European Journal of Clinical Investigation最新文献_第6页

The biology of lipoprotein(a): From genetics to molecular mechanisms 脂蛋白生物学(a)：从遗传学到分子机制。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2025-10-03 DOI: 10.1111/eci.70133

Mark Atallah, Nadim Nasrallah, Tarek Harb, Gary Gerstenblith, Thorsten M. Leucker

Background

Lipoprotein(a) [Lp(a)] is a primarily genetically determined, low-density lipoprotein-like particle that plays an important role in atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). Despite optimal control of traditional lipid levels, elevated lipoprotein(a) [Lp(a)] remains a significant contributor to residual cardiovascular risk, affecting up to 20% of the global population.

Methods

We performed a literature search of PubMed/Medline and Google Scholar until July 2025 to provide a comprehensive overview of the genetics, structure, metabolism, and molecular mechanisms underlying Lp(a)'s pathogenicity.

Results

Structurally, Lp(a) consists of an LDL-like core covalently bound to apolipoprotein(a) [apo(a)], a polymorphic glycoprotein characterized by kringle IV type 2 (KIV-2) repeat variability. This copy number variation is the primary determinant of apo(a) isoform size and plasma Lp(a) levels. Small isoforms are produced more efficiently, resulting in higher concentrations. Lp(a) is synthesized in hepatocytes, and its plasma levels are predominantly governed by production rather than clearance. It carries a high burden of oxidized phospholipids (OxPLs), which confer pro-inflammatory and pro-atherogenic properties. Lp(a) promotes arterial inflammation, endothelial dysfunction, monocyte activation and impaired fibrinolysis via competition with plasminogen. It also plays a direct pathogenic role in valvular calcification by delivering OxPLs and autotaxin to valve interstitial cells, triggering osteogenic signaling cascades.

Conclusion

While environmental factors such as inflammation and hormonal status can transiently modulate levels, genetic variation overwhelmingly dictates lifelong Lp(a) burden. As novel agents targeting Lp(a) enter late-stage clinical trials, mechanistic insights into Lp(a) biology will be essential to risk stratification and future clinical management.

背景：脂蛋白(a) [Lp(a)]是一种主要由遗传决定的低密度脂蛋白样颗粒，在动脉粥样硬化性心血管疾病（ASCVD）和钙化性主动脉瓣疾病（CAVD）中起重要作用。尽管传统的脂质水平得到了最佳控制，但脂蛋白(a)升高[Lp(a)]仍然是剩余心血管风险的重要因素，影响着全球高达20%的人口。方法：到2025年7月，我们在PubMed/Medline和谷歌Scholar上进行了文献检索，以提供Lp(a)致病性的遗传、结构、代谢和分子机制的全面概述。结果：在结构上，Lp(a)由一个类似ldl的核心与载脂蛋白(a) [apo(a)]共价结合，载脂蛋白(a)是一种多态糖蛋白，具有kringle IV型2 （KIV-2）重复变异性。拷贝数变异是载脂蛋白(a)亚型大小和血浆脂蛋白(a)水平的主要决定因素。小的同工异构体更有效地产生，从而产生更高的浓度。Lp(a)在肝细胞中合成，其血浆水平主要受其产生而非清除的影响。它携带高负荷的氧化磷脂（OxPLs），赋予促炎和促动脉粥样硬化特性。Lp(a)通过与纤溶酶原竞争促进动脉炎症、内皮功能障碍、单核细胞活化和纤维蛋白溶解受损。它还通过将OxPLs和autotaxin传递到瓣膜间质细胞，触发成骨信号级联，在瓣膜钙化中起直接的致病作用。结论：虽然炎症和激素状态等环境因素可以短暂调节Lp(a)水平，但遗传变异在很大程度上决定了终身Lp(a)负担。随着靶向Lp(a)的新型药物进入后期临床试验，对Lp(a)生物学机制的深入了解将对风险分层和未来的临床管理至关重要。

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引用次数: 0

Machine learning prediction of moderate-to-severe acute kidney injury after ICU admission and cardiac surgery with urine trace elements 尿微量元素对ICU入院及心脏手术后中重度急性肾损伤的机器学习预测。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2025-10-03 DOI: 10.1111/eci.70131

Yang Chen, Ying Gue, Gregory Y. H. Lip, David S. Gardner, Mark A. J. Devonald

Background

Acute kidney injury (AKI) is common and linked to poor outcomes, but early detection remains challenging. Previous research identified urinary trace elements (TE) as early AKI biomarkers in intensive care unit (ICU) or cardiac surgery patients. We aimed to explore whether urinary TE enhance machine learning (ML) models for AKI prediction.

