Shoaib Fakhri, Luiz Campedelli, Michael G. Risbano
Background
Preload insufficiency is an underrecognized cause of exercise intolerance identified during invasive cardiopulmonary exercise testing, and defined hemodynamically by decreased biatrial filling pressures, cardiac output, and oxygen consumption (V̇O2) at peak effort. Patients with preload insufficiency, however, typically present with symptoms of dyspnea on exertion, and/or exercise intolerance at submaximal efforts, particularly when performing activities of daily living. The cardiopulmonary hemodynamics and physiology at submaximal work levels of preload insufficiency have not been previously investigated. We hypothesized that preload insufficiency hemodynamics exist along a continuum, with submaximal exercise values reflecting peak exercise cardiopulmonary hemodynamics.
Methods
We compared submaximal cardiopulmonary hemodynamics, measured at anaerobic threshold, between preload insufficiency patients and age-matched controls referred for dyspnea but with normal exercise responses.
Results
Our study included 66 patients: 41 with preload insufficiency and 25 controls. Preload insufficiency patients exhibit significantly reduced V̇O2, watts, and METS at submaximal levels compared to controls, alongside earlier anaerobic threshold achievement and similar heart rates at anaerobic threshold.
Conclusions
These findings underscore the profound impact of preload insufficiency on submaximal exercise capacity, emphasizing the importance of its recognition and management. This insight sets the stage for further investigations into interventions targeting preload insufficiency at submaximal exercise levels to enhance both exercise performance and quality of life.
{"title":"Hemodynamic responses at anaerobic threshold during exercise in preload insufficiency","authors":"Shoaib Fakhri, Luiz Campedelli, Michael G. Risbano","doi":"10.1111/eci.14343","DOIUrl":"10.1111/eci.14343","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Preload insufficiency is an underrecognized cause of exercise intolerance identified during invasive cardiopulmonary exercise testing, and defined hemodynamically by decreased biatrial filling pressures, cardiac output, and oxygen consumption (V̇O<sub>2</sub>) at peak effort. Patients with preload insufficiency, however, typically present with symptoms of dyspnea on exertion, and/or exercise intolerance at submaximal efforts, particularly when performing activities of daily living. The cardiopulmonary hemodynamics and physiology at submaximal work levels of preload insufficiency have not been previously investigated. We hypothesized that preload insufficiency hemodynamics exist along a continuum, with submaximal exercise values reflecting peak exercise cardiopulmonary hemodynamics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We compared submaximal cardiopulmonary hemodynamics, measured at anaerobic threshold, between preload insufficiency patients and age-matched controls referred for dyspnea but with normal exercise responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our study included 66 patients: 41 with preload insufficiency and 25 controls. Preload insufficiency patients exhibit significantly reduced V̇O<sub>2</sub>, watts, and METS at submaximal levels compared to controls, alongside earlier anaerobic threshold achievement and similar heart rates at anaerobic threshold.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings underscore the profound impact of preload insufficiency on submaximal exercise capacity, emphasizing the importance of its recognition and management. This insight sets the stage for further investigations into interventions targeting preload insufficiency at submaximal exercise levels to enhance both exercise performance and quality of life.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616987","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}
Josef E. Gillson, Sooin Byeon, Angela Chou, Sarah Maloney, Nick Pavlakis, Stephen J. Clarke, David L. Chan, Connie I. Diakos, Anthony J. Gill, Jaswinder S. Samra, Anubhav Mittal, Sumit Sahni
Background
Neoadjuvant chemotherapy (NAC) can provide improved survival outcomes in pancreatic ductal adenocarcinoma (PDAC) patients who respond to treatment, but currently available biomarkers cannot reliably predict NAC response. This study aimed to determine the potential of a previously identified diagnostic and prognostic biomarker panel (i.e. Ca-125, S100A2, S100A4, Mesothelin and Ca19-9) for the monitoring of NAC-response in PDAC patients.
