European Journal of Clinical Investigation最新文献_第2页

Antifungal treatment strategies in intensive care unit patients 重症监护病房患者的抗真菌治疗策略。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2026-01-22 DOI: 10.1111/eci.70177

Claudia Bartalucci, Laura Mezzogori, Riccardo Schiavoni, Antonio Vena, Daniele Roberto Giacobbe, Matteo Bassetti

Background

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among critically ill patients. In the intensive care unit (ICU), invasive candidiasis (IC), invasive pulmonary aspergillosis (IPA), and Pneumocystis jirovecii pneumonia (PjP) represent the most prevalent and clinically relevant fungal diseases. Their diagnosis is often hampered by nonspecific clinical and radiological findings, delayed or negative cultures, and suboptimal performance of fungal biomarkers in this population. As a result, antifungal treatment strategies in the ICU must balance the need for early initiation with the risk of overtreatment and resistance.

Methods

This review summarizes current therapeutic approaches, evidence-based recommendations, and recent advances for the treatment of IC, IPA, and PjP in critically ill patients. Pharmacokinetic/pharmacodynamic (PK/PD) considerations, therapeutic drug monitoring, and emerging antifungal agents are also discussed.

Results

For IC, echinocandins remain the cornerstone of therapy, while biomarker-guided strategies appear more useful for treatment discontinuation than initiation. In IPA, voriconazole and isavuconazole are first-line agents, with liposomal amphotericin B as an alternative in case of azole resistance or intolerance; the role of combination therapy remains uncertain. For PjP, trimethoprim–sulfamethoxazole is the treatment of choice, while adjunctive corticosteroids are recommended mainly for people with HIV and severe disease. Emerging antifungal agents, including rezafungin, fosmanogepix, and olorofim, may enhance future treatment options.

Conclusions

Optimizing antifungal stewardship through individualized therapy and early diagnosis remains essential to improve outcomes in this high-risk population.

背景：侵袭性真菌感染（IFIs）是危重患者发病和死亡的主要原因。在重症监护病房（ICU），侵袭性念珠菌病（IC），侵袭性肺曲霉病（IPA）和肺孢子虫肺炎（PjP）是最常见和临床相关的真菌疾病。他们的诊断常常受到非特异性临床和放射学发现、延迟或阴性培养以及真菌生物标志物在该人群中的次优表现的阻碍。因此，ICU的抗真菌治疗策略必须在早期启动的需要与过度治疗和耐药性的风险之间取得平衡。方法：本文综述了目前重症患者IC、IPA和PjP的治疗方法、循证建议和最新进展。药代动力学/药效学（PK/PD）的考虑，治疗药物监测和新兴的抗真菌药物也进行了讨论。结果：对于IC，棘白菌素仍然是治疗的基石，而生物标志物引导的策略似乎对治疗停止比开始更有用。在IPA中，伏立康唑和异戊康唑是一线药物，在唑耐药或不耐受的情况下，可选择脂质体两性霉素B；联合治疗的作用仍不确定。对于PjP，甲氧苄啶-磺胺甲恶唑是首选的治疗方法，而辅助性皮质类固醇主要建议用于艾滋病毒感染者和重症患者。新出现的抗真菌药物，包括rezafungin， fosmangepix和olorofilm，可能会增加未来的治疗选择。结论：通过个体化治疗和早期诊断优化抗真菌管理对于改善这一高危人群的预后至关重要。

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引用次数: 0

Stress testing in the diagnosis and early screening of chronic thromboembolic pulmonary disease with and without pulmonary hypertension 应激试验在慢性血栓栓塞性肺部疾病伴和不伴肺动脉高压的诊断和早期筛查中的应用

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2026-01-21 DOI: 10.1111/eci.70175

Giorgia Tocci, Matteo Santi, Cipollini Viola, Roberta Pancani, Laura Carrozzi, Raffaele De Caterina, Rosalinda Madonna

Background

Chronic thromboembolic pulmonary disease (CTEPD) and its hemodynamic counterpart chronic thromboembolic pulmonary hypertension (CTEPH) are long-term sequelae of acute pulmonary embolism (PE), often underdiagnosed. Often, patients with CTEPD without PH may, however, develop exercise-induced PH (ExPH), a clinical condition detectable only under stress conditions.

Objective

This narrative review aims at evaluating current evidence on the role of stress testing in the early diagnosis, screening and clinical management of CTEPD and CTEPH, with a particular focus on exercise-induced hemodynamic abnormalities.

Methods

A literature search was conducted using PubMed, including observational studies, clinical trials and international guidelines published from 1998 to 2025 Studies investigating the use of cardiopulmonary exercise testing (CPET), exercise stress echocardiography (ESE), stress cardiac magnetic resonance imaging (MRI), the 6-min walk test (6MWT) and exercise right heart catheterization (exRHC) in both CTEPD and CTEPH were selected.

