Jesús Jurado-Palomo, José Luis Martin-Conty, Begoña Polonio-López, Juan J. Bernal-Jiménez, Rosa Conty-Serrano, Michele Dileone, Miguel A. Castro Villamor, Carlos del Pozo Vegas, Raúl López-Izquierdo, Cristina Rivera-Picón, Francisco Martín-Rodríguez, Ancor Sanz-García
Introduction
The use of medications by emergency medical services (EMS) is increasing. Conventional scores are time-consuming and therefore difficult to use in an emergency setting. For early decision-making, an easy-to-use score based on the medications administered by the EMS may have prognostic value. The primary objective of this study was to develop the prehospital drug-derived score (PDDS) for 2-day mortality.
Methods
A prospective, multicenter, ambulance-based cohort study was conducted in adults with undifferentiated acute diseases treated by EMS and transferred to the emergency department. Demographic data, prehospital diagnosis data, prehospital medication and variables for the calculation of the National Early Warning Score 2 (NEWS2), Rapid Emergency Medicine Score (REMS), and Rapid Acute Physiology Score (RAPS) were collected. The PDDS was developed and validated, establishing three levels of risk of 2-day mortality. The predictive capability of each score was determined by the area under the curve of the receiver operating characteristic curve (AUROC) and compared using the Delong's test (p-value).
Results
A total of 6401 patients were included. The PDDS included age and the use of norepinephrine, analgesics, neuromuscular blocking agents, diuretics, antihypertensive agents, tranexamic acid, and bicarbonate. The AUROC of PDDS was .86 (95% CI: .816–.903) versus NEWS2 .866 (95% CI: .822–.911), p = .828; versus REMS .885 (95% CI: .845–.924), p = .311; versus RAPS .886 (95% CI: .846–.926), p = .335, respectively.
Conclusion
The newly developed easy-to-use prehospital drug-derived PDDS score has an excellent predictive value of early mortality. The PDDS score was comparable to the conventional risk scores and therefore might serve as an alternative score in the prehospital emergency setting.
{"title":"A newly developed, easy-to-use prehospital drug-derived score compared with three conventional scores: A prospective multicenter study","authors":"Jesús Jurado-Palomo, José Luis Martin-Conty, Begoña Polonio-López, Juan J. Bernal-Jiménez, Rosa Conty-Serrano, Michele Dileone, Miguel A. Castro Villamor, Carlos del Pozo Vegas, Raúl López-Izquierdo, Cristina Rivera-Picón, Francisco Martín-Rodríguez, Ancor Sanz-García","doi":"10.1111/eci.14329","DOIUrl":"10.1111/eci.14329","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The use of medications by emergency medical services (EMS) is increasing. Conventional scores are time-consuming and therefore difficult to use in an emergency setting. For early decision-making, an easy-to-use score based on the medications administered by the EMS may have prognostic value. The primary objective of this study was to develop the prehospital drug-derived score (PDDS) for 2-day mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prospective, multicenter, ambulance-based cohort study was conducted in adults with undifferentiated acute diseases treated by EMS and transferred to the emergency department. Demographic data, prehospital diagnosis data, prehospital medication and variables for the calculation of the National Early Warning Score 2 (NEWS2), Rapid Emergency Medicine Score (REMS), and Rapid Acute Physiology Score (RAPS) were collected. The PDDS was developed and validated, establishing three levels of risk of 2-day mortality. The predictive capability of each score was determined by the area under the curve of the receiver operating characteristic curve (AUROC) and compared using the Delong's test (<i>p</i>-value).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 6401 patients were included. The PDDS included age and the use of norepinephrine, analgesics, neuromuscular blocking agents, diuretics, antihypertensive agents, tranexamic acid, and bicarbonate. The AUROC of PDDS was .86 (95% CI: .816–.903) versus NEWS2 .866 (95% CI: .822–.911), <i>p</i> = .828; versus REMS .885 (95% CI: .845–.924), <i>p</i> = .311; versus RAPS .886 (95% CI: .846–.926), <i>p</i> = .335, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The newly developed easy-to-use prehospital drug-derived PDDS score has an excellent predictive value of early mortality. The PDDS score was comparable to the conventional risk scores and therefore might serve as an alternative score in the prehospital emergency setting.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valerie Dicenta-Baunach, Zoi Laspa, David Schaale, Manuel Sigle, Alp Bayrak, Tatsiana Castor, Thanigaimalai Pillaiyar, Stefan Laufer, Meinrad Paul Gawaz, Anne-Katrin Rohlfing
Background
Platelet receptors ACKR3 and CXCR4 play a crucial role in a variety of cardiovascular diseases. Like most chemokine receptors, CXCR4 is a G protein coupled receptor that induces platelet activation. In contrast, the atypical chemokine receptor 3 (ACKR3) lacks the ability to activate heterotrimeric G proteins and its activation leads to platelet inhibition and attenuates thrombus formation. In nucleated cells, heterodimerization of ACKR3 with CXCR4 regulates CXCL12-dependent signalling. The aim of our study was to investigate the formation of ACKR3/CXCR4 heterodimers in platelets and the subsequent consequences for platelet function.