Methods
This single-centre, retrospective study, utilised serum from NAC treated PDAC patients to determine the levels of biomarkers by Enzyme-Linked Immunosorbent Assay (ELISA). The percentage of the tumour bed occupied by viable carcinoma (PVC) was used to divide patients into good (PVC < 50%) and poor (PVC ≥ 50%) NAC-responders. Statistical analysis was performed to measure the ability of individual biomarkers and a biomarker panel in NAC treatment response and patient survival.
Results
Serum specimens from a total of 108 PDAC patients were assessed. Ca-125, Ca19-9 and S100A2 showed a significant positive correlation with PVC. Ca-125 demonstrated a superior ability to monitor NAC treatment response (Area under receiver operating curve (AUC): .6954) compared to the more widely used clinical biomarker, Ca19-9 (AUC: .6291). A panel of Ca-125 and Ca19-9 showed good ability to monitor NAC response in PDAC patients (AUC: .7349). Patients with high levels of both Ca-125 and Ca19-9 were shown to have the poorest overall survival (median overall survival: 17 vs. 30 months).
Conclusion
A serum biomarker panel of Ca-125 and Ca19-9 could be used for effective clinical management of PDAC patients undergoing NAC treatment.
{"title":"Promising biomarker panel to monitor therapeutic efficacy of neoadjuvant chemotherapy in pancreatic cancer patients","authors":"Josef E. Gillson, Sooin Byeon, Angela Chou, Sarah Maloney, Nick Pavlakis, Stephen J. Clarke, David L. Chan, Connie I. Diakos, Anthony J. Gill, Jaswinder S. Samra, Anubhav Mittal, Sumit Sahni","doi":"10.1111/eci.14341","DOIUrl":"10.1111/eci.14341","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neoadjuvant chemotherapy (NAC) can provide improved survival outcomes in pancreatic ductal adenocarcinoma (PDAC) patients who respond to treatment, but currently available biomarkers cannot reliably predict NAC response. This study aimed to determine the potential of a previously identified diagnostic and prognostic biomarker panel (i.e. Ca-125, S100A2, S100A4, Mesothelin and Ca19-9) for the monitoring of NAC-response in PDAC patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This single-centre, retrospective study, utilised serum from NAC treated PDAC patients to determine the levels of biomarkers by Enzyme-Linked Immunosorbent Assay (ELISA). The percentage of the tumour bed occupied by viable carcinoma (PVC) was used to divide patients into good (PVC < 50%) and poor (PVC ≥ 50%) NAC-responders. Statistical analysis was performed to measure the ability of individual biomarkers and a biomarker panel in NAC treatment response and patient survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Serum specimens from a total of 108 PDAC patients were assessed. Ca-125, Ca19-9 and S100A2 showed a significant positive correlation with PVC. Ca-125 demonstrated a superior ability to monitor NAC treatment response (Area under receiver operating curve (AUC): .6954) compared to the more widely used clinical biomarker, Ca19-9 (AUC: .6291). A panel of Ca-125 and Ca19-9 showed good ability to monitor NAC response in PDAC patients (AUC: .7349). Patients with high levels of both Ca-125 and Ca19-9 were shown to have the poorest overall survival (median overall survival: 17 vs. 30 months).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A serum biomarker panel of Ca-125 and Ca19-9 could be used for effective clinical management of PDAC patients undergoing NAC treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564113","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}
Abdulrahman Ismaiel, Vera Ciornolutchii, Thelva Esposito Herrera, Mohamed Ismaiel, Daniel-Corneliu Leucuta, Stefan-Lucian Popa, Dan L. Dumitrascu
Introduction
Adiponectin, a key adipokine, shows promise as a non-invasive biomarker for liver cirrhosis by reflecting inflammation and metabolic changes, but conflicting findings highlight the need for a systematic review and meta-analysis to clarify its role. Our study aimed to evaluate adiponectin levels across various stages of liver cirrhosis, compare them with other chronic liver diseases (CLD) and hepatocellular carcinoma (HCC), and assess its potential as a diagnostic and prognostic biomarker.
