European Journal of Clinical Investigation最新文献

{"title":"Fatigue and itch severity in patients with PBC and PSC: Prospective analysis of two large cohorts","authors":"Beata Kruk,&nbsp;Joanna Raszeja-Wyszomirska,&nbsp;Marcin Krawczyk,&nbsp;Piotr Milkiewicz","doi":"10.1111/eci.70041","DOIUrl":"10.1111/eci.70041","url":null,"abstract":"<p>Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are rare liver diseases that significantly impair quality of life (QoL). In this study, we analysed two large cohorts comprising a total of 1267 patients with PBC and PSC, showing that fatigue is a frequent symptom in both conditions, particularly among females. Fatigue was associated with liver function markers (ALP/GGT in PSC) and with cirrhosis (in PBC). It was also often linked to cholestatic pruritus, further compromising QoL.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 7","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771733","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":"Pulmonary hypertension and associated heart failure: New insights on emerging signalling pathways.","authors":"Rosalinda Madonna, Elisa Montemaggi","doi":"10.1111/eci.70038","DOIUrl":"https://doi.org/10.1111/eci.70038","url":null,"abstract":"<p><p>Pulmonary hypertension associated with left heart disease (PH-LHD) represents the hemodynamic condition at rest resulting from pathologies that affect the left ventricle and/or the left atrium. Among the left heart diseases, heart failure is the most frequent cause of PH. PH-LHD is the most common cause of PH, accounting for 65-80% of diagnoses. Several drugs targeting specific signalling pathways involved in the pulmonary remodelling in PH-LHD, including nitric oxide, MAP kinase and endothelin-1, have been tested in randomized clinical trials (RCTs), with disappointing results in terms of efficacy and safety. Therefore, PH-LHD still remains orphan of specific therapies able to counteract the pre- and post-capillary remodelling of the pulmonary circulation. In this article, we will discuss the pathophysiology and molecular mechanisms of PH-LHD. We will focus on the emerging signalling pathways involved in the pathophysiology of PH-LHD that could suggest novel molecular targets for the treatment of this condition.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70038"},"PeriodicalIF":4.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735647","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":"Afterload mismatch after transcatheter edge-to-edge repair in functional mitral regurgitation: A propensity-score matched analysis.","authors":"Filippo Angelini, Stefano Pidello, Simone Frea, Pier Paolo Bocchino, Alessandro Mandurino Mirizzi, Anna Giulia Pavon, Carolina Montonati, Francesco Giannini, Davide Giovannini, Antonio Mangieri, Bernhard Reimers, Paolo Boretto, Guglielmo Gallone, Veronica Dusi, Elena Cavallone, Ovidio De Filippo, Gabriele Crimi, Giuseppe Tarantini, Claudia Raineri, Giovanni Pedrazzini, Fabrizio D'Ascenzo, Luigi Biasco, Gaetano Maria De Ferrari","doi":"10.1111/eci.70040","DOIUrl":"https://doi.org/10.1111/eci.70040","url":null,"abstract":"<p><strong>Background: </strong>Transcatheter edge-to-edge repair (TEER) for severe functional mitral regurgitation (FMR) in patients with reduced left ventricular ejection fraction (LVEF) may lead to an acute increase in left ventricular afterload, termed afterload mismatch (AM). This study aimed to redefine AM clinically, analyse its determinants, and assess its prognostic impact post-TEER in FMR patients.</p><p><strong>Methods: </strong>A multicenter case-control study was conducted, involving FMR patients with LVEF ≤35% undergoing TEER. AM post-TEER was defined as the acute (within 24 h) need for escalation of inotropic or mechanical circulatory support. Sixty-eight AM cases were compared with 68 propensity-matched patients. Primary endpoints included in-hospital mortality post-TEER and 2-year all-cause mortality.</p><p><strong>Results: </strong>Median age was 68 years, 76% male. Procedural success was achieved in 92% of patients. Proportionate MR was associated with a higher risk of AM (adj-HR 1.6, 95% CI 1.01-2.6, p = .04). Conversely, pretreatment with levosimendan (adj-HR .29, 95% CI .12-.70, p < .01) and higher furosemide dose (adj-HR per furosemide 10 mg increase .86, 95% CI .76-.98, p = .03) were protective. In-hospital mortality was higher in the AM cohort (10% vs. 2%, p = .03), while 2-year mortality rates were similar (34% vs. 20%, p = .09). Multivariable analysis revealed higher AM grades and post-procedural MR as predictors of in-hospital mortality and lack of procedural success for 2-year mortality.