Methods

We constructed ML models using the ICU cohort. We filtered the variables and optimized hyperparameters before predicting Kidney Disease: Improving Global Outcomes stage 2–3 AKI using eight ML classifiers: light gradient boosting machine (LightGBM), random forest (RF), ML logistic regression, support vector machine, multilayer perceptron, eXtreme gradient boosting (XGBoost), Gaussian Naive Bayes and k-nearest neighbors. External validation was performed in the cardiac surgery cohort.

Results

Among 149 ICU patients (median age 56.0 [interquartile range (IQR): 43.5–67.0], 63.1% male), 25 developed stage 2–3 AKI; among 144 cardiac surgery patients (median age 70.0 [IQR: 62.0–76.0], 72.9% male), 12 developed stage 2–3 AKI. Each ML in the internal validation had area under the curve (AUC) above .7, with XGBoost having the highest (.813); LightGBM had the second highest AUC (.799), highest G-mean (.567) and F1-score (.545). In external validation, RF had the highest AUC (.740), XGBoost had the highest G-mean (.289) and F1-score (.286). Age, strontium and boron were consistently ranked among the top five most important features in LightGBM, RF and XGBoost.

Conclusion

ML models primarily based on urinary TE can identify AKI risk in both clinical groups (ICU and cardiac surgery), with LightGBM, RF and XGBoost serving as high-performance models for early prediction of stage 2–3 AKI.

背景：急性肾损伤（AKI）很常见，且与不良预后有关，但早期发现仍然具有挑战性。先前的研究发现尿微量元素（TE）是重症监护病房（ICU）或心脏手术患者早期AKI的生物标志物。我们的目的是探讨尿TE是否增强了AKI预测的机器学习（ML）模型。方法：采用ICU队列构建ML模型。在预测肾脏疾病：改善全球结果2-3期AKI之前，我们过滤了变量并优化了超参数，使用了8个ML分类器：光梯度增强机（LightGBM）、随机森林（RF）、ML逻辑回归、支持向量机、多层感知机、极端梯度增强（XGBoost）、高斯朴素贝叶斯和k近邻。在心脏外科队列中进行外部验证。结果：149例ICU患者（中位年龄56.0岁[四分位间距43.5 ~ 67.0]，男性占63.1%），25例发生2-3期AKI；144例心脏手术患者（中位年龄70.0岁[IQR: 62.0 ~ 76.0]，男性72.9%），12例发展为2-3期AKI。内验证的每个ML均具有上述曲线下面积（AUC）。7，其中XGBoost最高（.813）；LightGBM的AUC次之。799)，最高G-mean（.567）和F1-score（.545）。在外部验证中，RF具有最高的AUC(。XGBoost的g均值最高（0.289），f1评分最高（0.286）。在LightGBM、RF和XGBoost中，年龄、锶和硼一直排在前五大最重要的特征之列。结论：主要基于尿TE的ML模型可以识别临床组（ICU和心脏外科）的AKI风险，其中LightGBM、RF和XGBoost是早期预测2-3期AKI的高性能模型。

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引用次数: 0

Clinical outcomes of transcatheter edge-to-edge repair in patients with functional mitral regurgitation and pulmonary hypertension 经导管边缘对边缘修复治疗功能性二尖瓣反流合并肺动脉高压的临床效果。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2025-10-03 DOI: 10.1111/eci.70130

Alessandro Mandurino-Mirizzi, Luca Raone, Andrea Raffaele Munafò, Fabrizio Gazzoli, Marco Mussardo, Claudio Montalto, Francesco Germinal, Marco Ferlini, Italo Porto, Giuseppe Colonna, Jacopo Oreglia, Gabriele Crimi

Background

Pulmonary hypertension (PH) is frequently observed in patients with functional mitral regurgitation (FMR) and heart failure with reduced ejection fraction (HFrEF) and adversely impacts prognosis. However, limited data exist on the outcomes of transcatheter edge-to-edge mitral valve repair (M-TEER) in patients with PH, particularly regarding hemodynamic subtypes.

