Peri-operative Inflammaging in the Elderly After Surgery (POPIMAGE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Complications; Aging; Surgery; Immunology

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

• Study Contact: Name: Christian Bode, MD; Phone Number: +4922828714110; Email: christian.bode@ukbonn.de

Study Locations

• Germany
  • Bonn, Germany, 53127
    • Recruiting
    • University Hospital Bonn
    • Contact: Christian Bode, MD; Phone Number: +4922828714110; Email: christian.bode@ukbonn.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 80 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients ≥ 80 years undergoing major surgery

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Elderly patients with postoperative complications after major surger; Patients >80 years that will undergo major visceral or orthopedic surgery

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Bonn
• Investigators: Study Chair: Mark Coburn, Prof, mark.coburn@ukbonn.de

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Anticipated): December 30, 2024
• Study Completion (Anticipated): March 30, 2025

Study Registration Dates

• First Submitted: April 5, 2022
• First Submitted That Met QC Criteria: May 5, 2022
• First Posted (Actual): May 10, 2022

Study Record Updates

• Last Update Posted (Estimate): February 28, 2023
• Last Update Submitted That Met QC Criteria: February 25, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Frailty; innate immunity; Neuro-Degenerative Disease; immunphenotyping
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications
• Other Study ID Numbers: KAI-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No