Daniele Pastori, Danilo Menichelli, Yan-Guang Li, Tommaso Brogi, Flavio Giuseppe Biccirè, Pasquale Pignatelli, Alessio Farcomeni, Gregory Y. H. Lip
Background
The incidence of new-onset atrial fibrillation (NOAF) is increasing in the last decades. NOAF is associated with worse long-term prognosis. The C2HEST score has been recently proposed to stratify the risk of NOAF. Pooled data on the performance of the C2HEST score are lacking.
Methods
Systematic review and meta-analysis of observational studies reporting data on NOAF according to the C2HEST score. We searched PubMed, Web of Science and Google scholar databases without time restrictions until June 2023 according to PRISMA guidelines. Meta-analysis of the area under the curve (AUC) with 95% confidence interval (95% CI) and a sensitivity analysis according to setting of care and countries were performed.
Results
Of 360 studies, 17 were included in the analysis accounting for 11,067,496 subjects/patients with 307,869 NOAF cases. Mean age ranged from 41.3 to 71.2 years. The prevalence of women ranged from 10.6 to 54.75%. The pooled analysis gave an AUC of .70 (95% CI .66–.74). A subgroup analysis on studies from general population/primary care yielded an AUC of 0.69 (95% CI 0.64–0.75). In the subgroup of patients with cardiovascular disease, the AUC was .71 (.69–.79). The C2HEST score performed similarly in Asian (AUC .72, 95% CI .68–.77), and in Western patients (AUC .68, 95% CI .62–.75). The best performance was observed in studies with a mean age <50 years (n = 3,144,704 with 25,538 NOAF, AUC .78, 95% CI .76–.79).
Conclusion
The C2HEST score may be used to predict NOAF in primary and secondary prevention patients, and in patients across different countries. Early detection of NOAF may aid prompt initiation of management and follow-up, potentially leading to a reduction of AF-related complications.
{"title":"Usefulness of the C2HEST score to predict new onset atrial fibrillation. A systematic review and meta-analysis on >11 million subjects","authors":"Daniele Pastori, Danilo Menichelli, Yan-Guang Li, Tommaso Brogi, Flavio Giuseppe Biccirè, Pasquale Pignatelli, Alessio Farcomeni, Gregory Y. H. Lip","doi":"10.1111/eci.14293","DOIUrl":"10.1111/eci.14293","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The incidence of new-onset atrial fibrillation (NOAF) is increasing in the last decades. NOAF is associated with worse long-term prognosis. The C<sub>2</sub>HEST score has been recently proposed to stratify the risk of NOAF. Pooled data on the performance of the C<sub>2</sub>HEST score are lacking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Systematic review and meta-analysis of observational studies reporting data on NOAF according to the C<sub>2</sub>HEST score. We searched PubMed, Web of Science and Google scholar databases without time restrictions until June 2023 according to PRISMA guidelines. Meta-analysis of the area under the curve (AUC) with 95% confidence interval (95% CI) and a sensitivity analysis according to setting of care and countries were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 360 studies, 17 were included in the analysis accounting for 11,067,496 subjects/patients with 307,869 NOAF cases. Mean age ranged from 41.3 to 71.2 years. The prevalence of women ranged from 10.6 to 54.75%. The pooled analysis gave an AUC of .70 (95% CI .66–.74). A subgroup analysis on studies from general population/primary care yielded an AUC of 0.69 (95% CI 0.64–0.75). In the subgroup of patients with cardiovascular disease, the AUC was .71 (.69–.79). The C<sub>2</sub>HEST score performed similarly in Asian (AUC .72, 95% CI .68–.77), and in Western patients (AUC .68, 95% CI .62–.75). The best performance was observed in studies with a mean age <50 years (<i>n</i> = 3,144,704 with 25,538 NOAF, AUC .78, 95% CI .76–.79).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The C<sub>2</sub>HEST score may be used to predict NOAF in primary and secondary prevention patients, and in patients across different countries. Early detection of NOAF may aid prompt initiation of management and follow-up, potentially leading to a reduction of AF-related complications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14293","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141770715","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}
Andrea Saglietto, Giulio Falasconi, Diego Penela, Pietro Francia, Arunashis Sau, Fu Siong Ng, Veronica Dusi, Davide Castagno, Fiorenzo Gaita, Antonio Berruezo, Gaetano Maria De Ferrari, Matteo Anselmino
Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are new anti-hyperglycaemic drugs with proven cardiovascular (CV) benefit in diabetic and non-diabetic patients at high CV risk. Despite a neutral class effect on arrhythmia risk, data on semaglutide suggest a possible drug-specific benefit in reducing atrial fibrillation (AF) occurrence.
