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The Neuro-epigenetics Biomarkers of Postoperative Delirium in Elderly Patients Undergoing Hip/Knee Replacement

Conditions
Postoperative Delirium
Interventions
Procedure: hip/knee replacement
Registration Number
NCT04923243
Lead Sponsor
Zhongnan Hospital
Brief Summary

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.

Detailed Description

Method:

1. Study design: This study is a prospective investigation that searches for neuro-epigenetics biomarkers to predict and diagnose POD.

2. Inclusion criteria / Exclusion Criteria

Inclusion criteria: Eligible patients were at least 65 years old and were scheduled to have hip/knee replacement.

Exclusion Criteria:

1. a past medical history of neurological or clinically evident neurovascular disease (e.g., Alzheimer's disease, other forms of dementia, stroke);

2. Patients diagnosed with malignant or benign tumors;

3. Mini-Mental State Examination (MMSE) scores of 26 or less;

4. 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;

5. a history of alcohol abuse and drug dependence;

6. inability to read or severe visual or auditory deficits;

7. unwillingness to comply with the protocol or procedures.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
300
Inclusion Criteria

Eligible patients were at least 65 years old and were scheduled to have hip/knee replacement.

Exclusion Criteria
  1. a past medical history of neurological or clinically evident neurovascular disease (e.g., Alzheimer's disease, other forms of dementia, stroke);
  2. patients diagnosed with malignant or benign tumors;
  3. Mini-Mental State Examination (MMSE) scores of 26 or less;
  4. American Society of Anesthesiologists (ASA) score greater than 3;
  5. a history of alcohol abuse and drug dependence;
  6. inability to read or severe visual or auditory deficits;
  7. unwillingness to comply with the protocol or procedures.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Delirium grouphip/knee replacementGroup of patients with postoperative delirium
Non delirium grouphip/knee replacementGroup of patients without postoperative delirium
Primary Outcome Measures
NameTimeMethod
genome-specific difference between POD and non-POD patientsjust before surgery

Compare the exon sequence in blood samples of the participants, as assessed by whole exome sequencing.

cell-free DNA, cell-free RNA and exosomal RNA level in blood and urinejust 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.

candidate cell-free DNA, cell-free RNA and exosomal RNA level in blood and urinepost 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.

Secondary Outcome Measures
NameTimeMethod
Delirium severity assessment - Delirium Severity based on 3D-CAM (3D-CAM-S)post operative day 7 or the day after delirium disappeared

ranging from 0 to 7 points

Delirium subtype assessment - Richmond Agitation-Sedation Scale (RASS)post operative day 7 or the day after delirium disappeared

ranging from -5 to +4 points

Delirium assessment - 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM)post operative day 7 or the day after delirium disappeared

positive or negative

Trial Locations

Locations (1)

Zhongnan Hospital of Wuhan University

🇨🇳

Wuhan, Hubei, China

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