Methods
Our systematic search was conducted on September 2023 using PubMed, EMBASE and Scopus, searching for observational studies evaluating serum and plasma adiponectin levels in liver cirrhosis. Inclusion and exclusion criteria were applied, and study quality was assessed using the Newcastle-Ottawa Scale. To evaluate the overall effect size, we utilized a random-effects model along with a mean difference (MD) analysis. The principal summary outcome was the MD in adiponectin levels.
Results
We included 16 articles involving 2617 subjects in our qualitative and quantitative synthesis. We found significantly higher adiponectin levels in liver cirrhosis patients (8.181 [95% CI 3.676, 12.686]), especially in Child-Pugh B individuals (13.294 [95% CI 4.955, 21.634]), compared to controls. Child-Pugh A patients did not show significant differences compared to controls. In addition, adiponectin levels were significantly elevated in primary biliary cholangitis (PBC) patients compared to controls (8.669 [95% CI .291, 17.047]), as well as in liver cirrhosis compared to other CLD patients (4.805 [95% CI 1.247, 8.363]), including non-alcoholic fatty liver disease (NAFLD) (8.532 [95% CI 3.422, 13.641]), but not viral hepatitis. No significant MD was observed between liver cirrhosis and HCC patients.
Conclusion
Adiponectin levels are significantly elevated in liver cirrhosis, especially in advanced stages, potentially serving as a biomarker for advanced cirrhosis. Adiponectin also differentiates cirrhosis from other CLD, including NAFLD. However, its role in distinguishing cirrhosis from viral hepatitis and HCC is limited.
简介脂联素是一种关键的脂肪因子，通过反映炎症和代谢变化，有望成为肝硬化的非侵入性生物标志物，但研究结果相互矛盾，因此需要进行系统回顾和荟萃分析以明确其作用。我们的研究旨在评估肝硬化不同阶段的脂肪连蛋白水平，将其与其他慢性肝病（CLD）和肝细胞癌（HCC）进行比较，并评估其作为诊断和预后生物标志物的潜力：我们于 2023 年 9 月使用 PubMed、EMBASE 和 Scopus 进行了系统性检索，搜索评估肝硬化患者血清和血浆脂肪连蛋白水平的观察性研究。研究采用了纳入和排除标准，并使用纽卡斯尔-渥太华量表对研究质量进行了评估。为了评估总体效应大小，我们采用了随机效应模型和平均差（MD）分析。主要的总结性结果是脂肪连素水平的 MD：我们在定性和定量综述中纳入了 16 篇文章，涉及 2617 名受试者。我们发现，与对照组相比，肝硬化患者（8.181 [95% CI 3.676, 12.686]），尤其是 Child-Pugh B 患者（13.294 [95% CI 4.955, 21.634]）的脂肪连素水平明显更高。Child-Pugh A 患者与对照组相比没有明显差异。此外，原发性胆汁性胆管炎（PBC）患者与对照组相比（8.669 [95% CI .291, 17.047]），肝硬化患者与其他 CLD 患者相比（4.805 [95% CI 1.247, 8.363]），包括非酒精性脂肪肝（NAFLD）患者（8.532 [95% CI 3.422, 13.641]），脂肪连素水平均显著升高，但病毒性肝炎患者不升高。在肝硬化和 HCC 患者之间没有观察到明显的 MD：结论：肝硬化患者，尤其是晚期肝硬化患者的脂肪连接蛋白水平明显升高，有可能成为晚期肝硬化的生物标志物。脂肪连接蛋白还能区分肝硬化和其他慢性疾病，包括非酒精性脂肪肝。但是，它在区分肝硬化与病毒性肝炎和 HCC 方面的作用有限。
{"title":"Adiponectin as a biomarker in liver cirrhosis—A systematic review and meta-analysis","authors":"Abdulrahman Ismaiel, Vera Ciornolutchii, Thelva Esposito Herrera, Mohamed Ismaiel, Daniel-Corneliu Leucuta, Stefan-Lucian Popa, Dan L. Dumitrascu","doi":"10.1111/eci.14328","DOIUrl":"10.1111/eci.14328","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Adiponectin, a key adipokine, shows promise as a non-invasive biomarker for liver cirrhosis by reflecting inflammation and metabolic changes, but conflicting findings highlight the need for a