Objective
To perform a meta-analysis of randomized clinical trials (RCTs) to assess the risk of incident AF in patients treated with semaglutide compared to placebo.
Methods and Results
Ten RCTs were included in the analysis. Study population encompassed 12,651 patients (7285 in semaglutide and 5366 in placebo arms), with median follow-up of 68 months. A random effect meta-analytic model was adopted to pool relative risk (RR) of incident AF. Semaglutide reduces the risk of AF by 42% (RR .58, 95% CI .40–.85), with low heterogeneity across the studies (I2 0%). At subgroup analysis, no differences emerged between oral and subcutaneous administration (oral: RR .53, 95% CI .23–1.24, I2 0%; subcutaneous: RR .59, 95% CI .39–.91, I2 0%; p-value .83). In addition, meta-regression analyses did not show any potential influence of baseline study covariates, in particular the proportion of diabetic patients (p-value .14) and body mass index (BMI) (p-value .60).
Conclusions
Semaglutide significantly reduces the occurrence of incident AF by 42% as compared to placebo in individuals at high CV risk, mainly affected by type 2 diabetes mellitus. This effect appears to be consistent independently of the route of administration of the drug (oral or subcutaneous), the presence of underlying diabetes and BMI.
背景：胰高血糖素样肽-1受体激动剂（GLP-1 RAs）是新型抗高血糖药物，已被证实对心血管风险较高的糖尿病和非糖尿病患者有益。尽管该类药物对心律失常风险的影响是中性的，但有关semaglutide的数据表明，该类药物在降低心房颤动（AF）发生率方面可能具有特异性优势：对随机临床试验（RCT）进行荟萃分析，评估与安慰剂相比，接受塞马鲁肽治疗的患者发生房颤的风险：分析共纳入了十项随机临床试验。研究对象包括12651名患者（7285人接受了舍马鲁肽治疗，5366人接受了安慰剂治疗），中位随访时间为68个月。研究采用随机效应荟萃分析模型对房颤发生的相对风险（RR）进行汇总。塞马鲁肽可将房颤风险降低 42% (RR .58, 95% CI .40-.85)，各项研究的异质性较低（I2 0%）。在亚组分析中，口服与皮下注射之间没有差异（口服：RR .53，95% CI .23-1.24，I2 0%；皮下注射：RR .59，95% CI .3-1.24，I2 0%）：RR .59，95% CI .39-.91，I2 0%；P 值 .83）。此外，元回归分析未显示基线研究协变量的任何潜在影响，尤其是糖尿病患者比例（P值.14）和体重指数（BMI）（P值.60）：结论：与安慰剂相比，塞马鲁肽能明显降低冠心病高危人群（主要是受2型糖尿病影响的人群）42%的房颤发生率。这一效果似乎与给药途径（口服或皮下注射）、是否存在潜在糖尿病和体重指数无关。
{"title":"Glucagon-like peptide-1 receptor agonist semaglutide reduces atrial fibrillation incidence: A systematic review and meta-analysis","authors":"Andrea Saglietto, Giulio Falasconi, Diego Penela, Pietro Francia, Arunashis Sau, Fu Siong Ng, Veronica Dusi, Davide Castagno, Fiorenzo Gaita, Antonio Berruezo, Gaetano Maria De Ferrari, Matteo Anselmino","doi":"10.1111/eci.14292","DOIUrl":"10.1111/eci.14292","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are new anti-hyperglycaemic drugs with proven cardiovascular (CV) benefit in diabetic and non-diabetic patients at high CV risk. Despite a neutral class effect on arrhythmia risk, data on semaglutide suggest a possible drug-specific benefit in reducing atrial fibrillation (AF) occurrence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To perform a meta-analysis of randomized clinical trials (RCTs) to assess the risk of incident AF in patients treated with semaglutide compared to placebo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Ten RCTs were included in the analysis. Study population encompassed 12,651 patients (7285 in semaglutide and 5366 in placebo arms), with median follow-up of 68 months. A random effect meta-analytic model was adopted to pool relative risk (RR) of incident AF. Semaglutide reduces the risk of AF by 42% (RR .58, 95% CI .40–.85), with low heterogeneity across the studies (<i>I</i><sup>2</sup> 0%). At subgroup analysis, no differences emerged between oral and subcutaneous administration (oral: RR .53, 95% CI .23–1.24, <i>I</i><sup>2</sup> 0%; subcutaneous: RR .59, 95% CI .39–.91, <i>I</i><sup>2</sup> 0%; <i>p</i>-value .83). In addition, meta-regression analyses did not show any potential influence of baseline study covariates, in particular the proportion of diabetic patients (<i>p</i>-value .14) and body mass index (BMI) (<i>p</i>-value .60).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Semaglutide significantly reduces the occurrence of incident AF by 42% as compared to placebo in individuals at high CV risk, mainly affected by type 2 diabetes mellitus. This effect appears to be consistent independently of the route of administration of the drug (oral or subcutaneous), the presence of underlying diabetes and BMI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14292","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757966","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}
Willian das Neves, Christiano R. R. Alves, Gabriela dos Santos, Maria-Janieire N. N. Alves, Amy Deik, Kerry Pierce, Courtney Dennis, Lily Buckley, Clary B. Clish, Kathryn J. Swoboda, Patricia C. Brum, Gilberto de Castro Junior
Background
Low physical performance is associated with higher mortality rate in multiple pathological conditions. Here, we aimed to determine whether body composition and physical performance could be prognostic factors in non-small cell lung cancer (NSCLC) patients. Moreover, we performed an exploratory approach to determine whether plasma samples from NSCLC patients could directly affect metabolic and structural phenotypes in primary muscle cells.
