Caecilia S. E. Doorenbos, Adrian Post, Mariken E. Stegmann, Casper F. M. Franssen, Robin P. F. Dullaart, Gerjan Navis, Margery A. Connelly, Stephan J. L. Bakker
Background
Creatine, an endogenous compound essential for energy metabolism and cellular function, has been associated with numerous beneficial effects in sports and overall health. Here, we investigated relationships between plasma creatine concentration, estimated intramuscular creatine concentration, and all-cause mortality in the general population.
Methods
In a Dutch prospective population-based cohort, plasma creatine concentration, 24-h urinary creatinine excretion and muscle mass (assessed with bio-electrical impedance analysis) were measured in 5127 participants. Total creatine pool size, calculated from 24-h creatinine excretion (assuming a 1.7% daily excretion of the total creatine pool), was divided by muscle mass to estimate intramuscular creatine concentrations. Transcellular gradient was calculated as intramuscular concentration divided by plasma concentration. Hazard ratios for mortality per doubling were assessed using multivariable Cox proportional hazard models, adjusting for common cardiovascular risk factors for mortality.
Results
Median plasma creatine concentrations were 41 [30–54] μmol/L in females and 28 [21–38] μmol/L in males. Mean intramuscular creatine concentrations were 30 ± 5.0 mmol/kg in females and 27.4 ± 5.0 mmol/kg in males. Median transcellular creatine gradients were 734 [550–1011] in females and 955 [715–1324] in males. Higher intramuscular creatine concentrations were associated with lower mortality in females (HR (95% CI) = .43 (.2; .66)); with a weaker trend in males (HR (95% CI) = .73 (.53; 1.02)). Plasma creatine concentrations were not associated with mortality.
Conclusion
Higher estimated intramuscular creatine concentrations are strongly associated with lower all-cause mortality in females, with a weaker trend in males. Future research should explore causality, as well as further explore the remarkable sex difference.
{"title":"Plasma creatine, estimated intramuscular creatine, transcellular gradient and the risk of mortality: Results from the PREVEND study","authors":"Caecilia S. E. Doorenbos, Adrian Post, Mariken E. Stegmann, Casper F. M. Franssen, Robin P. F. Dullaart, Gerjan Navis, Margery A. Connelly, Stephan J. L. Bakker","doi":"10.1111/eci.70110","DOIUrl":"10.1111/eci.70110","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Creatine, an endogenous compound essential for energy metabolism and cellular function, has been associated with numerous beneficial effects in sports and overall health. Here, we investigated relationships between plasma creatine concentration, estimated intramuscular creatine concentration, and all-cause mortality in the general population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a Dutch prospective population-based cohort, plasma creatine concentration, 24-h urinary creatinine excretion and muscle mass (assessed with bio-electrical impedance analysis) were measured in 5127 participants. Total creatine pool size, calculated from 24-h creatinine excretion (assuming a 1.7% daily excretion of the total creatine pool), was divided by muscle mass to estimate intramuscular creatine concentrations. Transcellular gradient was calculated as intramuscular concentration divided by plasma concentration. Hazard ratios for mortality per doubling were assessed using multivariable Cox proportional hazard models, adjusting for common cardiovascular risk factors for mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Median plasma creatine concentrations were 41 [30–54] μmol/L in females and 28 [21–38] μmol/L in males. Mean intramuscular creatine concentrations were 30 ± 5.0 mmol/kg in females and 27.4 ± 5.0 mmol/kg in males. Median transcellular creatine gradients were 734 [550–1011] in females and 955 [715–1324] in males. Higher intramuscular creatine concentrations were associated with lower mortality in females (HR (95% CI) = .43 (.2; .66)); with a weaker trend in males (HR (95% CI) = .73 (.53; 1.02)). Plasma creatine concentrations were not associated with mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Higher estimated intramuscular creatine concentrations are strongly associated with lower all-cause mortality in females, with a weaker trend in males. Future research should explore causality, as well as further explore the remarkable sex difference.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12811838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947864","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}
R. Peksöz, E. Ağırman, T. Tavacı, A. S. Topatan, S. Özmen, Z. Kutlu, V. Atış, Z. Halıcı, S. S. Atamanalp
Background
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, characterised by excessive oxidative stress and cytokine release. This study evaluated the protective effects of avasopasem manganese (AVA), a superoxide dismutase mimetic, on sepsis-induced lung injury in a murine model.