Methods

This multicenter, retrospective analysis included 144 HFrEF patients with moderate-to-severe or severe FMR who underwent M-TEER across four Italian centers. Baseline hemodynamic assessment was performed using right heart catheterization (RHC) in conscious patients. Procedural outcomes and clinical follow-up were evaluated at 1 year. The endpoints studied included death from any cause, heart failure hospitalization and a composite endpoint of both.

Results

Among the 144 patients, 84% had PH (64% combined post- and pre-capillary-PH (Cpc-PH), 20% isolated post-capillary-PH (Ipc-PH)). Procedural success was achieved in 92%, with significant improvements in New York Heart Association (NYHA) functional class (p < .001) and echocardiographic parameters. At 1 year, the composite endpoint occurred in 30% of patients, with higher rates in PH patients compared to no PH group (34% vs. 9%, respectively, p = .039). Among PH patients, Cpc-PH patients demonstrated the worst outcomes (for the composite endpoint at 1 year Cpc-PH 37% vs. Ipc-PH 24% vs. no-PH 9%, p = .031). Multivariate analysis confirmed Cpc-PH as a significant predictor of adverse outcomes at 1 year.

Conclusions

M-TEER is an effective therapeutic option for patients with HFrEF and FMR, providing significant procedural success and clinical improvements. However, patients with PH, particularly those with Cpc-PH, exhibit worse long-term clinical outcomes.

背景：肺动脉高压（PH）常见于功能性二尖瓣反流（FMR）和心力衰竭伴射血分数降低（HFrEF）患者，并对预后有不利影响。然而，关于PH患者经导管边缘到边缘二尖瓣修复（M-TEER）的结果，特别是关于血流动力学亚型的数据有限。方法：这项多中心、回顾性分析包括144名中重度或重度FMR的HFrEF患者，他们在意大利的四个中心接受了M-TEER治疗。在意识清醒的患者中使用右心导管（RHC）进行基线血流动力学评估。1年时评估手术结果和临床随访。研究的终点包括任何原因导致的死亡、心力衰竭住院以及两者的复合终点。结果：144例患者中，84%有PH(64%合并后和前毛细血管PH （Cpc-PH)， 20%分离后毛细血管PH (Ipc-PH)）。手术成功率达到92%，纽约心脏协会（NYHA）功能分级显著改善(p)。结论：M-TEER是HFrEF和FMR患者的有效治疗选择，提供了显著的手术成功率和临床改善。然而，PH患者，特别是Cpc-PH患者，表现出更差的长期临床结果。

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引用次数: 0

Office and out-of-office blood pressure in the European guidelines on hypertension: A clinical perspective 欧洲高血压指南中的办公室和办公室外血压：临床观点

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2025-10-01 DOI: 10.1111/eci.70129

Guido Grassi, Pasquale Ambrosino, Giuseppe Mancia

引用次数: 0

Target trial emulation of statin discontinuation in multimorbid older adults with polypharmacy 他汀类药物停药对多病老年人多重用药的目标试验模拟。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2025-09-30 DOI: 10.1111/eci.70126

Valerie Aponte Ribero, Oliver Baretella, Cinzia Del Giovane, Moa Haller, Martin Feller, Benoît Boland, Antoine Christiaens, Wilma Knol, Denis O'Mahony, Viktoria Gastens, Baris Gencer, Stéphanie Baggio, Nicolas Rodondi

Background

The benefit of statins in multimorbid older adults is controversial. Prior observational studies evaluating statin discontinuation in older adults were retrospective cohorts, did not focus on multimorbidity, or lacked adjustment for geriatric syndromes. We aimed to assess the effect of statin discontinuation on cardiovascular and mortality outcomes using the target trial emulation framework.