Methods
This prospective cohort study included 55 metastatic NSCLC patients and seven age-matched control subjects. Assessments included physical performance, body composition, quality of life and overall survival rate. Plasma samples from a sub cohort of 18 patients were collected for exploratory studies in cell culture and metabolomic analysis.
Results
We observed a higher survival rate in NSCLC patients with high performance in the timed up-and-go (+320%; p = .007), sit-to-stand (+256%; p = .01) and six-minute walking (+323%; p = .002) tests when compared to NSCLC patients with low physical performance. There was no significant association for similar analysis with body composition measurements (p > .05). Primary human myotubes incubated with plasma from NSCLC patients with low physical performance had impaired oxygen consumption rate (−54.2%; p < .0001) and cell proliferation (−44.9%; p = .007). An unbiased metabolomic analysis revealed a list of specific metabolites differentially expressed in the plasma of NSCLC patients with low physical performance.
Conclusion
These novel findings indicate that physical performance is a prognostic factor for overall survival in NSCLC patients and provide novel insights into circulating factors that could impair skeletal muscle metabolism.
{"title":"Physical performance and plasma metabolic profile as potential prognostic factors in metastatic lung cancer patients","authors":"Willian das Neves, Christiano R. R. Alves, Gabriela dos Santos, Maria-Janieire N. N. Alves, Amy Deik, Kerry Pierce, Courtney Dennis, Lily Buckley, Clary B. Clish, Kathryn J. Swoboda, Patricia C. Brum, Gilberto de Castro Junior","doi":"10.1111/eci.14288","DOIUrl":"10.1111/eci.14288","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Low physical performance is associated with higher mortality rate in multiple pathological conditions. Here, we aimed to determine whether body composition and physical performance could be prognostic factors in non-small cell lung cancer (NSCLC) patients. Moreover, we performed an exploratory approach to determine whether plasma samples from NSCLC patients could directly affect metabolic and structural phenotypes in primary muscle cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective cohort study included 55 metastatic NSCLC patients and seven age-matched control subjects. Assessments included physical performance, body composition, quality of life and overall survival rate. Plasma samples from a sub cohort of 18 patients were collected for exploratory studies in cell culture and metabolomic analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed a higher survival rate in NSCLC patients with high performance in the timed up-and-go (+320%; <i>p</i> = .007), sit-to-stand (+256%; <i>p</i> = .01) and six-minute walking (+323%; <i>p</i> = .002) tests when compared to NSCLC patients with low physical performance. There was no significant association for similar analysis with body composition measurements (<i>p</i> > .05). Primary human myotubes incubated with plasma from NSCLC patients with low physical performance had impaired oxygen consumption rate (−54.2%; <i>p</i> < .0001) and cell proliferation (−44.9%; <i>p</i> = .007). An unbiased metabolomic analysis revealed a list of specific metabolites differentially expressed in the plasma of NSCLC patients with low physical performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These novel findings indicate that physical performance is a prognostic factor for overall survival in NSCLC patients and provide novel insights into circulating factors that could impair skeletal muscle metabolism.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757968","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}
Bárbara Guerra-Carvalho, David F. Carrageta, Tatiana Maurício, Sara C. Pereira, Alberto Barros, Rui A. Carvalho, Marco G. Alves, Pedro Domingues, Pedro F. Oliveira
Background
Infertility is a major health issue, affecting 15% of reproductive-age couples with male factors contributing to 50% of cases. Asthenozoospermia (AS), or low sperm motility, is a common cause of male infertility with complex aetiology, involving genetic and metabolic alterations, inflammation and oxidative stress. However, the molecular mechanisms behind low motility are unclear. In this study, we used a metabolomics approach to identify metabolic biomarkers and pathways involved in sperm motility.