Results

Non-invasive stress tests such as CPET and ESE demonstrated high sensitivity and negative predictive value in detecting ExPH, particularly in oligosymptomatic patients with persistent symptoms after PE. ExRHC remains the gold standard for confirming ExPH, defined by a mPAP/CO slope >3 mmHg/L/min with normal pulmonary arterial wedge pressure (PAWP) and elevated pulmonary vascular resistance (PVR) during exercise. Nevertheless, due to its invasive nature and limited availability, ExRHC is not suitable for first-line screening. For early evaluation, non-invasive tests such as CPET and ESE may be preferred, as they provide a broader, safer and more accessible functional assessment.

Conclusion

Stress testing is a valuable tool in the functional assessment of CTEPD without PH and should be systematically integrated into post-PE screening protocols. Early use of CPET and ESE allows detection of subclinical pulmonary vascular dysfunction, guiding appropriate referral and treatment, while exercise RHC should be reserved for selected cases with inconclusive findings or complex physiology.

背景：慢性血栓栓塞性肺病（CTEPD）及其血流动力学对应的慢性血栓栓塞性肺动脉高压（CTEPH）是急性肺栓塞（PE）的长期后遗症，通常未被确诊。然而，通常，没有PH的CTEPD患者可能会发展为运动诱导的PH (ExPH)，这是一种只有在应激条件下才能检测到的临床状况。目的：本综述旨在评估压力测试在CTEPD和CTEPH的早期诊断、筛查和临床管理中的作用，并特别关注运动引起的血流动力学异常。方法：通过PubMed检索文献，包括1998年至2025年发表的观察性研究、临床试验和国际指南，选择心肺运动试验（CPET）、运动应激超声心动图（ESE）、应激性心脏磁共振成像（MRI）、6分钟步行试验（6MWT）和运动右心导管（exRHC）在CTEPD和CTEPH中的应用研究。结果：CPET和ESE等非侵入性压力测试在检测ExPH方面具有较高的敏感性和阴性预测价值，特别是在PE后症状持续的少症状患者中。ExRHC仍然是确认ExPH的金标准，由运动期间肺动脉楔压（PAWP）正常、肺血管阻力（PVR）升高的mPAP/CO斜率bbbb30 mmHg/L/min定义。然而，由于其侵袭性和有限的可用性，ExRHC不适合一线筛查。对于早期评估，CPET和ESE等非侵入性测试可能是首选，因为它们提供了更广泛、更安全、更容易获得的功能评估。结论：压力测试是无PH CTEPD功能评估的重要工具，应系统地纳入pe后筛查方案。早期使用CPET和ESE可以发现亚临床肺血管功能障碍，指导适当的转诊和治疗，而运动性RHC应保留给未确定结果或生理复杂的特定病例。

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引用次数: 0

The fat-heart entanglement and the role of ‘osteopontin mechanics’ in cardiometabolic senescence 脂肪-心脏纠缠和“骨桥蛋白力学”在心脏代谢衰老中的作用。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2026-01-21 DOI: 10.1111/eci.70181

Cristina Michelauz, Fabrizio Montecucco, Luca Liberale, Federico Carbone

Background

Residual cardiovascular (CV) risk persists despite therapeutic advances. Obesity is heterogeneous, and visceral adipose tissue (VAT) dysfunction (‘adiposopathy’) complicates risk stratification. Osteopontin (OPN) is a pleiotropic mediator implicated in VAT inflammation, senescence-associated pathways, atherosclerosis and myocardial remodelling.

Methods

We performed a narrative synthesis of preclinical and clinical evidence on OPN across three domains: (i) VAT biology and senescence-associated secretory phenotype (SASP); (ii) atherosclerosis and plaque vulnerability; and (iii) myocardial fibrosis/remodelling and cardiometabolic heart failure. We also summarize biomarker and therapeutic implications.

Results

OPN is increased in obesity, particularly within VAT, where it contributes to SASP-related signalling, macrophage dysfunction, low-grade systemic inflammation, insulin resistance and cardiometabolic risk. Clinical and translational studies link circulating and tissue OPN levels to vascular inflammation, plaque vulnerability and adverse CV events. In the myocardium, OPN appears to act as a remodelling-specific mediator connecting extracardiac adiposity-related signals to interstitial fibrosis, with the strongest evidence in heart failure with preserved ejection fraction and diabetic cardiomyopathy. Across settings, OPN shows promise as an early biomarker for detection and risk stratification. Experimental modulation of OPN attenuates fibrosis and improves cardiac function in multiple models, supporting its candidacy as a mechanistic therapeutic target.

Conclusions

OPN likely bridges the fat–heart axis through senescence-related pathways and may help explain residual CV risk in obesity-related cardiometabolic disease. Standardized assays, prospective validation and interventional studies are required to establish clinical utility for OPN as a biomarker and therapeutic target.