</p><p><strong>Conclusions: </strong>Among patients with LVEF ≤35% and severe FMR undergoing TEER, AM was associated with in-hospital mortality but did not impact long-term outcomes. Proportionate MR increased the risk of AM, while pretreatment with levosimendan and higher furosemide doses was protective.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70040"},"PeriodicalIF":4.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729460","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":"Cellular composition and transcriptomics of subcutaneous adipose tissue linked to blood glycated haemoglobin.","authors":"Sara Paulí, Núria Oliveras-Cañellas, José Maria Moreno-Navarrete, Anna Castells-Nobau, Francisco José Ortega, Jose Ignacio Rodriguez-Hermosa, Ernesto Castro, Birong Zhang, You Zhou, Javier Gómez-Ambrosi, Ana Belén Crujeiras, Oriol Alberto Rangel-Zuñiga, Lourdes Garrido-Sanchez, Sara Becerril, María Pardo, Juan Luis Romero-Cabrera, Carolina Gutierrez-Repiso, Marcos C Carreira, Manuel Macias-Gonzalez, Miguel Ángel Martinez-Olmos, Gema Frühbeck, Luisa Maria Seoane, José López-Miranda, Francisco José Tinahones, Carlos Diéguez, Jordi Mayneris-Perxachs, José Manuel Fernández-Real","doi":"10.1111/eci.70033","DOIUrl":"https://doi.org/10.1111/eci.70033","url":null,"abstract":"<p><strong>Objective: </strong>Despite growing evidence, the mechanisms connecting adipose tissue (AT) function to type 2 diabetes (T2DM) remain incompletely understood. A detailed analysis of AT transcriptomes could offer valuable insights into this relationship. Here, we examined gene expression patterns in bulk subcutaneous AT, focusing on biological pathways and cellular composition associated with glycated haemoglobin (HbA1c) levels.</p><p><strong>Methods: </strong>A transcriptomic dataset was obtained from subcutaneous AT samples of 901 adults collected during elective surgical procedures. We characterized cellular composition within subcutaneous AT in association with blood HbA1c levels by performing bulk adipose transcriptomes cell deconvolution analysis. We also conducted differential gene expression and overrepresentation analyses. We validated our cross-sectional study using two independent validation cohorts, performing further downstream analyses.</p><p><strong>Results: </strong>Subcutaneous AT from subjects with increased HbA1c had lower adipocytes, smooth muscle, pericytes and other endothelial cell numbers. Pathways associated with HbA1c levels included cellular senescence and telomere-related pathways and extracellular matrix organisation. We identified the expression of RHO GTPases associated with HbA1c not previously linked to glucose homeostasis, with a possible sexual dimorphism shaped by the obesity state. The findings were confirmed in both longitudinal cohorts. At the gene level, HLA-DR, CCL13, and S100A4 mRNA levels were strongly correlated with HbA1c levels.</p><p><strong>Conclusions: </strong>This study underscores the utility of AT transcriptome analysis in unravelling T2DM complexities. Our findings enhance knowledge of glucose homeostasis' molecular and cellular underpinnings, paving the way for potential therapeutic targets to mitigate the impact of AT dysfunction in metabolic diseases.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70033"},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709257","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":"Serum fibulin-1 levels and target organ damage in patients at high cardiovascular risk: A prospective observational study.","authors":"Hack-Lyoung Kim, Jung Pyo Lee, Jeonghwan Lee","doi":"10.1111/eci.70039","DOIUrl":"https://doi.org/10.1111/eci.70039","url":null,"abstract":"<p><strong>Background: </strong>Fibulin-1, an extracellular matrix protein, is a potential biomarker for cardiovascular disease, but its association with target organ damage (TOD) in high-risk patients remains unclear.</p><p><strong>Methods: </strong>We prospectively analysed 330 patients undergoing invasive coronary angiography (ICA) (mean age, 64.7 ± 10.7 years; female, 37.9%). Blood samples obtained just before invasive coronary angiography (ICA) were stored for subsequent measurement of fibulin-1 levels using an enzyme-linked immunosorbent assay. During index admission, eight TOD parameters (obstructive coronary artery disease, impaired kidney function, increased arterial stiffness, left ventricular hypertrophy, left ventricular diastolic dysfunction and arterial occlusive disease of peripheral arteries) were assessed. Long-term clinical follow-up data on major adverse cardiovascular events (MACE) were also collected.