Methods
We compared the metabolome and lipidome of spermatozoa of men with normozoospermia (n = 44) and AS (n = 22) using untargeted LC–MS and the metabolome of seminal fluid using 1H-NMR. Additionally, we evaluated the seminal fluid redox status to assess the oxidative stress in the ejaculate.
Results
We identified 112 metabolites and 209 lipids in spermatozoa and 27 metabolites in the seminal fluid of normozoospermic and asthenozoospermic men. PCA analysis of the spermatozoa's metabolomics and lipidomics data showed a clear separation between groups. Spermatozoa of asthenozoospermic men presented lower levels of several amino acids, and increased levels of energetic substrates and lysophospholipids. However, the metabolome and redox status of the seminal fluid was not altered inAS.
Conclusions
Our results indicate impaired metabolic pathways associated with redox homeostasis and amino acid, energy and lipid metabolism in AS. Taken together, these findings suggest that the metabolome and lipidome of human spermatozoa are key factors influencing their motility and that oxidative stress exposure during spermatogenesis or sperm maturation may be in the aetiology of decreased motility in AS.
{"title":"Metabolomics analysis of human spermatozoa reveals impaired metabolic pathways in asthenozoospermia","authors":"Bárbara Guerra-Carvalho, David F. Carrageta, Tatiana Maurício, Sara C. Pereira, Alberto Barros, Rui A. Carvalho, Marco G. Alves, Pedro Domingues, Pedro F. Oliveira","doi":"10.1111/eci.14289","DOIUrl":"10.1111/eci.14289","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Infertility is a major health issue, affecting 15% of reproductive-age couples with male factors contributing to 50% of cases. Asthenozoospermia (AS), or low sperm motility, is a common cause of male infertility with complex aetiology, involving genetic and metabolic alterations, inflammation and oxidative stress. However, the molecular mechanisms behind low motility are unclear. In this study, we used a metabolomics approach to identify metabolic biomarkers and pathways involved in sperm motility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We compared the metabolome and lipidome of spermatozoa of men with normozoospermia (<i>n</i> = 44) and AS (<i>n</i> = 22) using untargeted LC–MS and the metabolome of seminal fluid using <sup>1</sup>H-NMR. Additionally, we evaluated the seminal fluid redox status to assess the oxidative stress in the ejaculate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified 112 metabolites and 209 lipids in spermatozoa and 27 metabolites in the seminal fluid of normozoospermic and asthenozoospermic men. PCA analysis of the spermatozoa's metabolomics and lipidomics data showed a clear separation between groups. Spermatozoa of asthenozoospermic men presented lower levels of several amino acids, and increased levels of energetic substrates and lysophospholipids. However, the metabolome and redox status of the seminal fluid was not altered inAS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results indicate impaired metabolic pathways associated with redox homeostasis and amino acid, energy and lipid metabolism in AS. Taken together, these findings suggest that the metabolome and lipidome of human spermatozoa are key factors influencing their motility and that oxidative stress exposure during spermatogenesis or sperm maturation may be in the aetiology of decreased motility in AS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751419","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}
Peter Libby, Robin Smith, Eric J. Rubin, Marilyn K. Glassberg, Michael E. Farkouh, Robert S. Rosenson
Background
Inflammation and immunity contribute pivotally to diverse acute and chronic diseases. Inflammatory pathways have become increasingly targets for therapy. Yet, despite substantial similarity in mechanisms and pathways, the scientific, medical, pharma and biotechnology sectors have generally focused programs finely on a single disease entity or organ system. This insularity may impede progress in innovation and the harnessing of powerful new insights into inflammation biology ripe for clinical translation.
Methods
A multidisciplinary thinktank reviewed highlights how inflammation contributes to diverse diseases, disturbed homeostasis, ageing and impaired healthspan. We explored how common inflammatory and immune mechanisms that operate in key conditions in their respective domains. This consensus review highlights the high degree of commonality of inflammatory mechanisms in a diverse array of conditions that together contribute a major part of the global burden of morbidity and mortality and present an enormous challenge to public health and drain on resources.
Results
We demonstrate how that shared inflammatory mechanisms unite many seemingly disparate diseases, both acute and chronic. The examples of infection, cardiovascular conditions, pulmonary diseases, rheumatological disorders, dementia, cancer and ageing illustrate the overlapping pathogenesis. We outline opportunities to synergize, reduce duplication and consolidate efforts of the clinical, research and pharmaceutical communities. Enhanced recognition of these commonalties should promote cross-fertilization and hasten progress in this rapidly moving domain.
