Yao Du, Yuwen Zeng, Sixin Xu, Qiwei Shen, Jinzhu Hu, Gregory Y. H. Lip
Background
Patients with atrial fibrillation (AF) with end-stage renal failure on renal replacement therapy are at high risk of stroke and bleeding, but the optimal oral anticoagulation (OAC) strategy is uncertain. To investigate the most effective OAC therapy for patients with AF on long-term dialysis.
Methods
PubMed, EMBASE and Web of Science databases were systematically searched from inception to 9 October 2024 to identify relevant studies on OAC strategy for patients with AF on long-term dialysis. The effectiveness outcomes were ischaemic stroke and/or systemic thromboembolism, all-cause mortality and the safety endpoint was major bleeding.
Results
The present study encompassed a comprehensive analysis of 33 studies involving a total of 137,574 patients with AF on long-term dialysis. All OACs, including warfarin (hazard ratio [HR], .963; 95% confidence interval [CI], .841–1.104), did not show a statistically significant decrease in the risk of ischaemic stroke and/or systemic thromboembolism compared to no anticoagulant therapy. Only apixaban 5 mg twice daily was associated with a lower risk of all-cause mortality compared to non-OAC use (HR, .671; 95% CI, .490–.919). Dabigatran (HR, 2.140; 95% CI, 1.734–2.642) and phenprocoumon (HR, 2.419; 95% CI, 1.241–4.713) were associated with a significantly higher risk of major bleeding than non-OAC use.
Conclusions
All OACs were not associated with a reduced risk of ischaemic stroke and/or systemic thromboembolism in patients with AF on long-term dialysis. Only apixaban 5 mg twice daily was associated with a decrease in all-cause mortality when compared with non-OAC use.
{"title":"Oral anticoagulant therapy for patients with atrial fibrillation on long-term dialysis: A network meta-analysis of 137,574 patients","authors":"Yao Du, Yuwen Zeng, Sixin Xu, Qiwei Shen, Jinzhu Hu, Gregory Y. H. Lip","doi":"10.1111/eci.70120","DOIUrl":"10.1111/eci.70120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with atrial fibrillation (AF) with end-stage renal failure on renal replacement therapy are at high risk of stroke and bleeding, but the optimal oral anticoagulation (OAC) strategy is uncertain. To investigate the most effective OAC therapy for patients with AF on long-term dialysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PubMed, EMBASE and Web of Science databases were systematically searched from inception to 9 October 2024 to identify relevant studies on OAC strategy for patients with AF on long-term dialysis. The effectiveness outcomes were ischaemic stroke and/or systemic thromboembolism, all-cause mortality and the safety endpoint was major bleeding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The present study encompassed a comprehensive analysis of 33 studies involving a total of 137,574 patients with AF on long-term dialysis. All OACs, including warfarin (hazard ratio [HR], .963; 95% confidence interval [CI], .841–1.104), did not show a statistically significant decrease in the risk of ischaemic stroke and/or systemic thromboembolism compared to no anticoagulant therapy. Only apixaban 5 mg twice daily was associated with a lower risk of all-cause mortality compared to non-OAC use (HR, .671; 95% CI, .490–.919). Dabigatran (HR, 2.140; 95% CI, 1.734–2.642) and phenprocoumon (HR, 2.419; 95% CI, 1.241–4.713) were associated with a significantly higher risk of major bleeding than non-OAC use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>All OACs were not associated with a reduced risk of ischaemic stroke and/or systemic thromboembolism in patients with AF on long-term dialysis. Only apixaban 5 mg twice daily was associated with a decrease in all-cause mortality when compared with non-OAC use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 12","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014146","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}
Nicolò Gilardi, Massimo Ballabio, Francesco Ravera, Lorenzo Ferrando, Mario Stabile, Andrea Bellodi, Giovanni Talerico, Benedetta Cigolini, Carlo Genova, Federico Carbone, Fabrizio Montecucco, Christian Bracco, Alberto Ballestrero, Gabriele Zoppoli
This pilot study evaluated the influence of medical background on the diagnostic quality of ChatGPT-4's responses in Internal Medicine. Third-year students, residents and specialists summarised five complex NEJM clinical cases before querying ChatGPT-4. Diagnostic ranking, assessed by independent experts, revealed that residents significantly outperformed students (OR 2.33, p = .007); though overall performance was low. These findings indicate that user expertise and concise case summaries are critical for optimising AI diagnostics, highlighting the need for enhanced AI training and user interaction strategies.
