoted gastric cancer progression by influencing GCC proliferation and motility as well as macrophage polarization.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 Suppl 2 ","pages":"e14352"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","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, M Paula Macedo","doi":"10.1111/eci.14362","DOIUrl":"https://doi.org/10.1111/eci.14362","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 Suppl 2 ","pages":"e14362"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","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":"<p><strong>Background: </strong>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><p><strong>Methods: </strong>A literature review was performed on the role of CEACAMs in neutrophil function.</p><p><strong>Results: </strong>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><p><strong>Conclusions: </strong>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>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 Suppl 2 ","pages":"e14349"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","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, Uwe Rueckschloss, Süleyman Ergün, Florian Kleefeldt","doi":"10.1111/eci.14345","DOIUrl":"10.1111/eci.14345","url":null,"abstract":"<p><strong>Introduction: </strong>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><p><strong>Methods: </strong>Directed literature research was conducted using databases, such as PubMed, and relevant studies were categorized based on the physiological effects of CEACAM1.</p><p><strong>Results: </strong>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><p><strong>Conclusion: </strong>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>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 Suppl 2 ","pages":"e14345"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","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, Maria João Meneses, Hilda E Ghadieh, Laura Herrera, Sérgio Duarte, Rogério T Ribeiro, João F Raposo, Verena Schmitt, Bernhard B Singer, Amalia Gastaldelli, Carlos Penha-Gonçalves, Sonia M Najjar, M Paula Macedo","doi":"10.1111/eci.14344","DOIUrl":"10.1111/eci.14344","url":null,"abstract":"<p><strong>Background: </strong>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><p><strong>Methods: </strong>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><p><strong>Results: </strong>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><p><strong>Conclusions: </strong>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>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 Suppl 2 ","pages":"e14344"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","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}