systematic review and meta-analysis to clarify its role. Our study aimed to evaluate adiponectin levels across various stages of liver cirrhosis, compare them with other chronic liver diseases (CLD) and hepatocellular carcinoma (HCC), and assess its potential as a diagnostic and prognostic biomarker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Our systematic search was conducted on September 2023 using PubMed, EMBASE and Scopus, searching for observational studies evaluating serum and plasma adiponectin levels in liver cirrhosis. Inclusion and exclusion criteria were applied, and study quality was assessed using the Newcastle-Ottawa Scale. To evaluate the overall effect size, we utilized a random-effects model along with a mean difference (MD) analysis. The principal summary outcome was the MD in adiponectin levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 16 articles involving 2617 subjects in our qualitative and quantitative synthesis. We found significantly higher adiponectin levels in liver cirrhosis patients (8.181 [95% CI 3.676, 12.686]), especially in Child-Pugh B individuals (13.294 [95% CI 4.955, 21.634]), compared to controls. Child-Pugh A patients did not show significant differences compared to controls. In addition, adiponectin levels were significantly elevated in primary biliary cholangitis (PBC) patients compared to controls (8.669 [95% CI .291, 17.047]), as well as in liver cirrhosis compared to other CLD patients (4.805 [95% CI 1.247, 8.363]), including non-alcoholic fatty liver disease (NAFLD) (8.532 [95% CI 3.422, 13.641]), but not viral hepatitis. No significant MD was observed between liver cirrhosis and HCC patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Adiponectin levels are significantly elevated in liver cirrhosis, especially in advanced stages, potentially serving as a biomarker for advanced cirrhosis. Adiponectin also differentiates cirrhosis from other CLD, including NAFLD. However, its role in distinguishing cirrhosis from viral hepatitis and HCC is limited.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564094","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}
Nicolas Vallet, Laurianne Drieu Larochelle, Maria-Joao Santiago-Ribeiro, Alban Villate, Martin Eloit, Arnaud Cirée, Laura Zaragoza, Virginie André, Marie Prat-Lepesant, Olivier Hérault, Flavie Arbion, Hélène Blasco, Emmanuel Gyan
Energy metabolism of chimeric antigen receptor-T cells (CAR-T) activation in humans remains unexplored. As a glycolytic activity surrogate, we investigated the dynamics of peripheral blood (PB) lactate in the first weeks post-CAR-T infusion. In 17 patients treated with CD28 harbording anti-CD19 CAR-T for relapsed/refractory non-Hodgkin lymphomas, PB lactate levels increased following CAR-T infusion. Elevated lactate levels correlated with longer CAR-T persistence and higher CD8+/CD4+ ratio. Peripheral blood lactate kinetics may reflect immune cells activation and be useful for bedside monitoring.
