European Journal of Clinical Investigation最新文献

{"title":"Associations between colonization with Helicobacter pylori and risk of gastrointestinal tract cancers: An umbrella review of meta-analyses.","authors":"Tiago Paiva Prudente, Eleazar Mezaiko, Henrique Nunes Pereira Oliva, Fernanda Paula Yamamoto-Silva, Brunno Santos de Freitas Silva, Isabela Oliveira Oliva, Harvey Risch","doi":"10.1111/eci.14394","DOIUrl":"https://doi.org/10.1111/eci.14394","url":null,"abstract":"<p><strong>Background: </strong>Several studies have investigated the association between Helicobacter pylori colonization and gastrointestinal malignancies. However, inconsistent results have been found, leaving no clear consensus.</p><p><strong>Materials and methods: </strong>Umbrella review of meta-analyses of observational studies aiming to understand the association between Helicobacter pylori colonization and gastrointestinal cancers in humans. MEDLINE, the Cochrane Library of Systematic Reviews, EMBASE, Scopus and Google Scholar were searched from their inception to January 2025. Quality assessment was performed with the AMSTAR 2 tool. The study was registered on PROSPERO (CRD42024523832).</p><p><strong>Results: </strong>Of 1320 records, 38 meta-analyses were included, investigating biliary tract, colorectal, oesophageal, gastric, liver and pancreatic cancers. After dealing with primary study overlap and updating meta-analyses with over 160 studies, Helicobacter pylori was positively associated with biliary tract [OR 2.67 (1.57-4.52)], colorectal [OR 1.40 (1.23-1.60)], gastric [OR 2.10 (1.34-3.31)], liver [OR 5.13 (3.14-8.38)] and pancreatic [OR 1.24 (1.04-1.48)] cancers, while oesophageal adenocarcinoma (EAC) was inversely associated with it [OR .58 (.46-.72)]. The cytotoxic-associated gene A (CagA) protein was positively associated with biliary [OR 2.19 (1.07-4.50)], colorectal [OR 2.04 (1.47-2.82)], oesophageal squamous cell carcinoma [OR 1.56 (1.30-1.89)] and gastric cancers [OR 2.53 (1.94-3.30)], and inversely associated with EAC [OR .60 (.44-.81)] and pancreatic [OR .85 (.75-.97)] cancers. Our results sprout from mostly critically low-quality meta-analyses and moderate to high quality primary studies.</p><p><strong>Conclusion: </strong>Exposure to Helicobacter pylori colonization and its proteins is associated with not only gastric cancer, but also other GI tract cancers. Directionally different results may be seen when specific virulence factors/organ sites are investigated.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14394"},"PeriodicalIF":4.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058486","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":"Sodium-glucose cotransporter 2 inhibitors and outcomes in transthyretin amyloid cardiomyopathy: Systematic review and meta-analysis.","authors":"Paschalis Karakasis, Panagiotis Theofilis, Dimitrios Patoulias, Art Schuermans, Panayotis K Vlachakis, Aleksandra Klisic, Manfredi Rizzo, Nikolaos Fragakis","doi":"10.1111/eci.14392","DOIUrl":"https://doi.org/10.1111/eci.14392","url":null,"abstract":"<p><strong>Background: </strong>Transthyretin amyloid cardiomyopathy (ATTR-CM) commonly leads to heart failure but has traditionally been an exclusion criterion in randomized clinical trials (RCTs) of sodium-glucose cotransporter 2 inhibitors (SGLT2i); therefore, the effects of these drugs in this population remain undocumented. In light of recent studies, this meta-analysis aimed to investigate the effect of SGLT2i on the prognosis of patients with ATTR-CM.</p><p><strong>Methods: </strong>A comprehensive search of Medline, Scopus, and the Cochrane Library was conducted up to November 17, 2024. Study selection, data extraction and quality assessment were carried out independently by two investigators. Associations of SGLT2i with outcomes were pooled using random-effects meta-analyses.