The Role of Inflammation after Surgery for Elders (RISE) study: Study design, procedures, and cohort profile

Abstract

Introduction The Role of Inflammation after Surgery for Elders study correlates novel inflammatory markers measured in blood, cerebrospinal fluid (CSF) assays, and [11C]‐PBR28 positron‐emission tomography imaging. Methods This study involved a prospective cohort design with patients who underwent elective hip and knee arthroplasty under spinal anesthesia. Sixty‐five adults participated with their family members. Inflammatory biomarker assays were measured preoperatively on day 1 and postoperatively at one month. Results On average, participants were 75 years old, and 72% were female. 54% underwent total knee arthroplasty, and 46% underwent total hip arthroplasty. The mean Modified Mini‐Mental State (3MS) Examination score was 89.3; four patients (6%) scored ≤77 points. Plasma assays were completed in 63 (97%) participants, cerebrospinal fluid assays in 61 (94%), and PET imaging in 44 (68%). Discussion This complex study presents an innovative effort to correlate peripheral and central inflammatory biomarkers before and after major surgery in older adults. Strengths include collecting concurrent blood, cerebrospinal fluid, and positron‐emission tomography with detailed clinical characterization of delirium, cognition, and functional status.

Preoperative red cell distribution width predicts postoperative cognitive dysfunction after coronary artery bypass grafting

“…The inflammation factors and inflammatory cells are usually at high levels in people who have ever received surgery. Neuroinflammation happens more easily in stress situations and leads to the impairment of cognitive function [30]. The neuroinflammatory mechanism of POCD includes several aspects.…”

Neurovascular and immune mechanisms that regulate postoperative delirium superimposed on dementia

“…Postoperative delirium provides a unique clinical setting because we know exactly when inflammatory processes begin as the elective surgical procedures are typically scheduled weeks to months in advance. 106 and ASCRIBED (the impact of Acute SystematiC inflammation upon CSF and blood BiomarkErs of brain inflammation and injury in dementia) 107 will provide large cohort data on immune biomarkers in orthopedic patients during aging and ongoing neurodegeneration. These combined approaches are likely to contribute to a better understanding of delirium and AD pathology to refine therapeutic targets.…”

The Role of Inflammation after Surgery for Elders (RISE) study: Examination of [11C]PBR28 binding and exploration of its link to post-operative delirium

“…The overall design and protocol of the study have been described in detail elsewhere ( Hshieh et al, 2019 ), and will be briefly reported here.…”

“…Total hip and knee arthroplasties were targeted because of their delirium risk and frequent use of spinal anesthesia ( Bruce et al, 2007 ), to avoid the potential confound of general anesthesia ( Hines et al, 2013 ). Exclusion criteria included any active psychiatric disorders, total blindness, and contraindication to spinal anesthesia/lumbar puncture, MRI, or [ 11 C]PBR28 PET (for details, see Hshieh et al, 2019 ). Importantly, all prospective patients were genotyped for the Ala147Thr polymorphism in the TSPO gene and those with predicted low-binding affinity for [ 11 C]PBR28 (Thr/Thr) ( Kreisl et al, 2013 , Owen et al, 2012 ) were excluded.…”

“…In the present study, [ 11 C]PBR28 PET and magnetic resonance (MR) brain imaging, CSF, and blood plasma biomarkers of inflammation were assessed pre-operatively and approximately 1-month post-operatively in a cohort of patients undergoing major orthopedic surgery under spinal anesthesia (for a detailed description of the study design and protocol, see Hshieh et al, 2019 ). This study builds upon prior work by investigating the effect of surgery on [ 11 C]PBR28 binding in a group of older adults of both sexes over the age of 70, who are at increased risk for post-operative cognitive decline.…”