Giuseppe Armentaro, Graziella D'Arrigo, Daniele Pastori, Giulia Crudo, Mario Daidone, Luca Soraci, Carlo Alberto Pastura, Marcello Divino, Annalisa Pitino, Mercedes Gori, Giovanni Tripepi, Egidio Imbalzano, Andrea Corsonello, Pasquale Pignatelli, Francesco Andreozzi, Antonino Tuttolomondo, Angela Sciacqua
Background
Atrial fibrillation is associated with several comorbidities, particularly cognitive impairment and dementia, especially in older patients. Non-vitamin K oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) were used to prevent thromboembolic events. However, data on the real benefit of these drugs on cognitive function decline remains controversial. In this study we evaluated the effect of NOACs compared to VKAs on the absolute and relative decline in cognitive function over time.
Methods
Nine hundred and eighty-three older patients with nonvalvular AF were enrolled (76 ± 6 years; 291 on VKAs and 692 on NOACs). The cognitive function was assessed with Mini Mental State examination (MMSE) score. The between-arms difference of cognitive evolution over time was investigated by Linear Mixed Models and group-based trajectory model analyses.
Results
In the whole multicenter observational study, after a long follow-up of 7.2 ± 3.4 years, the patients of the NOACs versus VKAs group had lowest absolute reduction of the MMSE score between baseline and follow-up (−0.3 ± 0.03 vs.−1.7 ± 0.1, p < 0.001). After stratification into five subgroups according to trajectories of MMSE score over time, the probability to belong to trajectories with lower decline in cognitive functions was higher in patients on NOACs than in those on VKAs (3.93–13.88 times).
Conclusion
In older patients with atrial fibrillation, the use of NOACs was associated with a smaller decline of cognitive function over time compared to the VKAs, regardless that patients in the NOACs group were older and with a higher burden of comorbidities.
{"title":"Long-term cognitive function changes with non-vitamin K oral anticoagulants in older patients with atrial fibrillation. A multicenter cohort study","authors":"Giuseppe Armentaro, Graziella D'Arrigo, Daniele Pastori, Giulia Crudo, Mario Daidone, Luca Soraci, Carlo Alberto Pastura, Marcello Divino, Annalisa Pitino, Mercedes Gori, Giovanni Tripepi, Egidio Imbalzano, Andrea Corsonello, Pasquale Pignatelli, Francesco Andreozzi, Antonino Tuttolomondo, Angela Sciacqua","doi":"10.1111/eci.14321","DOIUrl":"10.1111/eci.14321","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Atrial fibrillation is associated with several comorbidities, particularly cognitive impairment and dementia, especially in older patients. Non-vitamin K oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) were used to prevent thromboembolic events. However, data on the real benefit of these drugs on cognitive function decline remains controversial. In this study we evaluated the effect of NOACs compared to VKAs on the absolute and relative decline in cognitive function over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nine hundred and eighty-three older patients with nonvalvular AF were enrolled (76 ± 6 years; 291 on VKAs and 692 on NOACs). The cognitive function was assessed with Mini Mental State examination (MMSE) score. The between-arms difference of cognitive evolution over time was investigated by Linear Mixed Models and group-based trajectory model analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the whole multicenter observational study, after a long follow-up of 7.2 ± 3.4 years, the patients of the NOACs versus VKAs group had lowest absolute reduction of the MMSE score between baseline and follow-up (−0.3 ± 0.03 vs.−1.7 ± 0.1, <i>p</i> < 0.001). After stratification into five subgroups according to trajectories of MMSE score over time, the probability to belong to trajectories with lower decline in cognitive functions was higher in patients on NOACs than in those on VKAs (3.93–13.88 times).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In older patients with atrial fibrillation, the use of NOACs was associated with a smaller decline of cognitive function over time compared to the VKAs, regardless that patients in the NOACs group were older and with a higher burden of comorbidities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282404","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}
Eliane Swely Sanches, Daniela Simões, Filipa Isabel Baptista, Ana Paula Silva
Background
Neurovascular interfaces, specifically the blood–brain barrier (BBB) and blood–retinal barrier (BRB), play pivotal roles in maintaining the homeostasis of the central nervous system (CNS). For a long time, these structures were seen only as a way of protection, but we currently know that they have a critical role in CNS (dys)function. Several studies have identified neurovascular alterations in early stages of brain and eye diseases, contributing to the pathophysiology of such conditions. More recently, interesting data have also highlighted the importance of neurovasculature in psychiatric disorders.