背景：尽管治疗取得进展，但残留的心血管（CV）风险仍然存在。肥胖是异质性的，内脏脂肪组织（VAT）功能障碍（“脂肪病”）使风险分层复杂化。骨桥蛋白（OPN）是一种多效介质，涉及VAT炎症、衰老相关途径、动脉粥样硬化和心肌重构。方法：我们在三个领域对OPN的临床前和临床证据进行了叙述性综合：(i) VAT生物学和衰老相关分泌表型（SASP）；（ii）动脉粥样硬化和斑块易损性；（iii）心肌纤维化/重构和心脏代谢心力衰竭。我们还总结了生物标志物和治疗意义。结果：OPN在肥胖中增加，特别是在VAT中，它有助于sasp相关信号，巨噬细胞功能障碍，低度全身炎症，胰岛素抵抗和心脏代谢风险。临床和转化研究将循环和组织OPN水平与血管炎症、斑块易损和不良心血管事件联系起来。在心肌中，OPN似乎作为一种重构特异性介质，将心外脂肪相关信号与间质纤维化联系起来，在射血分数保留的心力衰竭和糖尿病性心肌病中得到了最有力的证据。在各种情况下，OPN有望成为检测和风险分层的早期生物标志物。在多种模型中，实验调节OPN可减轻纤维化并改善心功能，支持其作为机制治疗靶点的候选性。结论：OPN可能通过衰老相关途径连接脂肪-心脏轴，并可能有助于解释肥胖相关心脏代谢疾病的剩余CV风险。标准化分析、前瞻性验证和介入研究需要确立OPN作为生物标志物和治疗靶点的临床效用。

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引用次数: 0

Association between Helicobacter pylori infection and Parkinson's disease: A systematic review and meta-analysis 幽门螺杆菌感染与帕金森病的关系：一项系统综述和荟萃分析。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2026-01-12 DOI: 10.1111/eci.70164

Chang Seok Bang, Md Hasanuzzaman, Jae Jun Lee, Eun Jeong Gong

Background

Helicobacter pylori infection is epidemiologically linked to Parkinson's disease (PD), though findings remain inconsistent. This study aimed to determine whether patients with PD have a higher prevalence of H. pylori infection than controls through an updated systematic review and meta-analysis and to explore heterogeneity through subgroup analyses.

Methods

A comprehensive literature search of relevant studies published till October 2024 was performed using PubMed, EMBASE and Cochrane Library databases. Studies examining the prevalence of H. pylori infection in patients with PD were included. Pooled odds ratios (OR) with 95% confidence intervals (CI) and pooled prevalence rates were calculated. Subgroup analyses were conducted based on geographical region, H. pylori detection methods and exclusion of individuals with prior eradication therapy. Sensitivity analyses and publication bias assessments were also performed.

Results

Twenty-three studies involving 7205 patients with PD and 41,937 controls were included in meta-analysis. Among studies reporting prevalence, the pooled prevalence of H. pylori infection in patients with PD was 39.0% (95% CI 26.5%–53.1%). In 13 studies comparing the prevalence of H. pylori infection between patients with PD and controls, H. pylori infection was found to be associated with PD (OR 1.328, 95% CI 1.165–1.514). Subgroup analyses showed consistent results and sensitivity analyses confirmed the robustness of the findings. Furthermore, no publication bias was observed.

Conclusions

Patients with PD exhibit a higher prevalence of H. pylori infection than controls. These findings support a potential role of H. pylori infection in PD pathogenesis, although causality cannot be established.

背景：幽门螺杆菌感染在流行病学上与帕金森病（PD）有关，尽管研究结果仍不一致。本研究旨在通过更新的系统评价和荟萃分析确定PD患者是否比对照组有更高的幽门螺杆菌感染患病率，并通过亚组分析探讨异质性。方法：综合检索PubMed、EMBASE和Cochrane图书馆数据库，检索截止2024年10月发表的相关研究。纳入了PD患者幽门螺杆菌感染流行率的研究。计算合并优势比（OR）、95%置信区间（CI）和合并患病率。根据地理区域、幽门螺杆菌检测方法和排除既往根除治疗的个体进行亚组分析。还进行了敏感性分析和发表偏倚评估。结果：23项研究包括7205名PD患者和41937名对照纳入meta分析。在报告患病率的研究中，PD患者幽门螺杆菌感染的总患病率为39.0% （95% CI 26.5%-53.1%）。在13项比较PD患者与对照组幽门螺杆菌感染率的研究中，发现幽门螺杆菌感染与PD相关（OR 1.328, 95% CI 1.165-1.514）。亚组分析结果一致，敏感性分析证实了研究结果的稳健性。此外，未观察到发表偏倚。结论：PD患者的幽门螺杆菌感染率高于对照组。这些发现支持幽门螺杆菌感染在PD发病机制中的潜在作用，尽管不能确定因果关系。