Methods and Results
Using a proximity ligation assay (PLA, Duolink®) to screen for CXCR4/ACKR3 heterodimerization inducing compounds, we found that ACKR3 agonism but not conventional platelet agonists or endogen ligands lead to heterodimer formation. To further characterize the formation of ACKR3/CXCR4 heterodimers, we studied the CXCL12-dependent platelet activation via CXCR4. Both, CXCL12-dependent platelet aggregation and collagen-dependent ex vivo thrombus formation were significantly downregulated by ACKR3 agonism. Moreover, platelet intracellular calcium and Akt signalling were increased by CXCL12 and again suppressed by ACKR3-specific agonists. Previously, CXCL12 was shown to decrease platelet cAMP levels via CXCR4. Treatment with a specific ACKR3 agonist counteracted this CXCL12/CXCR4-dependent cAMP decrease.
Conclusion
Our results reveal that the formation of platelet ACKR3/CXCR4 heterodimers is dependent on ACKR3 rather than CXCR4. Furthermore, ACKR3 agonism induced heterodimerization is associated with mitigating CXCL12/CXCR4-dependent platelet activation possibly by modulating CXCR4-dependent G protein signalling. Our results indicate possible ACKR3 agonist functions and reinforce the potential therapeutic applications of ACKR3 agonists.
{"title":"ACKR3 agonism induces heterodimerization with chemokine receptor CXCR4 and attenuates platelet function","authors":"Valerie Dicenta-Baunach, Zoi Laspa, David Schaale, Manuel Sigle, Alp Bayrak, Tatsiana Castor, Thanigaimalai Pillaiyar, Stefan Laufer, Meinrad Paul Gawaz, Anne-Katrin Rohlfing","doi":"10.1111/eci.14327","DOIUrl":"10.1111/eci.14327","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Platelet receptors ACKR3 and CXCR4 play a crucial role in a variety of cardiovascular diseases. Like most chemokine receptors, CXCR4 is a G protein coupled receptor that induces platelet activation. In contrast, the atypical chemokine receptor 3 (ACKR3) lacks the ability to activate heterotrimeric G proteins and its activation leads to platelet inhibition and attenuates thrombus formation. In nucleated cells, heterodimerization of ACKR3 with CXCR4 regulates CXCL12-dependent signalling. The aim of our study was to investigate the formation of ACKR3/CXCR4 heterodimers in platelets and the subsequent consequences for platelet function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Using a proximity ligation assay (PLA, Duolink®) to screen for CXCR4/ACKR3 heterodimerization inducing compounds, we found that ACKR3 agonism but not conventional platelet agonists or endogen ligands lead to heterodimer formation. To further characterize the formation of ACKR3/CXCR4 heterodimers, we studied the CXCL12-dependent platelet activation via CXCR4. Both, CXCL12-dependent platelet aggregation and collagen-dependent ex vivo thrombus formation were significantly downregulated by ACKR3 agonism. Moreover, platelet intracellular calcium and Akt signalling were increased by CXCL12 and again suppressed by ACKR3-specific agonists. Previously, CXCL12 was shown to decrease platelet cAMP levels via CXCR4. Treatment with a specific ACKR3 agonist counteracted this CXCL12/CXCR4-dependent cAMP decrease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results reveal that the formation of platelet ACKR3/CXCR4 heterodimers is dependent on ACKR3 rather than CXCR4. Furthermore, ACKR3 agonism induced heterodimerization is associated with mitigating CXCL12/CXCR4-dependent platelet activation possibly by modulating CXCR4-dependent G protein signalling. Our results indicate possible ACKR3 agonist functions and reinforce the potential therapeutic applications of ACKR3 agonists.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380339","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}
Antonio Gallo, Wilfried Le Goff, Raul D. Santos, Isabella Fichtner, Stefano Carugo, Alberto Corsini, Cesare Sirtori, Massimiliano Ruscica
Background
Maintaining low concentrations of plasma low-density lipoprotein cholesterol (LDLc) over time decreases the number of LDL particles trapped within the artery wall, slows the progression of atherosclerosis and delays the age at which mature atherosclerotic plaques develop. This substantially reduces the lifetime risk of atherosclerotic cardiovascular disease (ASCVD) events. In this context, plaque development and vulnerability result not only from lipid accumulation but also from inflammation.
Results
Changes in the composition of immune cells, including macrophages, dendritic cells, T cells, B cells, mast cells and neutrophils, along with altered cytokine and chemokine release, disrupt the equilibrium between inflammation and anti-inflammatory mechanisms at plaque sites. Considering that it is not a competition between LDLc and inflammation, but instead that they are partners in crime, the present narrative review aims to give an overview of the main inflammatory molecular pathways linked to raised LDLc concentrations and to describe the impact of lipid-lowering approaches on the inflammatory and lipid burden. Although remarkable changes in LDLc are driven by the most recent lipid lowering combinations, the relative reduction in plasma C-reactive protein appears to be independent of the magnitude of LDLc lowering.