Methods
Sepsis was induced in mice via cecal ligation and puncture (CLP). The study included five groups (n = 8/group): Sham (control), CLP (Sepsis) and CLP + AVA at doses of 2.5, 5 or 10 mg/kg. Serum and lung tissue samples were analysed for pro-inflammatory cytokines (tumour necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6), oxidative stress markers (malondialdehyde, MDA) and antioxidant enzyme activity (superoxide dismutase, SOD; glutathione, GSH; catalase, CAT). Quantitative real-time PCR (qRT-PCR) assessed cytokine mRNA expression, while histopathological examination evaluated lung tissue damage.
Results
Serum and lung tissue levels of TNF-α, IL-1β, IL-6 and MDA were lowest in the healthy control group and highest in the sepsis group (p < .001). A significant dose-dependent decrease in cytokine levels was observed with increasing doses of AVA. Regarding antioxidants, SOD, GSH and CAT enzyme activities were highest in the control group and lowest in the sepsis group (p < .05). A significant increase in antioxidant enzyme activity was observed with increasing doses of AVA. In molecular analyses, the expression levels of TNF-α, IL-1β and IL-6 were highest in the sepsis group, while relative messenger RNA (mRNA) expression results changed inversely with the drug dosage. Histopathological analyses revealed inflammation, edema and hyaline membrane formation in the sepsis group, whereas increasing doses of the drug showed improvement in lung tissue.
Conclusions
AVA demonstrated a significant protective effect against sepsis-induced lung injury through its antioxidant and anti-inflammatory properties. The most effective dose was determined to be 10 mg/kg. These findings suggest the potential use of AVA as an adjunctive agent in sepsis treatment.
{"title":"Protective effects of avasopasem manganese (GC4419) against sepsis-induced acute lung injury: A comprehensive experimental study","authors":"R. Peksöz, E. Ağırman, T. Tavacı, A. S. Topatan, S. Özmen, Z. Kutlu, V. Atış, Z. Halıcı, S. S. Atamanalp","doi":"10.1111/eci.70111","DOIUrl":"10.1111/eci.70111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, characterised by excessive oxidative stress and cytokine release. This study evaluated the protective effects of avasopasem manganese (AVA), a superoxide dismutase mimetic, on sepsis-induced lung injury in a murine model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sepsis was induced in mice via cecal ligation and puncture (CLP). The study included five groups (<i>n</i> = 8/group): Sham (control), CLP (Sepsis) and CLP + AVA at doses of 2.5, 5 or 10 mg/kg. Serum and lung tissue samples were analysed for pro-inflammatory cytokines (tumour necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6), oxidative stress markers (malondialdehyde, MDA) and antioxidant enzyme activity (superoxide dismutase, SOD; glutathione, GSH; catalase, CAT). Quantitative real-time PCR (qRT-PCR) assessed cytokine mRNA expression, while histopathological examination evaluated lung tissue damage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Serum and lung tissue levels of TNF-α, IL-1β, IL-6 and MDA were lowest in the healthy control group and highest in the sepsis group (<i>p</i> < .001). A significant dose-dependent decrease in cytokine levels was observed with increasing doses of AVA. Regarding antioxidants, SOD, GSH and CAT enzyme activities were highest in the control group and lowest in the sepsis group (<i>p</i> < .05). A significant increase in antioxidant enzyme activity was observed with increasing doses of AVA. In molecular analyses, the expression levels of TNF-α, IL-1β and IL-6 were highest in the sepsis group, while relative messenger RNA (mRNA) expression results changed inversely with the drug dosage. Histopathological analyses revealed inflammation, edema and hyaline membrane formation in the sepsis group, whereas increasing doses of the drug showed improvement in lung tissue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>AVA demonstrated a significant protective effect against sepsis-induced lung injury through its antioxidant and anti-inflammatory properties. The most effective dose was determined to be 10 mg/kg. These findings suggest the potential use of AVA as an adjunctive agent in sepsis treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Critical reflections on methodological uncertainties and the validity of a study on the association between lung damage in subjects who died from COVID-19 and mRNA vaccines, and on ethical issues of data sharing","authors":"Marco Alessandria, Alberto Donzelli","doi":"10.1111/eci.70109","DOIUrl":"10.1111/eci.70109","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872063","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}
Alan Abboud, Amin Tajerian, Sharon Charles, Michael Clores, Marc Goldschmidt, Olga Aroniadis, Andreas Kalogeropoulos
Background
Data on colorectal cancer (CRC) risk in heart transplant (HT) patients are limited, and screening recommendations specific to this population, especially patients under age 45, are lacking. We aimed to assess the incidence of post-HT CRC, with a focus on the effect of age.
