Peri-operative Inflammaging in the Elderly After Surgery

Recruiting

• Conditions: Postoperative Complications; Surgery; Aging; Immunology

• Registration Number: NCT05368896
• Lead Sponsor: University of Bonn

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-04-05
• Study First Submitted QC: 2022-05-05
• Study First Posted: 2022-05-10
• Study Start: 2022-12-01
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-25
• Last Update Posted: 2023-02-28
• Primary Completion: 2024-12-30
• Study Completion: 2025-03-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
In-hospital outcome according to the ACS National Surgical Quality Improvement Program® (ACS NSQIP®)	30 days	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
Peri-interventional (surgical and non-surgical interventional) all-cause mortality rate on day 30	30 days	Number of patients with death from any cause

Secondary Outcome Measures

Name	Time	Method
Unplanned intensive care unit admission	30 days	Number of patients
Analysis of the new-onset surgical side infection	30 days	Number of patients
Analysis of the new-onset thrombosis	30 days	number of patients with (deep) vein thrombosis
all cause mortality	12 month	Number of patients with death from any cause
Analysis of the new-onset of sepsis	30 days	Number of patients diagnoses by SEPSIS-3 definition
Analysis of the new-onset of serious cardiac complications	30 days	Number of patients with serious cardiac complication; Cardiac complication is defined according to the American Heart Association
Analysis of the new-onset of acute kidney injury	30 days	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.
Analysis of the new-onset of acute stroke	30 days	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.
Unplanned intubation after intervention	30 days	Number of patients
Ventilator dependency >48 h	48 hours	duration of mechanical ventilation
Analysis of the new-onset of serious pulmonary complications	30 days	Number of patients with; Pneumonia: Clinical or radiological diagnosis. or Pulmonary embolism: Radiological diagnosis. Signs of pneumonia or pulmonary embolism in the autopsy

Trial Locations

Locations (1)

University Hospital Bonn; 🇩🇪 Bonn, Germany