Conclusion
Identifying clinical biomarkers of inflammation (e.g. interleukin-6) and possible targets for therapy holds promise for monitoring and reducing the ASCVD burden in suitable patients.
{"title":"Hypercholesterolemia and inflammation—Cooperative cardiovascular risk factors","authors":"Antonio Gallo, Wilfried Le Goff, Raul D. Santos, Isabella Fichtner, Stefano Carugo, Alberto Corsini, Cesare Sirtori, Massimiliano Ruscica","doi":"10.1111/eci.14326","DOIUrl":"10.1111/eci.14326","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Maintaining low concentrations of plasma low-density lipoprotein cholesterol (LDLc) over time decreases the number of LDL particles trapped within the artery wall, slows the progression of atherosclerosis and delays the age at which mature atherosclerotic plaques develop. This substantially reduces the lifetime risk of atherosclerotic cardiovascular disease (ASCVD) events. In this context, plaque development and vulnerability result not only from lipid accumulation but also from inflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Changes in the composition of immune cells, including macrophages, dendritic cells, T cells, B cells, mast cells and neutrophils, along with altered cytokine and chemokine release, disrupt the equilibrium between inflammation and anti-inflammatory mechanisms at plaque sites. Considering that it is not a competition between LDLc and inflammation, but instead that they are partners in crime, the present narrative review aims to give an overview of the main inflammatory molecular pathways linked to raised LDLc concentrations and to describe the impact of lipid-lowering approaches on the inflammatory and lipid burden. Although remarkable changes in LDLc are driven by the most recent lipid lowering combinations, the relative reduction in plasma C-reactive protein appears to be independent of the magnitude of LDLc lowering.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Identifying clinical biomarkers of inflammation (e.g. interleukin-6) and possible targets for therapy holds promise for monitoring and reducing the ASCVD burden in suitable patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380340","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}
Fabian Starnecker, J. J. Coughlan, Lisette Okkels Jensen, Sarah Bär, Sebastian Kufner, Salvatore Brugaletta, Lorenz Räber, Michael Maeng, Luis Ortega-Paz, Dik Heg, Karl-Ludwig Laugwitz, Manel Sabaté, Stephan Windecker, Adnan Kastrati, Kevin Kris Warnakula Olesen, Salvatore Cassese
Background
Investigations of very long-term outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) according to clinical presentation are scarce. Here, we investigated the 10-year clinical outcomes of patients undergoing DES-PCI according to clinical presentation.
Methods
Patient-level data from five randomized trials with 10-year follow-up after DES-PCI were pooled. Patients were dichotomized into acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) groups as per clinical presentation. The primary outcome was all-cause death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST) and repeat revascularization involving the target lesion (TLR), target vessel (TVR) or non-target vessel (nTVR).
Results
Of the 9700 patients included in this analysis, 4557 presented with ACS and 5143 with CCS. Compared with CCS patients, ACS patients had a higher risk of all-cause death and nTVR in the first year, but comparable risk thereafter. In addition, ACS patients had a higher risk of MI [adjusted hazard ratio 1.21, 95% confidence interval (1.04–1.41)] and definite ST [adjusted hazard ratio 1.48, 95% confidence interval (1.14–1.92)], while the risk of TLR and TVR was not significantly different up to 10-year follow-up.
Conclusions
Compared to CCS patients, ACS patients treated with PCI and DES implantation have an increased risk of all-cause death and repeat revascularization of remote vessels up to 1 year, with no significant differences thereafter and up to 10-year follow-up. ACS patients have a consistently higher risk of MI and definite ST. Whether these differences persist with current antithrombotic and secondary prevention therapies requires further investigation.
{"title":"Ten-year clinical outcomes after drug-eluting stents implantation according to clinical presentation—Insights from the DECADE cooperation","authors":"Fabian Starnecker, J. J. Coughlan, Lisette Okkels Jensen, Sarah Bär, Sebastian Kufner, Salvatore Brugaletta, Lorenz Räber, Michael Maeng, Luis Ortega-Paz, Dik Heg, Karl-Ludwig Laugwitz, Manel Sabaté, Stephan Windecker, Adnan Kastrati, Kevin Kris Warnakula Olesen, Salvatore Cassese","doi":"10.1111/eci.14323","DOIUrl":"10.1111/eci.14323","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Investigations of very long-term outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) according to clinical presentation are scarce. Here, we investigated the 10-year clinical outcomes of patients undergoing DES-PCI according to clinical presentation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patient-level data from five randomized trials with 10-year follow-up after DES-PCI were pooled. Patients were dichotomized into acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) groups as per clinical presentation. The primary outcome was all-cause death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST) and repeat revascularization involving the target lesion (TLR), target vessel (TVR) or non-target vessel (nTVR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 9700 patients included in this analysis, 4557 presented with ACS and 5143 with CCS. Compared with CCS patients, ACS patients had a higher risk of all-cause death and nTVR in the first year, but comparable risk thereafter. In addition, ACS patients had a higher risk of MI [adjusted hazard ratio 1.21, 95% confidence interval (1.04–1.41)] and definite ST [adjusted hazard ratio 1.48, 95% confidence interval (1.14–1.92)], while the risk of TLR and TVR was not significantly different up to 10-year follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Compared to CCS patients, ACS patients treated with PCI and DES implantation have an increased risk of all-cause death and repeat revascularization of remote vessels up to 1 year, with no significant differences thereafter and up to 10-year follow-up. ACS patients have a consistently higher risk of MI and definite ST. Whether these differences persist with current antithrombotic and secondary prevention therapies requires further investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344182","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}
Jan Gerrit van der Stouwe, Konstantin Godly, Simon Kraler, Julia Godly, Christian M. Matter, Florian A. Wenzl, Arnold von Eckardstein, Lorenz Räber, François Mach, Slayman Obeid, Christian Templin, Thomas F. Lüscher, David Niederseer, the SPUM-ACS investigators
Background
Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low-cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS.