Methods
Using data from the TriNetX Research Network, we identified 4516 adults (≥18 years) who received HT between 1996 and 2024 in the United States, based on CPT codes for HT (33945) and combined lung-HT (33935). CRC was identified from ICD-10 CM codes (C18, C19, & C20). Because mortality was higher than CRC risk, we used a competing risks framework to estimate CRC incidence.
Results
After a median follow-up of 3.6 years (25th–75th percentile, 1.4–6.7), 48 patients developed CRC. Median time from HT to CRC was 4.5 years (.7–8.0). The cumulative incidence of CRC was 1.73% (CI: 1.22%–2.45%) at 10 years, corresponding to 173/100,000 person-years. In comparison, the United States age-adjusted general population rate was 36.5/100,000 between 2016 and 2020. Age at HT was not significantly associated with CRC risk (p = .22); patients age < 45 at HT experienced similar risk as patients ≥45. The CRC risk difference between men and women was not significant (1.89% vs. 1.23% at 10 years; p = .74). All-cause mortality was 20.4% at 5 years and 38.8% at 10 years.
Conclusions
In this HT cohort, CRC risk was markedly higher compared to the general population and did not differ by age, suggesting that HT recipients may require screening for CRC regardless of age.
{"title":"Colorectal cancer in heart transplant recipients: A competing risk analysis","authors":"Alan Abboud, Amin Tajerian, Sharon Charles, Michael Clores, Marc Goldschmidt, Olga Aroniadis, Andreas Kalogeropoulos","doi":"10.1111/eci.70107","DOIUrl":"10.1111/eci.70107","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Data on colorectal cancer (CRC) risk in heart transplant (HT) patients are limited, and screening recommendations specific to this population, especially patients under age 45, are lacking. We aimed to assess the incidence of post-HT CRC, with a focus on the effect of age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using data from the TriNetX Research Network, we identified 4516 adults (≥18 years) who received HT between 1996 and 2024 in the United States, based on CPT codes for HT (33945) and combined lung-HT (33935). CRC was identified from ICD-10 CM codes (C18, C19, & C20). Because mortality was higher than CRC risk, we used a competing risks framework to estimate CRC incidence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After a median follow-up of 3.6 years (25th–75th percentile, 1.4–6.7), 48 patients developed CRC. Median time from HT to CRC was 4.5 years (.7–8.0). The cumulative incidence of CRC was 1.73% (CI: 1.22%–2.45%) at 10 years, corresponding to 173/100,000 person-years. In comparison, the United States age-adjusted general population rate was 36.5/100,000 between 2016 and 2020. Age at HT was not significantly associated with CRC risk (<i>p</i> = .22); patients age < 45 at HT experienced similar risk as patients ≥45. The CRC risk difference between men and women was not significant (1.89% vs. 1.23% at 10 years; <i>p</i> = .74). All-cause mortality was 20.4% at 5 years and 38.8% at 10 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this HT cohort, CRC risk was markedly higher compared to the general population and did not differ by age, suggesting that HT recipients may require screening for CRC regardless of age.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803913","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}
Fernández-Avilés C, Ruiz Ortiz M, Fernández Ruiz A, Heredia Campos G, Resúa Collazo A, González-Manzanares R, Delgado Ortega M, Rodríguez Almodóvar A, Esteban Martínez F, Maestre Luque LC, Morán Salinas A, Torres Zamudio A, Herrera Flores J, Díaz Andrade M, López Aguilera J, Anguita Sánchez M, Pan Álvarez-Osorio M, Mesa Rubio D. Prognostic scores in patients with severe tricuspid regurgitation: An external validation study. Eur J Clin Invest. 2025;55:e14379. doi: 10.1111/eci.14379.