Conclusions
Greater appreciation of the shared mechanisms should simplify understanding seemingly disparate diseases for clinicians and help them to recognize inflammation as a therapeutic target which the development of novel therapies is rendering actionable.
{"title":"Inflammation unites diverse acute and chronic diseases","authors":"Peter Libby, Robin Smith, Eric J. Rubin, Marilyn K. Glassberg, Michael E. Farkouh, Robert S. Rosenson","doi":"10.1111/eci.14280","DOIUrl":"10.1111/eci.14280","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inflammation and immunity contribute pivotally to diverse acute and chronic diseases. Inflammatory pathways have become increasingly targets for therapy. Yet, despite substantial similarity in mechanisms and pathways, the scientific, medical, pharma and biotechnology sectors have generally focused programs finely on a single disease entity or organ system. This insularity may impede progress in innovation and the harnessing of powerful new insights into inflammation biology ripe for clinical translation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A multidisciplinary thinktank reviewed highlights how inflammation contributes to diverse diseases, disturbed homeostasis, ageing and impaired healthspan. We explored how common inflammatory and immune mechanisms that operate in key conditions in their respective domains. This consensus review highlights the high degree of commonality of inflammatory mechanisms in a diverse array of conditions that together contribute a major part of the global burden of morbidity and mortality and present an enormous challenge to public health and drain on resources.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We demonstrate how that shared inflammatory mechanisms unite many seemingly disparate diseases, both acute and chronic. The examples of infection, cardiovascular conditions, pulmonary diseases, rheumatological disorders, dementia, cancer and ageing illustrate the overlapping pathogenesis. We outline opportunities to synergize, reduce duplication and consolidate efforts of the clinical, research and pharmaceutical communities. Enhanced recognition of these commonalties should promote cross-fertilization and hasten progress in this rapidly moving domain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Greater appreciation of the shared mechanisms should simplify understanding seemingly disparate diseases for clinicians and help them to recognize inflammation as a therapeutic target which the development of novel therapies is rendering actionable.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757967","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}
Yingqi Xue, Yan Zhang, Yale Su, Jiangqi Zhao, Daoquan Yu, Yunju Jo, Jongkil Joo, Hyun Joo Lee, Dongryeol Ryu, Shibo Wei
Background
Growth differentiation factor 15 (GDF15), a stress-responsive cytokine from transforming growth factor superfamily, is highly expressed in mammalian tissues, including pancreas, stomach and intestine under pathological conditions. In particular, elevated levels of GDF15 might play an important role in the development and progression of various gastrointestinal cancers (GCs), suggesting its potential as a promising target for disease prediction and treatment.
Methods
In this review, systematic reviews addressing the role of GDF15 in GCs were updated, along with the latest clinical trials focussing on the GDF15-associated digestive malignancies.
Results
The multiple cellular pathways through which GDF15 is involved in the regulation of physiological and pathological conditions were first summarized. Then, GDF15 was also established as a valuable clinical index, functioning as a predictive marker in diverse GCs. Notably, latest clinical treatments targeting GDF15 were also highlighted, demonstrating its promising potential in mitigating and curing digestive malignancies.
Conclusions
This review unveils the pivotal roles of GDF15 and its potential as a promising target in the pathogenesis of GCs, which may provide insightful directions for future investigations.
{"title":"The implicated role of GDF15 in gastrointestinal cancer","authors":"Yingqi Xue, Yan Zhang, Yale Su, Jiangqi Zhao, Daoquan Yu, Yunju Jo, Jongkil Joo, Hyun Joo Lee, Dongryeol Ryu, Shibo Wei","doi":"10.1111/eci.14290","DOIUrl":"10.1111/eci.14290","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Growth differentiation factor 15 (GDF15), a stress-responsive cytokine from transforming growth factor superfamily, is highly expressed in mammalian tissues, including pancreas, stomach and intestine under pathological conditions. In particular, elevated levels of GDF15 might play an important role in the development and progression of various gastrointestinal cancers (GCs), suggesting its potential as a promising target for disease prediction and treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this review, systematic reviews addressing the role of GDF15 in GCs were updated, along with the latest clinical trials focussing on the GDF15-associated digestive malignancies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The multiple cellular pathways through which GDF15 is involved in the regulation of physiological and pathological conditions were first summarized. Then, GDF15 was also established as a valuable clinical index, functioning as a predictive marker in diverse GCs. Notably, latest clinical treatments targeting GDF15 were also highlighted, demonstrating its promising potential in mitigating and curing digestive malignancies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This review unveils the pivotal roles of GDF15 and its potential as a promising target in the pathogenesis of GCs, which may provide insightful directions for future investigations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751420","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}
Navdeep Tangri, Christian S. Alvarez, Matthew Arnold, Salvatore Barone, Ana Cebrián, Hungta Chen, Luca De Nicola, Krister Järbrink, Naresh Kanumilli, Kean-Seng Lim, Toshiki Moriyama, Roberto Pecoits Filho, Maria Cristina Ribeiro de Castro, Rafael Santamaria, Markus P. Schneider, Jean Blaise Virgitti, Pamela Kushner
Background
Clinical practice guidelines for patients with chronic kidney disease (CKD) recommend regular monitoring and management of kidney function and CKD risk factors. However, the majority of patients with stage 3 CKD lack a diagnosis code, and data on the implementation of these recommendations in the real world are limited.