Methods

We conducted a prospective cohort study using data from the OPERAM trial in adults aged ≥70 years with ≥3 chronic conditions and ≥5 chronic drugs, comparing statin discontinuation to continuation. The primary composite outcome was cardiovascular events or all-cause mortality at 12 months. We calculated adjusted hazard ratios (HR) using weighted pooled logistic regressions without (model-A) and with adjustment for two geriatric syndromes (falls and weight loss; model-B).

Results

Of 2668 person-trial units (mean age 78.5 years), 2533 (95%) continued and 133 (5%) discontinued statins. Discontinuation was associated with higher composite outcome risk (27% vs. 18%; HR model-A 1.53 [95% CI 1.14–2.06]; model-B 1.49 [1.12–1.99]). This was mainly attributable to increased non-cardiovascular deaths (20% vs. 11%; HR model-A 1.56 [1.08–2.27]; model-B 1.52 [1.06–2.19]); there was no clear evidence for an association with cardiovascular events (7% vs. 8%; HR model-A 1.36 [.86–2.14]; model-B 1.35 [.86–2.12]).

Conclusion

In this first target trial emulation in a multimorbid older population, statin discontinuation was associated with increased risk of the composite of cardiovascular events or all-cause mortality, primarily driven by non-cardiovascular deaths. Geriatric syndromes did not modify these increased risks. Only clinical trials can clarify the safety of statin discontinuation.

背景：他汀类药物对多病老年人的益处是有争议的。先前评估老年人停用他汀类药物的观察性研究是回顾性队列研究，没有关注多病，也缺乏对老年综合征的调整。我们的目的是使用目标试验模拟框架评估他汀类药物停药对心血管和死亡率结果的影响。方法：我们使用来自OPERAM试验的数据进行了一项前瞻性队列研究，研究对象为年龄≥70岁、有≥3种慢性疾病和≥5种慢性药物的成年人，比较他汀类药物停药和继续停药。主要综合结局是心血管事件或12个月时的全因死亡率。我们使用加权合并logistic回归计算调整后的风险比（HR），不考虑（模型a），并对两种老年综合征（跌倒和体重减轻，模型b）进行调整。结果：在2668人试验单位（平均年龄78.5岁）中，2533人（95%）继续服用他汀类药物，133人（5%）停用他汀类药物。停药相关的综合结局风险较高（27%对18%；HR模型a为1.53 [95% CI 1.14-2.06]；模型b为1.49[1.12-1.99]）。这主要是由于非心血管死亡增加（20% vs 11%； HR模型a为1.56[1.08-2.27]；模型b为1.52 [1.06-2.19]）；没有明确的证据表明与心血管事件相关（7%对8%；HR模型a 1.36[.86-2.14]；模型b 1.35[.86-2.12]）。结论：在多病老年人群的第一个目标试验模拟中，他汀类药物停药与心血管事件或全因死亡率的综合风险增加相关，主要由非心血管死亡驱动。老年综合症并没有改变这些增加的风险。只有临床试验才能阐明他汀类药物停药的安全性。

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引用次数: 0

Mental stress as a trigger of cardiovascular events: A narrative review 精神压力作为心血管事件的触发因素：一个叙述性回顾。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2025-09-30 DOI: 10.1111/eci.70128

Paolo Raggi

Background

Several mental disorders has been associated with cardiovascular disease (CVD), although stress may have the strongest correlation. In this narrative review, we examine how stress is linked to CVD.

Results

Stress can be secondary to multiple factors and it can be imposed on an individual in more or less manifest ways. Psychosocial stress can result from adverse social circumstances such as poverty, racial, gender, religious disparities or discrimination, violence and environmental pollution. Large segments of the population are forced to endure poor working conditions, low food quality, physical and verbal abuse not only in the developing world but also in more flourishing societies as well. Wars that have ignited widely of late are inherently stressful events with potential enduring effects after the conflicts. Isolation and loneliness are growing issues in modern societies and impose a heavy burden of stress. Epidemiological studies have shown that stress is linked to CVD through an increased incidence of traditional risk factors (smoking, hypertension, insulin resistance and obesity). Experimental and laboratory evidence has shown a link between stress and CVD via neuro-endocrine, inflammatory and immune pathways. Patients with prior CV events affected by stress are at higher risk of recurrent events compared to similar patients without stressful conditions.