Methods
Using the PubMed database, we brought together the evidence concerning the changes in BBB and BRB under psychiatric conditions, with a focus on anxiety, major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD) and drug abuse, specifically related with methamphetamine (METH) and cocaine consumption.
Results
We summarized the main findings obtained from in vitro and animal studies, as well as clinical research that has been undertaken to identify neurovascular abnormalities upon such neuropsychiatric disorders. The drivers of barrier alterations were examined, namely the role of neuroinflammation, while reporting putative barrier-associated biomarkers of these disorders.
Conclusion
This review underscores the critical need for a deeper understanding of BBB and BRB function in neuropsychiatric conditions and their potential as therapeutic targets while elucidating the key players involved. The innovative approaches to managing these complex disorders are also addressed while bridging the gap concerning what is currently known regarding the association between neuropsychiatric conditions and their vascular implications.
{"title":"Neurovascular dysfunction in psychiatric disorders: Underlying mechanisms and therapeutic approaches","authors":"Eliane Swely Sanches, Daniela Simões, Filipa Isabel Baptista, Ana Paula Silva","doi":"10.1111/eci.14319","DOIUrl":"10.1111/eci.14319","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neurovascular interfaces, specifically the blood–brain barrier (BBB) and blood–retinal barrier (BRB), play pivotal roles in maintaining the homeostasis of the central nervous system (CNS). For a long time, these structures were seen only as a way of protection, but we currently know that they have a critical role in CNS (dys)function. Several studies have identified neurovascular alterations in early stages of brain and eye diseases, contributing to the pathophysiology of such conditions. More recently, interesting data have also highlighted the importance of neurovasculature in psychiatric disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the PubMed database, we brought together the evidence concerning the changes in BBB and BRB under psychiatric conditions, with a focus on anxiety, major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD) and drug abuse, specifically related with methamphetamine (METH) and cocaine consumption.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We summarized the main findings obtained from in vitro and animal studies, as well as clinical research that has been undertaken to identify neurovascular abnormalities upon such neuropsychiatric disorders. The drivers of barrier alterations were examined, namely the role of neuroinflammation, while reporting putative barrier-associated biomarkers of these disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This review underscores the critical need for a deeper understanding of BBB and BRB function in neuropsychiatric conditions and their potential as therapeutic targets while elucidating the key players involved. The innovative approaches to managing these complex disorders are also addressed while bridging the gap concerning what is currently known regarding the association between neuropsychiatric conditions and their vascular implications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282405","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}
Huiqi Sun, Xutong Lv, Dongbin Zhang, Yue Shen, Hongxiu Lu
Background
Inflammatory cytokines and migraines have been associated in previous research, but the underlying mechanisms of action are still elusive. The biological functions of metabolites are crucial in the onset of migraine. Our goals were to clarify the cause-and-effect connection between inflammatory cytokines and migraines and explore the potential mediating function of metabolites.
Methods
Utilizing summary-level data from genome-wide association studies (GWAS), we conducted two-sample Mendelian randomization (MR) analyses to evaluate the possible causal connection between inflammatory cytokines and migraines. A two-step MR analysis was employed to further investigate the potential mediating pathways of metabolites.
Results
MR analysis identified a total of 9 inflammatory cytokines that were genetically associated with migraines, and we subsequently identified 21 mediated relationships, with 20 metabolites (13 metabolites, 7 ratios) acting as potential mediators between 8 inflammatory cytokines and migraine. The 9 inflammatory cytokines were beta-nerve growth factor levels (β-NGF), T-cell surface glycoprotein CD5 levels (CD5), T-cell surface glycoprotein CD6 isoform levels (CD6), C-X-C motif chemokine 11 levels (CXCL11), interleukin-4 levels (IL-4), oncostatin-M levels (OSM), signalling lymphocytic activation molecule levels (SLAM), C-C motif chemokine 25 levels (CCL25) and monocyte chemoattractant protein-1 levels (MCP-1).