本初步研究评估了医学背景对ChatGPT-4在内科诊断质量的影响。在查询ChatGPT-4之前，三年级学生、住院医师和专家总结了五个复杂的NEJM临床病例。由独立专家评估的诊断排名显示，住院医生的表现明显优于学生（OR 2.33, p = .007）；尽管整体表现不佳。这些发现表明，用户专业知识和简明的案例摘要对于优化人工智能诊断至关重要，强调了加强人工智能培训和用户交互策略的必要性。
{"title":"Influence of medical educational background on the diagnostic quality of ChatGPT-4 responses in internal medicine: A pilot study","authors":"Nicolò Gilardi, Massimo Ballabio, Francesco Ravera, Lorenzo Ferrando, Mario Stabile, Andrea Bellodi, Giovanni Talerico, Benedetta Cigolini, Carlo Genova, Federico Carbone, Fabrizio Montecucco, Christian Bracco, Alberto Ballestrero, Gabriele Zoppoli","doi":"10.1111/eci.70113","DOIUrl":"10.1111/eci.70113","url":null,"abstract":"<p>This pilot study evaluated the influence of medical background on the diagnostic quality of ChatGPT-4's responses in Internal Medicine. Third-year students, residents and specialists summarised five complex NEJM clinical cases before querying ChatGPT-4. Diagnostic ranking, assessed by independent experts, revealed that residents significantly outperformed students (OR 2.33, <i>p</i> = .007); though overall performance was low. These findings indicate that user expertise and concise case summaries are critical for optimising AI diagnostics, highlighting the need for enhanced AI training and user interaction strategies.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023036","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}
Marco Tomasino, Ravi Vazirani, Jorge Salamanca, Sergio Raposeiras-Roubin, Clara Fernández-Cordón, Miguel Corbí-Pascual, Oscar Vedia, Agustín C. Martín-García, Emilia Blanco-Ponce, Manuel Almendro Delia, Alberto Piserra-López, Jaime Francisco Larre Guerra, Francisco Gonzalez-Santorum, Carmen Lluch-Requerey, Marta Guillén-Marzo, Alberto Pérez-Castellanos, Francisco Ridocci-Soriano, Javier Lopez-País, Rut Andrea, Alessandro Sionis, Iván J. Núñez-Gil, Aitor Uribarri
Background
Age-related differences in Takotsubo Syndrome (TTS) have been described, but there is limited information regarding TTS patients who develop cardiogenic shock (CS).
Methods and Results
We analysed data from 408 CS-TTS patients in the RETAKO registry. Patients were stratified into three age groups: ≤50 years (9%), 51–74 years (48%), and ≥75 years (43%). In the youngest group, compared to the middle-aged and the oldest groups, patients were more likely to be male (35% vs. 16% and 14%, p = .01), have a physical trigger (65% vs. 43% and 49%, p = .04), exhibit atypical echocardiographic patterns (27% vs. 11% and 11%, p = .02), and experienced a higher incidence of ventricular arrhythmias (24% vs. 8% and 7%, p = .01). In-hospital mortality rates were 5% in younger patients, 12% in middle-aged patients, and 15% in older patients (p = .15). Older age independently predicted both in-hospital mortality (OR 2.33, 95% CI 1.05–5.17; reference: middle-aged) and 5-year mortality (HR 3.69, 95% CI 1.77–7.67), regardless of shock severity.
Conclusions
In CS-TTS, younger patients exhibit distinct clinical features but have better outcomes. Older age is associated with higher in-hospital and long-term mortality, regardless of comorbidities and shock severity. These findings underscore the need for age-specific management strategies and further research into the mechanisms underlying age-related differences in CS-TTS.
