Clinical Research Directory

The Role of Neuroinflammation on Neurocognitive Outcome in Cardiac Surgery

RATIONALE: Postoperative cognitive changes are common after cardiac surgery and can be categorised into three main types: postoperative delirium (POD), delayed neurocognitive recovery (DNCR) and postoperative neurocognitive disorder (PNCD). DNCR is diagnosed until postoperative day 30 and PNCD is diagnosed at least 30 days after the operation. Both conditions can be mild or major, and can affect the quality of life of these patients. The incidence of PNCD in cardiac surgery is around 40%. Despite this high incidence, screening for PNCD is absent in current postoperative care since the diagnosis of PNCD is difficult and very time intensive. Furthermore, the underlying pathogenesis is incompletely understood. The identification of a biomarker and/or validated short diagnostic instrument would be of paramount importance to easily identify patients at risk, or to diagnose patients with PNCD in order to identify therapeutical pathways for this disease. OBJECTIVES: The main objective of this prospective clinical trial is to evaluate the performance of the short NPA and/or biochemical markers for the diagnosis of DNCR and PNCD in cardiac surgery patients aged 60 years or older. STUDY DESIGN: Single-centre interventional observational study STUDY INTERVENTIONS: Patients will undergo a neurophysiological assessment (NPA) pre-operatively and at two timepoints post-operatively, namely 6 (+/-1) days and 40 (+/- 10) days after surgery. During the stay at the intensive care unit, they will be screened daily for delirium, using the CAM-ICU and 3D-CAM. To evaluate whether the development of DNCR or POD has an important effect on quality of recovery , the quality of recovery scale 15 (QOR-15), muscle strength (handgrip strength) and the Chalder fatigue score will be scored post-operative (postop day 1, 3 and 5). To evaluate whether PNCD has an effect on quality of live the EQ5D5L score will be measured at 40 (+/- 10) days after surgery, compared to preoperative values. On several time points, blood samples will be drawn to measure markers of neuroinflammation. The time points will be preoperatively, at the moment of arrival on ICU, postoperative day 1, 2 and 3, if still on ICU. Two repeat blood sample will be taken at the moment of NPA performed after 6 (+/- 1) days and 40 (+/- 10) days after surgery, if the patient is willing (not obligatory). STUDY POPULATION: Patients aged 60 years or older who are scheduled for cardiac surgery. Inclusion criteria: * aged 60 years or older; * scheduled for cardiac surgery. Exclusion criteria: * dementia, as diagnosed by a neurologist; * urgent, not elective surgery. MAIN STUDY ENDPOINTS: Primary outcome PNCD defined as a decline of \> 1 SD on \> 2 tests in one or more cognitive domains or a decline of \> 1 SD on total cognitive domain score. Secondary outcomes Postoperative delirium - CAM-ICU will be evaluated twice daily (morning and evening) on every day when the patient is awake (not intubated) on the ICU. This is standard of care and is part of the routine clinical care in the hospital. Furthermore, once daily a 3D-CAM will be performed on day 1, 3 and 5. Quality of recovery * QOR-15, a validated measurement of quality of recovery in the short term postoperative recovery, will be evaluated pre-operatively and postoperatively day 1, 3 and 5. * EQ5D5L, a validated measurement of quality of recovery in the long term postoperative recovery, will be evaluated preoperatively and at the moment of the third NPA measurement. * Postoperative muscle function (upper extremity, by hand grip strength) on day 1, 3 and 5 after surgery and at the moment of the second and third NPA measurement (being day 6 (+/-1) and day 40 (+/-10) postoperatively), as compared to preoperative values. * Chalder Fatigue questionnaire on day 1, 3 and day 5 and on the second and third NPA measurement, as compared to preoperative. Biochemical analysis \- Blood samples will be drawn for analysis before induction of anaesthesia (preoperatively), at the end of the operation (immediately postoperatively on arrival in ICU), on day 1, 2 and 3 postoperatively (if still at the ICU) and at the time of the postoperative follow-up visits with the NPA testing (day 6 (+/-1) and day 40 (+/-10) days post-surgery). At each time point, markers of neuroinflammation and -degeneration will be determined. Tertiary outcomes * Length of CPB * Duration of mechanical ventilation * Administered anaesthetic drugs during surgery * Transfusion need * Length of ICU stay (days) * Length of in-hospital stay (days) * Readmission to ICU or hospital within 28 days after surgery * Cardiovascular outcome: atrial fibrillation, , thrombo-embolic events, myocardial injury, myocardial infarction, cardiac arrest, cardiac death * Pulmonary outcome: postoperative pulmonary complications, postoperative pneumonia, postoperative respiratory failure * Postoperative infection within 28 days after surgery