Methods
From 2012 until 2017, a total of 1044 ACS patients, 517 with STEMI and 527 with NSTE-ACS, were prospectively recruited at the University Hospital Zurich. BT was measured by digital tympanic thermometer along with high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin-T (hs-cTnT) levels prior to coronary angiography. Patients were stratified according to initial BT and uni- and multivariable regression models were fit to assess associations of BT with future MACE risk.
Results
Among patients with STEMI, BT was not predictive of 1-year MACE, but a U-shaped relationship between BT and MACE risk was noted in those with NSTE-ACS (p = .029), translating into a 2.4-fold (HR, 2.44, 95% CI, 1.16–5.16) increased 1-year MACE risk in those with BT >36.8°C (reference: 36.6–36.8°C). Results remained robust in multivariable-adjusted analyses accounting for sex, age, diabetes, renal function and hs-cTnT. However, when introducing hs-CRP, the BT-MACE association did not prevail.
Conclusions
In prospectively recruited patients with ACS, initial BT shows a U-shaped relationship with 1-year MACE risk among those with NSTE-ACS, but not in those with STEMI. BT is a broadly available low-cost marker to identify ACS patients with high inflammatory burden, at high risk for recurrent ischaemic events, and thus potentially suitable for an anti-inflammatory intervention.
{"title":"Body temperature, systemic inflammation and risk of adverse events in patients with acute coronary syndromes","authors":"Jan Gerrit van der Stouwe, Konstantin Godly, Simon Kraler, Julia Godly, Christian M. Matter, Florian A. Wenzl, Arnold von Eckardstein, Lorenz Räber, François Mach, Slayman Obeid, Christian Templin, Thomas F. Lüscher, David Niederseer, the SPUM-ACS investigators","doi":"10.1111/eci.14314","DOIUrl":"10.1111/eci.14314","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low-cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From 2012 until 2017, a total of 1044 ACS patients, 517 with STEMI and 527 with NSTE-ACS, were prospectively recruited at the University Hospital Zurich. BT was measured by digital tympanic thermometer along with high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin-T (hs-cTnT) levels prior to coronary angiography. Patients were stratified according to initial BT and uni- and multivariable regression models were fit to assess associations of BT with future MACE risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among patients with STEMI, BT was not predictive of 1-year MACE, but a <i>U</i>-shaped relationship between BT and MACE risk was noted in those with NSTE-ACS (<i>p</i> = .029), translating into a 2.4-fold (HR, 2.44, 95% CI, 1.16–5.16) increased 1-year MACE risk in those with BT >36.8°C (reference: 36.6–36.8°C). Results remained robust in multivariable-adjusted analyses accounting for sex, age, diabetes, renal function and hs-cTnT. However, when introducing hs-CRP, the BT-MACE association did not prevail.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In prospectively recruited patients with ACS, initial BT shows a <i>U</i>-shaped relationship with 1-year MACE risk among those with NSTE-ACS, but not in those with STEMI. BT is a broadly available low-cost marker to identify ACS patients with high inflammatory burden, at high risk for recurrent ischaemic events, and thus potentially suitable for an anti-inflammatory intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Registration</h3>\u0000 \u0000 <p>ClinicalTrials.gov Identifier: NCT01000701.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 12","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.14314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344179","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}
Katharina Burger, Finn Jung, Raphaela Staltner, Katja Csarmann, Kerstin Schweiger, Annette Brandt, Anja Baumann, Julia Scholda, Florian Kopp, Ina Bergheim
Background
4-methylpyrazole (4MP, fomepizole) is a competitive inhibitor of alcohol dehydrogenase (ADH) preventing the metabolism of ethylene glycol and methanol, respectively, into their toxic metabolites. 4MP seems also to possess a potential in the treatment of intoxication from other substance, for example, acetaminophen, and to modulate JNK-dependent signalling. Here, we determined if a treatment with 4MP once weekly affects the development of diet-induced non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) in C57BL/6 mice.
Methods
Male C57BL/6 mice (6–8 weeks old, n = 7-8/group) were pair-fed either a liquid control diet (C) or a liquid sucrose-, fat- and cholesterol-rich diet (SFC) for 8 weeks while being concomitantly treated with 4MP (50 mg/kg bw i.p.) or vehicle once a week. Liver damage, inflammatory markers and glucose tolerance were assessed. Moreover, in endotoxin-challenged J774A.1 cells pretreated with 4MP, pro-inflammatory markers were assessed.