{"title":"Association between Helicobacter pylori infection and Parkinson's disease: A systematic review and meta-analysis","authors":"Chang Seok Bang, Md Hasanuzzaman, Jae Jun Lee, Eun Jeong Gong","doi":"10.1111/eci.70164","DOIUrl":"10.1111/eci.70164","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>Helicobacter pylori</i> infection is epidemiologically linked to Parkinson's disease (PD), though findings remain inconsistent. This study aimed to determine whether patients with PD have a higher prevalence of <i>H. pylori</i> infection than controls through an updated systematic review and meta-analysis and to explore heterogeneity through subgroup analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature search of relevant studies published till October 2024 was performed using PubMed, EMBASE and Cochrane Library databases. Studies examining the prevalence of <i>H. pylori</i> infection in patients with PD were included. Pooled odds ratios (OR) with 95% confidence intervals (CI) and pooled prevalence rates were calculated. Subgroup analyses were conducted based on geographical region, <i>H. pylori</i> detection methods and exclusion of individuals with prior eradication therapy. Sensitivity analyses and publication bias assessments were also performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-three studies involving 7205 patients with PD and 41,937 controls were included in meta-analysis. Among studies reporting prevalence, the pooled prevalence of <i>H. pylori</i> infection in patients with PD was 39.0% (95% CI 26.5%–53.1%). In 13 studies comparing the prevalence of <i>H. pylori</i> infection between patients with PD and controls, <i>H. pylori</i> infection was found to be associated with PD (OR 1.328, 95% CI 1.165–1.514). Subgroup analyses showed consistent results and sensitivity analyses confirmed the robustness of the findings. Furthermore, no publication bias was observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients with PD exhibit a higher prevalence of <i>H. pylori</i> infection than controls. These findings support a potential role of <i>H. pylori</i> infection in PD pathogenesis, although causality cannot be established.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959027","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}

引用次数: 0

Amyloid-beta (1–40) peptide is associated with systemic metabolic health 淀粉样蛋白- β(1-40)肽与全身代谢健康有关。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2026-01-08 DOI: 10.1111/eci.70171

Kateryna Sopova, Dimitrios Delialis, Evmorfia Aivalioti, Georgios Georgiopoulos, Stravros Athanasopoulos, Georgios Zervas, Christina Konstantaki, Marco Sachse, Martin Sigl, Daniel Duerschmied, Simon Tual-Chalot, Kimon Stamatelopoulos, Konstantinos Stellos

Background

Amyloid-beta 1–40 peptide (Aβ40) has recently emerged as a blood-based biomarker of cardiovascular disease (CVD). However, whether plasma levels of Aβ40 are associated with metabolic traits in humans without established CVD remains poorly understood.

Methods

Aβ40 was measured in plasma by ELISA and metabolic traits (waist circumference, fasting triglycerides, fasting HDL cholesterol and fasting glucose) were determined in a general population (n = 449) of individuals who did not have clinically overt CVD. Triglyceride-glucose index (TyG) was used to calculate the risk for insulin resistance. BARD score was used to calculate the risk for metabolic liver disease.

Results

Aβ40 levels were associated with the presence of metabolic syndrome (OR: 1.41 95% CI: 1.13–1.76, p = .003), and with higher odds for increasing incidence of metabolic syndrome components, characterized by decreased HDL-C levels (OR: 1.31 95% CI: 1.03–1.58, p = .017) and increased triglyceride levels (OR: 1.30 95% CI: 1.04–1.57, p = .033) after adjustment for traditional cardiovascular risk factors. Further, Aβ40 levels were associated with increased odds for TyG (OR: 1.26 95% CI: 1.03–1.57, p = .042) and increased odds for the presence of diabetes mellitus (OR: 1.35 95% CI: 1.04–1.76, p = .018) after adjustment for age and sex, smoking status, hypertension and dyslipidemia. Increased Aβ40 levels were associated with increased odds for BARD score ≥2 (OR: 1.41 95% CI: 1.04–2.04, p = .045) after adjustment for traditional cardiovascular risk factors.

Conclusion

Our findings suggest that Aβ40 peptide is associated with metabolic traits and risk for metabolic disease. Future longitudinal studies are warranted to determine the prognostic value of Aβ40 for the development and progression of metabolic diseases.

背景：淀粉样蛋白- β 1-40肽（a - β40）最近被认为是一种基于血液的心血管疾病（CVD）生物标志物。然而，在没有心血管疾病的人群中，血浆Aβ40水平是否与代谢特征相关仍然知之甚少。方法：采用ELISA法测定血浆中a β40的含量，并测定无临床明显CVD的一般人群（n = 449）的代谢特征（腰围、空腹甘油三酯、空腹高密度脂蛋白胆固醇和空腹血糖）。使用甘油三酯-葡萄糖指数（TyG）计算胰岛素抵抗的风险。BARD评分用于计算代谢性肝病的风险。结果：Aβ40水平与代谢综合征的存在相关(OR: 1.41 95% CI: 1.13-1.76, p =。003)，并且代谢综合征成分发生率增加的几率更高，其特征是HDL-C水平降低(OR: 1.31 95% CI: 1.03-1.58, p =。017)和甘油三酯水平升高(OR: 1.30 95% CI: 1.04-1.57, p =。033)在调整传统心血管危险因素后。此外，Aβ40水平与TyG发病几率增加相关（OR: 1.26 95% CI: 1.03-1.57, p =）。042)和糖尿病存在的几率增加(OR: 1.35 95% CI: 1.04-1.76, p =。（18）在调整了年龄、性别、吸烟状况、高血压和血脂异常后。Aβ40水平升高与BARD评分≥2的几率增加相关（OR: 1.41 95% CI: 1.04-2.04, p =）。045)在调整传统心血管危险因素后。结论：我们的研究结果提示Aβ40肽与代谢特征和代谢性疾病的风险相关。未来的纵向研究有必要确定Aβ40对代谢性疾病的发生和进展的预后价值。