</p><p><strong>Results: </strong>Fibulin-1 levels were significantly higher in patients with multiple TOD compared to those without (506 ± 229 vs. 354 ± 148 mcg/mL; p < .001). Serum fibulin-1 levels increased proportionally with the number of TODs (p < .001). Multivariable analyses identified that each 100 mcg/mL increase in serum fibulin-1 level was significantly associated with an increased risk of multiple TOD, even after adjustment for potential confounders (odds ratio: 1.29-1.45; p < .05). Similarly, each 100 mcg/mL increase in serum fibulin-1 level was associated with a 29% higher incidence of MACE (95% confidence interval, 1.14-1.46; p < .001).</p><p><strong>Conclusions: </strong>Fibulin-1 is strongly associated with the extent of TOD and may serve as a useful biomarker for risk stratification in high-risk patients.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70039"},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718486","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 cost of emulated target trials: Is real-world data cheaper than randomized studies?","authors":"Mariana Barosa,&nbsp;Vinay Prasad","doi":"10.1111/eci.70035","DOIUrl":"10.1111/eci.70035","url":null,"abstract":"<p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 7","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700033","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 relationship between excess sodium intake and metabolic syndrome: Worth consideration?","authors":"Baris Afsar, Rengin Elsurer Afsar, Said Mowaffaq, Geetha Maddukuri, Krista L Lentine","doi":"10.1111/eci.70036","DOIUrl":"https://doi.org/10.1111/eci.70036","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of metabolic syndrome (MetS) is increasing worldwide. The change in nutrition and eating patterns contributes partly to this rise. On the other hand, increased sodium intake is common in most of the world. There are some studies showing that increased sodium intake may be associated with MetS.</p><p><strong>Methods: </strong>To provide an overview of the current evidence regarding the relationship between excess sodium/salt intake and MetS, we performed a literature search of PubMed/Medline, Web of Science and Google Scholar until October 2024 to recruit studies examining the relationship between sodium/salt intake and MetS.</p><p><strong>Results: </strong>Our review showed that most but not all cross-sectional studies have shown that excess sodium/salt intake is associated with the presence of MetS. Additionally, few longitudinal studies also demonstrated that excess sodium intake is related with the development of new MetS. These studies are mostly observational, and mechanistic studies explaining underlying mechanisms are lacking. The most correlated components of MetS associated with high salt intake were blood pressure and waist circumference, while the correlations between HDL-C, TG and FG were variable.</p><p><strong>Conclusions: </strong>These findings suggest that excess sodium/salt intake may be a risk factor for the development of MetS.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70036"},"PeriodicalIF":4.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699958","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":"Correction to ‘Lung damage in SARS-CoV-2 patients: An autopsy study in the era of vaccination’","authors":"","doi":"10.1111/eci.70037","DOIUrl":"10.1111/eci.70037","url":null,"abstract":"<p>Bussani R, Porcari A, Pinamonti M, Iacobucci A, Belladonna E, Tomasini A, Zanconati F, Collesi C, Giacca M, Berlot G, Sinagra G, Silvestri F. Lung damage in SARS-CoV-2 patients: An autopsy study in the era of vaccination. <i>Eur J Clin Invest</i>. 2025 Jan;55(1):e14325. doi: 10.1111/eci.14325.</p><p>In paragraph ‘Data Availability Statement’, the text ‘De-identified patient data collected for the study will be made available by writing to AP (<span>[email protected]</span>) or RB (<span>[email protected]</span>)’ was incorrect. This should have read ‘The data underlying this article cannot be shared publicly because of the privacy of individuals who participated in the study and the policy of the hospital's regulatory authorities’.</p><p>We apologize for this error.