Results
The concomitant treatment of SFC-fed mice with 4MP attenuated the increase in JNK phosphorylation and pro-inflammatory markers like IFNγ, IL-6 and 3-nitrotyrosine protein adducts in liver tissue found in vehicle-treated SFC-fed mice, while not affecting impairments of glucose tolerance or the increase in portal endotoxin levels. Moreover, a pretreatment of endotoxin-stimulated J774A.1 cells with 4MP significantly attenuated the increases in JNK phosphorylation and pro-inflammatory mediators like IL-6 and Mcp1.
Conclusions
Taken together, our results suggest that a treatment with 4MP once weekly attenuates the activation of JNK and dampens the development of non-obese MASLD in mice.
{"title":"A weekly 4-methylpyrazole treatment attenuates the development of non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) in male mice: Role of JNK","authors":"Katharina Burger, Finn Jung, Raphaela Staltner, Katja Csarmann, Kerstin Schweiger, Annette Brandt, Anja Baumann, Julia Scholda, Florian Kopp, Ina Bergheim","doi":"10.1111/eci.14320","DOIUrl":"10.1111/eci.14320","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>4-methylpyrazole (4MP, fomepizole) is a competitive inhibitor of alcohol dehydrogenase (ADH) preventing the metabolism of ethylene glycol and methanol, respectively, into their toxic metabolites. 4MP seems also to possess a potential in the treatment of intoxication from other substance, for example, acetaminophen, and to modulate JNK-dependent signalling. Here, we determined if a treatment with 4MP once weekly affects the development of diet-induced non-obese metabolic dysfunction-associated steatotic liver disease (MASLD) in C57BL/6 mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male C57BL/6 mice (6–8 weeks old, <i>n</i> = 7-8/group) were pair-fed either a liquid control diet (C) or a liquid sucrose-, fat- and cholesterol-rich diet (SFC) for 8 weeks while being concomitantly treated with 4MP (50 mg/kg bw i.p.) or vehicle once a week. Liver damage, inflammatory markers and glucose tolerance were assessed. Moreover, in endotoxin-challenged J774A.1 cells pretreated with 4MP, pro-inflammatory markers were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The concomitant treatment of SFC-fed mice with 4MP attenuated the increase in JNK phosphorylation and pro-inflammatory markers like IFNγ, IL-6 and 3-nitrotyrosine protein adducts in liver tissue found in vehicle-treated SFC-fed mice, while not affecting impairments of glucose tolerance or the increase in portal endotoxin levels. Moreover, a pretreatment of endotoxin-stimulated J774A.1 cells with 4MP significantly attenuated the increases in JNK phosphorylation and pro-inflammatory mediators like IL-6 and <i>Mcp1</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Taken together, our results suggest that a treatment with 4MP once weekly attenuates the activation of JNK and dampens the development of non-obese MASLD in mice.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344177","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}
The contribution of SARS-CoV-2 infection on lung damage and the effect of vaccination on either containing the number of deaths or mitigating lung damage has not been systematically investigated.
Methods
Post-mortem analysis was performed among consecutive in-patients with COVID-19 deceased in the Province of Trieste (2020–2022). The outcomes of the study were (i) rates of in-hospital mortality, (ii) contribution of COVID-19 to death, (iii) histological extent of lung injury and (iv) impact of vaccination.
Results
A total of 1038 consecutive hospitalized patients who died with SARS-CoV-2 infection were autopsied and deep histological analysis of the lungs was performed in a randomly selected sample of 508 cases. Among them, SARS-CoV-2 infection was (a) the cause of death (n = 90), (b) contributing to death (n = 304) and (c) an accompanying feature (n = 114). The incidence of SARS-CoV-2 infection as the primary cause of mortality decreased over time (23.8% in 2020, 20.9% in 2021 and 7.9% in 2022). On multivariable analysis, vaccination (any dose) was independently associated with lower rates of death related to SARS-CoV-2 infection (HR .15, p < .001), after adjusting for other independent predictors. A total of 172 patients were vaccinated at least with two doses at the time of death: 93% triple-vaccinated, 7% double-vaccinated. On histological analysis, vaccinated patients had a greater frequency of pneumonia severity score 0 and 1 (20.3% vs. 5.4% and 20.9% vs. 7.7%, p < .001, respectively), and a substantially lower proportion of pneumonia severity score 3 (26.2% vs. 55.1%, p < .001) compared to unvaccinated patients.
Conclusions
COVID-19 vaccination has substantially reduced rates of death related to SARS-CoV-2 infection over time and may have the ability to mitigate lung damage.