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引用次数: 0

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2026-01-07 DOI: 10.1111/eci.70168

Óscar Fonseca, Paulo J. Oliveira, Martina U. Muckenthaler, Ana C. Moreira, M. Salomé Gomes

Background

The liver is widely recognized as a central hub for metabolic processes. Additionally, it plays critical roles in immune responses and in the regulation of iron homeostasis. Liver disorders have a profound impact on overall health and often involve iron dysregulation. Different cell types contribute to the completion of the plethora of different liver functions, including iron homeostasis.

Methods

A comprehensive literature search was conducted to identify recent advances in the understanding of the main mechanisms of intercellular communication in the liver that determine iron regulation and flow in health and disease.

Results

Hepatocytes are crucial to secure proper and safe iron storage and to regulate systemic iron distribution. For that, they contribute with the production of key proteins, such as ferritin, transferrin and hepcidin. Hepcidin production by hepatocytes is regulated by other liver cell types, including endothelial cells and macrophages. Macrophages significantly contribute to iron homeostasis by recycling iron from erythrocytes. Moreover, they modulate the physiology of other liver cells through the production of cytokines. Paracrine communication, involving soluble factors, extracellular vesicles or mitochondrial transfer, has been described as important mechanisms of iron regulation in the liver, critically contributing to its pathophysiology. Juxtacrine communication involving gap junctions or tunnelling nanotubes are mechanisms under investigation. This review highlights the recent advances in our understanding of the main mechanisms of intercellular communication in the liver that determine iron regulation and flow in health and disease.

Conclusions

Iro-nrelated communication between different liver cell types is fundamental to maintaining its proper function.

背景：肝脏被广泛认为是代谢过程的中心枢纽。此外，它在免疫反应和铁稳态调节中起关键作用。肝脏疾病对整体健康有深远的影响，通常涉及铁调节失调。不同的细胞类型有助于完成大量不同的肝功能，包括铁稳态。方法：进行了全面的文献检索，以确定对肝脏细胞间通讯的主要机制的理解的最新进展，这些机制决定了铁在健康和疾病中的调节和流动。结果：肝细胞在保证铁的安全储存和调节全身铁分布中起着至关重要的作用。为此，它们有助于产生关键蛋白质，如铁蛋白、转铁蛋白和肝磷脂。肝细胞产生Hepcidin受其他肝细胞类型的调节，包括内皮细胞和巨噬细胞。巨噬细胞通过从红细胞中回收铁，显著促进铁稳态。此外，它们还通过产生细胞因子来调节其他肝细胞的生理机能。分泌旁通讯，包括可溶性因子、细胞外囊泡或线粒体转移，已被描述为肝脏铁调节的重要机制，对其病理生理有重要贡献。涉及间隙连接或隧道纳米管的近距离通信机制正在研究中。这篇综述强调了我们对肝脏细胞间通讯的主要机制的理解的最新进展，这些机制决定了铁在健康和疾病中的调节和流动。结论：不同类型肝细胞之间的铁非相关通讯是维持其正常功能的基础。

{"title":"Iron-related intercellular communication in the liver: Main players and mechanisms","authors":"Óscar Fonseca, Paulo J. Oliveira, Martina U. Muckenthaler, Ana C. Moreira, M. Salomé Gomes","doi":"10.1111/eci.70168","DOIUrl":"10.1111/eci.70168","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The liver is widely recognized as a central hub for metabolic processes. Additionally, it plays critical roles in immune responses and in the regulation of iron homeostasis. Liver disorders have a profound impact on overall health and often involve iron dysregulation. Different cell types contribute to the completion of the plethora of different liver functions, including iron homeostasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature search was conducted to identify recent advances in the understanding of the main mechanisms of intercellular communication in the liver that determine iron regulation and flow in health and disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hepatocytes are crucial to secure proper and safe iron storage and to regulate systemic iron distribution. For that, they contribute with the production of key proteins, such as ferritin, transferrin and hepcidin. Hepcidin production by hepatocytes is regulated by other liver cell types, including endothelial cells and macrophages. Macrophages significantly contribute to iron homeostasis by recycling iron from erythrocytes. Moreover, they modulate the physiology of other liver cells through the production of cytokines. Paracrine communication, involving soluble factors, extracellular vesicles or mitochondrial transfer, has been described as important mechanisms of iron regulation in the liver, critically contributing to its pathophysiology. Juxtacrine communication involving gap junctions or tunnelling nanotubes are mechanisms under investigation. This review highlights the recent advances in our understanding of the main mechanisms of intercellular communication in the liver that determine iron regulation and flow in health and disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Iro-nrelated communication between different liver cell types is fundamental to maintaining its proper function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12827848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917386","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}

引用次数: 0

Sex differences in cholesterol metabolism and their association with SCORE2 cardiovascular risk based on cholesterol homeostasis markers and principal component analysis 基于胆固醇稳态标志物和主成分分析的胆固醇代谢的性别差异及其与SCORE2心血管风险的关联

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2026-01-05 DOI: 10.1111/eci.70169

Sandra Vladimirov, Tamara Gojković, Nataša Bogavac-Stanojevic, Aleksandra Zeljković, Vesna Spasojević-Kalimanovska

Background

Sex-related differences in cholesterol metabolism may influence cardiovascular disease risk and outcomes. Understanding these differences in the context of SCORE2 predicted cardiovascular risk could support the implementation of sex-specific prevention and therapeutic protocols.

