European Journal of Clinical Investigation最新文献

{"title":"Type 2 diabetes and chronic kidney disease as long-term predictors of cardiovascular events in patients with coronary artery disease.","authors":"Laura Schnetzer, Andreas Leiherer, Andreas Festa, Axel Mündlein, Thomas Plattner, Gert Mayer, Christoph Saely, Heinz Drexel","doi":"10.1111/eci.14374","DOIUrl":"https://doi.org/10.1111/eci.14374","url":null,"abstract":"<p><strong>Background: </strong>Both chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) confer a high risk of cardiovascular disease and mortality. These entities frequently coincide. The separate and joint impact of CKD and T2DM on the risk of major cardiovascular events (MACE) and survival is unclear.</p><p><strong>Methods: </strong>In this prospective cohort study, patients with angiographically proven coronary artery disease were investigated according to their CKD and T2DM status (T2DM-/CKD-, T2DM+/CKD-, T2DM-/CKD+, T2DM+/CKD+) and followed for up to 18 years.</p><p><strong>Results: </strong>A total of 1441 patients were included in the study of whom 39% experienced MACE (T2DM-/CKD-: 31%, T2DM+/CKD-: 43%, T2DM-/CKD+: 53%, T2DM+/CKD+: 61%) and 53% died. A log-rank test revealed significant differences between the event-free time period of the four groups (χ² (3) = 112.57, p < 0.001). The presence of T2DM and CKD was associated with a 2.72-fold increase [1.98-3.73] in MACE compared to patients who suffered from neither condition (p < 0.001). T2DM alone led to a 1.37-fold increase [1.1-1.7], (p = 0.004), CKD alone to a 1.71-fold increase [1.31-2.25], (p < 0.001).</p><p><strong>Conclusion: </strong>T2DM and CKD in patients with coronary artery disease are mutually independent predictors of cardiovascular events. Patients with both CKD and T2DM are at an extremely high risk for cardiovascular events.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14374"},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863753","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":"Inflammation, lipids and cardiovascular risk: The quest for improving risk stratification and prognosis in ischemic heart disease.","authors":"Giulio Francesco Romiti, Giovanni Buoninfante, Stefania Basili","doi":"10.1111/eci.14373","DOIUrl":"https://doi.org/10.1111/eci.14373","url":null,"abstract":"<p><p>Lp(a): Lipoprotein (a). Created in BioRender. Romiti, G. (2024) BioRender.com/g02a734.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14373"},"PeriodicalIF":4.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834707","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":"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, Yang Chen, Ivan Olier, Sandra Ortega-Martorell, Bi Huang, Hironori Ishiguchi, Ho Man Lam, Kui Hong, Menno V Huisman, Gregory Y H Lip","doi":"10.1111/eci.14371","DOIUrl":"https://doi.org/10.1111/eci.14371","url":null,"abstract":"<p><strong>Background: </strong>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><p><strong>Methods: </strong>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><p><strong>Results: </strong>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><p><strong>Conclusion: </strong>ML algorithms can improve the prediction of residual risk of anticoagulated AF patients compared to clinical risk factor-based scores.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14371"},"PeriodicalIF":4.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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, Praveen Singh, Shantanu Sengupta, Manoj Kushwaha, Zuhaibur Rahman, Divya Bhalla, Pumanshi Talwar, Manabesh Nath, Rahul Chakraborty, Pradeep Kumar, Amit Kumar, Praveen Aggarwal, Achal K Srivastava, Awadh K Pandit, Dheeraj Mohania, Kameshwar Prasad, Nishant K Mishra, Deepti Vibha","doi":"10.1111/eci.14372","DOIUrl":"https://doi.org/10.1111/eci.14372","url":null,"abstract":"<p><strong>Background: </strong>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><p><strong>Methods: </strong>We collected serum samples within 24 h from acute stroke (IS & 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><p><strong>Results: </strong>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% (p < .001). Additionally, nine biomarkers differentiated IS from ICH within 6 h, while three biomarkers differentiated IS from mimics.</p><p><strong>Conclusions: </strong>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>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14372"},"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, 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":"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":"https://doi.org/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":"","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":"","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":"","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":"","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":"https://doi.org/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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}