背景：Takotsubo综合征（TTS）的年龄相关差异已被描述，但关于TTS患者发生心源性休克（CS）的信息有限。方法和结果：我们分析了RETAKO登记处408例CS-TTS患者的数据。患者分为三个年龄组：≤50岁（9%）、51-74岁（48%）和≥75岁（43%）。与中年组和老年组相比，最年轻组的患者更有可能是男性(35%对16%和14%，p =。01)，有物理触发(65%对43%和49%，p =。2004)，表现出非典型超声心动图模式(27%对11%和11%，p =。2002年)，室性心律失常发生率较高（24%比8%和7%，p = 0.01）。住院死亡率年轻患者为5%，中年患者为12%，老年患者为15% （p = .15）。无论休克严重程度如何，老年人独立预测住院死亡率（OR 2.33, 95% CI 1.05-5.17；参考：中年人）和5年死亡率（HR 3.69, 95% CI 1.77-7.67）。结论：在CS-TTS中，年轻患者表现出明显的临床特征，但预后较好。无论合并症和休克严重程度如何，年龄越大，住院死亡率和长期死亡率越高。这些发现强调了针对年龄的管理策略和进一步研究CS-TTS年龄相关差异机制的必要性。
{"title":"Age-related differences in cardiogenic shock secondary to Takotsubo syndrome","authors":"Marco Tomasino, Ravi Vazirani, Jorge Salamanca, Sergio Raposeiras-Roubin, Clara Fernández-Cordón, Miguel Corbí-Pascual, Oscar Vedia, Agustín C. Martín-García, Emilia Blanco-Ponce, Manuel Almendro Delia, Alberto Piserra-López, Jaime Francisco Larre Guerra, Francisco Gonzalez-Santorum, Carmen Lluch-Requerey, Marta Guillén-Marzo, Alberto Pérez-Castellanos, Francisco Ridocci-Soriano, Javier Lopez-País, Rut Andrea, Alessandro Sionis, Iván J. Núñez-Gil, Aitor Uribarri","doi":"10.1111/eci.70119","DOIUrl":"10.1111/eci.70119","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Age-related differences in Takotsubo Syndrome (TTS) have been described, but there is limited information regarding TTS patients who develop cardiogenic shock (CS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>We analysed data from 408 CS-TTS patients in the RETAKO registry. Patients were stratified into three age groups: ≤50 years (9%), 51–74 years (48%), and ≥75 years (43%). In the youngest group, compared to the middle-aged and the oldest groups, patients were more likely to be male (35% vs. 16% and 14%, <i>p</i> = .01), have a physical trigger (65% vs. 43% and 49%, <i>p</i> = .04), exhibit atypical echocardiographic patterns (27% vs. 11% and 11%, <i>p</i> = .02), and experienced a higher incidence of ventricular arrhythmias (24% vs. 8% and 7%, <i>p</i> = .01). In-hospital mortality rates were 5% in younger patients, 12% in middle-aged patients, and 15% in older patients (<i>p</i> = .15). Older age independently predicted both in-hospital mortality (OR 2.33, 95% CI 1.05–5.17; reference: middle-aged) and 5-year mortality (HR 3.69, 95% CI 1.77–7.67), regardless of shock severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In CS-TTS, younger patients exhibit distinct clinical features but have better outcomes. Older age is associated with higher in-hospital and long-term mortality, regardless of comorbidities and shock severity. These findings underscore the need for age-specific management strategies and further research into the mechanisms underlying age-related differences in CS-TTS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12811834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Response to the comment on ‘Branched-chain amino acids and all-cause mortality in patients with liver cirrhosis, and the onset of diabetes in liver transplant recipients’","authors":"Yakun Li, Robin P. F. Dullaart","doi":"10.1111/eci.70118","DOIUrl":"10.1111/eci.70118","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991948","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}
López-Baizán J, Ruiz Ortiz M, Delgado Ortega M, et al. Risk scores for predicting incident heart failure admission in patients with chronic coronary syndromes: Validation in a prospective, monocentric, long-term, cohort study. Eur J Clin Invest. 2023;53: e13941. doi: 10.1111/eci.13941.
The following affiliations are incomplete:
1Cardiology Department, Reina Sofia University Hospital, Córdoba, Spain.