The following affiliations:
1. Cardiology Department, University Hospital Reina Sofia, Córdoba, Spain.
2. Maimonides Institute for Biomedical Research of Córdoba, IMIBIC, Córdoba, Spain.
are incomplete.
These should have read:
1. Cardiology Department, University Hospital Reina Sofia, University of Córdoba, Córdoba, Spain.
2. Maimonides Institute for Biomedical Research of Córdoba, IMIBIC, University of Córdoba, Córdoba, Spain.
{"title":"Correction to “Prognostic Scores in Patients With Severe Tricuspid Regurgitation: An External Validation Study”","authors":"","doi":"10.1111/eci.70105","DOIUrl":"10.1111/eci.70105","url":null,"abstract":"<p>Fernández-Avilés C, Ruiz Ortiz M, Fernández Ruiz A, Heredia Campos G, Resúa Collazo A, González-Manzanares R, Delgado Ortega M, Rodríguez Almodóvar A, Esteban Martínez F, Maestre Luque LC, Morán Salinas A, Torres Zamudio A, Herrera Flores J, Díaz Andrade M, López Aguilera J, Anguita Sánchez M, Pan Álvarez-Osorio M, Mesa Rubio D. Prognostic scores in patients with severe tricuspid regurgitation: An external validation study. <i>Eur J Clin Invest</i>. 2025;55:e14379. doi: 10.1111/eci.14379.</p><p>The following affiliations:</p><p>1. Cardiology Department, University Hospital Reina Sofia, Córdoba, Spain.</p><p>2. Maimonides Institute for Biomedical Research of Córdoba, IMIBIC, Córdoba, Spain.</p><p>are incomplete.</p><p>These should have read:</p><p>1. Cardiology Department, University Hospital Reina Sofia, University of Córdoba, Córdoba, Spain.</p><p>2. Maimonides Institute for Biomedical Research of Córdoba, IMIBIC, University of Córdoba, Córdoba, Spain.</p><p>We apologize for this error.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798556","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 Mascherbauer, Christina Kronberger, Manuel Gruber, Carolina Donà, Matthias Koschutnik, Varius Dannenberg, Michael Poledniczek, Laura Lunzer, Christian Nitsche, Franz Duca, Gregor Heitzinger, Kseniya Halavina, Dietrich Beitzke, Christian Loewe, Michael Trauner, Philipp Bartko, Julia Mascherbauer, Christian Hengstenberg, Andreas Kammerlander, Elisabeth Waldmann
Background
Cardiac magnetic resonance (CMR) derived hepatic T1-time is associated with outcome. However, the interplay between tricuspid regurgitation (TR), which can cause congestive hepatopathy and liver T1-time is unclear.
Methods
We measured hepatic T1-time in CMR all-comers, who underwent echocardiography within 3 weeks of CMR. Kaplan–Meier estimates and Cox regression models were used to investigate the association between hepatic T1-time, TR severity and a composite endpoint of heart failure hospitalisation and all-cause death.
