Milton Fabian Suárez-Ortegón, Stela McLachlan, José Manuel Fernández-Real, James F. Wilson, Sarah H. Wild
{"title":"Both low and high body iron stores relate to metabolic syndrome in postmenopausal women: Findings from the VIKING Health Study-Shetland (VIKING I)","authors":"Milton Fabian Suárez-Ortegón, Stela McLachlan, José Manuel Fernández-Real, James F. Wilson, Sarah H. Wild","doi":"10.1111/eci.14312","DOIUrl":"10.1111/eci.14312","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There are conflicting results among studies on the association between serum ferritin (SF) and metabolic syndrome (MetS), and by groups of sex/menopausal status. To date, there are no studies on British populations. The SF-MetS association might be U/J-shaped. We evaluated whether SF was independently associated with MetS (harmonized definition) in people from Shetland, Scotland.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed cross-sectional data from the Viking Health Study-Shetland (589 premenopausal women [PreMW], 625 postmenopausal women [PostW] and 832 men). Logistic regressions using two approaches, one with the lowest sex and menopausal status-specific ferritin quartile (Q) as the reference and other using the middle two quartiles combined (2–3) as the reference, were conducted to estimate the SF-MetS association. The shape of the association was verified via cubic spline analyses. The associations were adjusted for age, inflammatory and hepatic injury markers, alcohol intake, smoking and BMI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Prevalence of MetS was 18.3%. Among PostMW both low and high SF were associated with MetS (fully adjusted odds ratios [95% confidence interval] compared to the middle two quartiles combined were: 1.99 [1.17–3.38] <i>p</i> =.011 for Q1 and 2.10 [1.27–3.49] <i>p</i> =.004 for Q4) This <i>U</i>-shaped pattern was confirmed in the cubic spline analysis in PostMW with a ferritin range of 15–200 ug/L. In men, a positive association between ferritin quartiles with Q1 as the reference, did not remain significant after adjustment for BMI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Extreme quartiles of iron status were positively associated with MetS in PostMW, while no SF-MetS associations were found in men or PreMW. The ferritin-MetS association pattern differs between populations and U/J-shaped associations may exist.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14312","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139688","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}
Juan Antonio Valera-Calero, Umut Varol, Ricardo Ortega-Santiago, Marcos José Navarro-Santana, María José Díaz-Arribas, Jorge Buffet-García, Gustavo Plaza-Manzano
{"title":"MyofAPPcial: Construct validity of a novel technological aid for improving clinical reasoning in the management of myofascial pain syndrome","authors":"Juan Antonio Valera-Calero, Umut Varol, Ricardo Ortega-Santiago, Marcos José Navarro-Santana, María José Díaz-Arribas, Jorge Buffet-García, Gustavo Plaza-Manzano","doi":"10.1111/eci.14313","DOIUrl":"10.1111/eci.14313","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Physiotherapists encounter challenges in diagnosing myofascial trigger points (MTrPs), which are crucial for managing myofascial pain but difficult due to their complex referred pain patterns. We aimed to assess if an interactive software (MyofAPPcial) can enhance the ability of physical therapists specialized in musculoskeletal disorders (as clinicians and as researchers and educators) to identify referred pain patterns associated with specific MTrPs and to explore their opinion about incorporating this technology regularly into their professional setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>After developing the app, a descriptive cross-sectional survey study was conducted. Participants were asked about their demographic characteristics, professional experience, two knowledge tests (first without and later with MyofAPPcial support) and the 18-item mHealth app usability questionnaire.