Conclusions

The close association between stress and CVD suggests that interventions to limit the effect of stress may result in a reduced incidence of de novo and recurrent CV events. Physicians should be aware of the importance of screening for stress in patients with CVD. Future efforts should be directed to the development of easily implementable screening tools and targeted interventions within healthcare frameworks.

背景：一些精神障碍与心血管疾病（CVD）有关，尽管压力可能有最强的相关性。在这篇叙述性综述中，我们研究了压力是如何与心血管疾病联系在一起的。结果：压力可以是次要的多种因素，它可以施加在个人或多或少的显着方式。社会心理压力可由不利的社会环境造成，如贫穷、种族、性别、宗教差异或歧视、暴力和环境污染。不仅在发展中国家，而且在更繁荣的社会，很大一部分人口被迫忍受恶劣的工作条件、低质量的食物、身体和语言虐待。最近广泛爆发的战争本质上是紧张事件，在冲突结束后可能会产生持久的影响。孤立和孤独是现代社会日益严重的问题，给人带来沉重的压力。流行病学研究表明，压力通过增加传统风险因素（吸烟、高血压、胰岛素抵抗和肥胖）的发生率与心血管疾病有关。实验和实验室证据表明，压力与心血管疾病之间存在神经内分泌、炎症和免疫途径的联系。既往CV事件受压力影响的患者与无压力条件的类似患者相比，复发事件的风险更高。结论：压力与心血管疾病之间的密切联系表明，限制压力影响的干预措施可能会降低新生和复发性心血管事件的发生率。医生应该意识到心血管疾病患者压力筛查的重要性。今后的工作应着眼于在保健框架内开发易于实施的筛查工具和有针对性的干预措施。

{"title":"Mental stress as a trigger of cardiovascular events: A narrative review","authors":"Paolo Raggi","doi":"10.1111/eci.70128","DOIUrl":"10.1111/eci.70128","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Several mental disorders has been associated with cardiovascular disease (CVD), although stress may have the strongest correlation. In this narrative review, we examine how stress is linked to CVD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Stress can be secondary to multiple factors and it can be imposed on an individual in more or less manifest ways. Psychosocial stress can result from adverse social circumstances such as poverty, racial, gender, religious disparities or discrimination, violence and environmental pollution. Large segments of the population are forced to endure poor working conditions, low food quality, physical and verbal abuse not only in the developing world but also in more flourishing societies as well. Wars that have ignited widely of late are inherently stressful events with potential enduring effects after the conflicts. Isolation and loneliness are growing issues in modern societies and impose a heavy burden of stress. Epidemiological studies have shown that stress is linked to CVD through an increased incidence of traditional risk factors (smoking, hypertension, insulin resistance and obesity). Experimental and laboratory evidence has shown a link between stress and CVD via neuro-endocrine, inflammatory and immune pathways. Patients with prior CV events affected by stress are at higher risk of recurrent events compared to similar patients without stressful conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The close association between stress and CVD suggests that interventions to limit the effect of stress may result in a reduced incidence of de novo and recurrent CV events. Physicians should be aware of the importance of screening for stress in patients with CVD. Future efforts should be directed to the development of easily implementable screening tools and targeted interventions within healthcare frameworks.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12817239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198840","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

The intergenerational effects of low parental socio-economic position on cardiometabolic and inflammatory outcomes: A systematic review and meta-analysis 父母低社会经济地位对心脏代谢和炎症结果的代际影响：系统回顾和荟萃分析。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2025-09-29 DOI: 10.1111/eci.70125

Juan Carlos Rivillas-García, Emilie Courtin, Eleanor Winpenny, Olaide Adebayo-Clement, Raúl Devia-Rodríguez, Ornella Moreno-Mattar, Paolo Vineis

Background

Evidence on the impacts of parental and early life socio-economic position (SEP) on health outcomes in adulthood remains mixed. This systematic review and meta-analysis investigated the association between low parental SEP and adult cardiometabolic and inflammatory markers in individuals aged 18 years and older.

