Alexander M. Cao Zhang, Efthymios Ziogos, Tarek Harb, Gary Gerstenblith, Thorsten M. Leucker
Background
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily recognized for its role in lipid metabolism, but recent evidence suggests that it may have broader implications due to its diverse tissue expression.
Objective
This review aims to explore the multifaceted functions of PCSK9, highlighting its pro-atherosclerotic effects, including its impact on circulating lipoprotein variables, non-low-density lipoprotein receptors, and various cell types involved in atherosclerotic plaque development.
Conclusions
PCSK9 exhibits diverse roles beyond lipid metabolism, potentially contributing to atherosclerosis through multiple pathways. Understanding these mechanisms could offer new insights into therapeutic strategies targeting PCSK9 for cardiovascular disease management.
背景：Proprotein convertase subtilisin/kexin type 9 (PCSK9)主要被认为在脂质代谢中发挥作用，但最近的证据表明，由于其在不同组织中的表达，它可能具有更广泛的影响：本综述旨在探讨 PCSK9 的多方面功能，强调其促进动脉粥样硬化的作用，包括对循环脂蛋白变量、非低密度脂蛋白受体以及参与动脉粥样硬化斑块形成的各种细胞类型的影响：PCSK9在脂质代谢之外还具有多种作用，可能通过多种途径导致动脉粥样硬化。了解这些机制可为针对 PCSK9 的治疗策略提供新的见解，从而控制心血管疾病。
{"title":"Emerging clinical role of proprotein convertase subtilisin/kexin type 9 inhibition—Part one: Pleiotropic pro-atherosclerotic effects of PCSK9","authors":"Alexander M. Cao Zhang, Efthymios Ziogos, Tarek Harb, Gary Gerstenblith, Thorsten M. Leucker","doi":"10.1111/eci.14273","DOIUrl":"10.1111/eci.14273","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Proprotein convertase subtilisin/kexin type 9 (PCSK9) is primarily recognized for its role in lipid metabolism, but recent evidence suggests that it may have broader implications due to its diverse tissue expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This review aims to explore the multifaceted functions of PCSK9, highlighting its pro-atherosclerotic effects, including its impact on circulating lipoprotein variables, non-low-density lipoprotein receptors, and various cell types involved in atherosclerotic plaque development.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>PCSK9 exhibits diverse roles beyond lipid metabolism, potentially contributing to atherosclerosis through multiple pathways. Understanding these mechanisms could offer new insights into therapeutic strategies targeting PCSK9 for cardiovascular disease management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456088","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}
For decades standard teaching recommended salt intake (sodium) reduction in patients suffering from heart failure. Neurohumoral activation with subsequent fluid retention provided a solid rationale for this long-standing recommendation. Until recently no large randomized clinical trial of sodium restriction was available, while some observational studies and metanalyses even suggested a worse outcome with strict sodium restriction in patients with heart failure.
Methods
In this narrative review we aimed to extricate from the literature whether strict sodium restriction is beneficial in patients with heart failure. We searched PubMed indexed articles between 2000 and 2023 for these terms: heart failure, salt, sodium, fluid intake.
Results
Most randomized trials were small and showed a wide heterogeneity of interventions. A single large, randomized clinical trial was stopped early due to futility. Overall, there is no evidence that severe sodium restriction reduces the incidence of mortality and hospitalization in patients with heart failure. Quality of life and functional class may improve slightly with sodium restriction.
Conclusion
Morbidity and mortality are not reduced with sodium restriction in patients with heart failure, although some symptomatic improvement may be expected.