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty-nine participants completed the survey (47.5% clinicians and 62.5% researchers/educators). Groups were comparable in terms of age, gender and professional experience (<i>p</i> > .05). However, clinicians coursed shorter specific MPS trainings (<i>p</i> = .007) and handle more cases a week (<i>p</i> < .001). In the first knowledge test, participants in both the groups were more accurate in identifying pain maps of highly prevalent MTrPs than those with a moderate or low prevalence (<i>p</i> < .001), with no differences between the groups for individual items (all, <i>p</i> > .05) nor the total score (<i>p</i> > .05). In the second knowledge test, perfect scores were obtained for all items in both the groups. Finally, MyofAPPcial scored high satisfaction and app usefulness, with no difference between clinicians and researchers/educators (except greater convenience of use for researchers/educators <i>p</i> = .02).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MyofAPPcial enhances physiotherapists' ability to accurately identify MTrPs, with a good acceptation among clinicians and researchers/educators.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14313","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139689","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}
Henri-Corto Stoeklé, Philippe Beuzeboc, Tara Payet, Christian Hervé, Jaafar Bennouna
{"title":"Early-phase clinical trials in oncology for adults in France: A preliminary empirical bioethics study","authors":"Henri-Corto Stoeklé, Philippe Beuzeboc, Tara Payet, Christian Hervé, Jaafar Bennouna","doi":"10.1111/eci.14315","DOIUrl":"10.1111/eci.14315","url":null,"abstract":"<p>The last few years have seen the improvement of cancer management through the arrival of a continuous stream of innovative new molecules known as ‘targeted therapies’ and ‘new immunotherapies’.<span><sup>1</sup></span> One characteristic common to all these treatments is a specific link to a precise cellular and/or molecular profile. Some of these treatments are already improving therapeutic results for certain types and subtypes of cancer.<span><sup>2</sup></span> However, a non-negligible proportion of these molecules remain inaccessible to patients other than through clinical trials, particularly early-phase clinical trials.<span><sup>3</sup></span> The aims of such clinical trials were initially limited to identifying toxicities associated with the molecules tested, but they now extend to the evaluation of efficacy and possible therapeutic benefits for participants. We performed a preliminary empirical bioethics work at national scale in France, with specific protocolization,<span><sup>4</sup></span> based on a non-systematic literature review, to deal with the ‘macro-bio-ethical issues’.</p><p>HCS, PB, CH and JB are the principal investigators. They contributed to the conception of the paper, the drafting of sections and discussions about how the different sections should be refined and integrated. TP is an undergraduate trainee who helped collect and process the data.</p><p>Foch Hospital.</p><p>HCS, TP and CH have no conflicts of interest to declare for the submitted work. PB has received personal fees from Astellas (educational sessions) and Pfizer (travel expenses to ASCO 2023), all outside of the submitted work. JB has received personal fees from AstraZeneca, Bristol-Myers Squibb, MSD, Janssen Cilag, Daiichi and Sanofi Aventis (advisory board, educational symposium and honorarium), all outside of the submitted work.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132213","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}
Luis Jara-Palomares, Behnood Bikdeli, David Jiménez, Alfonso Muriel, Pablo Demelo-Rodríguez, Isabelle Mahé, Juan José López-Núñez, Joaquín Alfonso Megido, Begoña Fernández Jiménez, Manuel Monreal, the RIETE Investigators
{"title":"Rate of recurrence after discontinuing anticoagulation in patients with venous thromboembolism within 30 days after COVID-19 vaccine","authors":"Luis Jara-Palomares, Behnood Bikdeli, David Jiménez, Alfonso Muriel, Pablo Demelo-Rodríguez, Isabelle Mahé, Juan José López-Núñez, Joaquín Alfonso Megido, Begoña Fernández Jiménez, Manuel Monreal, the RIETE Investigators","doi":"10.1111/eci.14310","DOIUrl":"10.1111/eci.14310","url":null,"abstract":"<p>This study generated evidence to guide anticoagulation in patients with VTE after vaccination for COVID-19. We provided data on the low recurrence rate after cessation of anticoagulant therapy and the findings for this study offer timely insights into the management of a potentially vaccine-related adverse event.\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":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132214","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}
Emma M. Wade, Elizabeth A. Goodin, Tim Morgan, Stephana Pereira, Adele G. Woolley, Zandra A. Jenkins, Philip B. Daniel, Stephen P. Robertson