Conclusion
Our research findings provide evidence for both a causal connection between inflammatory cytokines and migraines, as well as a metabolite-mediated pathway. These biomarkers facilitate the detection, diagnosis and treatment of migraines while offering fresh perspectives on their underlying mechanisms.
{"title":"The 1400 metabolite-mediated relationship between 91 inflammatory cytokines and migraine: An exploratory two-step Mendelian randomization study","authors":"Huiqi Sun, Xutong Lv, Dongbin Zhang, Yue Shen, Hongxiu Lu","doi":"10.1111/eci.14316","DOIUrl":"10.1111/eci.14316","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inflammatory cytokines and migraines have been associated in previous research, but the underlying mechanisms of action are still elusive. The biological functions of metabolites are crucial in the onset of migraine. Our goals were to clarify the cause-and-effect connection between inflammatory cytokines and migraines and explore the potential mediating function of metabolites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Utilizing summary-level data from genome-wide association studies (GWAS), we conducted two-sample Mendelian randomization (MR) analyses to evaluate the possible causal connection between inflammatory cytokines and migraines. A two-step MR analysis was employed to further investigate the potential mediating pathways of metabolites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>MR analysis identified a total of 9 inflammatory cytokines that were genetically associated with migraines, and we subsequently identified 21 mediated relationships, with 20 metabolites (13 metabolites, 7 ratios) acting as potential mediators between 8 inflammatory cytokines and migraine. The 9 inflammatory cytokines were beta-nerve growth factor levels (β-NGF), T-cell surface glycoprotein CD5 levels (CD5), T-cell surface glycoprotein CD6 isoform levels (CD6), C-X-C motif chemokine 11 levels (CXCL11), interleukin-4 levels (IL-4), oncostatin-M levels (OSM), signalling lymphocytic activation molecule levels (SLAM), C-C motif chemokine 25 levels (CCL25) and monocyte chemoattractant protein-1 levels (MCP-1).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our research findings provide evidence for both a causal connection between inflammatory cytokines and migraines, as well as a metabolite-mediated pathway. These biomarkers facilitate the detection, diagnosis and treatment of migraines while offering fresh perspectives on their underlying mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282406","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}
Laura Girardi, Marcello Di Nisio, Matteo Candeloro, Emanuele Valeriani, Walter Ageno
Background
Catheter-related thrombosis (CRT) is one of the major complications affecting patients with indwelling venous catheters, usually involving the upper extremity deep venous system. This condition can lead to potentially life-threatening complications such as pulmonary embolism and sepsis. The risk of developing CRT varies depending on type of catheters and patient characteristics. Despite advances in materials and technologies, the actual incidence of CRT is still considerable. Available evidence on CRT management remains controversial, and clinical guidelines base their recommendations on data from non-catheter related upper extremity or lower extremity deep venous thromboses.
Aims
This narrative review aims to describe the epidemiology of CRT, to review the available evidence on its management and to highlight the current unmet needs.
Methods
No formal search strategy was applied for the revision of the literature. The main sources of information used were Medline and guidelines from international societies.
Content
The management of CRT requires a careful balance between the risk of thrombus progression, recurrent events, and systemic embolization and the increased bleeding risk in often fragile patients. Open issues include the optimal management of the catheter and the type and duration of anticoagulant therapy. Direct oral anticoagulants are increasingly prescribed, representing an important alternative to the standard of care low molecular weight heparins in selected cases. The development of new anticoagulant drugs such as factors XI and XII inhibitors may offer further advantages in this context.
Conclusions
The management of CRT is still challenging with constant need for updated evidence to support tailored approaches.
