Association of MicroRNA-151-5p Expression With Systemic Inflammatory Response and Cognitive Status in Patients After Coronary Artery Bypass Surgery (MiRNACOG)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Perioperative changes in microRNA 151-5p expression.
研究概览
简要总结
Postoperative cognitive decline (POCD) is one of the most common complications after cardiac surgery. It is characterized by impaired memory, attention, and executive functions and can have long-term consequences. The goal of this observational study was to investigate the mechanisms of cognitive decline after cardiac surgery and potential biomarkers that could aid in the diagnosis, prevention, and treatment of POCD. The investigators focused on the role of microRNAs (miRNAs) and systemic inflammatory response to surgery, extracorporeal circulation, and anesthesia as potential factors involved in the development of the neuroinflammatory response and subsequent POCD. The main question this study aims to answer is whether perioperative miRNA 151-5p expression is associated with POCD after surgery. The second aim is to examine the association between miRNA-151-5p and systemic inflammation. The investigators measured circulating miRNA-151-5p levels and plasma levels of inflammatory biomarkers in patients undergoing surgical myocardial revascularization. To assess cognitive function, participants completed the Montreal Cognitive Assessment (MoCA Test). Changes in the measured values of miRNA-151-5p expression and inflammatory markers, as well as changes in cognitive status after surgery, were assessed in relation to the preoperative state.
详细描述
Surgical myocardial revascularization is a procedure used in patients with ischemic heart disease to bypass atherosclerotic narrowings or blockages of the coronary arteries using an arterial or venous graft (Coronary Artery Bypass Grafting - CABG). One of the most common complications after cardiac surgery is postoperative cognitive decline (POCD). It is characterized by impaired memory, attention, and executive functions and can have long-term consequences, such as delayed physical therapy and mobilization, prolonged stay in the intensive care unit and hospital, more frequent discharge to nursing homes, reduced quality of life, and increased mortality.
The causes of POCD are multifactorial. The systemic inflammatory response to surgery, extracorporeal circulation, and anesthesia is considered a factor in the development of the neuroinflammatory response and subsequent POCD. Neuroinflammation can cause dysfunction or death of brain cells and damage to the blood-brain barrier, leading to an increase in the level of biochemical markers of brain injury in the blood. Studies indicate that numerous microRNAs (miRNAs) play a role in controlling the inflammatory response. MiRNAs are small, endogenous, non-coding RNA molecules, typically 18-25 nucleotides long, that regulate gene expression at the post-transcriptional level. They are central mediators of cellular proliferation, differentiation, and apoptosis. MiRNA levels in tissues and peripheral blood are similar, and circulating miRNAs are stable and suitable for measurement. Specific miRNAs (miRNA 151-5p, 505, 499, 625, and others) may be potential early biomarkers of brain damage after a mild traumatic brain injury. Anesthesia and surgery also, through complex mechanisms, can cause changes in brain cells that can lead to the release of specific miRNAs, and these miRNAs can be detected in blood and various biological fluids.
Hypothesis: Higher levels of perioperative miRNA-151-5p expression are associated with the systemic inflammatory response and with the development of POCD.
Aim of this study is:
- To investigate the association between miRNA-151-5p expression levels and biochemical parameters of systemic inflammation, as well as the association of both with cognitive status in patient undergoing CABG surgery.
- To investigate the association between patients' demographic and clinical characteristics and miRNA-151-5p expression levels, the level of biochemical parameters of systemic inflammation, and patients' cognitive status.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 65 Years 至 80 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •patients undergoing coronary artery bypass graft surgery to treat coronary artery disease
- •two or more coronary bypass surgery with the use of extracorporeal circulation
- •patients between the ages of 65 and 80
- •patients according to the classification of the American Society of Anesthesiologists (ASA) classified in groups III and IV
- •patients who agreed to participate in the research and signed an informed consent
排除标准
- •patients with communication difficulties (severe visual, hearing and speech impairment)
- •illiterate patients
- •patients with a history of dementia, schizophrenia, Parkinson's disease, Alzheimer's disease, alcoholism
- •patients with previously known liver failure of any grade according to the Child-Pough classification
- •patients with previously known renal failure greater than grade 2
- •patients taking immunosuppressive, corticosteroid and anticholinergic therapy
- •intraoperatively used cell-saver and/or hemofilter
- •patients in whom the planned procedure is not performed
- •patients in whom it is not possible to assess cognitive functions postoperatively (patients sedated due to intra- or postoperative surgical complications)
结局指标
主要结局
Perioperative changes in microRNA 151-5p expression.
时间窗: Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission
MicroRNA-151-5p expression levels will be measured in tree time points: preoperative before induction of anaesthesia, postoperative within 2 hours of Intensive Care Unit (ICU) admission and 48 hours after admission to the ICU. Levels of microRNA expression will be calculated relative to reference microRNA-16-5p using 2-∆∆cT method.
Perioperative changes in cognitive function measured by Montreal Cognitive Assessment (MoCA Test).
时间窗: 1 day before surgery and once daily postoperatively, up to the 6th postoperative day.
Cognitive function will be assessed in all patients at enrollment one day before surgery, and daily for the following six postoperative days using the Montreal Cognitive Assessment (MoCA test). Montreal Cognitive Assessment scale: minimum score is 0 and maximum score is 30 points, a score of 26 or above is considered normal, while scores below this may indicate cognitive impairment. A score of 18-25 suggests mild cognitive impairment, 10-17 suggests moderate impairment, and a score 0-9 suggests severe impairment.
次要结局
- Perioperative changes in levels of white blood cells.(Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission.)
- Perioperative changes in levels of C-reactive protein.(Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission)
- Perioperative changes in levels of procalcitonin.(Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission)
- Perioperative changes in levels of interleukin-6.(Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission)
- Perioperative changes in levels of cholinesterase.(Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission)
- Perioperative changes in levels of protein S-100B.(Preoperative, within 2 hours of ICU admission, 48 hours after ICU admission)
- Patient demographic data.(From enrollment to the end of cognitive testing at 6th postoperative day.)
研究者
Visnja Ikic, MD
Doctor of medicine, Specialist in anaesthesiology, reanimatology and intensive care medicine, Subspecialist in intensive care medicine
Osijek University Hospital