{"title":"The hinge-1 domain of Flna is not necessary for diverse physiological functions in mice","authors":"Emma M. Wade, Elizabeth A. Goodin, Tim Morgan, Stephana Pereira, Adele G. Woolley, Zandra A. Jenkins, Philip B. Daniel, Stephen P. Robertson","doi":"10.1111/eci.14308","DOIUrl":"10.1111/eci.14308","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The filamins are cytoskeletal binding proteins that dynamically crosslink actin into orthogonal networks or bundle it into stress fibres. The domain structure of filamin proteins is very well characterised, with an N-terminal actin-binding region, followed by 24 immunoglobulin-like repeat units. The repeat domains are separated into distinct segments by two regions of low-complexity known as hinge-1 and hinge-2. The role of hinge-1 especially has been proposed to be essential for protein function as it provides flexibility to the otherwise rigid protein, and is a target for cleavage by calpain. Hinge-1 protects cells from otherwise destructive forces, and the products of calpain cleavage are involved in critical cellular signalling processes, such as survival during hypoxia. Pathogenic variants in <i>FLNA</i> encoding Filamin A, including those that remove the hinge-1 domain, cause a wide range of survivable developmental disorders. In contrast, complete loss of function of this gene is embryonic lethal in human and mouse.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>In this study, we show that removing filamin A hinge-1 from mouse (<i>Flna</i><sup><i>ΔH1</i></sup>), while preserving its expression level leads to no obvious developmental phenotype. Detailed characterisation of the skeletons of <i>Flna</i><sup><i>ΔH1</i></sup> mice showed no skeletal phenotype reminiscent of that found in the <i>FLNA-</i>causing skeletal dysplasia. Furthermore, nuclear functions of FLNA are maintained with loss of Filamin A hinge-1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We conclude that hinge-1 is dispensable for filamin A protein function during development over the murine lifespan.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14308","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105809","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}
Aida Fiz-López, Ángel De Prado, Elisa Arribas-Rodríguez, Francisco Javier García-Alonso, Sandra Izquierdo, Álvaro Martín-Muñoz, José A. Garrote, Eduardo Arranz, Jesús Barrio, Luis Fernández-Salazar, David Bernardo
{"title":"Biological variability of human intraepithelial lymphocytes throughout the human gastrointestinal tract in health and coeliac disease","authors":"Aida Fiz-López, Ángel De Prado, Elisa Arribas-Rodríguez, Francisco Javier García-Alonso, Sandra Izquierdo, Álvaro Martín-Muñoz, José A. Garrote, Eduardo Arranz, Jesús Barrio, Luis Fernández-Salazar, David Bernardo","doi":"10.1111/eci.14304","DOIUrl":"10.1111/eci.14304","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intraepithelial lymphocytes are the first line of defence of the human intestinal immune system. Besides, their composition is altered on patients with coeliac disease (CD), so they are considered as biomarkers with utility on their diagnose and/or monitoring. Our aim is to address their variability through the human gastrointestinal tract in health and characterized them in further depth in the coeliac duodenum.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Intraepithelial lymphocytes were isolated from human gastric, duodenal, ileal and colonic biopsies, then stained with specific antibodies and acquired by flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results confirmed that the profile of Intraepithelial lymphocytes change through the length of the human gastrointestinal tract. Besides and given the central role that Interleukin-15 (IL-15) elicits on CD pathogenesis; we also assessed the expression of its receptor revealing that there was virtually no functional IL-15 receptor on duodenal Intraepithelial lymphocytes. Nevertheless and contrary to our expectations, the active IL-15 receptor was not increased either on Intraepithelial lymphocytes from CD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>IL-15 might require additional stimulus to activate intraepithelial lymphocytes. These findings may provide novel tools to aid on a CD diagnosis and/or monitoring, at the time that provide the bases to perform functional studies in order of getting a deeper insight in the specific function that Intraepithelial lymphocytes elicit on CD pathogenesis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14304","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105808","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":"Expression of concern","authors":"","doi":"10.1111/eci.14306","DOIUrl":"10.1111/eci.14306","url":null,"abstract":"<p>Expression of Concern: Rahmani E, Jamilian M, Dadpour B, Nezami Z, Vahedpoor Z, Mahmoodi S, Aghadavod E, Taghizadeh M, Beiki Hassan A, Asemi Z. The effects of fish oil on gene expression in patients with polycystic ovary syndrome. <i>Eur J Clin Invest</i>. 