Methods

In this cross-sectional study, serum levels of non-cholesterol sterols, desmosterol, lathosterol (markers of cholesterol synthesis) and campesterol and β-sitosterol (markers of cholesterol absorption) were analysed in 100 healthy adults (50 men, 50 women). CVD risk was assessed with SCORE2. Principal component analysis (PCA) was used to identify latent structures linking cholesterol homeostasis to sex and cardiovascular risk. K-means clustering and linear regression were used to examine sex-specific and SCORE2-related patterns.

Results

Men had significantly higher cholesterol synthesis markers, while women had higher cholesterol absorption markers. The desmosterol/lathosterol ratio was significantly higher in women, indicating preferential utilization of the Bloch biosynthetic pathway. PCA revealed three principal components (PCs), with PC1 distinguishing sex (p < .0001) and PC2 correlating with SCORE2 risk category (p < .0001). Cluster analysis based on PC1 and PC2 revealed two groups that correlated strongly with biological sex (χ² = 18.7, p < .0001). Elevated synthesis and absorption markers were associated with a higher risk according to SCORE2, especially in women.

Conclusions

Our results showed higher cholesterol synthesis in men and higher cholesterol absorption in women. PC1 reflected sex-specific differences, while PC2 was sex-independent but SCORE2-dependent. D/L, L, K, B, which contributed to PC3, accounted for a substantial proportion of the variance encompassing both sex and SCORE2 risk. These findings suggest differences in cholesterol metabolism between sexes, with possible implications for future CVD risk management.

背景：与性别相关的胆固醇代谢差异可能影响心血管疾病的风险和结局。在SCORE2预测心血管风险的背景下了解这些差异可以支持实施性别特异性预防和治疗方案。方法：在这项横断面研究中，分析了100名健康成人（50名男性，50名女性）血清中非胆固醇固醇、去氨甾醇、胆甾醇（胆固醇合成标志物）、油菜甾醇和β-谷甾醇（胆固醇吸收标志物）的水平。用SCORE2评估CVD风险。主成分分析（PCA）被用于识别将胆固醇稳态与性别和心血管风险联系起来的潜在结构。k均值聚类和线性回归用于检验性别特异性和score2相关模式。结果：男性有较高的胆固醇合成标记，而女性有较高的胆固醇吸收标记。去氨甾醇/胆甾醇比例在女性中显著较高，表明Bloch生物合成途径优先被利用。结论：我们的研究结果显示，男性胆固醇合成较高，女性胆固醇吸收较高。PC1反映了性别特异性差异，而PC2与性别无关，但与score2相关。D/L、L、K、B对PC3有贡献，在包含性别和SCORE2风险的方差中占相当大的比例。这些发现提示了两性之间胆固醇代谢的差异，可能对未来心血管疾病风险管理产生影响。

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引用次数: 0

Atherogenic dyslipidaemia and residual cardiovascular risk: Understanding the link to heart disease 动脉粥样硬化性血脂异常和剩余心血管风险：了解与心脏病的联系。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2026-01-03 DOI: 10.1111/eci.70167

Gabriela O. Girón, Sergi Otero, Panagiota Efstathia Nikolaou, Sebastià Alcover, Lisaidy Ramos-Regalado, Carlos Zaragoza, Luca Liberale, María Borrell-Pages, Teresa Padró, Rosa Suades, Gemma Vilahur

Background

A significant proportion of patients continue to experience cardiovascular (CV) events despite achieving recommended low-density lipoprotein cholesterol (LDL-C) targets, a phenomenon referred to as residual CV risk.

Methods

Clinical evidence from large outcome trials highlights the impact of residual risk on cardiovascular disease (CVD) burden, underscoring the need for therapeutic strategies beyond LDL-C lowering. Residual CV risk arises from diverse mechanisms, including persistent atherogenic dyslipidaemia [elevated triglyceride-rich lipoproteins (TRL), high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C) levels and increased apolipoprotein B (ApoB), Lipoprotein(a) (Lp[a]) and non-HDL-C], chronic inflammation, metabolic disorders and a prothrombotic state. These abnormalities continue to drive atherosclerotic progression in optimally treated patients, underscoring that managing residual CV risk requires a multifaceted approach.