{"title":"Lung damage in SARS-CoV-2 patients: An autopsy study in the era of vaccination","authors":"Rossana Bussani, Aldostefano Porcari, Maurizio Pinamonti, Anthea Iacobucci, Eleonora Belladonna, Ariella Tomasini, Fabrizio Zanconati, Chiara Collesi, Mauro Giacca, Giorgio Berlot, Gianfranco Sinagra, Furio Silvestri","doi":"10.1111/eci.14325","DOIUrl":"10.1111/eci.14325","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The contribution of SARS-CoV-2 infection on lung damage and the effect of vaccination on either containing the number of deaths or mitigating lung damage has not been systematically investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Post-mortem analysis was performed among consecutive in-patients with COVID-19 deceased in the Province of Trieste (2020–2022). The outcomes of the study were (i) rates of in-hospital mortality, (ii) contribution of COVID-19 to death, (iii) histological extent of lung injury and (iv) impact of vaccination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1038 consecutive hospitalized patients who died with SARS-CoV-2 infection were autopsied and deep histological analysis of the lungs was performed in a randomly selected sample of 508 cases. Among them, SARS-CoV-2 infection was (a) the cause of death (<i>n</i> = 90), (b) contributing to death (<i>n</i> = 304) and (c) an accompanying feature (<i>n</i> = 114). The incidence of SARS-CoV-2 infection as the primary cause of mortality decreased over time (23.8% in 2020, 20.9% in 2021 and 7.9% in 2022). On multivariable analysis, vaccination (any dose) was independently associated with lower rates of death related to SARS-CoV-2 infection (HR .15, <i>p</i> < .001), after adjusting for other independent predictors. A total of 172 patients were vaccinated at least with two doses at the time of death: 93% triple-vaccinated, 7% double-vaccinated. On histological analysis, vaccinated patients had a greater frequency of pneumonia severity score 0 and 1 (20.3% vs. 5.4% and 20.9% vs. 7.7%, <i>p</i> < .001, respectively), and a substantially lower proportion of pneumonia severity score 3 (26.2% vs. 55.1%, <i>p</i> < .001) compared to unvaccinated patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>COVID-19 vaccination has substantially reduced rates of death related to SARS-CoV-2 infection over time and may have the ability to mitigate lung damage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344181","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}
Although the risk of depression is well-known in the patients with kidney dysfunction, especially at the late stages, little is known about the exact point at which the decline in estimated glomerular filtration rate (eGFR) begins to significantly increase the risk of depression. In the present study, we analysed a nationwide epidemiological dataset to investigate the dose-dependent association between baseline eGFR and a future risk of developing depression in a general population.
Methods
We retrospectively analysed 1,518,885 individuals (male: 46.3%) without a history of depression identified between April 2014 and November 2022 within a nationwide epidemiological database, provided by DeSC Healthcare (Tokyo, Japan). We investigated the association of eGFR with the incidence of depression using Cox regression analyses and also conducted cubic spline analysis to investigate the dose-dependent association between eGFR and depression.
Results
In the mean follow-up of 1218 ± 693 days, 45,878 cases (3.0% for total participants, 2.6% for men and 3.3% for women) of depression were recorded. The risk of depression increased with the eGFR decline as well as the presence of proteinuria. Multivariable Cox regression analysis showed the hazard ratio (95% CI) of depression in each kidney function category (eGFR ≥90, 60–89, 45–59, 30–44, 15–29, and < 15 mL/min/1.73 m2) was 1.14 (1.11–1.17), 1 (reference), 1.11 (1.08–1.14), 1.51 (1.43–1.59), 1.77 (1.57–1.99) and 1.77 (1.26–2.50), respectively. In the cubic spline analysis, the risk of depression continued to increase monotonically as the eGFR declined when the eGFR fell below approximately 65 mL/min/1.73 m2.
Conclusions
Our analysis using a large-scale epidemiological dataset presented the dose-dependent association between eGFR decline and the risk of depression, which highlights the importance of incorporating mental health assessments into the routine care of patients with kidney dysfunction, regardless of the stage of their disease.
