Peri-operative Inflammaging in the Elderly After Surgery

Study Overview
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Brief Summary
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The population older than 80 years will significantly increase in the near future. Older patients' cognitive and physical status is known to deteriorate after surgery, leading to a high 30-day mortality due to post-operative comorbidities. Aging and related diseases share immune-related pathomechanisms. During aging, a chronic, low-grade sterile inflammation, called inflamaging, gradually develops. This likely results from low-grade innate immune activation and a functional, epigenomic and transcriptomic reprogramming of immune cells. Based on the hypothesis that surgical trauma leads to misplaced or altered self-molecules, which exacerbate inflammation and the postoperative risk for morbidity and mortality in elderly patients. There is increasing evidence that the individual's pre-operative immunobiography determines the susceptibility to peri-operative inflammation and post-operative outcome. Current exploratory pilot study will thus perform phenotyping of patients above 80 years undergoing major surgery. Participants will be evaluated for acute and long-term outcomes, including all-cause mortality, physical and cognitive function. To assess the individual's immunobiography, participants will be characterised by inflammation biomarkers combined with immunophenotyping, functional assays, and (epi-) genomic analyses before and after surgery. The cognitive impairment will be evaluated by measuring markers of neurodegeneration and neuropsychiatric testing and relate findings to volumetric imaging using high-resolution MRI to identify brain changes associated with cognitive decline.

Official Title
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Peri-OPerative InflamMAGing in Elderly Patients Undergoing Major Surgery: Prediction and Pathomechanisms of Post-operative Morbidities

Conditions
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Aging, Immunology, Postoperative Complications, Surgery

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 80 years elective major surgery defined as knee / hip replacement, spondylodesis (> 2 levels), gastrectomy, resection of esophagus, liver, pancreas, colon, rectum or lung Exclusion Criteria: no informed consent not able to perform neurocognitive testing preexisting infection systemic: CRP>100 mg/l, Leukos >12.0 G/l or clinical signs Prosthetic joint infection (MSIS 2011 criteria): PJI is present when 1 major criteria exist or 4 out of 6 minor criteria exist Major criteria: 2 positive periprosthetic cultures with phenotypically identical organisms A sinus tract communicating with the joint Minor criteria: Elevated CRP and ESR Elevated synovial fluid WBC count or ++ change on leukocyte esterase test strip Elevated synovial fluid PMN% Presence of purulence in the affected joint Positive histologic analysis of periprosthetic tissue A single positive culture Immunosuppression (HIV, glucocorticoids, immunosupressants) Autoimmune diseases ongoing or recent (<3 months) chemo/radiotherapy

Ages Eligible for Study
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Minimum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Elderly patients with postoperative complications after major surger<br>Patients >80 years that will undergo major visceral or orthopedic surgery | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peri-interventional (surgical and non-surgical interventional) all-cause mortality rate on day 30 | Number of patients with death from any cause | 30 days | 
| In-hospital outcome according to the ACS National Surgical Quality Improvement Program® (ACS NSQIP®) | Number of patients with e.g. pneumonia, cardiovascular complication, surgical site infection, urinary tract infection, venous thromboembolism, acute or progressive renal failure and re-surgery | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of the new-onset of serious cardiac complications | Number of patients with serious cardiac complication Cardiac complication is defined according to the American Heart Association | 30 days | 
| Analysis of the new-onset of serious pulmonary complications | Number of patients with Pneumonia: Clinical or radiological diagnosis. or Pulmonary embolism: Radiological diagnosis. Signs of pneumonia or pulmonary embolism in the autopsy | 30 days | 
| Analysis of the new-onset of acute stroke | Number of patients with new-onset of acute stroke, defined as a new focal or generalised neurological deficit of >24h duration in motor, sensory, or coordination functions with compatible brain imaging and confirmed by a neurologist. Transient ischemic attack is not considered as acute stroke. Signs of stroke in the autopsy. | 30 days | 
| Analysis of the new-onset of acute kidney injury | Number of patients with new-onset of acute kidney injury, defined according to the AKIN classification as AKI stage ≥2. This means increase of creatinine >2-3x from baseline within the hospital stay. Or urine output less than 0.5 ml kg-1 per hour for more than 12 hours. Or signs of acute kidney injury in the autopsy. | 30 days | 
| Unplanned intensive care unit admission | Number of patients | 30 days | 
| Unplanned intubation after intervention | Number of patients | 30 days | 
| Analysis of the new-onset of sepsis | Number of patients diagnoses by SEPSIS-3 definition | 30 days | 
| Analysis of the new-onset surgical side infection | Number of patients | 30 days | 
| Ventilator dependency >48 h | duration of mechanical ventilation | 48 hours | 
| Analysis of the new-onset thrombosis | number of patients with (deep) vein thrombosis | 30 days | 
| all cause mortality | Number of patients with death from any cause | 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Frailty, Neuro-Degenerative Disease, innate immunity, immunphenotyping