{"title":"Salt versus no salt restriction in heart failure a review","authors":"Paolo Raggi","doi":"10.1111/eci.14265","DOIUrl":"10.1111/eci.14265","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>For decades standard teaching recommended salt intake (sodium) reduction in patients suffering from heart failure. Neurohumoral activation with subsequent fluid retention provided a solid rationale for this long-standing recommendation. Until recently no large randomized clinical trial of sodium restriction was available, while some observational studies and metanalyses even suggested a worse outcome with strict sodium restriction in patients with heart failure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this narrative review we aimed to extricate from the literature whether strict sodium restriction is beneficial in patients with heart failure. We searched PubMed indexed articles between 2000 and 2023 for these terms: heart failure, salt, sodium, fluid intake.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Most randomized trials were small and showed a wide heterogeneity of interventions. A single large, randomized clinical trial was stopped early due to futility. Overall, there is no evidence that severe sodium restriction reduces the incidence of mortality and hospitalization in patients with heart failure. Quality of life and functional class may improve slightly with sodium restriction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Morbidity and mortality are not reduced with sodium restriction in patients with heart failure, although some symptomatic improvement may be expected.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456090","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}
Julia Mascherbauer, Tanja Rudolph, Justus T. Strauch, Moritz Seiffert, Sabine Bleiziffer, Philipp Emanuel Bartko, Marie Zielinski, Anjaly Vijayan, Peter Bramlage, Christian Hengstenberg
Background
Invasive coronary angiography (ICA) is the standard for pre-procedural assessment of coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI). However, it requires hospitalization and can be associated with complications. Computed tomography angiography (CTA) may be a viable alternative to rule out prognostically relevant CAD.
Methods
The EASE-IT CT Registry is an investigator-initiated, prospective, observational, multicentre pilot registry involving patients aged ≥75 years with severe aortic stenosis (AS) intended to implant a transcatheter heart valve (THV) of the SAPIEN family. A total of 150 patients will be recruited from four sites in Germany and Austria. The registry will consist of two prospective cohorts: the investigational CTA-only cohort and the CTA + ICA control cohort. The CTA-only cohort will enrol 100 patients in whom significant (≥50%) left main (LM) and/or proximal left anterior descending artery (LAD) stenosis are ruled out on CTA. The CTA + ICA control cohort will enrol 50 patients who have undergone both CTA and ICA before TAVI and in whom ≥50% LM/proximal LAD stenosis has been ruled out by CTA. Three composite endpoints will be assessed at 3 months post-TAVI: CAD-specific endpoints, VARC-3-defined device success and early safety.
Conclusion
The EASE-IT CT Registry evaluates whether TAVI can be carried out safely without performing ICA if prognostically relevant CAD of the LM/proximal LAD is ruled out with CTA. If so, the omission of ICA would help streamline the pre-procedural workup of TAVI patients.
{"title":"Preprocedural assessment of coronary artery disease in patients undergoing transcatheter aortic valve implantation: Rationale and design of the EASE-IT CT registry","authors":"Julia Mascherbauer, Tanja Rudolph, Justus T. Strauch, Moritz Seiffert, Sabine Bleiziffer, Philipp Emanuel Bartko, Marie Zielinski, Anjaly Vijayan, Peter Bramlage, Christian Hengstenberg","doi":"10.1111/eci.14274","DOIUrl":"10.1111/eci.14274","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Invasive coronary angiography (ICA) is the standard for pre-procedural assessment of coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI). However, it requires hospitalization and can be associated with complications. Computed tomography angiography (CTA) may be a viable alternative to rule out prognostically relevant CAD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The EASE-IT CT Registry is an investigator-initiated, prospective, observational, multicentre pilot registry involving patients aged ≥75 years with severe aortic stenosis (AS) intended to implant a transcatheter heart valve (THV) of the SAPIEN family. A total of 150 patients will be recruited from four sites in Germany and Austria. The registry will consist of two prospective cohorts: the investigational CTA-only cohort and the CTA + ICA control cohort. The CTA-only cohort will enrol 100 patients in whom significant (≥50%) left main (LM) and/or proximal left anterior descending artery (LAD) stenosis are ruled out on CTA. The CTA + ICA control cohort will enrol 50 patients who have undergone both CTA and ICA before TAVI and in whom ≥50% LM/proximal LAD stenosis has been ruled out by CTA. Three composite endpoints will be assessed at 3 months post-TAVI: CAD-specific endpoints, VARC-3-defined device success and early safety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The EASE-IT CT Registry evaluates whether TAVI can be carried out safely without performing ICA if prognostically relevant CAD of the LM/proximal LAD is ruled out with CTA. If so, the omission of ICA would help streamline the pre-procedural workup of TAVI patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 11","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14274","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456089","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}
Alexander M. Cao Zhang, Efthymios Ziogos, Tarek Harb, Gary Gerstenblith, Thorsten M. Leucker
Background
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have emerged as a novel class of drugs with cardioprotective effects through their lipid-lowering effects.