{"title":"Dose-dependent association between estimated glomerular filtration rate and the subsequent risk of depression: An analysis of a nationwide epidemiological dataset","authors":"Toshiyuki Ko, Hidehiro Kaneko, Yuta Suzuki, Akira Okada, Tatsuhiko Azegami, Katsuhito Fujiu, Norifumi Takeda, Hiroyuki Morita, Takashi Yokoo, Kaori Hayashi, Issei Komuro, Hideo Yasunaga, Masaomi Nangaku, Norihiko Takeda","doi":"10.1111/eci.14322","DOIUrl":"10.1111/eci.14322","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although the risk of depression is well-known in the patients with kidney dysfunction, especially at the late stages, little is known about the exact point at which the decline in estimated glomerular filtration rate (eGFR) begins to significantly increase the risk of depression. In the present study, we analysed a nationwide epidemiological dataset to investigate the dose-dependent association between baseline eGFR and a future risk of developing depression in a general population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively analysed 1,518,885 individuals (male: 46.3%) without a history of depression identified between April 2014 and November 2022 within a nationwide epidemiological database, provided by DeSC Healthcare (Tokyo, Japan). We investigated the association of eGFR with the incidence of depression using Cox regression analyses and also conducted cubic spline analysis to investigate the dose-dependent association between eGFR and depression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the mean follow-up of 1218 ± 693 days, 45,878 cases (3.0% for total participants, 2.6% for men and 3.3% for women) of depression were recorded. The risk of depression increased with the eGFR decline as well as the presence of proteinuria. Multivariable Cox regression analysis showed the hazard ratio (95% CI) of depression in each kidney function category (eGFR ≥90, 60–89, 45–59, 30–44, 15–29, and < 15 mL/min/1.73 m<sup>2</sup>) was 1.14 (1.11–1.17), 1 (reference), 1.11 (1.08–1.14), 1.51 (1.43–1.59), 1.77 (1.57–1.99) and 1.77 (1.26–2.50), respectively. In the cubic spline analysis, the risk of depression continued to increase monotonically as the eGFR declined when the eGFR fell below approximately 65 mL/min/1.73 m<sup>2</sup>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our analysis using a large-scale epidemiological dataset presented the dose-dependent association between eGFR decline and the risk of depression, which highlights the importance of incorporating mental health assessments into the routine care of patients with kidney dysfunction, regardless of the stage of their disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344180","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}
Mehmet Kanbay, Mustafa Guldan, Lasin Ozbek, Sidar Copur, Francesca Mallamaci, Carmine Zoccali
Background
Shared anatomical, histological and physiological pathways between the kidney and the eye are well documented, demonstrating that ocular manifestations serve as valuable prognostic indicators in chronic kidney disease (CKD), providing insights into disease severity and progression. Through non-invasive imaging modalities such as retinal fundus photography, early retinal microvascular alterations indicative of CKD progression can be detected, enabling timely intervention and risk stratification. However, the conclusions drawn from the review primarily demonstrate a strong or independent association between glaucoma or retinopathy and CKD.
Results and Conclusion
Multiple shared pathophysiological events have been implicated in the pathogenesis in the alterations at eye and kidney including renin-angiotensin-aldosterone system. Patients with CKD are more likely to experience glaucoma, age-related macular degeneration, cataracts, uremic optic neuropathy and retinopathy. To establish the role of ocular manifestations in predicting CKD progression, it is crucial to address the limitations of correlation and explore the underlying causality with further research on common disease pathogenesis. Additionally, specific methods for risk stratification based on retinal changes, the effectiveness of timely interventions, and the development of predictive tools combining ocular and renal data are of utmost importance research topics to enlighten the bidirectional causality.
{"title":"Unveiling the intricacies of chronic kidney disease: From ocular manifestations to therapeutic frontiers","authors":"Mehmet Kanbay, Mustafa Guldan, Lasin Ozbek, Sidar Copur, Francesca Mallamaci, Carmine Zoccali","doi":"10.1111/eci.14324","DOIUrl":"10.1111/eci.14324","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Shared anatomical, histological and physiological pathways between the kidney and the eye are well documented, demonstrating that ocular manifestations serve as valuable prognostic indicators in chronic kidney disease (CKD), providing insights into disease severity and progression. Through non-invasive imaging modalities such as retinal fundus photography, early retinal microvascular alterations indicative of CKD progression can be detected, enabling timely intervention and risk stratification. However, the conclusions drawn from the review primarily demonstrate a strong or independent association between glaucoma or retinopathy and CKD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results and Conclusion</h3>\u0000 \u0000 <p>Multiple shared pathophysiological events have been implicated in the pathogenesis in the alterations at eye and kidney including renin-angiotensin-aldosterone system. Patients with CKD are more likely to experience glaucoma, age-related macular degeneration, cataracts, uremic optic neuropathy and retinopathy. To establish the role of ocular manifestations in predicting CKD progression, it is crucial to address the limitations of correlation and explore the underlying causality with further research on common disease pathogenesis. Additionally, specific methods for risk stratification based on retinal changes, the effectiveness of timely interventions, and the development of predictive tools combining ocular and renal data are of utmost importance research topics to enlighten the bidirectional causality.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344183","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}
Jolien Hendrix, Lara Fanning, Arne Wyns, Ishtiaq Ahmed, Madhura Shekhar Patil, Emma Richter, Jente Van Campenhout, Kelly Ickmans, Rembert Mertens, Jo Nijs, Lode Godderis, Andrea Polli
Background
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are comorbid disorders with overlapping symptoms. Research highlights autonomic dysfunction compared to healthy individuals, particularly involving the sympathetic branch. While past reviews focused on neurophysiological assessments, this systematic review summarises biological adrenergic markers, offering deeper insights into the observed sympathetic dysfunction in ME/CFS and FM aiming to identify targetable pathophysiological mechanisms.
Methods
A systematic search was performed on PubMed, Web of Science, Embase and Scopus. Studies investigating peripheral biological markers of adrenergic function in patients with ME/CFS or FM compared to healthy controls at baseline were included. Meta-analyses were performed using R statistical software.