Methods

A systematic search across five databases (EMBASE, Ovid MEDLINE, Cinahl, Global Health and Maternity and Infant Care until January 01, 2022) identified observational studies linking parental SEP with adult cardiometabolic and inflammatory markers. Pooled Standardized Mean Differences (SMD) were estimated using random-effects models. Risk of bias, heterogeneity and publication bias were assessed using the Cochrane tool, subgroup analysis and Egger's test, respectively.

Results

The review included 38 studies (12 in meta-analysis, n = 388,674). Findings showed that lower parental SEP was significantly associated with elevated blood pressure (SMD = .30 mmHg; 95% CI: .10, .50; I² 94%; n = 5), increased adiposity (SMD = .56; 95% CI: .05, 1.07: I² 98%; n = 6), higher C-reactive protein levels (SMD = 1.45 mg/dL; 95% CI: .06, 2.85; I² 80%; n = 9), elevated IL-6 (SMD = 2.12 pg./mL; 95% CI: −.72, 4.97; I² 100%; n = 4) and higher allostatic load (SMD = .85; 95% CI: .30, 1.40; I² 99%; n = 4). No consistent associations were found for glucose or lipid markers. Gender-specific variations were observed.

Conclusions

Low parental socio-economic position negatively impacts adult offspring health, manifesting as higher blood pressure, elevated C-reactive protein, increased interleukin-6, greater adiposity and higher allostatic load. Future research should prioritise three critical areas: mechanistic specificity, intersectional pathways and life-course timing and critical period detection.

背景：关于父母和早期生活社会经济地位（SEP）对成年期健康结果影响的证据仍然是混合的。本系统综述和荟萃分析调查了父母低SEP与18岁及以上成人心脏代谢和炎症标志物之间的关系。方法：系统检索5个数据库（EMBASE、Ovid MEDLINE、Cinahl、Global Health和妇幼保健，截止2022年1月1日），确定观察性研究将父母SEP与成人心脏代谢和炎症标志物联系起来。使用随机效应模型估计合并标准化平均差异（SMD）。分别采用Cochrane工具、亚组分析和Egger检验评估偏倚风险、异质性和发表偏倚。结果：纳入38项研究（12项荟萃分析，n = 388,674）。结果显示，父母低SEP与血压升高显著相关(SMD = 0.30 mmHg; 95% CI：。10、50;I2 94%;n = 5)，肥胖增加(SMD = 0.56; 95% CI：。05, 1.07: i2 98%；n = 6)，较高的c反应蛋白水平(SMD = 1.45 mg/dL; 95% CI：。06年,2.85;I2 80%;n = 9)， IL-6升高（SMD = 2.12 pg./mL; 95% CI: - 0.72, 4.97; I2 100%; n = 4）和更高的适应负荷(SMD = 0.85; 95% CI：。30日,1.40;I2 99%;n = 4)。没有发现葡萄糖或脂质标记物的一致关联。观察到性别差异。结论：父母社会经济地位低会对成年后代的健康产生负面影响，表现为血压升高、c反应蛋白升高、白细胞介素-6升高、肥胖和适应负荷增加。未来的研究应优先考虑三个关键领域：机制特异性、交叉通路和生命过程定时和关键时期检测。

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引用次数: 0

PD-L1 expression pattern as predictive factor of biological behaviour in intracranial meningiomas: A single-center retrospective study PD-L1表达模式作为颅内脑膜瘤生物学行为的预测因素：一项单中心回顾性研究。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2025-09-24 DOI: 10.1111/eci.70124

Gabriele Gaggero, Alessandro Pesaresi, Debora Giunti, Andrea Bianconi, Monica Truffelli, Massimiliano Grassi, Luca Valle, Sharon Duzioni, Paolo Nozza, Mariella Dono, Giorgia Anselmi, Gianluigi Zona, Valerio Vellone, Pietro Fiaschi

Background

Molecular expression of meningiomas has become increasingly important for predicting their biological behaviour. However, the factors influencing tumour recurrence and progression after surgery remain unclear. Recent studies suggest that programmed death-ligand 1 (PD-L1) could be a key predictive and therapeutic factor in these tumours.