Aim
To assess the implementation of guideline-directed monitoring and management practices in the real world in patients with stage 3 CKD without a recorded diagnosis code.
Methods
REVEAL-CKD (NCT04847531) is a multinational, observational study of patients with stage 3 CKD. Eligible patients had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements indicative of stage 3 CKD recorded >90 and ≤730 days apart, lacked an International Classification of Diseases 9/10 diagnosis code corresponding to CKD any time before and up to 6 months after the second eGFR measurement. Testing of key measures of care quality were assessed.
Results
The study included 435,971 patients from 9 countries. In all countries, the prevalence of urinary albumin–creatinine ratio and albuminuria testing was low. Angiotensin-converting enzyme inhibitor, angiotensin receptor blocker and statin prescriptions were highly variable, and sodium–glucose cotransporter-2 inhibitor prescriptions remained below 21%. Blood pressure measurements were recorded in 20.2%–89.9% of patients.
Conclusions
Overall, a large proportion of patients with evidence of stage 3 CKD did not receive recommended, guideline-directed monitoring and management. The variability in standard of care among countries demonstrates a clear opportunity to improve monitoring and management of these patients, most likely improving long-term outcomes.
{"title":"Suboptimal monitoring and management in patients with unrecorded stage 3 chronic kidney disease in real-world settings: Insights from REVEAL-CKD","authors":"Navdeep Tangri, Christian S. Alvarez, Matthew Arnold, Salvatore Barone, Ana Cebrián, Hungta Chen, Luca De Nicola, Krister Järbrink, Naresh Kanumilli, Kean-Seng Lim, Toshiki Moriyama, Roberto Pecoits Filho, Maria Cristina Ribeiro de Castro, Rafael Santamaria, Markus P. Schneider, Jean Blaise Virgitti, Pamela Kushner","doi":"10.1111/eci.14282","DOIUrl":"10.1111/eci.14282","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Clinical practice guidelines for patients with chronic kidney disease (CKD) recommend regular monitoring and management of kidney function and CKD risk factors. However, the majority of patients with stage 3 CKD lack a diagnosis code, and data on the implementation of these recommendations in the real world are limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To assess the implementation of guideline-directed monitoring and management practices in the real world in patients with stage 3 CKD without a recorded diagnosis code.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>REVEAL-CKD (NCT04847531) is a multinational, observational study of patients with stage 3 CKD. Eligible patients had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements indicative of stage 3 CKD recorded >90 and ≤730 days apart, lacked an International Classification of Diseases 9/10 diagnosis code corresponding to CKD any time before and up to 6 months after the second eGFR measurement. Testing of key measures of care quality were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included 435,971 patients from 9 countries. In all countries, the prevalence of urinary albumin–creatinine ratio and albuminuria testing was low. Angiotensin-converting enzyme inhibitor, angiotensin receptor blocker and statin prescriptions were highly variable, and sodium–glucose cotransporter-2 inhibitor prescriptions remained below 21%. Blood pressure measurements were recorded in 20.2%–89.9% of patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overall, a large proportion of patients with evidence of stage 3 CKD did not receive recommended, guideline-directed monitoring and management. The variability in standard of care among countries demonstrates a clear opportunity to improve monitoring and management of these patients, most likely improving long-term outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14282","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632992","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}
Portal hypertension leads to lethal complications in liver cirrhosis. Oxidative stress induced hepatic vascular dysfunction, which exaggerated vasoconstriction and increases hepatic vascular resistance (HVR). Gut dysbiosis further exacerbates portal hypertension. Fructooligosaccharides are prebiotics with potent antioxidant effect. This study aimed to evaluate the roles of fructooligosaccharides in portal hypertension-related vascular dysregulation and gut microbiome.