{"title":"Catheter-related deep vein thrombosis: Where are we at and where are we going? Updates and ongoing unmet clinical needs","authors":"Laura Girardi, Marcello Di Nisio, Matteo Candeloro, Emanuele Valeriani, Walter Ageno","doi":"10.1111/eci.14311","DOIUrl":"10.1111/eci.14311","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Catheter-related thrombosis (CRT) is one of the major complications affecting patients with indwelling venous catheters, usually involving the upper extremity deep venous system. This condition can lead to potentially life-threatening complications such as pulmonary embolism and sepsis. The risk of developing CRT varies depending on type of catheters and patient characteristics. Despite advances in materials and technologies, the actual incidence of CRT is still considerable. Available evidence on CRT management remains controversial, and clinical guidelines base their recommendations on data from non-catheter related upper extremity or lower extremity deep venous thromboses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This narrative review aims to describe the epidemiology of CRT, to review the available evidence on its management and to highlight the current unmet needs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>No formal search strategy was applied for the revision of the literature. The main sources of information used were Medline and guidelines from international societies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Content</h3>\u0000 \u0000 <p>The management of CRT requires a careful balance between the risk of thrombus progression, recurrent events, and systemic embolization and the increased bleeding risk in often fragile patients. Open issues include the optimal management of the catheter and the type and duration of anticoagulant therapy. Direct oral anticoagulants are increasingly prescribed, representing an important alternative to the standard of care low molecular weight heparins in selected cases. The development of new anticoagulant drugs such as factors XI and XII inhibitors may offer further advantages in this context.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The management of CRT is still challenging with constant need for updated evidence to support tailored approaches.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201286","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}
Zeyang Li, Rachael Ngu, Aditya Anil Naik, Kaitlyn Trinh, Vladislava Paharkova, Hanyue Liao, Yulu Liu, Cindy Zhuang, Danh Le, Hua Pei, Isaac Asante, Steven D. Mittelman, Stan Louie
Introduction
Acute lymphoblastic leukaemia (ALL) is the most common type of childhood leukaemia with effective chemotherapeutic treatment. However, obesity has been associated with higher ALL chemoresistance rates and lower event-free survival rates. The molecular mechanism of how obesity promotes chemotherapy resistance is not well delineated.
Objectives
This study evaluated the effect of adipocyte maturation on sequestration and metabolism of chemotherapeutic drug daunorubicin (DNR).
Methods
Using targeted LC-MS/MS multi-analyte assay, DNR sequestration and metabolism were studied in human preadipocyte and adipocyte cell lines, where expressions of DNR-metabolizing enzymes aldo-keto reductases (AKR) and carbonyl reductases (CBR) were also evaluated. In addition, to identify the most DNR-metabolizing AKR/CBR isoforms, recombinant human AKR and CBR enzymes were subject to DNR metabolism. The results were further validated by AKR-, CBR-specific inhibitors.
Results
This report shows that adipocyte maturation upregulates expressions of AKR and CBR enzymes (by 4- to 60- folds, p < .05), which is positively associated with enhanced sequestration and metabolism of DNR in adipocytes compared to preadipocytes (by ~30%, p < .05). In particular, adipocyte maturation upregulates AKR1C3 and CBR1, which are the predominate metabolic enzyme isoforms responsible for DNR biotransformation to its metabolites.
Conclusion
Fat is an expandable tissue that can sequester and detoxify DNR when stimulated by obesity, likely through the upregulation of DNR-metabolizing enzymes AKR1C3 and CBR1. Our data partially explains why obese ALL patients may be more likely to become chemoresistant towards DNR, and provides evidence for potential clinical investigation targeting obesity to reduce DNR chemoresistance.