2Maimonides Institute for Biomedical Research of Córdoba, IMIBIC, Córdoba, Spain.
These should have read as follows:
1Cardiology Department, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain.
2Maimonides Institute for Biomedical Research of Córdoba, IMIBIC, University of Córdoba, Córdoba, Spain.
{"title":"Correction to “Risk scores for predicting incident heart failure admission in patients with chronic coronary syndromes: Validation in a prospective, monocentric, long-term, cohort study”","authors":"","doi":"10.1111/eci.70116","DOIUrl":"10.1111/eci.70116","url":null,"abstract":"<p>López-Baizán J, Ruiz Ortiz M, Delgado Ortega M, et al. Risk scores for predicting incident heart failure admission in patients with chronic coronary syndromes: Validation in a prospective, monocentric, long-term, cohort study. <i>Eur J Clin Invest</i>. 2023;53: e13941. doi: 10.1111/eci.13941.</p><p>The following affiliations are incomplete:</p><p><sup>1</sup>Cardiology Department, Reina Sofia University Hospital, Córdoba, Spain.</p><p><sup>2</sup>Maimonides Institute for Biomedical Research of Córdoba, IMIBIC, Córdoba, Spain.</p><p>These should have read as follows:</p><p><sup>1</sup>Cardiology Department, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain.</p><p><sup>2</sup>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 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comment on “Branched-chain amino acids and all-cause mortality in patients with liver cirrhosis, and the onset of diabetes in liver transplant recipients”","authors":"Rachana Mehta, Ranjana Sah","doi":"10.1111/eci.70117","DOIUrl":"10.1111/eci.70117","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947845","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}
Heart failure (HF) and pulmonary hypertension (PH) due to left heart disease (PH-LHD) are complex and heterogeneous syndromes with diverse underlying mechanisms and variable clinical courses. Despite significant progress in clinical management, current diagnostic and prognostic approaches often fail to capture the underlying molecular diversity of these conditions. Unbiased serum proteomics offers a promising solution to enable novel biomarkers and pathophysiological pathways directly from patient samples. Using high-throughput mass spectrometry (MS) and aptamer-based platforms, proteomic profiling enables the simultaneous quantification of thousands of proteins across a wide dynamic range, offering a multidimensional perspective on disease mechanisms. In HF, proteomic signatures differentiate phenotypes such as HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) through distinct inflammatory, metabolic and remodelling pathways, supporting more accurate diagnosis and risk assessment. In PH-LHD, dysregulated protein networks reflect pressure overload, atrial remodelling and right ventricular adaptation, supporting more refined phenotypic stratification. Integrating proteomic data with clinical, imaging and genomic variables enhances predictive accuracy and opens new avenues for individualized therapy. However, challenges remain, including pre-analytical variability, data interpretation and the need for rigorous validation across independent cohorts. This review discusses current advances in serum proteomics applied to HF and PH-LHD, methodological strengths and limitations and outlines the translational potential of proteomic findings to improve patient outcomes and support precision medicine.
{"title":"Unbiased serum proteomics in heart failure and associated pulmonary hypertension: From biomarkers discovery to precision medicine","authors":"Matteo Santi, Rosalinda Madonna","doi":"10.1111/eci.70115","DOIUrl":"10.1111/eci.70115","url":null,"abstract":"<p>Heart failure (HF) and pulmonary hypertension (PH) due to left heart disease (PH-LHD) are complex and heterogeneous syndromes with diverse underlying mechanisms and variable clinical courses. Despite significant progress in clinical management, current diagnostic and prognostic approaches often fail to capture the underlying molecular diversity of these conditions. Unbiased serum proteomics offers a promising solution to enable novel biomarkers and pathophysiological pathways directly from patient samples. Using high-throughput mass spectrometry (MS) and aptamer-based platforms, proteomic profiling enables the simultaneous quantification of thousands of proteins across a wide dynamic range, offering a multidimensional perspective on disease mechanisms. In HF, proteomic signatures differentiate phenotypes such as HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) through distinct inflammatory, metabolic and remodelling pathways, supporting more accurate diagnosis and risk assessment. In PH-LHD, dysregulated protein networks reflect pressure overload, atrial remodelling and right ventricular adaptation, supporting more refined phenotypic stratification. Integrating proteomic data with clinical, imaging and genomic variables enhances predictive accuracy and opens new avenues for individualized therapy. However, challenges remain, including pre-analytical variability, data interpretation and the need for rigorous validation across independent cohorts. This review discusses current advances in serum proteomics applied to HF and PH-LHD, methodological strengths and limitations and outlines the translational potential of proteomic findings to improve patient outcomes and support precision medicine.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947867","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}
COVID-19 remains a potentially severe condition for immunocompromised individuals, such as patients with hematologic malignancy. These patients are at increased risk of progressing to severe–critical or prolonged COVID-19. Prompt treatment with antivirals has proven effective in preventing disease progression and is recommended by current guidelines. We discuss here the position of remdesivir in the management of onco-hematologic patients infected with SARS-CoV-2 and strategies for its use.