Objective
This review aims to discuss existing and novel strategies of PCSK9 inhibition, providing an overview of established randomized controlled trials and ongoing outcome trials that assess the efficacy and long-term safety of PCSK9 inhibitors. It also explores the evolving role of PCSK9 beyond lipid metabolism and outlines the pleiotropic actions of PCSK9 inhibition in various disorders and future directions including novel strategies to target PCSK9.
Conclusion
PCSK9 inhibition shows promise not only in lipid metabolism but also in other disease processes, including atherosclerotic plaque remodeling, acute coronary syndrome, stroke, inflammation, and immune response.
背景： Proprotein convertase subtilisin/kexin type 9 (PCSK9) 抑制剂通过降脂作用成为一类具有心脏保护作用的新型药物：Proprotein convertase subtilisin/kexin type 9 (PCSK9)抑制剂已成为一类新型药物，通过其降脂作用起到保护心脏的作用：本综述旨在讨论现有的和新型的 PCSK9 抑制策略，概述已完成的随机对照试验和正在进行的结果试验，以评估 PCSK9 抑制剂的疗效和长期安全性。报告还探讨了PCSK9在脂质代谢之外不断演变的作用，概述了PCSK9抑制剂在各种疾病中的多效应以及未来的发展方向，包括针对PCSK9的新策略：结论：PCSK9抑制不仅在脂质代谢方面大有可为，而且在其他疾病过程中也大有可为，包括动脉粥样硬化斑块重塑、急性冠状动脉综合征、中风、炎症和免疫反应。
{"title":"Emerging clinical role of proprotein convertase subtilisin/kexin type 9 inhibition–Part two: Current and emerging concepts in the clinical use of PCSK9 inhibition","authors":"Alexander M. Cao Zhang, Efthymios Ziogos, Tarek Harb, Gary Gerstenblith, Thorsten M. Leucker","doi":"10.1111/eci.14272","DOIUrl":"10.1111/eci.14272","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have emerged as a novel class of drugs with cardioprotective effects through their lipid-lowering effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This review aims to discuss existing and novel strategies of PCSK9 inhibition, providing an overview of established randomized controlled trials and ongoing outcome trials that assess the efficacy and long-term safety of PCSK9 inhibitors. It also explores the evolving role of PCSK9 beyond lipid metabolism and outlines the pleiotropic actions of PCSK9 inhibition in various disorders and future directions including novel strategies to target PCSK9.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PCSK9 inhibition shows promise not only in lipid metabolism but also in other disease processes, including atherosclerotic plaque remodeling, acute coronary syndrome, stroke, inflammation, and immune response.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456087","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}
I. Cavero-Redondo, N. Moreno-Herraiz, A. Del Saz-Lara, I. Otero-Luis, J. I. Recio-Rodriguez, A. Saz-Lara
Background
Atherosclerosis, a leading cause of mortality, necessitates effective management of hypercholesterolemia, specifically elevated low-density lipoprotein cholesterol (LDL-C). The emergence of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has revolutionised lipid-lowering. PCSK9i demonstrates substantial LDL-C reduction and cardiovascular benefits, particularly in statin-intolerant or nonresponsive individuals. However, the potential pleiotropic effects of PCSK9i, especially on arterial stiffness, remain a subject of investigation. This systematic review and meta-analysis seek to provide a nuanced understanding of the potential pleiotropic effects of PCSK9i, specifically on arterial health. The primary objective was to analyse the influence of PCSK9i on arterial stiffness, extending beyond traditional lipid-lowering metrics and contributing to a more comprehensive approach to cardiovascular risk reduction.
Methods
A systematic search was conducted across major databases, clinical trial registries and grey literature. Inclusion criteria comprised adults in prospective cohort studies undergoing PCSK9i augmentation in lipid-lowering therapy, with a focus on arterial stiffness measured by pulse wave velocity (PWv). Random-effects meta-analyses, sensitivity analyses and meta-regression models were employed to assess the pooled effect of adding PCSK9i to lipid-lowering interventions on arterial stiffness.
Results
Five studies (158 participants) met the inclusion criteria, demonstrating a significant reduction in PWv (mean difference: −2.61 m/s [95% CI: −3.70, −1.52]; ES: −1.62 [95% CI: −2.53, −.71]) upon adding PCSK9i to lipid-lowering interventions. Subgroup analysis and meta-regression models suggested potential sex-based and baseline PWv-dependent variations, emphasising patient-specific characteristics.