{"title":"Glycolytic activity following anti-CD19 CAR-T cell infusion in non-Hodgkin lymphoma","authors":"Nicolas Vallet, Laurianne Drieu Larochelle, Maria-Joao Santiago-Ribeiro, Alban Villate, Martin Eloit, Arnaud Cirée, Laura Zaragoza, Virginie André, Marie Prat-Lepesant, Olivier Hérault, Flavie Arbion, Hélène Blasco, Emmanuel Gyan","doi":"10.1111/eci.14342","DOIUrl":"10.1111/eci.14342","url":null,"abstract":"<p>Energy metabolism of chimeric antigen receptor-T cells (CAR-T) activation in humans remains unexplored. As a glycolytic activity surrogate, we investigated the dynamics of peripheral blood (PB) lactate in the first weeks post-CAR-T infusion. In 17 patients treated with CD28 harbording anti-CD19 CAR-T for relapsed/refractory non-Hodgkin lymphomas, PB lactate levels increased following CAR-T infusion. Elevated lactate levels correlated with longer CAR-T persistence and higher CD8+/CD4+ ratio. Peripheral blood lactate kinetics may reflect immune cells activation and be useful for bedside monitoring.\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 2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564111","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}
Valerie Aponte Ribero, Orestis Efthimiou, Nazanin Abolhassani, Heba Alwan, Douglas C. Bauer, Séverine Henrard, Antoine Christiaens, Denis O’Mahony, Wilma Knol, Mike J. L. Peters, Arnaud Chiolero, Drahomir Aujesky, Gérard Waeber, Nicolas Rodondi, Cinzia Del Giovane, Baris Gencer
Background
Guidelines and studies provide conflicting information on whether type 2 diabetes (T2D) should be considered a coronary heart disease risk (CHD) equivalent in older adults.
Methods
We synthesized participant-level data on 82,723 individuals aged ≥65 years from five prospective studies in two-stage meta-analyses. We estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of T2D (presence versus absence) on a primary composite outcome defined as cardiovascular events or all-cause mortality. Secondary outcomes were the components of the composite. We evaluated CHD risk equivalence by comparing outcomes between individuals with T2D but no CHD versus CHD but no T2D.
Results
The median age of participants was 71 years, 20% had T2D and 17% had CHD at baseline. A total of 29,474 participants (36%) experienced the composite outcome. Baseline T2D was associated with higher risk of cardiovascular events or all-cause mortality versus no T2D (HR 1.44, 95% CI [1.40–1.49]). The association was weaker in individuals aged ≥75 years versus 65–74 years (HR 1.32 [1.19–1.46] vs. 1.56 [1.50–1.62]; p-value for interaction = .032). Compared to individuals with CHD but no T2D, individuals with T2D but no CHD had a similar risk of the composite outcome (HR 0.95 [0.85–1.07]), but a lower risk of cardiovascular events (HR 0.76 [0.59–0.98]).
Conclusions
T2D was associated with increased risk of cardiovascular events and all-cause mortality in older adults, but T2D without CHD conferred lower risk of cardiovascular events compared to CHD without T2D. Our results suggest that T2D should not be considered a CHD risk equivalent in older adults.
{"title":"Diabetes and the risk of cardiovascular events and all-cause mortality among older adults: an individual participant data analysis of five prospective studies","authors":"Valerie Aponte Ribero, Orestis Efthimiou, Nazanin Abolhassani, Heba Alwan, Douglas C. Bauer, Séverine Henrard, Antoine Christiaens, Denis O’Mahony, Wilma Knol, Mike J. L. Peters, Arnaud Chiolero, Drahomir Aujesky, Gérard Waeber, Nicolas Rodondi, Cinzia Del Giovane, Baris Gencer","doi":"10.1111/eci.14340","DOIUrl":"10.1111/eci.14340","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Guidelines and studies provide conflicting information on whether type 2 diabetes (T2D) should be considered a coronary heart disease risk (CHD) equivalent in older adults.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We synthesized participant-level data on 82,723 individuals aged ≥65 years from five prospective studies in two-stage meta-analyses. We estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of T2D (presence versus absence) on a primary composite outcome defined as cardiovascular events or all-cause mortality. Secondary outcomes were the components of the composite. We evaluated CHD risk equivalence by comparing outcomes between individuals with T2D but no CHD versus CHD but no T2D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The median age of participants was 71 years, 20% had T2D and 17% had CHD at baseline. A total of 29,474 participants (36%) experienced the composite outcome. Baseline T2D was associated with higher risk of cardiovascular events or all-cause mortality versus no T2D (HR 1.44, 95% CI [1.40–1.49]). The association was weaker in individuals aged ≥75 years versus 65–74 years (HR 1.32 [1.19–1.46] vs. 1.56 [1.50–1.62]; <i>p</i>-value for interaction = .032). Compared to individuals with CHD but no T2D, individuals with T2D but no CHD had a similar risk of the composite outcome (HR 0.95 [0.85–1.07]), but a lower risk of cardiovascular events (HR 0.76 [0.59–0.98]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>T2D was associated with increased risk of cardiovascular events and all-cause mortality in older adults, but T2D without CHD conferred lower risk of cardiovascular events compared to CHD without T2D. Our results suggest that T2D should not be considered a CHD risk equivalent in older adults.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497507","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}