Methods
Sprague–Dawley rats received bile duct ligation to induce cirrhosis or sham operation as controls. The rats then randomly received fructooligosaccharides or vehicle for 4 weeks. Experiments were performed on the 29th day after operations.
Results
Fructooligosaccharides did not affect portal pressure. Interestingly, fructooligosaccharides significantly attenuated HVR (p = .03). Malondialdehyde, an oxidative stress marker, reduced significantly in the liver in fructooligosaccharides-treated group. In addition, superoxide dismutase and trolox equivalent antioxidant capacity increased in the treatment group. On the other hand, vasodilatation-related protein expressions, GTPCH and phospho-eNOS, enhanced significantly. Fructooligosaccharides had no adverse vasodilatation effects on splanchnic vascular system or porto-systemic collateral systems. Locomotor function was not affected by fructooligosaccharides. Faecal microbiota analysis showed that Negativicutes, Selenomonadales and Lactobacillus salivarius reduced in the fructooligosaccharides-treated group.
Conclusion
In conclusion, fructooligosaccharides attenuate hepatic vascular dysfunction in cirrhotic rats via at least partly, ameliorate of dysbiosis and oxidative stress.
{"title":"Fructooligosaccharides reverses hepatic vascular dysfunction and dysbiosis in rats with liver cirrhosis and portal hypertension","authors":"Chon Kit Pun, Hui-Chun Huang, Ching-Chih Chang, Chiao-Lin Chuang, Shao-Jung Hsu, Ming-Chih Hou, Fa-Yauh Lee","doi":"10.1111/eci.14287","DOIUrl":"10.1111/eci.14287","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Portal hypertension leads to lethal complications in liver cirrhosis. Oxidative stress induced hepatic vascular dysfunction, which exaggerated vasoconstriction and increases hepatic vascular resistance (HVR). Gut dysbiosis further exacerbates portal hypertension. Fructooligosaccharides are prebiotics with potent antioxidant effect. This study aimed to evaluate the roles of fructooligosaccharides in portal hypertension-related vascular dysregulation and gut microbiome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sprague–Dawley rats received bile duct ligation to induce cirrhosis or sham operation as controls. The rats then randomly received fructooligosaccharides or vehicle for 4 weeks. Experiments were performed on the 29th day after operations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fructooligosaccharides did not affect portal pressure. Interestingly, fructooligosaccharides significantly attenuated HVR (p = .03). Malondialdehyde, an oxidative stress marker, reduced significantly in the liver in fructooligosaccharides-treated group. In addition, superoxide dismutase and trolox equivalent antioxidant capacity increased in the treatment group. On the other hand, vasodilatation-related protein expressions, GTPCH and phospho-eNOS, enhanced significantly. Fructooligosaccharides had no adverse vasodilatation effects on splanchnic vascular system or porto-systemic collateral systems. Locomotor function was not affected by fructooligosaccharides. Faecal microbiota analysis showed that <i>Negativicutes</i>, Selenomonadales and <i>Lactobacillus salivarius</i> reduced in the fructooligosaccharides-treated group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, fructooligosaccharides attenuate hepatic vascular dysfunction in cirrhotic rats via at least partly, ameliorate of dysbiosis and oxidative stress.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626391","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}
Raffaella Cassano Cassano, Dario Genovesi, Giuseppe Vergaro, Assuero Giorgetti, Alberto Aimo, Maria Livia Del Giudice, Sara Galimberti, Michele Emdin, Gabriele Buda
Often differential diagnosis between AL and ATTR amyloidosis is difficult. Concerning ATTR, sensitive diagnostic tool, as diphosphonate scintigraphy, was validated, instead of no imaging approach is as accurate in AL. Cardiac ultrasound and circulating biomarkers may raise the clinical suspicion but biopsy remains the only option for diagnosis. We aimed to explore the sensitivity of 18F-Florbetaben PET respect to blood tests or periumbilical fat (POF), cardiac, bone marrow (BM) or other tissues biopsies in a cohort of 33 patients.