Conclusion
The meta-analysis provides robust evidence that adding PCSK9i to lipid-lowering interventions significantly improves arterial stiffness, indicating broader vascular benefits beyond LDL-C reduction.
{"title":"Effect of adding PCSK9 inhibitors to lipid-lowering interventions on arterial stiffness: A systematic review and meta-analysis","authors":"I. Cavero-Redondo, N. Moreno-Herraiz, A. Del Saz-Lara, I. Otero-Luis, J. I. Recio-Rodriguez, A. Saz-Lara","doi":"10.1111/eci.14269","DOIUrl":"10.1111/eci.14269","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Atherosclerosis, a leading cause of mortality, necessitates effective management of hypercholesterolemia, specifically elevated low-density lipoprotein cholesterol (LDL-C). The emergence of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has revolutionised lipid-lowering. PCSK9i demonstrates substantial LDL-C reduction and cardiovascular benefits, particularly in statin-intolerant or nonresponsive individuals. However, the potential pleiotropic effects of PCSK9i, especially on arterial stiffness, remain a subject of investigation. This systematic review and meta-analysis seek to provide a nuanced understanding of the potential pleiotropic effects of PCSK9i, specifically on arterial health. The primary objective was to analyse the influence of PCSK9i on arterial stiffness, extending beyond traditional lipid-lowering metrics and contributing to a more comprehensive approach to cardiovascular risk reduction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic search was conducted across major databases, clinical trial registries and grey literature. Inclusion criteria comprised adults in prospective cohort studies undergoing PCSK9i augmentation in lipid-lowering therapy, with a focus on arterial stiffness measured by pulse wave velocity (PWv). Random-effects meta-analyses, sensitivity analyses and meta-regression models were employed to assess the pooled effect of adding PCSK9i to lipid-lowering interventions on arterial stiffness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Five studies (158 participants) met the inclusion criteria, demonstrating a significant reduction in PWv (mean difference: −2.61 m/s [95% CI: −3.70, −1.52]; ES: −1.62 [95% CI: −2.53, −.71]) upon adding PCSK9i to lipid-lowering interventions. Subgroup analysis and meta-regression models suggested potential sex-based and baseline PWv-dependent variations, emphasising patient-specific characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The meta-analysis provides robust evidence that adding PCSK9i to lipid-lowering interventions significantly improves arterial stiffness, indicating broader vascular benefits beyond LDL-C reduction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14269","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141506308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Central role of pro-IGFII(68–88) (big IGFII) in the pathogenesis nonislet cell tumour-induced hypoglycaemia","authors":"Robin P. F. Dullaart","doi":"10.1111/eci.14268","DOIUrl":"10.1111/eci.14268","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426645","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}
Pregnancy represents a window of vulnerability to fetal development. Disruptions in the prenatal environment during this crucial period can increase the risk of the offspring developing diseases over the course of their lifetime. The central nervous system (CNS) has been shown to be particularly susceptible to changes during crucial developmental windows. To date, research focused on disruptions in the development of the CNS has predominantly centred on the brain, revealing a correlation between exposure to prenatal risk factors and the onset of neuropsychiatric disorders. Nevertheless, some studies indicate that the retina, which is part of the CNS, is also vulnerable to in utero alterations during pregnancy. Such changes may affect neuronal, glial and vascular components of the retina, compromising retinal structure and function and possibly impairing visual function.
Methods
A search in the PubMed database was performed, and any literature concerning prenatal risk factors (drugs, diabetes, unbalanced diet, infection, glucocorticoids) affecting the offspring retina were included.
Results
This review collects evidence on the cellular, structural and functional changes occurring in the retina triggered by maternal risk factors during pregnancy. We highlight the adverse impact on retinal development and its long-lasting effects, providing a critical analysis of the current knowledge while underlining areas for future research.
Conclusions
Appropriate recognition of the prenatal risk factors that negatively impact the developing retina may provide critical clues for the design of preventive strategies and for early therapeutic intervention that could change retinal pathology in the progeny.