{"title":"Adipocyte maturation impacts daunorubicin disposition and metabolism","authors":"Zeyang Li, Rachael Ngu, Aditya Anil Naik, Kaitlyn Trinh, Vladislava Paharkova, Hanyue Liao, Yulu Liu, Cindy Zhuang, Danh Le, Hua Pei, Isaac Asante, Steven D. Mittelman, Stan Louie","doi":"10.1111/eci.14307","DOIUrl":"10.1111/eci.14307","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Acute lymphoblastic leukaemia (ALL) is the most common type of childhood leukaemia with effective chemotherapeutic treatment. However, obesity has been associated with higher ALL chemoresistance rates and lower event-free survival rates. The molecular mechanism of how obesity promotes chemotherapy resistance is not well delineated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study evaluated the effect of adipocyte maturation on sequestration and metabolism of chemotherapeutic drug daunorubicin (DNR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using targeted LC-MS/MS multi-analyte assay, DNR sequestration and metabolism were studied in human preadipocyte and adipocyte cell lines, where expressions of DNR-metabolizing enzymes aldo-keto reductases (AKR) and carbonyl reductases (CBR) were also evaluated. In addition, to identify the most DNR-metabolizing AKR/CBR isoforms, recombinant human AKR and CBR enzymes were subject to DNR metabolism. The results were further validated by AKR-, CBR-specific inhibitors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This report shows that adipocyte maturation upregulates expressions of AKR and CBR enzymes (by 4- to 60- folds, <i>p</i> < .05), which is positively associated with enhanced sequestration and metabolism of DNR in adipocytes compared to preadipocytes (by ~30%, <i>p</i> < .05). In particular, adipocyte maturation upregulates AKR1C3 and CBR1, which are the predominate metabolic enzyme isoforms responsible for DNR biotransformation to its metabolites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Fat is an expandable tissue that can sequester and detoxify DNR when stimulated by obesity, likely through the upregulation of DNR-metabolizing enzymes AKR1C3 and CBR1. Our data partially explains why obese ALL patients may be more likely to become chemoresistant towards DNR, and provides evidence for potential clinical investigation targeting obesity to reduce DNR chemoresistance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14307","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201288","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}
Beta-blocker therapy, a treatment burdened by side effects including fatigue, erectile dysfunction and depression, was shown to reduce mortality and cardiovascular events after acute coronary syndromes (ACS) in the pre-coronary reperfusion era. Potential mechanisms include protection from ventricular arrhythmias, increased ischaemia threshold and prevention of left ventricular (LV) adverse remodelling. With the advent of early mechanical reperfusion and contemporary pharmacologic secondary prevention, the benefit of beta-blockers after ACS in the absence of LV dysfunction has been challenged.
Methods
The present narrative review discusses the contemporary evidence based on searching the PubMed database and references in identified articles.
Results
Recently, the REDUCE-AMI trial—the first adequately powered randomized trial in the reperfusion era to test beta-blocker therapy after myocardial infarction with preserved left ventricular ejection fraction (LVEF)—showed no benefit on the composite of all-cause death or myocardial infarction over a median 3.5-year follow-up. While the benefit of beta-blockers in patients with reduced LVEF remains undisputed, their value in post-ACS patients with mildly reduced systolic function (LVEF 41%–49%) has not been studied in contemporary randomized trials; in this setting, observational studies have suggested a reduction in cardiovascular events with these agents. The adequate duration of beta-blocker therapy remains unknown, but observational data suggests that any mortality benefit may be lost beyond 1–12 months after ACS in patients with LVEF >40%.
Conclusion
We believe that there is sufficient evidence to abandon routine beta-blocker prescription in post-ACS patients with preserved LV systolic function.
{"title":"Routine beta-blocker therapy after acute coronary syndromes: The end of an era?","authors":"Nicolas Johner, Baris Gencer, Marco Roffi","doi":"10.1111/eci.14309","DOIUrl":"10.1111/eci.14309","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Beta-blocker therapy, a treatment burdened by side effects including fatigue, erectile dysfunction and depression, was shown to reduce mortality and cardiovascular events after acute coronary syndromes (ACS) in the pre-coronary reperfusion era. Potential mechanisms include protection from ventricular arrhythmias, increased ischaemia threshold and prevention of left ventricular (LV) adverse remodelling. With the advent of early mechanical reperfusion and contemporary pharmacologic secondary prevention, the benefit of beta-blockers after ACS in the absence of LV dysfunction has been challenged.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The present narrative review discusses the contemporary evidence based on searching the PubMed database and references in identified articles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Recently, the REDUCE-AMI trial—the first adequately powered randomized trial in the reperfusion era to test beta-blocker therapy after myocardial infarction with preserved left ventricular ejection fraction (LVEF)—showed no benefit on the composite of all-cause death or myocardial infarction over a median 3.5-year follow-up. While the benefit of beta-blockers in patients with reduced LVEF remains undisputed, their value in post-ACS patients with mildly reduced systolic function (LVEF 41%–49%) has not been studied in contemporary randomized trials; in this setting, observational studies have suggested a reduction in cardiovascular events with these agents. The adequate duration of beta-blocker therapy remains unknown, but observational data suggests that any mortality benefit may be lost beyond 1–12 months after ACS in patients with LVEF >40%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We believe that there is sufficient evidence to abandon routine beta-blocker prescription in post-ACS patients with preserved LV systolic function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14309","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142201287","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}
Milton Fabian Suárez-Ortegón, Stela McLachlan, José Manuel Fernández-Real, James F. Wilson, Sarah H. Wild
Background
There are conflicting results among studies on the association between serum ferritin (SF) and metabolic syndrome (MetS), and by groups of sex/menopausal status. To date, there are no studies on British populations. The SF-MetS association might be U/J-shaped. We evaluated whether SF was independently associated with MetS (harmonized definition) in people from Shetland, Scotland.