</p><p><strong>Results: </strong>A total of five studies (9766 participants, 4 propensity score-matched) were included. The use of SGLT2i was associated with significant reductions in all-cause mortality [hazard ratio (HR) .54, 95% confidence interval (CI) .44-.66], cardiovascular mortality (HR .39, 95% CI .23-.65), major adverse cardiovascular events (HR .71, 95% CI .61-.83), and heart failure hospitalizations (HFHs) (HR .63, 95% CI .52-.77) compared to non-use. The odds of cardiac arrhythmias were significantly lower among SGLT2i users compared to non-users [odds ratio (OR) .73, 95% CI .65-.83]. Specifically, SGLT2i use was associated with significant reductions in the odds of atrial fibrillation (AF) (OR .75, 95% CI .62-.91), ventricular tachycardia (OR .72, 95% CI .59-.88), and sudden cardiac arrest (OR .71, 95% CI .50-.99).</p><p><strong>Conclusions: </strong>The use of SGLT2is may be associated with a more favourable prognosis in patients with ATTR-CM. Adequately powered, long-term RCTs are required to validate the available observational evidence.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14392"},"PeriodicalIF":4.4,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045950","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":"Trends and disparities in atrial fibrillation-related mortality among adults with co-morbid diabetes mellitus in the United States.","authors":"Usama Qamar, Farhan Naeem, Siddharth Agarwal","doi":"10.1111/eci.14393","DOIUrl":"https://doi.org/10.1111/eci.14393","url":null,"abstract":"<p><p>From 1999 to 2020, age-adjusted mortality rates (AAMR) for atrial fibrillation-related deaths among U.S. adults (age ≥25) with comorbid diabetes mellitus increased significantly with an annual percent change of 6.5%. The highest mortality rates were observed in males, older adults, non-Hispanic Whites, and residents of urban areas and the West region, underscoring the urgent need for targeted public health strategies.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14393"},"PeriodicalIF":4.4,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045951","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 use of the Crohn's disease exclusion diet (CDED) in adults with Crohn's disease: A randomized controlled trial.","authors":"Andrea Pasta, Elena Formisano, Francesco Calabrese, Monica Apollonio, Maria Giulia Demarzo, Elisa Marabotto, Manuele Furnari, Edoardo Giovanni Giannini, Livia Pisciotta, Giorgia Bodini","doi":"10.1111/eci.14389","DOIUrl":"https://doi.org/10.1111/eci.14389","url":null,"abstract":"<p><strong>Background: </strong>The Crohn's disease exclusion diet (CDED) has been shown to induce remission in adult Crohn's disease (CD) patients. The aim of the study is to provide additional evidence-based validation.</p><p><strong>Methods: </strong>We conducted an open-label, randomized trial on adult CD patients with mild-to-moderate symptoms to assess CDED efficacy in inducing symptomatic remission using Mediterranean diet as control. We evaluate demographic data, body mass index (BMI), Harvey-Bradshaw Index (HBI), faecal calprotectin, and serum inflammatory indices at baseline, 12, and 24 weeks. Bioelectrical impedance analysis (BIA) was used to ensure the safety of the CDED group every 12 weeks.</p><p><strong>Results: </strong>Twenty-four patients were assigned to CDED, and 21 to controls, with no baseline differences among the parameters considered. Five CDED patients dropped out due to intolerance within the first 6 weeks. At 12 weeks, CDED patients showed significantly lower HBI and higher remission rates than controls. By 24 weeks, remission rates increased (70.8% vs. 38.1% at 12 weeks and 79.2% vs. 42.9% at 24 weeks; p = .027 and p < .0001, respectively), with significantly lower fibrinogen levels in the CDED group. The administration of CDED was associated with a significant decrease in BMI (25.8 kg/m²-24.5 kg/m², p = .047), although BIA analysis showed a decrease in fat mass (18.2%-15.5%, p < .0001), while fat-free mass and body cellular mass significantly increased at 12 weeks (p = .001 and p = .042, respectively) and remained stable at 24 weeks.</p><p><strong>Conclusions: </strong>The CDED was effective in inducing remission among patients with mild-to-moderate CD and appeared to be safe and well-accepted.