Results
1029 participants (67 ± 17 y/o, 44% female) had a mean hepatic T1-time of 605 ± 79 ms. Overall, 41% (417) presented with non/trace, 38% (391) with mild, 13% (135) with moderate and 8% (85) with severe/massive/torrential TR. Liver T1-time was significantly associated with TR severity (no/trace: 586 ± 72 ms; mild: 601 ± 74 ms; moderate: 634 ± 84 ms; severe/massive/torrential: 665 ± 83 ms; β = 25.4 ms, [95% CI:19.7–31.2, p < .001]). After adjustment for serum NT-proBNP and right ventricular function in a linear regression model, TR severity remained significantly associated with hepatic T1-time (p < .001). During follow-up (mean 53 ± 36 months) 326 (32%) events occurred. Hepatic T1-time (adj.HR 1.69 [95% CI: 1.49–1.92] per 100 ms increase, p < .001) and TR (adj.HR 1.66 [95% CI: 1.49–1.84], p < .001) were both associated with outcome. Even after adjustment for serum NT-proBNP, cardiac structure and function, age, sex and TR severity, hepatic T1-time remained significantly associated with event-free survival (adj.HR 1.42 [95% CI: 1.20–1.68] per 100 ms increase, p < .001).
Conclusion
TR exerts a notable influence on hepatic T1-time. Nevertheless, after adjustment for serum NTproBNP, cardiac function and TR severity, hepatic T1-time still independently predicts outcomes. This underscores the importance of hepatic T1-time both as a marker of TR and prognosis.
{"title":"Association between CMR-derived hepatic T1-time, tricuspid regurgitation and survival","authors":"Katharina Mascherbauer, Christina Kronberger, Manuel Gruber, Carolina Donà, Matthias Koschutnik, Varius Dannenberg, Michael Poledniczek, Laura Lunzer, Christian Nitsche, Franz Duca, Gregor Heitzinger, Kseniya Halavina, Dietrich Beitzke, Christian Loewe, Michael Trauner, Philipp Bartko, Julia Mascherbauer, Christian Hengstenberg, Andreas Kammerlander, Elisabeth Waldmann","doi":"10.1111/eci.70106","DOIUrl":"10.1111/eci.70106","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cardiac magnetic resonance (CMR) derived hepatic T1-time is associated with outcome. However, the interplay between tricuspid regurgitation (TR), which can cause congestive hepatopathy and liver T1-time is unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We measured hepatic T1-time in CMR all-comers, who underwent echocardiography within 3 weeks of CMR. Kaplan–Meier estimates and Cox regression models were used to investigate the association between hepatic T1-time, TR severity and a composite endpoint of heart failure hospitalisation and all-cause death.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>1029 participants (67 ± 17 y/o, 44% female) had a mean hepatic T1-time of 605 ± 79 ms. Overall, 41% (417) presented with non/trace, 38% (391) with mild, 13% (135) with moderate and 8% (85) with severe/massive/torrential TR. Liver T1-time was significantly associated with TR severity (no/trace: 586 ± 72 ms; mild: 601 ± 74 ms; moderate: 634 ± 84 ms; severe/massive/torrential: 665 ± 83 ms; <i>β</i> = 25.4 ms, [95% CI:19.7–31.2, <i>p</i> < .001]). After adjustment for serum NT-proBNP and right ventricular function in a linear regression model, TR severity remained significantly associated with hepatic T1-time (<i>p</i> < .001). During follow-up (mean 53 ± 36 months) 326 (32%) events occurred. Hepatic T1-time (adj.HR 1.69 [95% CI: 1.49–1.92] per 100 ms increase, <i>p</i> < .001) and TR (adj.HR 1.66 [95% CI: 1.49–1.84], <i>p</i> < .001) were both associated with outcome. Even after adjustment for serum NT-proBNP, cardiac structure and function, age, sex and TR severity, hepatic T1-time remained significantly associated with event-free survival (adj.HR 1.42 [95% CI: 1.20–1.68] per 100 ms increase, <i>p</i> < .001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>TR exerts a notable influence on hepatic T1-time. Nevertheless, after adjustment for serum NTproBNP, cardiac function and TR severity, hepatic T1-time still independently predicts outcomes. This underscores the importance of hepatic T1-time both as a marker of TR and prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12811836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803912","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}
Marta Toledano-Fonseca, María Teresa Cano-Osuna, Elena Élez, Javier Soto-Alsar, David Páez, Ana Fernández-Montes, Begoña Graña, Antonieta Salud, Alfonso Yubero, Ismael Macías, Guillermo Quintero, Carlos López-López, Teresa Fernández-Rodríguez, María Victoria García-Ortiz, Javier Sastre, Pilar García-Alfonso, Antonio Rodríguez-Ariza, Enrique Aranda, the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Background
Metastatic colorectal cancer (mCRC) patients who progress on oxaliplatin-based chemotherapy benefit from second-line treatment with FOLFIRI plus the antiangiogenic drug aflibercept. However, the absence of validated biomarkers for antiangiogenic therapies remains a challenge. In this context, we previously reported that combining plasma VEGF-A levels, a circulating microRNA profile, and patient clinical characteristics predicts outcomes in FOLFIRI plus aflibercept treatment. In the present study, we now report biomarkers of response to FOLFIRI plus aflibercept in elderly mCRC patients who progressed after first-line oxaliplatin-based chemotherapy.