Methods
We analysed cross-sectional data from the Viking Health Study-Shetland (589 premenopausal women [PreMW], 625 postmenopausal women [PostW] and 832 men). Logistic regressions using two approaches, one with the lowest sex and menopausal status-specific ferritin quartile (Q) as the reference and other using the middle two quartiles combined (2–3) as the reference, were conducted to estimate the SF-MetS association. The shape of the association was verified via cubic spline analyses. The associations were adjusted for age, inflammatory and hepatic injury markers, alcohol intake, smoking and BMI.
Results
Prevalence of MetS was 18.3%. Among PostMW both low and high SF were associated with MetS (fully adjusted odds ratios [95% confidence interval] compared to the middle two quartiles combined were: 1.99 [1.17–3.38] p =.011 for Q1 and 2.10 [1.27–3.49] p =.004 for Q4) This U-shaped pattern was confirmed in the cubic spline analysis in PostMW with a ferritin range of 15–200 ug/L. In men, a positive association between ferritin quartiles with Q1 as the reference, did not remain significant after adjustment for BMI.
Conclusion
Extreme quartiles of iron status were positively associated with MetS in PostMW, while no SF-MetS associations were found in men or PreMW. The ferritin-MetS association pattern differs between populations and U/J-shaped associations may exist.
{"title":"Both low and high body iron stores relate to metabolic syndrome in postmenopausal women: Findings from the VIKING Health Study-Shetland (VIKING I)","authors":"Milton Fabian Suárez-Ortegón, Stela McLachlan, José Manuel Fernández-Real, James F. Wilson, Sarah H. Wild","doi":"10.1111/eci.14312","DOIUrl":"10.1111/eci.14312","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There are conflicting results among studies on the association between serum ferritin (SF) and metabolic syndrome (MetS), and by groups of sex/menopausal status. To date, there are no studies on British populations. The SF-MetS association might be U/J-shaped. We evaluated whether SF was independently associated with MetS (harmonized definition) in people from Shetland, Scotland.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed cross-sectional data from the Viking Health Study-Shetland (589 premenopausal women [PreMW], 625 postmenopausal women [PostW] and 832 men). Logistic regressions using two approaches, one with the lowest sex and menopausal status-specific ferritin quartile (Q) as the reference and other using the middle two quartiles combined (2–3) as the reference, were conducted to estimate the SF-MetS association. The shape of the association was verified via cubic spline analyses. The associations were adjusted for age, inflammatory and hepatic injury markers, alcohol intake, smoking and BMI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Prevalence of MetS was 18.3%. Among PostMW both low and high SF were associated with MetS (fully adjusted odds ratios [95% confidence interval] compared to the middle two quartiles combined were: 1.99 [1.17–3.38] <i>p</i> =.011 for Q1 and 2.10 [1.27–3.49] <i>p</i> =.004 for Q4) This <i>U</i>-shaped pattern was confirmed in the cubic spline analysis in PostMW with a ferritin range of 15–200 ug/L. In men, a positive association between ferritin quartiles with Q1 as the reference, did not remain significant after adjustment for BMI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Extreme quartiles of iron status were positively associated with MetS in PostMW, while no SF-MetS associations were found in men or PreMW. The ferritin-MetS association pattern differs between populations and U/J-shaped associations may exist.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14312","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juan Antonio Valera-Calero, Umut Varol, Ricardo Ortega-Santiago, Marcos José Navarro-Santana, María José Díaz-Arribas, Jorge Buffet-García, Gustavo Plaza-Manzano
Background
Physiotherapists encounter challenges in diagnosing myofascial trigger points (MTrPs), which are crucial for managing myofascial pain but difficult due to their complex referred pain patterns. We aimed to assess if an interactive software (MyofAPPcial) can enhance the ability of physical therapists specialized in musculoskeletal disorders (as clinicians and as researchers and educators) to identify referred pain patterns associated with specific MTrPs and to explore their opinion about incorporating this technology regularly into their professional setting.