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14389"},"PeriodicalIF":4.4,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032899","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":"Imaging predictors of adverse prognosis in Fabry disease cardiomyopathy: A systematic review and meta-analysis.","authors":"Kamil Stankowski, Stefano Figliozzi, Thanakorn Rojanathagoon, Dimitrios Bampatsias, Dimitrios Klettas, Lorenzo Monti, Renato Bragato, Pier-Giorgio Masci, Marco Francone, Gianluigi Condorelli, Massimo Imbriaco, Maurizio Pieroni, Antonia Camporeale, Georgios Georgiopoulos","doi":"10.1111/eci.14388","DOIUrl":"https://doi.org/10.1111/eci.14388","url":null,"abstract":"<p><strong>Background: </strong>Cardiac involvement represents the main cause of death in patients with Fabry disease (FD). Echocardiography and cardiovascular magnetic resonance (CMR) have an established diagnostic role, but their prognostic value remains unresolved. This systematic review and meta-analysis sought to assess the prognostic implications of imaging parameters in FD.</p><p><strong>Methods: </strong>PubMed, ClinicalTrials.gov, Embase, Cochrane Library and Web of Science databases were searched for studies from inception through 1 May 2024. Studies including FD patients undergoing baseline imaging assessment and clinical follow-up were selected. Pre-defined study outcomes were a cardiovascular endpoint and a composite clinical endpoint. The study protocol was registered in PROSPERO (ID CRD42022342394).</p><p><strong>Results: </strong>Fourteen studies, including 1713 FD patients (44.7% males), were selected. At pooled analysis, late gadolinium enhancement (hazard ratio [HR]: 4.45; 95% CI: 2.82-7.02), left atrium volume indexed (HR: 1.02 per mL/m²; 95% CI: 1.01-1.03), E/e' (HR: 1.14 per unit increase; 95% CI: 1.08-1.21), left ventricular (LV) mass indexed (HR: 1.01 per mg/m²; 95% CI: 1.00-1.02), maximum LV wall thickness (HR: 1.19 per mm, 95% CI: 1.04-1.36) and LV-global longitudinal strain (HR: 1.20 per unit increase; 95% CI: 1.16-1.25) were significantly associated with the cardiovascular endpoint, whereas T1-mapping and LV-ejection fraction were not. T1-mapping was associated with the composite endpoint (HR: 0.99 per msec increase; 95% CI: 0.98-1.00). Meta-regression analysis did not show any significant interaction between each of the potential effect modifiers.</p><p><strong>Conclusions: </strong>Several imaging parameters were significant predictors of adverse clinical outcomes in patients with FD. Late gadolinium enhancement showed the strongest association with adverse prognosis.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14388"},"PeriodicalIF":4.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002708","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":"Myths and challenges around anticoagulation in atrial fibrillation: A practicing clinician's perspective.","authors":"K E Juhani Airaksinen, Ville Langén, Konsta Teppo, Gregory Y H Lip","doi":"10.1111/eci.14390","DOIUrl":"https://doi.org/10.1111/eci.14390","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14390"},"PeriodicalIF":4.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002744","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":"Altered fibrin clot properties and elevated von Willebrand factor are associated with progression to permanent atrial fibrillation: A cohort study.","authors":"Karol Witold Nowak, Michal Zabczyk, Joanna Natorska, Maciej Polak, Jaroslaw Zalewski, Anetta Undas","doi":"10.1111/eci.14384","DOIUrl":"https://doi.org/10.1111/eci.14384","url":null,"abstract":"<p><strong>Background: </strong>The role of a prothrombotic state in atrial fibrillation (AF) progression to permanent arrythmia (PerAF) is unclear. Formation of denser and poorly lysable fibrin clots has been observed in AF patients also with sinus rhythm in association with higher stroke risk. We investigated whether altered fibrin clot properties and other prothrombotic state markers may contribute to AF transition to PerAF.</p><p><strong>Methods: </strong>In the cohort study, in 226 anticoagulated patients (median age 69 years, median CHA₂DS₂-VASc of 3) with paroxysmal (n = 83, 36.7%) or persistent (n = 143, 63.3%) AF, we assessed at baseline plasma clot permeability (K_s), clot lysis time (CLT), proteins involved in fibrinolysis and von Willebrand factor (vWF) antigen. We recorded patients with PerAF during a median follow-up of 58 months.