Digital Sleep Optimization for Brain Health Outcomes in Older Surgical Patients

The Sleep Optimization for Brain Health Outcomes in Older Surgical Patients (SLEEP-BOOST) is a pilot randomized, controlled, singled-blinded (participant) trial in major orthopedic joint surgery patients that will build on a previously clinically tested cognitive behavioral therapy for insomnia (CBT-I) mobile application paired with a wearable device (wrist actigraphy).

Prediction and Prevention of Postoperative Mortality and Morbidity

This study will contribute to creating a prospective and automated preoperative risk assessment algorithm for predicting 30-day mortality, major adverse cardiac and cerebrovascular events (MACCE), and postoperative neurocognitive outcomes following elective cardiac and vascular surgery in older adults. It will evaluate associations between perioperative factors and longer-term neurocognitive outcomes, including postoperative neurocognitive disorder and dementia. In addition, this study will assess scalable, multimodal preoperative and intraoperative interventions to improve perioperative outcomes. This study will explore two main hypotheses: 1. Preoperative personalized prehabilitation with proactive cognitive and behavioral interventions will improve postoperative cognitive outcomes, morbidity, and mortality in high-risk elderly surgical patients. 2. Proactive bundled intraoperative interventions are superior to reactive standard of care in reducing postoperative cognitive outcomes, MACCE, and mortality. Expected Outcome: Improved EHR algorithm will have higher predictive accuracy for MACCE and mortality while predicting postoperative cognitive outcomes.

Repetitive Transcranial Magnetic Stimulation and Postoperative Neurocognitive Recovery

Patients with preoperative cognitive impairment are at increased risks of delayed neurocognitive recovery (DNR) and postoperative neurocognitive disorder (POCD). Repetitive transcranial magnetic stimulation (rTMS) has been used to improve cognitive function in patients with cognitive impairement. This trial is designed to compare the effects of rTMS versus sham intervention on postoperative neurocognitive function in patients with preoperative cognitive impairment.

Correlation Analysis of POD and pNCD in Elderly Spinal Surgery Patients

This study is a prospective cohort study to investigate the differences in serum indexes between elderly spinal surgery patients with postoperative delirium (POD) who either develop or do not develop long-term postoperative neurocognitive disorders (pNCD).

Risk Warning Model of Postoperative Delirium and Long-term Cognitive Dysfunction in Elderly Patients

The incidence of postoperative delirium in elderly patients is high, which can lead to long-term postoperative neurocognitive disorders. Its high risk factors are not yet clear. At present, there is a lack of early diagnosis and alarm technology for perioperative neurocognitive disorders, which can not achieve early intervention and effective treatment. By artificial intelligence and autonomously evolutionary neural network algorithm, relying on multi-source clinical big data, we explored the use of Bayesian network to optimize the anesthesia decision-making system in enhanced recovery after surgery, and established risk prediction model for perioperative critical events. It is expected that this method will also help to establish a risk prediction model for postoperative delirium and long-term postoperative neurocognitive disorders. This project plans to collect the perioperative sensitive parameters of anesthesia machine, multi-parameter monitor, EEG monitor,fMRI and HIS system, to explore the evolution process of data characteristics by feature fusion.We also plan to quickly screen key perioperative risk characteristics of postoperative delirium from massive clinical data through feature selection, to explore the high risk factors of long-term postoperative neurocognitive disorders developing from postoperative delirium. Finally, with multi-center intelligent analysis，the risk prediction model of postoperative delirium and long-term postoperative neurocognitive disorders will be constructed.

Correlation Analysis of POD and pNCD in Elderly Patients With Gastrointestinal Neoplasms

This is a prospective cohort study to explore the differences of serum indicators between elderly gastrointestinal neoplasms patients with postoperative delirium (POD) who either develop or do not develop long-term postoperative neurocognitive disorders (pNCD).