Methods
After developing the app, a descriptive cross-sectional survey study was conducted. Participants were asked about their demographic characteristics, professional experience, two knowledge tests (first without and later with MyofAPPcial support) and the 18-item mHealth app usability questionnaire.
Results
Fifty-nine participants completed the survey (47.5% clinicians and 62.5% researchers/educators). Groups were comparable in terms of age, gender and professional experience (p > .05). However, clinicians coursed shorter specific MPS trainings (p = .007) and handle more cases a week (p < .001). In the first knowledge test, participants in both the groups were more accurate in identifying pain maps of highly prevalent MTrPs than those with a moderate or low prevalence (p < .001), with no differences between the groups for individual items (all, p > .05) nor the total score (p > .05). In the second knowledge test, perfect scores were obtained for all items in both the groups. Finally, MyofAPPcial scored high satisfaction and app usefulness, with no difference between clinicians and researchers/educators (except greater convenience of use for researchers/educators p = .02).
Conclusions
MyofAPPcial enhances physiotherapists' ability to accurately identify MTrPs, with a good acceptation among clinicians and researchers/educators.
{"title":"MyofAPPcial: Construct validity of a novel technological aid for improving clinical reasoning in the management of myofascial pain syndrome","authors":"Juan Antonio Valera-Calero, Umut Varol, Ricardo Ortega-Santiago, Marcos José Navarro-Santana, María José Díaz-Arribas, Jorge Buffet-García, Gustavo Plaza-Manzano","doi":"10.1111/eci.14313","DOIUrl":"10.1111/eci.14313","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Physiotherapists encounter challenges in diagnosing myofascial trigger points (MTrPs), which are crucial for managing myofascial pain but difficult due to their complex referred pain patterns. We aimed to assess if an interactive software (MyofAPPcial) can enhance the ability of physical therapists specialized in musculoskeletal disorders (as clinicians and as researchers and educators) to identify referred pain patterns associated with specific MTrPs and to explore their opinion about incorporating this technology regularly into their professional setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>After developing the app, a descriptive cross-sectional survey study was conducted. Participants were asked about their demographic characteristics, professional experience, two knowledge tests (first without and later with MyofAPPcial support) and the 18-item mHealth app usability questionnaire.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty-nine participants completed the survey (47.5% clinicians and 62.5% researchers/educators). Groups were comparable in terms of age, gender and professional experience (<i>p</i> > .05). However, clinicians coursed shorter specific MPS trainings (<i>p</i> = .007) and handle more cases a week (<i>p</i> < .001). In the first knowledge test, participants in both the groups were more accurate in identifying pain maps of highly prevalent MTrPs than those with a moderate or low prevalence (<i>p</i> < .001), with no differences between the groups for individual items (all, <i>p</i> > .05) nor the total score (<i>p</i> > .05). In the second knowledge test, perfect scores were obtained for all items in both the groups. Finally, MyofAPPcial scored high satisfaction and app usefulness, with no difference between clinicians and researchers/educators (except greater convenience of use for researchers/educators <i>p</i> = .02).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MyofAPPcial enhances physiotherapists' ability to accurately identify MTrPs, with a good acceptation among clinicians and researchers/educators.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14313","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Henri-Corto Stoeklé, Philippe Beuzeboc, Tara Payet, Christian Hervé, Jaafar Bennouna
The last few years have seen the improvement of cancer management through the arrival of a continuous stream of innovative new molecules known as ‘targeted therapies’ and ‘new immunotherapies’.1 One characteristic common to all these treatments is a specific link to a precise cellular and/or molecular profile. Some of these treatments are already improving therapeutic results for certain types and subtypes of cancer.2 However, a non-negligible proportion of these molecules remain inaccessible to patients other than through clinical trials, particularly early-phase clinical trials.3 The aims of such clinical trials were initially limited to identifying toxicities associated with the molecules tested, but they now extend to the evaluation of efficacy and possible therapeutic benefits for participants. We performed a preliminary empirical bioethics work at national scale in France, with specific protocolization,4 based on a non-systematic literature review, to deal with the ‘macro-bio-ethical issues’.