Results

Lifestyle and dietary interventions remain foundational, targeting weight reduction, smoking cessation or adoption of a Mediterranean diet. Pharmacological options include statins (as first-line therapy), or the use of ezetimibe, or bempedoic acid since they both have complementary effects to LDL-C lowering. Emerging therapies, including proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (ApoC3) and angiopoietin-like 3 (ANGPTL3) inhibitors, demonstrate potential efficacy in favourably modulating lipid profiles and targeting specific components of atherogenic dyslipidaemia (AD). Combination therapies tailored to individual lipid profiles show promise to reduce residual CV risk.

Conclusion

The following review aims to provide a comprehensive overview of the latest evidence on the factors driving residual CV risk and the therapeutic interventions available to treat atherogenic dyslipidaemia beyond LDL-C reduction.

背景：尽管达到了推荐的低密度脂蛋白胆固醇（LDL-C）目标，但仍有相当比例的患者继续经历心血管（CV）事件，这一现象被称为剩余CV风险。方法：来自大型结局试验的临床证据强调了剩余风险对心血管疾病（CVD）负担的影响，强调了降低LDL-C以外的治疗策略的必要性。剩余的心血管风险来自多种机制，包括持续的动脉粥样硬化性血脂异常（高甘油三酯脂蛋白（TRL）、高甘油三酯（TG）、低高密度脂蛋白胆固醇（HDL-C）水平和载脂蛋白B （ApoB）、脂蛋白（a) （Lp[a]）和非HDL-C）升高）、慢性炎症、代谢紊乱和血栓形成前状态。这些异常继续推动最佳治疗患者的动脉粥样硬化进展，强调管理剩余心血管风险需要多方面的方法。结果：生活方式和饮食干预仍然是基础，目标是减肥、戒烟或采用地中海饮食。药物选择包括他汀类药物（作为一线治疗），或使用依折麦布，或苯甲醚酸，因为它们都具有降低LDL-C的补充作用。新兴疗法，包括蛋白转化酶枯草杆菌素/酮素9型（PCSK9）、载脂蛋白C-III （ApoC3）和血管生成素样3 （ANGPTL3）抑制剂，在调节脂质谱和靶向动脉粥样硬化性血脂异常（AD）的特定成分方面显示出潜在的疗效。针对个体脂质特征的联合治疗有望降低剩余CV风险。结论：以下综述旨在全面概述驱动剩余CV风险因素的最新证据，以及除降低LDL-C外可用于治疗动脉粥样硬化性血脂异常血症的治疗干预措施。

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引用次数: 0

Albumin, urea-to-albumin ratio, or the albumin-to-creatinine ratio to predict outcomes in heart failure with mildly reduced ejection fraction 白蛋白、尿素-白蛋白比或白蛋白-肌酐比预测射血分数轻度降低的心力衰竭的预后。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2025-12-26 DOI: 10.1111/eci.70165

Alexander Schmitt, Ibrahim Akin, Marielen Reinhardt, Noah Abel, Felix Lau, Jonas Dudda, Mohammad Abumayyaleh, Kathrin Weidner, Thomas Bertsch, Daniel Duerschmied, Michael Behnes, Tobias Schupp

Background

This study investigates the prognostic impact of albumin, the urea-to-albumin ratio (UAR), and albumin-to-creatinine ratio (ACR) in patients with heart failure with mildly reduced ejection fraction (HFmrEF), since hypoalbuminemia, renal disease and malnutrition often coincide with heart failure (HF).

Methods

Consecutive patients hospitalized with HFmrEF at one university medical centre were retrospectively included from 2016 to 2022. Patients were stratified into quartiles based on albumin, the UAR, and ACR. The primary endpoint was all-cause mortality at 30 months (median follow-up), key secondary endpoint was long-term HF-related rehospitalization.

Results

The study cohort comprised 2,061 patients with HFmrEF with a median albumin level of 32.4 g/L. Albumin levels, the UAR and ACR were predictive for the risk of long-term all-cause mortality, which was still observed after multivariable adjustment (albumin Q1 vs. Q4: HR = 2.260; 95% CI 1.623–3.148; p = .001 / UAR Q4 vs. Q1: HR = 1.507; 95% CI 1.071–2.119; p = .019/ACR Q1 vs. Q4: HR = 2.208; 95% CI 1.528–3.190; p = .001). However, neither albumin nor the UAR or ACR predicted the risk of HF-related rehospitalization (albumin Q1 vs. Q4: HR = 1.117; 95% CI .678–1.842; p = .664 / UAR Q4 vs. Q1: HR = 1.589; 95% CI .922–2.738; p = .095 / ACR Q1 vs. Q4: HR = 1.112; 95% CI .624–1.981; p = .720).

Conclusions

Hypoalbuminemia is common in hospitalized HFmrEF patients. Low albumin levels, ACRs, and elevated UARs independently predicted long-term all-cause mortality, but not HF-related rehospitalization. The UAR and ACR did not provide a clinically significant predictive advantage over albumin levels alone.