Lourdes Chero-Sandoval, Andrea Higuera-Gómez, María Martínez-Urbistondo, Raquel Castejón, Susana Mellor-Pita, Víctor Moreno-Torres, Daniel de Luis, Amanda Cuevas-Sierra, J. Alfredo Martínez
Background
The relationship between systemic lupus erythematosus (SLE) and low-grade metabolic inflammation (MI) with the microbiota is crucial for understanding the pathogenesis of these diseases and developing effective therapeutic interventions. In this context, it has been observed that the gut microbiota plays a key role in the immune regulation and inflammation contributing to the exacerbation through inflammatory mediators. This research aimed to describe similarities/differences in anthropometric, biochemical, inflammatory, and hepatic markers as well as to examine the putative role of gut microbiota concerning two inflammatory conditions: SLE and MI.
Methods
Data were obtained from a cohort comprising adults with SLE and MI. Faecal samples were determined by 16S technique. Statistical analyses compared anthropometric and clinical variables, and LEfSe and MetagenomeSeq were used for metagenomic data. An interaction analysis was fitted to investigate associations of microbiota with fatty liver index (FLI) depending on the inflammatory condition.
Results
Participants with low-grade MI showed worse values in anthropometry and biochemicals compared with patients with SLE. The liver profile of patients with MI was unhealthier, while no relevant differences were found in most of the inflammatory markers between groups. LEfSe analysis revealed an overrepresentation of Bifidobacteriaceae family in SLE group. An interactive association between gut Bifidobacterium abundance and type of disease was identified for FLI values, suggesting an effect modification of the gut microbiota concerning liver markers depending on the inflammatory condition.
Conclusion
This study found phenotypical and microbial similarities and disparities between these two inflammatory conditions, evidenced in clinical and hepatic markers, and showed the interactive interplay between gut Bifidobacterium and liver health (measured by FLI) that occur in a different manner depending on the type of inflammatory disease. These results underscore the importance of personalized approaches and individual microbiota in the screening of different inflammatory situations, considering unique hepatic and microbiota profiles.
{"title":"Comparative assessment of phenotypic markers in patients with chronic inflammation: Differences on Bifidobacterium concerning liver status","authors":"Lourdes Chero-Sandoval, Andrea Higuera-Gómez, María Martínez-Urbistondo, Raquel Castejón, Susana Mellor-Pita, Víctor Moreno-Torres, Daniel de Luis, Amanda Cuevas-Sierra, J. Alfredo Martínez","doi":"10.1111/eci.14339","DOIUrl":"10.1111/eci.14339","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The relationship between systemic lupus erythematosus (SLE) and low-grade metabolic inflammation (MI) with the microbiota is crucial for understanding the pathogenesis of these diseases and developing effective therapeutic interventions. In this context, it has been observed that the gut microbiota plays a key role in the immune regulation and inflammation contributing to the exacerbation through inflammatory mediators. This research aimed to describe similarities/differences in anthropometric, biochemical, inflammatory, and hepatic markers as well as to examine the putative role of gut microbiota concerning two inflammatory conditions: SLE and MI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were obtained from a cohort comprising adults with SLE and MI. Faecal samples were determined by 16S technique. Statistical analyses compared anthropometric and clinical variables, and LEfSe and MetagenomeSeq were used for metagenomic data. An interaction analysis was fitted to investigate associations of microbiota with fatty liver index (FLI) depending on the inflammatory condition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants with low-grade MI showed worse values in anthropometry and biochemicals compared with patients with SLE. The liver profile of patients with MI was unhealthier, while no relevant differences were found in most of the inflammatory markers between groups. LEfSe analysis revealed an overrepresentation of Bifidobacteriaceae family in SLE group. An interactive association between gut <i>Bifidobacterium</i> abundance and type of disease was identified for FLI values, suggesting an effect modification of the gut microbiota concerning liver markers depending on the inflammatory condition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study found phenotypical and microbial similarities and disparities between these two inflammatory conditions, evidenced in clinical and hepatic markers, and showed the interactive interplay between gut <i>Bifidobacterium</i> and liver health (measured by FLI) that occur in a different manner depending on the type of inflammatory disease. These results underscore the importance of personalized approaches and individual microbiota in the screening of different inflammatory situations, considering unique hepatic and microbiota profiles.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521454","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}
Lisa Götz, Uwe Rueckschloss, Sonia M. Najjar, Süleyman Ergün, Florian Kleefeldt
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.