Methods
The study included 154 mCRC patients over 70 years of age enrolled in the clinical phase II trial AFEMA. Plasma samples were obtained before FOLFIRI plus aflibercept treatment, and circulating levels of VEGF-A and 13 miRNAs were analysed.
Results
The levels of VEGF-A and five of these 13 miRNAs (miR-193-3b, miR-432-5p, miR-29c-3p, miR-93-5p, miR-30a-3p) enabled the stratification of patients based on progression-free survival and time-to-treatment failure. Specifically, combining miR-29c-3p with VEGF-A improved prognostic accuracy.
Conclusion
Our study underscores the value of integrating miR-29c-3p analysis with VEGF-A as a biomarker strategy to advance the management of elderly mCRC patients receiving FOLFIRI plus aflibercept, improving outcome predictions and enabling more personalised therapeutic strategies.
{"title":"Circulating hsa-miR-29c-3p and VEGF-A levels predict the response to FOLFIRI plus aflibercept in elderly metastatic colorectal cancer patients","authors":"Marta Toledano-Fonseca, María Teresa Cano-Osuna, Elena Élez, Javier Soto-Alsar, David Páez, Ana Fernández-Montes, Begoña Graña, Antonieta Salud, Alfonso Yubero, Ismael Macías, Guillermo Quintero, Carlos López-López, Teresa Fernández-Rodríguez, María Victoria García-Ortiz, Javier Sastre, Pilar García-Alfonso, Antonio Rodríguez-Ariza, Enrique Aranda, the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)","doi":"10.1111/eci.70103","DOIUrl":"10.1111/eci.70103","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Metastatic colorectal cancer (mCRC) patients who progress on oxaliplatin-based chemotherapy benefit from second-line treatment with FOLFIRI plus the antiangiogenic drug aflibercept. However, the absence of validated biomarkers for antiangiogenic therapies remains a challenge. In this context, we previously reported that combining plasma VEGF-A levels, a circulating microRNA profile, and patient clinical characteristics predicts outcomes in FOLFIRI plus aflibercept treatment. In the present study, we now report biomarkers of response to FOLFIRI plus aflibercept in elderly mCRC patients who progressed after first-line oxaliplatin-based chemotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included 154 mCRC patients over 70 years of age enrolled in the clinical phase II trial AFEMA. Plasma samples were obtained before FOLFIRI plus aflibercept treatment, and circulating levels of VEGF-A and 13 miRNAs were analysed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The levels of VEGF-A and five of these 13 miRNAs (miR-193-3b, miR-432-5p, miR-29c-3p, miR-93-5p, miR-30a-3p) enabled the stratification of patients based on progression-free survival and time-to-treatment failure. Specifically, combining miR-29c-3p with VEGF-A improved prognostic accuracy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study underscores the value of integrating miR-29c-3p analysis with VEGF-A as a biomarker strategy to advance the management of elderly mCRC patients receiving FOLFIRI plus aflibercept, improving outcome predictions and enabling more personalised therapeutic strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12811837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759560","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}
Jinhang Che, Yi Wang, Lihong Luo, Yunxiang Tang, Jie Huai, Tao Zeng, Zengzhang Liu
Background
Hypertensive heart disease (HHD) remains a significant global health issue.