{"title":"Tracing the influence of prenatal risk factors on the offspring retina: Focus on development and putative long-term consequences","authors":"Filipa I. Baptista, António F. Ambrósio","doi":"10.1111/eci.14266","DOIUrl":"10.1111/eci.14266","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pregnancy represents a window of vulnerability to fetal development. Disruptions in the prenatal environment during this crucial period can increase the risk of the offspring developing diseases over the course of their lifetime. The central nervous system (CNS) has been shown to be particularly susceptible to changes during crucial developmental windows. To date, research focused on disruptions in the development of the CNS has predominantly centred on the brain, revealing a correlation between exposure to prenatal risk factors and the onset of neuropsychiatric disorders. Nevertheless, some studies indicate that the retina, which is part of the CNS, is also vulnerable to in utero alterations during pregnancy. Such changes may affect neuronal, glial and vascular components of the retina, compromising retinal structure and function and possibly impairing visual function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A search in the PubMed database was performed, and any literature concerning prenatal risk factors (drugs, diabetes, unbalanced diet, infection, glucocorticoids) affecting the offspring retina were included.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This review collects evidence on the cellular, structural and functional changes occurring in the retina triggered by maternal risk factors during pregnancy. We highlight the adverse impact on retinal development and its long-lasting effects, providing a critical analysis of the current knowledge while underlining areas for future research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Appropriate recognition of the prenatal risk factors that negatively impact the developing retina may provide critical clues for the design of preventive strategies and for early therapeutic intervention that could change retinal pathology in the progeny.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305706","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":"Proprotein convertase subtilisin/kexin type 9 (PCSK9) and clinical outcomes in patients with end-stage renal disease","authors":"Johann Auer, Lisa Auer","doi":"10.1111/eci.14262","DOIUrl":"10.1111/eci.14262","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 9","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295814","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}
Giorgio Busto, Andrea Morotti, Ilaria Casetta, Angelo Barra, Alessandro Fiorenza, Francesca Di Pasquale, Maria Giulia Maccaglia, Maddalena Toffali, Sara Mancini, Edoardo Carlesi, Vanessa Palumbo, Ivano Lombardo, Alessandro Padovani, Enrico Fainardi
Background
Hypoperfusion Intensity Ratio (HIR) is associated with collaterals and outcome in acute ischemic stroke (AIS). We investigated whether a combined assessment of HIR and collaterals could provide an added value.
Methods
Retrospective single-center study, including AIS patients with large vessel occlusion and endovascular treatment 0–24 h from onset. Predictors of FIV and outcome (90 days modified Rankin Scale 0–1) were investigated with linear and logistic regression respectively. Subjects were stratified in three groups: poor collaterals (grade 0–3) with poor HIR (≥.4), good collaterals (grade 4–5) with poor HIR/poor collaterals with good HIR (<.4) and good collaterals with good HIR.
Results
We included 337 patients (median age 77, 53.1% males), of whom 100 (29.7%) had excellent outcome. One hundred and forty five patients with favourable collateral and HIR profiles had smaller infarct (median poor collaterals with poor HIR 41 mL, good collaterals with poor HIR/poor collaterals with good HIR 21 mL and good collaterals with good HIR 11 mL, p <.001) and higher rates of excellent outcome (poor collaterals with poor HIR 15.7%, good collaterals with poor HIR/poor collaterals with good HIR 26.2% and good collaterals with good HIR 39.3% p =.001). Logistic regression showed that patients with favourable collateral and HIR profiles had the highest odds of good outcome (OR: 3.83, 95% CI 1.62–9.08, p =.002).
Conclusion
Collaterals and HIR are independent predictors of final infarct lesion and outcome in stroke patients and their integration provides an added value. These findings might inform clinical practice and future trials.