</p><p><strong>Results: </strong>During follow-up, PerAF was documented in 62 (27.4%, 5.7%/year) subjects, who had higher prevalence of heart failure, higher body mass index and longer history of arrhythmia. AF transition to PerAF was associated with 25.7% longer CLT in relation to 21.3% higher plasminogen activator inhibitor type 1, and 29% higher vWF compared to the remainder, with no differences in K_s, plasminogen or α2-antiplasmin. By multivariable analysis, CLT (per 10 min, odds ratio [OR] 2.734, 95% confidence interval [CI] 1.788-4.180, p < .001), vWF (per 10%, OR 1.352, 95% CI 1.145-1.596, p < .001) and heart failure (OR 2.637, 95% CI 1.008-6.900, p = .048) were associated with progression to PerAF.</p><p><strong>Conclusion: </strong>Suppressed fibrin clot susceptibility to lysis and elevated vWF could contribute to progression to PerAF despite anticoagulation, which suggests links between blood coagulation and AF progression.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14384"},"PeriodicalIF":4.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002639","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":"Meteorin-like protein plasma levels are associated with worse outcomes in de novo heart failure.","authors":"Laura Anido-Varela, Alana Aragón-Herrera, Adrián González-Maestro, Carlos Tilves Bellas, Estefanía Tarazón, Eduard Solé-González, Manuel Martínez-Sellés, José María Guerra-Ramos, Anna Carrasquer, Laura Morán-Fernández, David García-Vega, Ana Seoane-Blanco, María Moure-González, Jose Seijas-Amigo, Diego Rodríguez-Penas, Javier García-Seara, Sandra Moraña-Fernández, Xocas Vázquez-Abuín, Esther Roselló-Lletí, Manuel Portolés, Sonia Eiras, Rosa M Agra, Ezequiel Álvarez, José R González-Juanatey, Sandra Feijóo-Bandín, Francisca Lago","doi":"10.1111/eci.14380","DOIUrl":"https://doi.org/10.1111/eci.14380","url":null,"abstract":"<p><strong>Background and aims: </strong>Meteorin-like protein (Metrnl) has been recently suggested as a new adipokine with protective cardiovascular effects. Its circulating levels in patients seem to be associated with heart failure (HF), although with contradictory results. Our aim was to ascertain whether this adipokine could estimate the prognosis of HF in de novo HF (DNHF) patients.</p><p><strong>Methods: </strong>Metrnl plasma levels of 400 patients hospitalized with DNHF (55% of patients with HF with reduced ejection fraction, 17.3% HF with mid-range ejection fraction, 27.8% HF with preserved ejection fraction) were measured by enzyme-linked immunosorbent assay. We performed both sex-pooled and sex-specific analyses. A 12-month follow-up was conducted, during which clinical outcomes such as all-cause mortality, cardiovascular death and re-hospitalization due to HF were collected.</p><p><strong>Results: </strong>After a 12-month follow up, higher plasma Metrnl levels were associated with an increased risk for all-cause death and cardiovascular death after adjusting by sex, age, LVEF, hypertension, diabetes, ischemic aetiology, chronic renal failure, NT-proBNP and troponin (hazard ratio [HR] = 1.003, 95% confidence interval [CI] = 1.000-1.005; p-value<.05 and HR = 1.004, 95% CI = 1.001-1.007, p-value<.05, respectively). In line with this, DNHF patients with increased levels of circulating Metrnl had a higher number of occurrences of cardiovascular events. Regarding Metrnl associations with parameters implicated in the development and progression of HF, we found that Metrnl circulating levels were positively correlated with age (r = .322, p-value<.0001), NT-proBNP (r = .281, p-value<.0001) and with the renal dysfunction markers urea (r = .322, p-value<.0001) and creatinine (r = .353, p-value<.0001) and higher in women than men (473.7 [385.9-594.0] pg/mL vs. 428.7 [349.1-561.3] pg/mL, p-value<.006). Finally, concerning the subtype of HF, Metrnl plasma levels were higher in HF with preserved ejection fraction.</p><p><strong>Conclusion: </strong>Patients with higher Metrnl levels have a worse prognosis in DNHF. Our results reinforce the association of Metrnl plasma levels with HF progression and outcomes.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14380"},"PeriodicalIF":4.