Methods
This study analysed the global, regional, and national burden of HHD from 1990 to 2021.
Results
In 2021, the global prevalence, deaths, and disability-adjusted life years (DALYs) associated with HHD were 12.5 million, 1.3 million and 25.5 million, respectively, exhibiting age-standardized percentage changes of 18.2%, −22.0% and −25.8% compared to 1990. Jordan (341.9), Bulgaria (103.4) and Bulgaria (1739.3) had the highest age-standardized prevalence, death and DALY rates, respectively, while Belarus recorded the lowest rates. DALYs reached their zenith in the 70–74 age range, but age-standardized DALY rates were rising in the oldest age group (≥95). A negative correlation was observed between the sociodemographic index and DALY rates. The key risk factors identified were high systolic blood pressure (100%), high BMI (49.3%) and insufficient fruit intake (37.8%).
Conclusion
Although case numbers have increased, age-standardised death and DALY rates have declined since 1990. Targeted prevention strategies should prioritise blood pressure control, weight management and dietary measures to mitigate the burden of HHD.
{"title":"Burden of hypertensive heart disease and its attributable risk factors in 204 countries and territories, 1990–2021: Results from the global burden of disease study 2021","authors":"Jinhang Che, Yi Wang, Lihong Luo, Yunxiang Tang, Jie Huai, Tao Zeng, Zengzhang Liu","doi":"10.1111/eci.70104","DOIUrl":"10.1111/eci.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hypertensive heart disease (HHD) remains a significant global health issue.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study analysed the global, regional, and national burden of HHD from 1990 to 2021.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 2021, the global prevalence, deaths, and disability-adjusted life years (DALYs) associated with HHD were 12.5 million, 1.3 million and 25.5 million, respectively, exhibiting age-standardized percentage changes of 18.2%, −22.0% and −25.8% compared to 1990. Jordan (341.9), Bulgaria (103.4) and Bulgaria (1739.3) had the highest age-standardized prevalence, death and DALY rates, respectively, while Belarus recorded the lowest rates. DALYs reached their zenith in the 70–74 age range, but age-standardized DALY rates were rising in the oldest age group (≥95). A negative correlation was observed between the sociodemographic index and DALY rates. The key risk factors identified were high systolic blood pressure (100%), high BMI (49.3%) and insufficient fruit intake (37.8%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although case numbers have increased, age-standardised death and DALY rates have declined since 1990. Targeted prevention strategies should prioritise blood pressure control, weight management and dietary measures to mitigate the burden of HHD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741723","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}
Giuseppe Armentaro, Valentino Condoleo, Mattea Francica, Giandomenico Severini, Carlo Alberto Pastura, Marcello Divino, Alberto Panza, Marilisa Panza, Filippo Capilupi, Francesco Maruca, Carlo Fuoco, Angela Sciacqua
<div> <section> <h3> Background</h3> <p>Obstructive sleep apnoea (OSA) plays a key role in the pathogenesis of rapid kidney function decline (RKFD). Intermittent hypoxia, oxidative stress, inflammation and endothelial dysfunction cause structural and functional renal damage, leading to chronic kidney disease (CKD). Continuous positive airway pressure (CPAP) treatment potentially prevents these deleterious effects on kidney function.</p> </section> <section> <h3> Purpose</h3> <p>The purpose of this study was to evaluate the potential impact of CPAP therapy on RKFD, defined as annual GFR loss ≥5 mL/min/1.73m<sup>2</sup>, in elderly patients with moderate-to-severe OSA and multiple comorbidities.</p> </section> <section> <h3> Methods</h3> <p>This prospective single-centre observational study enrolled 469 elderly outpatients complaining of excessive daytime sleepiness (ESS) with a new diagnosis of moderate-to-severe OSA. During the enrolment visit, medical history, physical examination and blood samples were collected. A 1-week auto-CPAP trial was performed, and according to compliance, patients were divided into the CPAP group or best medical therapy (BMT) group. Follow-up was conducted as scheduled office visits. A log-rank test compared hazard function estimates between groups, followed by multivariable Cox regression analysis of variables significantly associated with RKFD occurrence.