Methods

This single-center retrospective study included 96 patients who underwent Simpson Grade I resection of intracranial meningiomas between 2001 and 2022. PD-L1 expression was assessed immunohistochemically (clone SP142) and categorized as overall (OE), membranous (mb), granular cytoplasmic (gr) and perinuclear dot-like. Associations with WHO grade, recurrence, mitotic count and Ki-67 index were analysed using univariate and multivariate statistics.

Results

118 samples were analysed. Grade 2 meningiomas showed significantly higher mitotic count (4.0 ± 5.5 vs. 1.0 ± 1.0 n/mm², p < .001) and Ki-67 index (7.6 ± 2.1% vs. 3.5 ± .2%, p < .001) than Grade 1. PD-L1 OE (2.0 ± 5.0% vs. .0 ± 1.0%, p < .001), gr (1.0 ± 2.5% vs. .0 ± 1.0%, p < .001) and mb (1.0 ± 1.0% vs. .0 ± .0%, p = .003) expressions were also higher in Grade 2. At recurrence, Grade 1 tumours progressing to Grade 2 showed increased PD-L1 OE (p = .025), gr (p = .024) and mb (p = .037). Multivariate analysis confirmed PD-L1 gr and mb as independent markers of high-grade tumours.

Conclusions

Granular cytoplasmic and membranous PD-L1 expression patterns are significantly associated with tumour grade, recurrence and progression, suggesting their potential role as prognostic biomarkers in meningiomas.

背景：脑膜瘤的分子表达在预测其生物学行为方面变得越来越重要。然而，影响术后肿瘤复发和进展的因素仍不清楚。最近的研究表明，程序性死亡配体1 （PD-L1）可能是这些肿瘤的关键预测和治疗因素。方法：这项单中心回顾性研究纳入了2001年至2022年间96例接受Simpson I级颅内脑膜瘤切除术的患者。免疫组织化学检测PD-L1的表达（克隆SP142），并将其分为整体（OE）、膜状（mb）、颗粒状细胞质（gr）和核周点状。采用单因素和多因素统计分析与WHO分级、复发率、有丝分裂计数和Ki-67指数的关系。结果：对118份样品进行了分析。2级脑膜瘤有丝分裂计数（4.0±5.5 vs. 1.0±1.0 n/mm2）显著高于2级脑膜瘤（4.0±5.5 vs. 1.0±1.0 n/mm2）。结论：颗粒状细胞质和膜质PD-L1表达模式与肿瘤分级、复发和进展显著相关，提示其作为脑膜瘤预后生物标志物的潜在作用。

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引用次数: 0

Central nervous system involvement in cardiac amyloidosis: Redefining the heart-brain axis 心脏淀粉样变涉及中枢神经系统：重新定义心脑轴。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2025-09-23 DOI: 10.1111/eci.70122

Domenico Mario Giamundo, Giuliano Cassataro, Stefano Ministrini, Simon F. Stämpfli

Background

Amyloidosis is characterised by the extracellular accumulation of misfolded proteins forming amorphous aggregates called amyloid. Cardiac amyloidosis results from myocardial involvement in systemic amyloidosis, leading to impaired heart function. Besides myocardial involvement, cardiac amyloidosis may also directly and indirectly affect the central nervous system.

Methods

This narrative review summarises current evidence about on central nervous system involvement in cardiac amyloidosis and the pathophysiological mechanisms linking heart and brain in the context of this systemic disease.

Results

Although the pathophysiological relationship between cardiac amyloidosis and cognitive decline remains poorly understood, central nervous system involvement likely results from the complex interplay of direct amyloid deposition, cerebrovascular changes, and cardiac dysfunction.