{"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>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":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Omer Genc, Abdullah Yildirim, Aslan Erdogan, Ersin Ibisoglu, Yeliz Guler, Gazi Capar, M. Mert Goksu, Huseyin Akgun, Gamze Acar, G. Cansu Ozdogan, Gunseli Uredi, Furkan Sen, Ufuk S. Halil, Fahri Er, Murside Genc, Eyup Ozkan, Ahmet Guler, Ibrahim H. Kurt
Aim
The relationship between inflammatory status and poor outcomes in acute coronary syndromes is a significant area of current research. This study investigates the association between in-hospital mortality and the modified Naples prognostic score (mNPS) as well as other inflammatory biomarkers in STEMI patients.
Methods
This single-centre, cross-sectional study included 2576 consecutive STEMI patients who underwent primary percutaneous coronary intervention between January 2022 and November 2023. Participants were randomly divided into derivation and validation cohorts in a 6:4 ratio. The following inflammatory indices were calculated: pan-immune-inflammation value (PIV), systemic immune-inflammation-index (SII), systemic inflammation-response index (SIRI) and conventional NPS. The mNPS was derived by integrating hs-CRP into the conventional NPS. The performance of these indices in determining in-hospital mortality was assessed using regression, calibration, discrimination, reclassification and decision curve analyses.
Results
Inflammatory biomarkers, including PIV, SII, SIRI, NPS and mNPS, were significantly higher in patients who died during in-hospital follow-up compared to those discharged alive in both the derivation and validation cohorts. Multivariable logistic regression analyses were performed separately for the derivation and validation cohorts. In the derivation cohort, mNPS was associated with in-hospital mortality (aOR = 1.490, p < .001). Similarly, in the validation cohort, mNPS was associated with in-hospital mortality (aOR = 2.023, p < .001). mNPS demonstrated better discriminative and reclassification power than other inflammatory markers (p < .05 for all). Additionally, regression models incorporating mNPS were well-calibrated and showed net clinical benefit in both cohorts.
Conclusion
mNPS may be a stronger predictor of in-hospital mortality in STEMI patients compared to the conventional scheme and other inflammatory indices.