</p> </section> <section> <h3> Results</h3> <p>We enrolled 469 elderly patients: 327 men, 142 women; mean age 74.41 ± 5.33 years. Following a seven-day CPAP titration period, 210 patients demonstrated good adherence (>4 h/night) and continued CPAP therapy, while the remaining 259 received only supportive care. After 20.7 ± 5.5 months of follow-up, 129 (27.5%) renal events were observed: 8.33 events/100 patients/year in the CPAP group versus 18.20 events/100 patients/year in the untreated group (<i>p</i> < .001). The difference in RKFD incidence was statistically significant between groups throughout follow-up (log-rank χ<sup>2</sup>-test <i>p</i> < .001). Multivariable Cox regression analysis indicated CPAP was associated with reduced RKFD risk (HR .376, CI 95% .254–.557, <i>p</i> < .001). SGLT2i therapy reduced risk (HR .293, 95% CI .177–.483, <i>p</i> < .001); atrial fibrillation, type 2 diabetes mellitus and previous TIA/stroke were associated with increased RKFD risk.</p> </section> <section> <h3> Conclusion</h3> <p>These findings confirm CPAP therapy's positive impact in slowing renal damage progression in elderly patients with several comorbidities.</
{"title":"Association between nocturnal continuous positive airway pressure and renal function decline in a cohort of elderly patients with obstructive sleep apnoea syndrome—An observational study","authors":"Giuseppe Armentaro, Valentino Condoleo, Mattea Francica, Giandomenico Severini, Carlo Alberto Pastura, Marcello Divino, Alberto Panza, Marilisa Panza, Filippo Capilupi, Francesco Maruca, Carlo Fuoco, Angela Sciacqua","doi":"10.1111/eci.70098","DOIUrl":"10.1111/eci.70098","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Obstructive sleep apnoea (OSA) plays a key role in the pathogenesis of rapid kidney function decline (RKFD). Intermittent hypoxia, oxidative stress, inflammation and endothelial dysfunction cause structural and functional renal damage, leading to chronic kidney disease (CKD). Continuous positive airway pressure (CPAP) treatment potentially prevents these deleterious effects on kidney function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>The purpose of this study was to evaluate the potential impact of CPAP therapy on RKFD, defined as annual GFR loss ≥5 mL/min/1.73m<sup>2</sup>, in elderly patients with moderate-to-severe OSA and multiple comorbidities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective single-centre observational study enrolled 469 elderly outpatients complaining of excessive daytime sleepiness (ESS) with a new diagnosis of moderate-to-severe OSA. During the enrolment visit, medical history, physical examination and blood samples were collected. A 1-week auto-CPAP trial was performed, and according to compliance, patients were divided into the CPAP group or best medical therapy (BMT) group. Follow-up was conducted as scheduled office visits. A log-rank test compared hazard function estimates between groups, followed by multivariable Cox regression analysis of variables significantly associated with RKFD occurrence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We enrolled 469 elderly patients: 327 men, 142 women; mean age 74.41 ± 5.33 years. Following a seven-day CPAP titration period, 210 patients demonstrated good adherence (>4 h/night) and continued CPAP therapy, while the remaining 259 received only supportive care. After 20.7 ± 5.5 months of follow-up, 129 (27.5%) renal events were observed: 8.33 events/100 patients/year in the CPAP group versus 18.20 events/100 patients/year in the untreated group (<i>p</i> < .001). The difference in RKFD incidence was statistically significant between groups throughout follow-up (log-rank χ<sup>2</sup>-test <i>p</i> < .001). Multivariable Cox regression analysis indicated CPAP was associated with reduced RKFD risk (HR .376, CI 95% .254–.557, <i>p</i> < .001). SGLT2i therapy reduced risk (HR .293, 95% CI .177–.483, <i>p</i> < .001); atrial fibrillation, type 2 diabetes mellitus and previous TIA/stroke were associated with increased RKFD risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings confirm CPAP therapy's positive impact in slowing renal damage progression in elderly patients with several comorbidities.</","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 12","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729042","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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