Trial Registration

ClinicalTrials.gov Identifier: NCT05603390 (date of registration: 10.10.2020)

背景：由于低白蛋白血症、肾脏疾病和营养不良常伴随心力衰竭（HF），本研究探讨了白蛋白、尿白蛋白比（UAR）和白蛋白与肌酐比（ACR）对心力衰竭伴轻度射血分数降低（HFmrEF）患者预后的影响。方法：回顾性纳入2016年至2022年在一所大学医疗中心连续住院的HFmrEF患者。根据白蛋白、UAR和ACR将患者分为四分位数。主要终点是30个月时的全因死亡率（中位随访），关键的次要终点是长期hf相关再住院。结果：研究队列包括2061例HFmrEF患者，中位白蛋白水平为32.4 g/L。白蛋白水平、UAR和ACR是长期全因死亡风险的预测指标，在多变量调整后仍可观察到(白蛋白Q1 vs. Q4: HR = 2.260; 95% CI 1.623-3.148; p =。001 / UAR Q4 vs. Q1: HR = 1.507；95% ci 1.071-2.119；p =。019/ACR Q1 vs. Q4: HR = 2.208；95% ci 1.528-3.190；p = .001)。然而，白蛋白、UAR或ACR均不能预测hf相关再住院的风险(白蛋白Q1 vs. Q4: HR = 1.117; 95% CI .678-1.842; p =。664 / UAR Q4 vs Q1: HR = 1.589；95% ci: 0.922 -2.738；p =。Q1 vs. Q4: HR = 1.112；95% ci为624-1.981；p = .720)。结论：低白蛋白血症在住院HFmrEF患者中很常见。低白蛋白水平、acr和uar升高独立预测长期全因死亡率，但不能预测hf相关的再住院。与单独的白蛋白水平相比，UAR和ACR没有提供临床显著的预测优势。试验注册：ClinicalTrials.gov标识符：NCT05603390（注册日期：10.10.2020）。

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引用次数: 0

Cellular senescence in giant cell arteritis and polymyalgia rheumatica: From mechanisms to therapeutic opportunities 巨细胞动脉炎和风湿性多肌痛的细胞衰老：从机制到治疗机会。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2025-12-24 DOI: 10.1111/eci.70166

Yiting Luo, Fan Yang, Yanlin He, Jin Lin, Weiqian Chen

Background

Giant cell arteritis (GCA) and (PMR) are inflammatory rheumatic disorders whose pathogenesis are unclear. The interleukin (IL)-6 receptor inhibitor is the first approved biologic agent for GCA and PMR, reducing relapse rates and cumulative glucocorticoid (GC) doses. Notably, IL-6, also a key pro-inflammatory factor secreted by senescent cells, contributes to tissue aging and chronic inflammation. We aim to explore the role of senescence-associated secretory phenotype (SASP) in the pathogenesis of GCA and PMR.

Methods

A narrative synthesis of literature published in the last 10 years was conducted utilizing keywords such as “Giant cell arteritis,” “Polymyalgia rheumatica,” “cellular senescence,” “senescence-associated secretory phenotype,” or “aging”.

Results

Evidence links cellular senescence and SASP to the pathogenesis of GCA and PMR, with key components like IL-6, IL-1β, and matrix metalloproteinases (MMPs) driving inflammation and tissue damage. We highlight how key SASP components, such as IL-6, IL-1β, and MMPs promote inflammation and tissue damage in GCA and PMR. Targeting SASP factors (senomorphics) or selectively eliminating senescent cells (senolytics) offers therapeutic potential. Further research into the mechanisms linking senescence to disease phenotypes is needed to develop effective therapies that mitigate disease progression and improve clinical outcomes.

Conclusion

We demonstrated age-related stress and senescence in the pathogenesis of GCA and PMR. We provide an overview of senomorphics, which have shown promise in clinical trials, and emphasize the need for further research to develop effective therapies.

背景：巨细胞动脉炎（GCA）和巨细胞动脉炎（PMR）是一种炎症性风湿性疾病，其发病机制尚不清楚。白介素(IL)-6受体抑制剂是首个被批准用于GCA和PMR的生物制剂，可降低复发率和累积糖皮质激素（GC）剂量。值得注意的是，IL-6也是衰老细胞分泌的关键促炎因子，有助于组织老化和慢性炎症。我们的目的是探讨衰老相关分泌表型（SASP）在GCA和PMR发病机制中的作用。方法：利用“巨细胞动脉炎”、“风湿性多肌痛”、“细胞衰老”、“衰老相关分泌表型”、“衰老”等关键词，对近10年发表的文献进行叙述性综合。结果：有证据表明细胞衰老和SASP与GCA和PMR的发病机制有关，关键成分如IL-6、IL-1β和基质金属蛋白酶（MMPs）驱动炎症和组织损伤。我们强调关键的SASP成分，如IL-6、IL-1β和MMPs如何促进GCA和PMR的炎症和组织损伤。靶向SASP因子（senomorphics）或选择性地消除衰老细胞（senolytics）提供了治疗潜力。需要进一步研究衰老与疾病表型之间的联系机制，以开发有效的治疗方法，减缓疾病进展并改善临床结果。结论：GCA和PMR的发病机制与年龄相关的应激和衰老有关。我们概述了在临床试验中显示出前景的同形物，并强调需要进一步研究以开发有效的治疗方法。

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引用次数: 0