{"title":"Modification, validation and comparison of Naples prognostic score to determine in-hospital mortality in ST-segment elevation myocardial infarction","authors":"Omer Genc, Abdullah Yildirim, Aslan Erdogan, Ersin Ibisoglu, Yeliz Guler, Gazi Capar, M. Mert Goksu, Huseyin Akgun, Gamze Acar, G. Cansu Ozdogan, Gunseli Uredi, Furkan Sen, Ufuk S. Halil, Fahri Er, Murside Genc, Eyup Ozkan, Ahmet Guler, Ibrahim H. Kurt","doi":"10.1111/eci.14332","DOIUrl":"10.1111/eci.14332","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The relationship between inflammatory status and poor outcomes in acute coronary syndromes is a significant area of current research. This study investigates the association between in-hospital mortality and the modified Naples prognostic score (mNPS) as well as other inflammatory biomarkers in STEMI patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This single-centre, cross-sectional study included 2576 consecutive STEMI patients who underwent primary percutaneous coronary intervention between January 2022 and November 2023. Participants were randomly divided into derivation and validation cohorts in a 6:4 ratio. The following inflammatory indices were calculated: pan-immune-inflammation value (PIV), systemic immune-inflammation-index (SII), systemic inflammation-response index (SIRI) and conventional NPS. The mNPS was derived by integrating hs-CRP into the conventional NPS. The performance of these indices in determining in-hospital mortality was assessed using regression, calibration, discrimination, reclassification and decision curve analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Inflammatory biomarkers, including PIV, SII, SIRI, NPS and mNPS, were significantly higher in patients who died during in-hospital follow-up compared to those discharged alive in both the derivation and validation cohorts. Multivariable logistic regression analyses were performed separately for the derivation and validation cohorts. In the derivation cohort, mNPS was associated with in-hospital mortality (aOR = 1.490, <i>p</i> < .001). Similarly, in the validation cohort, mNPS was associated with in-hospital mortality (aOR = 2.023, <i>p</i> < .001). mNPS demonstrated better discriminative and reclassification power than other inflammatory markers (<i>p</i> < .05 for all). Additionally, regression models incorporating mNPS were well-calibrated and showed net clinical benefit in both cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>mNPS may be a stronger predictor of in-hospital mortality in STEMI patients compared to the conventional scheme and other inflammatory indices.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461197","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}
Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is a widely used drug for the treatment of type 2 diabetes that offers significant cardiovascular benefits.
Results
This review systematically examines the proteomic and metabolomic indicators associated with the cardiovascular effects of semaglutide. A comprehensive literature search was conducted to identify relevant studies. The review utilizes advanced analytical technologies such as mass spectrometry and nuclear magnetic resonance (NMR) to investigate the molecular mechanisms underlying the effects of semaglutide on insulin secretion, weight control, anti-inflammatory activities and lipid metabolism. These “omics” approaches offer critical insights into metabolic changes associated with cardiovascular health. However, challenges remain such as individual variability in expression, the need for comprehensive validation and the integration of these data with clinical parameters. These issues need to be addressed through further research to refine these indicators and increase their clinical utility.
Conclusion
Future integration of proteomic and metabolomic data with artificial intelligence (AI) promises to improve prediction and monitoring of cardiovascular outcomes and may enable more accurate and effective management of cardiovascular health in patients with type 2 diabetes. This review highlights the transformative potential of integrating proteomics, metabolomics and AI to advance cardiovascular medicine and improve patient outcomes.
{"title":"Exploring omics signature in the cardiovascular response to semaglutide: Mechanistic insights and clinical implications","authors":"Rui Vitorino","doi":"10.1111/eci.14334","DOIUrl":"10.1111/eci.14334","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is a widely used drug for the treatment of type 2 diabetes that offers significant cardiovascular benefits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This review systematically examines the proteomic and metabolomic indicators associated with the cardiovascular effects of semaglutide. A comprehensive literature search was conducted to identify relevant studies. The review utilizes advanced analytical technologies such as mass spectrometry and nuclear magnetic resonance (NMR) to investigate the molecular mechanisms underlying the effects of semaglutide on insulin secretion, weight control, anti-inflammatory activities and lipid metabolism. These “omics” approaches offer critical insights into metabolic changes associated with cardiovascular health. However, challenges remain such as individual variability in expression, the need for comprehensive validation and the integration of these data with clinical parameters. These issues need to be addressed through further research to refine these indicators and increase their clinical utility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Future integration of proteomic and metabolomic data with artificial intelligence (AI) promises to improve prediction and monitoring of cardiovascular outcomes and may enable more accurate and effective management of cardiovascular health in patients with type 2 diabetes. This review highlights the transformative potential of integrating proteomics, metabolomics and AI to advance cardiovascular medicine and improve patient outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461195","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}
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