Results
This meta-analysis of 37 studies, encompassing 543 ME/CFS patients and 651 FM patients, compared with 747 and 447 healthy controls, respectively, revealed elevated adrenaline (SMD = .49 [.31–.67]; Z = 5.29, p < .01) and β1 adrenergic receptor expression (SMD = .79 [.06–1.52]; Z = 2.13; p = .03) in blood of ME/CFS patients at rest. Additionally, patients with ME/CFS had a greater increase in the expression of α2A adrenergic receptor (AR, SMD = .57 [.18–.97]; Z = 2.85, p < .01), β2 AR (SMD = .41 [.02–.81]; Z = 2.04; p = .04) and COMT (SMD = .42 [.03–.81]; Z = 2.11; p = .03) after exercise and an increased response of noradrenaline to an orthostatic test (SMD = .11 [−.47 to −.70]; Z = 2.10; p = .04), both found in blood. FM patients showed no significant differences at baseline but exhibited a diminished adrenaline response to exercise (SMD = −.79 [−1.27 to −.30]; Z = −3.14; p < .01).
Conclusion
This systematic review and meta-analysis revealed adrenergic dysfunction mainly in patients with ME/CFS. Higher baseline adrenaline levels and atypical responses to exercise in ME/CFS indicate that sympathetic dysfunction, underscored by adrenergic abnormalities, is more involved in the pathophysiology of ME/CFS rather than FM.
背景：肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）和纤维肌痛（FM）是症状重叠的合并症。与健康人相比，研究强调自律神经功能失调，尤其是涉及交感神经分支的自律神经功能失调。过去的综述侧重于神经生理学评估，而本系统性综述则总结了生物肾上腺素能标记物，对在 ME/CFS 和 FM 中观察到的交感神经功能障碍提供了更深入的见解，旨在确定可针对的病理生理机制：方法：在 PubMed、Web of Science、Embase 和 Scopus 上进行了系统检索。方法：在PubM、Web Science、Embase和Scopus上进行了系统搜索，纳入了调查ME/CFS或FM患者与基线健康对照组相比肾上腺素能功能的外周生物标志物的研究。使用R统计软件进行荟萃分析：该荟萃分析共纳入 37 项研究，包括 543 名 ME/CFS 患者和 651 名 FM 患者，分别与 747 名和 447 名健康对照者进行比较，结果显示肾上腺素升高（SMD = .49 [.31-.67]; Z = 5.29, p 结论：该荟萃分析发现，ME/CFS 患者和 FM 患者的肾上腺素功能与健康对照者存在显著差异：该系统综述和荟萃分析显示，肾上腺素功能障碍主要发生在 ME/CFS 患者身上。ME/CFS患者较高的肾上腺素基线水平和对运动的非典型反应表明，肾上腺素能异常所凸显的交感神经功能障碍在ME/CFS而非FM的病理生理学中占更大比重。
{"title":"Adrenergic dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia: A systematic review and meta-analysis","authors":"Jolien Hendrix, Lara Fanning, Arne Wyns, Ishtiaq Ahmed, Madhura Shekhar Patil, Emma Richter, Jente Van Campenhout, Kelly Ickmans, Rembert Mertens, Jo Nijs, Lode Godderis, Andrea Polli","doi":"10.1111/eci.14318","DOIUrl":"10.1111/eci.14318","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are comorbid disorders with overlapping symptoms. Research highlights autonomic dysfunction compared to healthy individuals, particularly involving the sympathetic branch. While past reviews focused on neurophysiological assessments, this systematic review summarises biological adrenergic markers, offering deeper insights into the observed sympathetic dysfunction in ME/CFS and FM aiming to identify targetable pathophysiological mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic search was performed on PubMed, Web of Science, Embase and Scopus. Studies investigating peripheral biological markers of adrenergic function in patients with ME/CFS or FM compared to healthy controls at baseline were included. Meta-analyses were performed using R statistical software.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This meta-analysis of 37 studies, encompassing 543 ME/CFS patients and 651 FM patients, compared with 747 and 447 healthy controls, respectively, revealed elevated adrenaline (SMD = .49 [.31–.67]; <i>Z</i> = 5.29, <i>p</i> < .01) and β1 adrenergic receptor expression (SMD = .79 [.06–1.52]; <i>Z</i> = 2.13; <i>p</i> = .03) in blood of ME/CFS patients at rest. Additionally, patients with ME/CFS had a greater increase in the expression of α2A adrenergic receptor (AR, SMD = .57 [.18–.97]; <i>Z</i> = 2.85, <i>p</i> < .01), β2 AR (SMD = .41 [.02–.81]; <i>Z</i> = 2.04; <i>p</i> = .04) and COMT (SMD = .42 [.03–.81]; <i>Z</i> = 2.11; <i>p</i> = .03) after exercise and an increased response of noradrenaline to an orthostatic test (SMD = .11 [−.47 to −.70]; <i>Z</i> = 2.10; <i>p</i> = .04), both found in blood. FM patients showed no significant differences at baseline but exhibited a diminished adrenaline response to exercise (SMD = −.79 [−1.27 to −.30]; <i>Z</i> = −3.14; <i>p</i> < .01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This systematic review and meta-analysis revealed adrenergic dysfunction mainly in patients with ME/CFS. Higher baseline adrenaline levels and atypical responses to exercise in ME/CFS indicate that sympathetic dysfunction, underscored by adrenergic abnormalities, is more involved in the pathophysiology of ME/CFS rather than FM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344178","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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