HCS, PB, CH and JB are the principal investigators. They contributed to the conception of the paper, the drafting of sections and discussions about how the different sections should be refined and integrated. TP is an undergraduate trainee who helped collect and process the data.
Foch Hospital.
HCS, TP and CH have no conflicts of interest to declare for the submitted work. PB has received personal fees from Astellas (educational sessions) and Pfizer (travel expenses to ASCO 2023), all outside of the submitted work. JB has received personal fees from AstraZeneca, Bristol-Myers Squibb, MSD, Janssen Cilag, Daiichi and Sanofi Aventis (advisory board, educational symposium and honorarium), all outside of the submitted work.
{"title":"Early-phase clinical trials in oncology for adults in France: A preliminary empirical bioethics study","authors":"Henri-Corto Stoeklé, Philippe Beuzeboc, Tara Payet, Christian Hervé, Jaafar Bennouna","doi":"10.1111/eci.14315","DOIUrl":"10.1111/eci.14315","url":null,"abstract":"<p>The last few years have seen the improvement of cancer management through the arrival of a continuous stream of innovative new molecules known as ‘targeted therapies’ and ‘new immunotherapies’.<span><sup>1</sup></span> One characteristic common to all these treatments is a specific link to a precise cellular and/or molecular profile. Some of these treatments are already improving therapeutic results for certain types and subtypes of cancer.<span><sup>2</sup></span> However, a non-negligible proportion of these molecules remain inaccessible to patients other than through clinical trials, particularly early-phase clinical trials.<span><sup>3</sup></span> The aims of such clinical trials were initially limited to identifying toxicities associated with the molecules tested, but they now extend to the evaluation of efficacy and possible therapeutic benefits for participants. We performed a preliminary empirical bioethics work at national scale in France, with specific protocolization,<span><sup>4</sup></span> based on a non-systematic literature review, to deal with the ‘macro-bio-ethical issues’.</p><p>HCS, PB, CH and JB are the principal investigators. They contributed to the conception of the paper, the drafting of sections and discussions about how the different sections should be refined and integrated. TP is an undergraduate trainee who helped collect and process the data.</p><p>Foch Hospital.</p><p>HCS, TP and CH have no conflicts of interest to declare for the submitted work. PB has received personal fees from Astellas (educational sessions) and Pfizer (travel expenses to ASCO 2023), all outside of the submitted work. JB has received personal fees from AstraZeneca, Bristol-Myers Squibb, MSD, Janssen Cilag, Daiichi and Sanofi Aventis (advisory board, educational symposium and honorarium), all outside of the submitted work.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14315","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luis Jara-Palomares, Behnood Bikdeli, David Jiménez, Alfonso Muriel, Pablo Demelo-Rodríguez, Isabelle Mahé, Juan José López-Núñez, Joaquín Alfonso Megido, Begoña Fernández Jiménez, Manuel Monreal, the RIETE Investigators
This study generated evidence to guide anticoagulation in patients with VTE after vaccination for COVID-19. We provided data on the low recurrence rate after cessation of anticoagulant therapy and the findings for this study offer timely insights into the management of a potentially vaccine-related adverse event.
{"title":"Rate of recurrence after discontinuing anticoagulation in patients with venous thromboembolism within 30 days after COVID-19 vaccine","authors":"Luis Jara-Palomares, Behnood Bikdeli, David Jiménez, Alfonso Muriel, Pablo Demelo-Rodríguez, Isabelle Mahé, Juan José López-Núñez, Joaquín Alfonso Megido, Begoña Fernández Jiménez, Manuel Monreal, the RIETE Investigators","doi":"10.1111/eci.14310","DOIUrl":"10.1111/eci.14310","url":null,"abstract":"<p>This study generated evidence to guide anticoagulation in patients with VTE after vaccination for COVID-19. We provided data on the low recurrence rate after cessation of anticoagulant therapy and the findings for this study offer timely insights into the management of a potentially vaccine-related adverse event.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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