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 6","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700009","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":"New approach to specific Alzheimer's disease diagnosis based on plasma biomarkers in a cognitive disorder cohort.","authors":"Lourdes Álvarez-Sánchez, Laura Ferré-González, Carmen Peña-Bautista, Ángel Balaguer, Julián Luis Amengual, Miguel Baquero, Laura Cubas, Bonaventura Casanova, Consuelo Cháfer-Pericás","doi":"10.1111/eci.70034","DOIUrl":"https://doi.org/10.1111/eci.70034","url":null,"abstract":"<p><strong>Background: </strong>The validation of a combination of plasma biomarkers and demographic variables is required to establish reliable cut-offs for Alzheimer's disease diagnosis (AD).</p><p><strong>Methods: </strong>Plasma biomarkers (Aβ42/Aβ40, p-Tau181, t-Tau, NfL, GFAP), ApoE genotype, and demographic variables were obtained from a retrospective clinical cohort of cognitive disorders (n = 478). These patients were diagnosed as AD (n = 254) or non-AD (n = 224) according to cerebrospinal fluid (CSF) Aβ42/Aβ40 levels. An analysis using a Ridge logistic regression model was performed to predict the occurrence of AD. The predictive performance of the model was assessed using the observations from a training set (70% of the sample) and validated using a test set (30% of the sample) in each group. Optimum cutoffs for the model were evaluated.</p><p><strong>Results: </strong>The model including plasma Aβ42/Aβ40, p-Tau181, GFAP, ApoE genotype and age was optimal for predicting CSF Aβ42/Aβ40 positivity (AUC .91, sensitivity .86, specificity .82). The model including only plasma biomarkers (Aβ42/Aβ40, p-Tau181, GFAP) provided reliable results (AUC .88, sensitivity .83, specificity .78). Also, GFAP, individually, showed the best performance in discriminating between AD and non-AD groups (AUC .859). The established cut-offs in a three-range strategy performed satisfactorily for the validated predictive model (probability) and individual plasma GFAP (concentration).</p><p><strong>Conclusions: </strong>The plasma GFAP levels and the validated predictive model based on plasma biomarkers represent a relevant step toward the development of a potential clinical approach for AD diagnosis, which should be assessed in further research.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e70034"},"PeriodicalIF":4.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676683","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":"Changes in ghrelin isoforms after sleeve gastrectomy or gastric plication and their association with adiposity and metabolic profile","authors":"Carlota Tuero,&nbsp;Sara Becerril,&nbsp;Beatriz Ramirez,&nbsp;Victoria Catalán,&nbsp;Javier A. Cienfuegos,&nbsp;María A. Burrell,&nbsp;Victor Valenti,&nbsp;Rafael Moncada,&nbsp;Javier Gomez-Ambrosi,&nbsp;Amaia Rodriguez,&nbsp;Gema Frühbeck","doi":"10.1111/eci.70031","DOIUrl":"10.1111/eci.70031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background &amp; Aims</h3>\u0000 \u0000 <p>Sleeve gastrectomy (SG) and gastric plication (GP) are two widely performed bariatric techniques reducing the size of the stomach. The improvements observed following these procedures are not fully explained only by caloric restriction. Thus, we aimed at the analysis of adiposity and metabolism modifications in diet-induced obesity (DIO) rats submitted to SG or GP and correlate the changes with total ghrelin concentrations and its two different ghrelin isoforms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Adiposity, lipolysis and circulating ghrelin isoforms were determined in 191 male Wistar rats submitted to surgery: sham (SO), SG, or GP. Results were compared with pair-fed (PF) controls fed either a normal diet (ND) or a high-fat diet (HFD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DIO rats submitted to SG had significantly lower (<i>p</i> &lt; .05) levels of desacyl ghrelin (DAG) and total ghrelin compared with SO and PF ones. Furthermore, they achieved a greater weight loss, adiposity and improvement in glucose and lipid metabolism, as well as brown adipose tissue mitochondrial morphology. No decrease in ghrelin concentrations was observed in GP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The differential effect on circulating ghrelin concentrations of SG and GP, despite both procedures reducing actual stomach size, probably underlies the better outcomes on weight control and lipolysis of the SG due to the fundus removal, the main site of ghrelin-producing cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 7","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669359","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}