AL 和 ATTR 淀粉样变性之间的鉴别诊断通常比较困难。关于 ATTR，敏感的诊断工具--二膦酸盐闪烁照相术已得到验证，但没有一种成像方法对 AL 的诊断同样准确。心脏超声和循环生物标志物可能会引起临床怀疑，但活检仍是诊断的唯一选择。我们的目的是在一组 33 例患者中探讨 18F-Florbetaben PET 相对于血液检测或脐周脂肪 (POF)、心脏、骨髓 (BM) 或其他组织活检的敏感性。
{"title":"[18F]-florbetaben PET/CT is sensitive for cardiac AL amyloidosis","authors":"Raffaella Cassano Cassano, Dario Genovesi, Giuseppe Vergaro, Assuero Giorgetti, Alberto Aimo, Maria Livia Del Giudice, Sara Galimberti, Michele Emdin, Gabriele Buda","doi":"10.1111/eci.14270","DOIUrl":"10.1111/eci.14270","url":null,"abstract":"<p>Often differential diagnosis between AL and ATTR amyloidosis is difficult. Concerning ATTR, sensitive diagnostic tool, as diphosphonate scintigraphy, was validated, instead of no imaging approach is as accurate in AL. Cardiac ultrasound and circulating biomarkers may raise the clinical suspicion but biopsy remains the only option for diagnosis. We aimed to explore the sensitivity of 18F-Florbetaben PET respect to blood tests or periumbilical fat (POF), cardiac, bone marrow (BM) or other tissues biopsies in a cohort of 33 patients.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14270","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632991","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}
Céline Ghidoni, Jan Gerrit van der Stouwe, Laura Würzburger, Patrick Wiech, Jan Vontobel, Philipp Bohm, Georg Moser, Gloria Petrasch, Valentina A. Rossi, Christian M. Schmied, Stefano Caselli, David Niederseer
Background
Hypertension and exercise testing are essential for cardiovascular risk assessment. However, an exact description of blood pressure (BP) in patients with a hypertensive response during exercise (HRE), especially in the recovery phase is lacking. Herein, we aimed to analyse BP and heart rate during exercise testing and recovery in patients with an HRE.
Methods
800 patients aged 17–90 with an HRE during a standardized bicycle ergometry test were recruited. The BP behaviour during exercise testing was correlated with clinical data. Furthermore, data were analysed according to the presence of pre-existent hypertension.
Results
Of the 800 patients included in this study 497 (62%) were previously diagnosed with hypertension. Analysis of covariance showed a significantly faster systolic (β [95% CI] 8.0 [4.9–11.1]) and diastolic (2.4 [0.4–4.4]) BP recovery 3 min after maximal exercise in patients without hypertension in univariable models. These results remained robust in fully adjusted models taking into account age, sex, body mass index, cardiovascular disease, and antihypertensive treatment for systolic (5.3 [1.2–9.4]) and diastolic BP (4.5 [1.9–7.0]). Furthermore, patients with hypertension displayed higher systolic BP during maximal exercise in univariable (3.8 [0.1–7.5]) and fully adjusted (5.5 [1.1–10.0]) models. There was no difference in maximum diastolic BP between groups.
Conclusion
In this large cohort study, patients without hypertension showed a faster systolic and diastolic BP recovery and lower maximal systolic BP compared to patients with hypertension. Overall, this study provides new insights into cardiovascular health during recovery phase.
{"title":"Blood pressure response during exercise testing in individuals with and without hypertension: The value of the recovery phase","authors":"Céline Ghidoni, Jan Gerrit van der Stouwe, Laura Würzburger, Patrick Wiech, Jan Vontobel, Philipp Bohm, Georg Moser, Gloria Petrasch, Valentina A. Rossi, Christian M. Schmied, Stefano Caselli, David Niederseer","doi":"10.1111/eci.14285","DOIUrl":"10.1111/eci.14285","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hypertension and exercise testing are essential for cardiovascular risk assessment. However, an exact description of blood pressure (BP) in patients with a hypertensive response during exercise (HRE), especially in the recovery phase is lacking. Herein, we aimed to analyse BP and heart rate during exercise testing and recovery in patients with an HRE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>800 patients aged 17–90 with an HRE during a standardized bicycle ergometry test were recruited. The BP behaviour during exercise testing was correlated with clinical data. Furthermore, data were analysed according to the presence of pre-existent hypertension.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 800 patients included in this study 497 (62%) were previously diagnosed with hypertension. Analysis of covariance showed a significantly faster systolic (<i>β</i> [95% CI] 8.0 [4.9–11.1]) and diastolic (2.4 [0.4–4.4]) BP recovery 3 min after maximal exercise in patients without hypertension in univariable models. These results remained robust in fully adjusted models taking into account age, sex, body mass index, cardiovascular disease, and antihypertensive treatment for systolic (5.3 [1.2–9.4]) and diastolic BP (4.5 [1.9–7.0]). Furthermore, patients with hypertension displayed higher systolic BP during maximal exercise in univariable (3.8 [0.1–7.5]) and fully adjusted (5.5 [1.1–10.0]) models. There was no difference in maximum diastolic BP between groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this large cohort study, patients without hypertension showed a faster systolic and diastolic BP recovery and lower maximal systolic BP compared to patients with hypertension. Overall, this study provides new insights into cardiovascular health during recovery phase.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589957","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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