{"title":"Hypoperfusion intensity ratio correlates with collaterals and predicts outcome and infarct volume in acute ischemic stroke patients","authors":"Giorgio Busto, Andrea Morotti, Ilaria Casetta, Angelo Barra, Alessandro Fiorenza, Francesca Di Pasquale, Maria Giulia Maccaglia, Maddalena Toffali, Sara Mancini, Edoardo Carlesi, Vanessa Palumbo, Ivano Lombardo, Alessandro Padovani, Enrico Fainardi","doi":"10.1111/eci.14264","DOIUrl":"10.1111/eci.14264","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hypoperfusion Intensity Ratio (HIR) is associated with collaterals and outcome in acute ischemic stroke (AIS). We investigated whether a combined assessment of HIR and collaterals could provide an added value.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective single-center study, including AIS patients with large vessel occlusion and endovascular treatment 0–24 h from onset. Predictors of FIV and outcome (90 days modified Rankin Scale 0–1) were investigated with linear and logistic regression respectively. Subjects were stratified in three groups: poor collaterals (grade 0–3) with poor HIR (≥.4), good collaterals (grade 4–5) with poor HIR/poor collaterals with good HIR (<.4) and good collaterals with good HIR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 337 patients (median age 77, 53.1% males), of whom 100 (29.7%) had excellent outcome. One hundred and forty five patients with favourable collateral and HIR profiles had smaller infarct (median poor collaterals with poor HIR 41 mL, good collaterals with poor HIR/poor collaterals with good HIR 21 mL and good collaterals with good HIR 11 mL, <i>p</i> <.001) and higher rates of excellent outcome (poor collaterals with poor HIR 15.7%, good collaterals with poor HIR/poor collaterals with good HIR 26.2% and good collaterals with good HIR 39.3% <i>p</i> =.001). Logistic regression showed that patients with favourable collateral and HIR profiles had the highest odds of good outcome (OR: 3.83, 95% CI 1.62–9.08, <i>p</i> =.002).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Collaterals and HIR are independent predictors of final infarct lesion and outcome in stroke patients and their integration provides an added value. These findings might inform clinical practice and future trials.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300445","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}
Dejiang Lin, Dongxia Hu, Youlin Song, Xingxiang He, Lei Wu
Background
Faecal microbiota transplantation holds promise in mitigating fat accumulation and improving obesity. This study aimed to evaluate the long-term efficacy of washed microbiota transplantation (WMT) among overweight patients.
Methods
The clinical data pertaining to the treatment of patients with WMT were collected retrospectively. Compared alterations in body mass index (BMI), blood glucose, blood lipids and blood pressure prior to and following WMT treatment. Comprehensive efficacy evaluation and atherosclerosis cardiovascular disease (ASCVD) grading evaluation were carried out, with an analysis of gut microbiota composition before and after WMT.
Results
A total of 186 patients were included (80 overweight, 106 normal weight). WMT not only had the effect of improving overweight patients to the normal weight patients (p < .001), but also could significantly reduce BMI in the long term by restoring gut microbiota homeostasis (p < .001). In addition, the BMI improvement value of multi course was more significant than that of single course or double course. WMT had a significant ASCVD downgrade effect on the high-risk and medium-risk groups outside 1 year, while it did not increase the risk of upgrading ASCVD for low-risk group.
Conclusions
WMT could significantly reduce the BMI of overweight patients and still had an improvement effect in the long term.
{"title":"Long-term efficacy of washed microbiota transplantation in overweight patients","authors":"Dejiang Lin, Dongxia Hu, Youlin Song, Xingxiang He, Lei Wu","doi":"10.1111/eci.14260","DOIUrl":"10.1111/eci.14260","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Faecal microbiota transplantation holds promise in mitigating fat accumulation and improving obesity. This study aimed to evaluate the long-term efficacy of washed microbiota transplantation (WMT) among overweight patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The clinical data pertaining to the treatment of patients with WMT were collected retrospectively. Compared alterations in body mass index (BMI), blood glucose, blood lipids and blood pressure prior to and following WMT treatment. Comprehensive efficacy evaluation and atherosclerosis cardiovascular disease (ASCVD) grading evaluation were carried out, with an analysis of gut microbiota composition before and after WMT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 186 patients were included (80 overweight, 106 normal weight). WMT not only had the effect of improving overweight patients to the normal weight patients (<i>p</i> < .001), but also could significantly reduce BMI in the long term by restoring gut microbiota homeostasis (<i>p</i> < .001). In addition, the BMI improvement value of multi course was more significant than that of single course or double course. WMT had a significant ASCVD downgrade effect on the high-risk and medium-risk groups outside 1 year, while it did not increase the risk of upgrading ASCVD for low-risk group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>WMT could significantly reduce the BMI of overweight patients and still had an improvement effect in the long term.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 10","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300446","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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