2018;48(3):e12893. https://doi.org/10.1111/eci.12893.</p><p>This Expression of Concern is for the above article, published online on 23 January 2018 in Wiley Online Library (wileyonlinelibrary.com), and has been published by agreement between the journal Editor-in-Chief, Hendrik Nathoe, European Society for Clinical Investigation and John Wiley & Sons Ltd. The Expression of Concern has been agreed due to concerns raised regarding the integrity of the research and discrepancies in reporting. An investigation has been conducted by the National Committee for Ethics in Biomedical Research Iran, in coordination with Kashan University of Medical Sciences (KAUMS). However, without the verification of clinical records, there remain sufficient doubts about the feasibility and integrity of the research undertaken. As a result, the journal has decided to issue an Expression of Concern to alert readers.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14306","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055281","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}
Giuseppe Panuccio, Nicole Carabetta, Daniele Torella, Salvatore De Rosa
{"title":"Percutaneous coronary revascularization versus medical therapy in chronic coronary syndromes: An updated meta-analysis of randomized controlled trials","authors":"Giuseppe Panuccio, Nicole Carabetta, Daniele Torella, Salvatore De Rosa","doi":"10.1111/eci.14303","DOIUrl":"10.1111/eci.14303","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Coronary artery disease (CAD) is a main cause of morbidity and mortality. The effectiveness of coronary revascularization in chronic coronary syndromes (CCS) is still debated. Our recent study showed the superiority of coronary revascularization over optimal medical therapy (OMT) in reducing cardiovascular (CV) mortality and myocardial infarction (MI). The recent publication of the ORBITA-2 trial suggested superiority of percutaneous coronary revascularization (PCI) in reducing angina and improving quality of life. Therefore, we aimed to provide an updated meta-analysis evaluating the impact of PCI on both clinical outcomes and angina in CCS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Relevant studies were screened in PubMed/Medline until 08/01/2024. Randomized controlled trials (RCTs) comparing PCI to OMT in CCS were selected. The primary outcome was CV death. Secondary outcomes were MI, all-cause mortality, stroke, major bleeding and angina severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nineteen RCTs involving 8616 patients were included. Median follow-up duration was 3.3 years. Revascularization significantly reduced CV death (4.2% vs. 5.5%; OR = .77; 95% CI .62–.96, <i>p</i> = .02). Subgroup analyses favoured revascularization in patients without chronic total occlusions (CTOs) (<i>p</i> = .052) and those aged <65 years (<i>p</i> = .02). Finally, a follow-up duration beyond 3 years showed increased benefit of coronary revascularization (<i>p</i> = .04). Secondary outcomes analyses showed no significant differences, except for a lower angina severity in the revascularization group according to the Seattle Angina Questionnaire (SAQ) (<i>p</i> = .04) and to the Canadian Cardiovascular Society (CCS) classification (<i>p</i> = .005).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>PCI compared to OMT significantly reduces CV mortality and angina severity, improving quality of life in CCS patients. This benefit was larger without CTOs, in patients aged <65 years and with follow-up duration beyond 3 years.