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感染、DNA甲基化和端粒长度对住院老年患者衰弱轨迹的影响:INFRAGEN研究方案

Effect of infections, DNA methylation and telomere length on frailty trajectories in hospitalized older patients: the INFRAGEN study protocol.

作者信息

Guo Wenxiang, Bencivenga Leonardo, Zanforlini Bruno Micael, Curreri Chiara, Ferrara Maria Cristina, Maisano Benedetta, Tinelli Luca, Ceparano Laura Andreea, Merenda Raffaella, Cosma Chiara, Manfron Lucia, Gentili Nicolò, Sturani Silvia, Cardi Monica, Campion Alice, Berardi Benedetta, Lombardi Martina, D'Aversa Elisabetta, Salvatori Francesca, Tisato Veronica, Vargas Joanne Vanessa, Femminella Grazia Daniela, Gemmati Donato, Sergi Giuseppe, Bellelli Giuseppe, Mazzola Paolo, Trevisan Caterina, Volpato Stefano

机构信息

School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

Department of Translational Medical Sciences, University of Naples "Federico II", Naples, Italy.

出版信息

BMC Geriatr. 2025 Jul 23;25(1):545. doi: 10.1186/s12877-025-06194-z.

Abstract

BACKGROUND

Infectious diseases are among the most common causes of hospitalization in older adults and may lead to a high burden on the individual's health and healthcare system. However, it is unclear whether and to which extent these events might affect frailty, fastening its development or hampering its reversion. The aims of the INFRAGEN project are 1) to assess the impact of acute infections on frailty trajectories in older inpatients, and 2) to evaluate the modifying effect of sociodemographic, clinical, functional, and genetic/epigenetic factors on that association.

METHODS

INFRAGEN is a multicenter prospective observational study that will be conducted in the acute Geriatric Units of four Italian centers (Ferrara, Padova, Monza, and Napoli). The project will involve individuals aged ≥ 70 with no or mild-to-moderate pre-admission frailty (Clinical Frailty Scale [CFS] < 6) and diagnosis of acute infectious diseases at the time of hospital admission or during hospitalization. For each participant, we will record data concerning the multidimensional geriatric assessment and the type and severity of infectious diseases (diagnosed according to ICD-9 codes). Blood samples will be collected to assess Global DNA methylation, Leukocyte Telomere Length (LTL), and levels of circulating markers associated with biological processes related to frailty (inflammatory state, dysmetabolism, brain modifications, and oxidative stress). Frailty status will be evaluated through the CFS and Frailty Index at admission (referring to the 2 weeks before hospitalization), hospital discharge, and after 3 months. In a subsample, genetic/epigenetic analyses will also be performed at the 3-month follow-up.

DISCUSSION

INFRAGEN will contribute to exploring the complex pathophysiologic mechanisms of frailty in the context of infections in older adults through a translational approach.

TRIAL REGISTRATIONS

NCT06430073 (ClinicalTrials.gov); Registration date: 2024-05-28.

摘要

背景

传染病是老年人住院治疗最常见的病因之一,可能给个人健康和医疗系统带来沉重负担。然而,目前尚不清楚这些疾病是否以及在何种程度上会影响衰弱,加速其发展或阻碍其逆转。INFRAGEN项目的目标是:1)评估急性感染对老年住院患者衰弱轨迹的影响;2)评估社会人口学、临床、功能和遗传/表观遗传因素对这种关联的调节作用。

方法

INFRAGEN是一项多中心前瞻性观察性研究,将在意大利四个中心(费拉拉、帕多瓦、蒙扎和那不勒斯)的急性老年病科进行。该项目将纳入年龄≥70岁、入院前无衰弱或有轻度至中度衰弱(临床衰弱量表[CFS]<6)且在入院时或住院期间诊断为急性传染病的患者。对于每位参与者,我们将记录有关多维度老年评估以及传染病类型和严重程度(根据ICD-9编码诊断)的数据。将采集血样以评估全球DNA甲基化、白细胞端粒长度(LTL)以及与衰弱相关生物过程(炎症状态、代谢紊乱、脑改变和氧化应激)相关的循环标志物水平。将通过CFS和衰弱指数在入院时(指住院前2周)、出院时和3个月后评估衰弱状态。在一个子样本中,还将在3个月随访时进行遗传/表观遗传分析。

讨论

INFRAGEN将通过转化医学方法,有助于探索老年人感染背景下衰弱的复杂病理生理机制。

试验注册

NCT06430073(ClinicalTrials.gov);注册日期:2月28日。 (此处原文Registration date: 2024-05-原文有误,按照2024-05-28翻译)

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