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002650","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":"Sexual dimorphism in exercise-induced response on steroid hormones to a 24-week supervised concurrent training intervention","authors":"Lourdes Herrera-Quintana,&nbsp;Héctor Vázquez-Lorente,&nbsp;Jonatan R. Ruiz,&nbsp;Francisco J. Amaro-Gahete","doi":"10.1111/eci.14377","DOIUrl":"10.1111/eci.14377","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Steroid hormones are key mediators of adaptative responses to exercise, a stimulus that may concurrently affect their blood concentrations. However, the chronic endocrine adaptations and whether these potential changes are dependent on exercise intensity remain undetermined. Moreover, it is also unknown if the exercise-induced effects on steroid hormonal status are related to the participant' sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study aimed to investigate the intensity effects of a 24-week supervised concurrent training intervention on steroid hormones in sedentary young men and women. A total of 106 untrained young adults (68% women) aged 18–25 years were randomly assigned to one of the three groups: (I) Control group (no exercise; <i>n</i> = 35); (II) Ex-Moderate group (concurrent training at moderate intensity; <i>n</i> = 36); (III) Ex-Vigorous group (concurrent training at vigorous intensity; <i>n</i> = 35). Steroid hormones (i.e. cortisol, testosterone and dehydroepiandrosterone sulfate (DHEAS)) were measured in plasma through a chemiluminescent method. Body composition parameters were determined using a dual-energy X-ray absorptiometry scanner.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No significant changes in steroid hormones levels were observed after the intervention (all <i>p</i> ≥ .129). However, a time x group interaction was noted in the testosterone/cortisol ratio (T/C ratio) only in women (<i>p</i> = .044). Concretely, our data showed a significant decrement of T/C ratio in both the Ex-Moderate group and in the Ex-Vigorous compared with the control group (Δ = −24.2 ± 2.0% and Δ = −38.9 ± 45.4%, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our 24-week supervised concurrent training intervention showed no significant changes in steroid hormone levels. However, a significant decrement of T/C ratio was observed only in women, indicating a sexual dimorphism in the effect on T/C ratio.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002759","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":"Sotatercept in pulmonary hypertension and beyond.","authors":"Rosalinda Madonna, Sandra Ghelardoni","doi":"10.1111/eci.14386","DOIUrl":"https://doi.org/10.1111/eci.14386","url":null,"abstract":"<p><p>Sotatercept binds free activins by mimicking the extracellular domain of the activin receptor type IIA (ACTRIIA). Additional ligands are BMP/TGF-beta, GDF8, GDF11 and BMP10. The binding with activins leads to the inhibition of the signalling pathway and the deactivation of the bone morphogenic protein (BMP) receptor type 2. In this way, sotatercept activates an antiproliferative signalling to the cells of the pulmonary arteries and arterioles with the aim of rebalancing the proliferative and antiproliferative pathway that characterizes the pulmonary arterial hypertension (PAH). Sotatercept is indicated for the treatment of group 1 PAH in combination with drugs that act through the endothelin receptor, nitric oxide or prostacyclin. Its effects, demonstrated in the STELLAR study, are the improvement of exercise capacity and the FC-WHO functional class, together with the reduction of the risk of clinical worsening events. In addition to its antiremodeling effects on the pulmonary circulation, sotatercept has several haematological effects that could suggest its use in the treatment of some blood disorders other than PAH. In this review, we will discuss the effects of the drug on PAH and in parallel provide an in-depth overview of its application in haematological disorders, focusing on clinical and preclinical studies.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14386"},"PeriodicalIF":4.4,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002765","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}