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016845","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":"First time ACS in patients with on-target lipid levels: Inflammation at admission and re-event rate at follow-up","authors":"Natàlia Muñoz-García, Alberto Cordero, Teresa Padro, Guiomar Mendieta, Gemma Vilahur, Emilio Flores, Lina Badimon","doi":"10.1111/eci.14305","DOIUrl":"10.1111/eci.14305","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dyslipidaemia, inflammation and elevated Lp(a) levels are associated with the progression of atherosclerosis. This study investigates whether patients with a first-time presentation of chest pain and on-target LDL-C levels and intermediate FRS/ESC-Score risks, display a high inflammatory burden linked to myocardial injury and whether inflammation at admission affects the re-event rate up to 6 years follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Blind assessments of novel inflammatory markers such as Glycoprotein A and B via nuclear magnetic resonance (NMR), cytokines, hsCRP, Neutrophil-to-Lymphocyte ratio (NLR) and Lipoprotein(a) levels were examined. Out of 198 chest pain patients screened, 97 met the inclusion criteria at admission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>cTnI(+) patients (>61 ng/L) with elevated Lipoprotein(a), showed significantly increased levels of Glycoprotein A and B, hsCRP, IL-6, a high NLR and a reduced left ventricular ejection fraction (%) compared to cTnI(−) individuals. Those patients, with a higher inflammatory burden at hospital admission (hsCRP, IL-6, Glycoprotein A and B, and Lipoprotein(a)) had a higher re-event rate at follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Inflammation and Lipoprotein(a) levels were particularly prominent in patients presenting with reduced left ventricular ejection fraction. Notably, Glycoproteins A/B emerge as novel markers of inflammation in these patients. Our study highlights the significantly higher impact of inflammatory burden in patients with chest pain and high level of myocardial damage than in those with lower myocardial affectation, even when they all had lipid levels well controlled. Inflammation at the time of admission influenced the re-event rate over a follow-up period of up to 6 years.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003921","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}
Ana Asenjo-Bueno, Elena Alcalde-Estévez, Gemma Olmos, Patricia Martínez-Miguel, María Piedad Ruiz-Torres, Susana López-Ongil
{"title":"Respiratory dysfunction in old mice could be related to inflammation and lung fibrosis induced by hyperphosphatemia","authors":"Ana Asenjo-Bueno, Elena Alcalde-Estévez, Gemma Olmos, Patricia Martínez-Miguel, María Piedad Ruiz-Torres, Susana López-Ongil","doi":"10.1111/eci.14302","DOIUrl":"10.1111/eci.14302","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>With age, lungs undergo typical changes that lead to a deterioration of respiratory function. Our aim was to assess the role of age-associated hyperphosphatemia in these changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used C57BL6 mice to study an ageing model in vivo and human lung fibroblasts were treated with a phosphate donor, beta-glycerophosphate (BGP), to explore mechanisms involved. Respiratory function was registered with a double chamber plethysmograph. Lung structure was analysed by different staining, phosphate and cytokines levels by colorimeric kits, expression of fibrosis, inflammation and ET-1 system by western blot or RT-PCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Old mice showed hyperphosphatemia, along with lung fibrosis, loss of elastin, increased expression of pro-inflammatory cytokines and impaired respiratory function. BGP induced inflammation and fibrosis in fibroblasts through the activation and binding of NF<span>k</span>B to the MCP-1 or FN promoters. BGP increased ECE-1 expression by inducing NF<span>k</span>B binding to the ECE-1 promoter. QNZ, an NF<span>k</span>B inhibitor, blocked these effects. When ECE-1 was inhibited with phosphoramidon, BGP-induced inflammation and fibrosis were significantly reduced, suggesting a role for ET-1 in BGP-mediated effects.ET-1 produced effects similar to those of BGP, which were also dependent on NF<span>k</span>B. To study the pathophysiological relevance of hyperphosphatemia in vivo, a low-P diet was administered to a group of old animals, showing an improvement in fibrosis, inflammation and respiratory function compared to old mice on a standard diet.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results suggest that age-related hyperphosphatemia induces inflammation, fibrosis, and impaired respiratory function in old mice; these effects appear to be mediated by ET-1 and NF<span>k</span>B activation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14302","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999704","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}