Methods
Narrative review of current evidence regarding remdesivir in the treatment of COVID-19 in patients with hematologic malignancy.
Results
Patients with non-severe COVID-19 should receive remdesivir as soon as possible after diagnosis, and within 7 days from symptom onset. A 3-day treatment duration is recommended. In patients at high risk of developing severe COVID-19 – patients with B-cell depletion and recipients of allogeneic HSCT or CAR T cell therapy or bispecific antibodies – treatment may be prolonged and/or combined with other COVID-19 therapeutics. Patients with severe COVID-19 requiring supplemental oxygen should receive remdesivir as soon as possible, preferentially for 10 days. In those at high risk of progressing to critical COVID-19, combination of remdesivir with other COVID-19 therapeutics can be considered. In case of relapse or persisting symptoms, remdesivir treatment can be prolonged and/or repeated or combined with other COVID-19 therapeutics.
Conclusions
Evidence from clinical trials and real-world studies shows that remdesivir is a valid option for the treatment of SARS-CoV-2-infected onco-hematologic patients, across a wide spectrum of COVID-19 severity. The drawback of remdesivir—intravenous administration mode—is counterbalanced by good tolerability, negligible drug–drug interactions and a high barrier to virus resistance.
{"title":"Role of remdesivir for the treatment of COVID-19 in patients with hematologic malignancy—A narrative review and expert opinion","authors":"Malgorzata Mikulska, Matteo Bassetti, Alessandro Busca, Valeria Cento, Maddalena Giannella, Michele Bartoletti","doi":"10.1111/eci.70108","DOIUrl":"10.1111/eci.70108","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>COVID-19 remains a potentially severe condition for immunocompromised individuals, such as patients with hematologic malignancy. These patients are at increased risk of progressing to severe–critical or prolonged COVID-19. Prompt treatment with antivirals has proven effective in preventing disease progression and is recommended by current guidelines. We discuss here the position of remdesivir in the management of onco-hematologic patients infected with SARS-CoV-2 and strategies for its use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Narrative review of current evidence regarding remdesivir in the treatment of COVID-19 in patients with hematologic malignancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with non-severe COVID-19 should receive remdesivir as soon as possible after diagnosis, and within 7 days from symptom onset. A 3-day treatment duration is recommended. In patients at high risk of developing severe COVID-19 – patients with B-cell depletion and recipients of allogeneic HSCT or CAR T cell therapy or bispecific antibodies – treatment may be prolonged and/or combined with other COVID-19 therapeutics. Patients with severe COVID-19 requiring supplemental oxygen should receive remdesivir as soon as possible, preferentially for 10 days. In those at high risk of progressing to critical COVID-19, combination of remdesivir with other COVID-19 therapeutics can be considered. In case of relapse or persisting symptoms, remdesivir treatment can be prolonged and/or repeated or combined with other COVID-19 therapeutics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Evidence from clinical trials and real-world studies shows that remdesivir is a valid option for the treatment of SARS-CoV-2-infected onco-hematologic patients, across a wide spectrum of COVID-19 severity. The drawback of remdesivir—intravenous administration mode—is counterbalanced by good tolerability, negligible drug–drug interactions and a high barrier to virus resistance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 12","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947848","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}
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}
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