The Neuro-epigenetics Biomarkers of Postoperative Delirium in Elderly Patients Undergoing Hip/Knee Replacement
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- genome-specific difference between POD and non-POD patients
研究概览
简要总结
Introduction: Postoperative delirium (POD), an acute, transient, fluctuating disturbance in attention, cognition, and level of consciousness, is a common (15-53%) postoperative complication, and it is associated with longer hospital stays, worse functional outcomes, higher healthcare costs, and increased mortality. However, at the current time, effective prevention and treatment are not only hampered by lack of knowledge about the neuropathogenesis of POD but also by a lack of biomarkers that could predict individual risk and assess diagnosis and severity of POD.
Recent studies have focused on inflammatory markers (IL-1, IL-6, IL-8, IL-10, CRP), Alzheimer's disease-related factors (Tau, Aβ40/42), and nerve injury factors (S100β, NSE), but failed to establishing causality between these markers and POD. Furthermore, these results were contradictory. Previous study of the investigators found that the dysregulation of preoperative microRNA (miR)-146a and miR-181c in cerebrospinal fluid (CSF) and serum was associated with the development and severity of POD. Therefore, the investigators hypothesized these neurimmiRs and other neuro-epigenetics biomarkers might participate in the neuropathogenesis of POD.
Purpose: Aims to search for neuro-epigenetics biomarkers to predict and diagnose POD.
详细描述
Method:
- Study design: This study is a prospective investigation that searches for neuro-epigenetics biomarkers to predict and diagnose POD.
- Inclusion criteria / Exclusion Criteria
Inclusion criteria: Eligible patients were at least 65 years old and were scheduled to have hip/knee replacement.
Exclusion Criteria:
- a past medical history of neurological or clinically evident neurovascular disease (e.g., Alzheimer's disease, other forms of dementia, stroke);
- Patients diagnosed with malignant or benign tumors;
- Mini-Mental State Examination (MMSE) scores of 26 or less;
- American Society of Anesthesiologists (ASA) score [a global score that assesses the physical status of patients before surgery, ranging from 1 (normal health) to 5 (moribund)] greater than 3;
- a history of alcohol abuse and drug dependence;
- inability to read or severe visual or auditory deficits;
- unwillingness to comply with the protocol or procedures.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 65 Years 至 100 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligible patients were at least 65 years old and were scheduled to have hip/knee replacement.
排除标准
- •a past medical history of neurological or clinically evident neurovascular disease (e.g., Alzheimer's disease, other forms of dementia, stroke);
- •patients diagnosed with malignant or benign tumors;
- •Mini-Mental State Examination (MMSE) scores of 26 or less;
- •American Society of Anesthesiologists (ASA) score greater than 3;
- •a history of alcohol abuse and drug dependence;
- •inability to read or severe visual or auditory deficits;
- •unwillingness to comply with the protocol or procedures.
结局指标
主要结局
genome-specific difference between POD and non-POD patients
时间窗: just before surgery
Compare the exon sequence in blood samples of the participants, as assessed by whole exome sequencing.
candidate cell-free DNA, cell-free RNA and exosomal RNA level in blood and urine
时间窗: post operative day 7 or the day after delirium disappeared
Candidate cell-free DNA, cell-free RNA and exosomal RNA were quantified by PCR or RT-PCR on post operative day 7 or the day after delirium disappeared.
cell-free DNA, cell-free RNA and exosomal RNA level in blood and urine
时间窗: just before surgery
Cell-free DNA, cell-free RNA and exosomal RNA level in blood and urine of the participants were measured by DNA sequencing or RNA sequencing before surgery.
次要结局
- Delirium severity assessment - Delirium Severity based on 3D-CAM (3D-CAM-S)(post operative day 7 or the day after delirium disappeared)
- Delirium subtype assessment - Richmond Agitation-Sedation Scale (RASS)(post operative day 7 or the day after delirium disappeared)
- Delirium assessment - 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM)(post operative day 7 or the day after delirium disappeared)