The Neuro-epigenetics Biomarkers of Postoperative Delirium in Elderly Patients Undergoing Hip/Knee Replacement
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
Method:
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Study design: This study is a prospective investigation that searches for neuro-epigenetics biomarkers to predict and diagnose POD.
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Inclusion criteria / Exclusion Criteria
Inclusion criteria: Eligible patients were at least 65 years old and were scheduled to have hip/knee replacement.
Exclusion Criteria:
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a past medical history of neurological or clinically evident neurovascular disease (e.g., Alzheimer's disease, other forms of dementia, stroke);
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Patients diagnosed with malignant or benign tumors;
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Mini-Mental State Examination (MMSE) scores of 26 or less;
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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;
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a history of alcohol abuse and drug dependence;
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inability to read or severe visual or auditory deficits;
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unwillingness to comply with the protocol or procedures.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Delirium group Group of patients with postoperative delirium |
Procedure: hip/knee replacement
hip/knee replacement
|
| Non delirium group Group of patients without postoperative delirium |
Procedure: hip/knee replacement
hip/knee replacement
|
Outcome Measures
Primary Outcome Measures
- cell-free DNA, cell-free RNA and exosomal RNA level in blood and urine [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.
- genome-specific difference between POD and non-POD patients [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 [post operative day 1]
Candidate cell-free DNA, cell-free RNA and exosomal RNA identified in the first outcome were quantified by PCR or RT-PCR on post operative day 1.
- candidate cell-free DNA, cell-free RNA and exosomal RNA level in blood and urine [post operative day 3]
Candidate cell-free DNA, cell-free RNA and exosomal RNA were quantified by PCR or RT-PCR on post operative day 3.
- candidate cell-free DNA, cell-free RNA and exosomal RNA level in blood and urine [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.
Secondary Outcome Measures
- Delirium assessment - 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) [before surgery (from 1 week before to the day before)]
positive or negative
- Delirium assessment - 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) [post operative day 1]
positive or negative
- Delirium severity assessment - Delirium Severity based on 3D-CAM (3D-CAM-S) [post operative day 1]
ranging from 0 to 7 points
- Delirium subtype assessment - Richmond Agitation-Sedation Scale (RASS) [post operative day 1]
ranging from -5 to +4 points
- Delirium assessment - 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) [post operative day 3]
positive or negative
- Delirium severity assessment - Delirium Severity based on 3D-CAM (3D-CAM-S) [post operative day 3]
ranging from 0 to 7 points
- Delirium subtype assessment - Richmond Agitation-Sedation Scale (RASS) [post operative day 3]
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
- 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
Eligibility Criteria
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 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Zhongnan Hospital of Wuhan University | Wuhan | Hubei | China | 430071 |
Sponsors and Collaborators
- Zhongnan Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HBRC202004072021014