Conclusion

The growing awareness of cognitive impairment in patients with cardiac amyloidosis highlights the need for further research and supports a multidisciplinary approach in the assessment and management of affected individuals.

背景：淀粉样变性的特征是细胞外积聚错误折叠的蛋白质，形成无定形的聚集体，称为淀粉样蛋白。心脏淀粉样变性是由心肌累及全身淀粉样变性引起的，导致心功能受损。除心肌受累外，心肌淀粉样变还可直接或间接影响中枢神经系统。方法：本文综述了目前关于中枢神经系统参与心脏淀粉样变的证据，以及在这种全身性疾病背景下心脏和大脑联系的病理生理机制。结果：尽管心脏淀粉样变性和认知能力下降之间的病理生理关系尚不清楚，但中枢神经系统的受累可能是淀粉样蛋白直接沉积、脑血管改变和心功能障碍的复杂相互作用的结果。结论：对心脏淀粉样变性患者认知功能障碍的认识日益提高，表明需要进一步研究，并支持对受影响个体进行多学科评估和管理。

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引用次数: 0

Machine learning-based prediction of atrial fibrillation in patients with atrial high-rate episodes 基于机器学习的心房颤动高发生率发作患者预测。

IF 3.6 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation

Pub Date : 2025-09-14 DOI: 10.1111/eci.70121

Amir Askarinejad, Tommaso Bucci, Niloofar Asgharzadeh, Zahra Amirjam, Enrico Tartaglia, Michele Rossi, Yang Chen, Yalin Zheng, Gregory Y. H. Lip, Majid Haghjoo

Background

Given the modest performance of available predictive models in estimating the risk of atrial fibrillation (AF) in patients with atrial high-rate episodes (AHREs) detected by cardiac implantable electronic devices (CIEDs), this study explores the potential use of machine learning (ML) algorithms in this context.

Purpose

To assess the ability of ML techniques in identifying patients with AHRE at high risk of AF.

Methods

In this prospective study, we enrolled patients without a prior history of AF who experienced at least one AHRE episode detected by CIEDs. ML techniques were applied to predict the 1-year risk of developing new-onset AF based on the following variables: age, BMI, sex, smoking, hypertension, diabetes, coronary artery disease, chronic kidney disease, dyslipidaema, history of stroke or transient ischaemic attack, vascular heart disease, left atrial enlargement (LAE) and congestive heart failure.

Results

Study population consists of 100 patients (48% male, mean age 66.0 ± 18.0 years), of whom 24 developed AF (24%) after 1-year follow-up. The CatBoost ML model achieved the highest AUC (.857, 95% CI .671–.999) when compared to other ML models and all clinical risk scores. The top four most influential predictors of AF in the CatBoost model were LAE, hypertension, diabetes and age.

Conclusions

ML techniques are robust in predicting AF in patients with AHREs. Further validation in larger, independent cohorts is warranted.

背景：鉴于可用的预测模型在估计心房高频率发作（AHREs）患者心房颤动（AF）风险方面的适度表现，本研究探讨了机器学习（ML）算法在这方面的潜在应用。目的：评估ML技术识别AF高风险AHRE患者的能力。方法：在这项前瞻性研究中，我们招募了没有AF病史且至少经历过一次cied检测到的AHRE发作的患者。基于以下变量，应用ML技术预测1年内发生新发房颤的风险：年龄、BMI、性别、吸烟、高血压、糖尿病、冠状动脉疾病、慢性肾脏疾病、血脂异常、中风或短暂性缺血发作史、血管性心脏病、左房扩大（LAE）和充血性心力衰竭。结果：研究人群包括100例患者（男性48%，平均年龄66.0±18.0岁），随访1年后发生房颤24例（24%）。CatBoost ML模型获得了最高的AUC(。857, 95% CI .671-.999)，与其他ML模型和所有临床风险评分相比。在CatBoost模型中，对房颤影响最大的4个预测因子是LAE、高血压、糖尿病和年龄。结论：ML技术在预测AHREs患者房颤方面是可靠的。需要在更大的独立队列中进一步验证。

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引用次数: 0