Clinical trial NCT05368896: Peri-operative Inflammaging in the Elderly After Surgery
Official title: Peri-OPerative InflamMAGing in Elderly Patients Undergoing Major Surgery: Prediction and Pathomechanisms of Post-operative Morbidities
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Aging
Immunology
Postoperative Complications
Surgery
Keywords: Frailty
Neuro-Degenerative Disease
innate immunity
immunphenotyping
Lead sponsor: University of Bonn
Sponsor class: OTHER
First posted: 2022-05-10
Enrollment: 150
Sex: ALL
Minimum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients ≥ 80 years undergoing major surgery

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.


Eligibility criteria: 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

Primary outcomes:
measure: Peri-interventional (surgical and non-surgical interventional) all-cause mortality rate on day 30
timeFrame: 30 days
measure: In-hospital outcome according to the ACS National Surgical Quality Improvement Program® (ACS NSQIP®)
timeFrame: 30 days
Secondary outcomes:
measure: Analysis of the new-onset of serious cardiac complications
timeFrame: 30 days
measure: Analysis of the new-onset of serious pulmonary complications
timeFrame: 30 days
measure: Analysis of the new-onset of acute stroke
timeFrame: 30 days
measure: Analysis of the new-onset of acute kidney injury
timeFrame: 30 days
measure: Unplanned intensive care unit admission
timeFrame: 30 days
measure: Unplanned intubation after intervention
timeFrame: 30 days
measure: Analysis of the new-onset of sepsis
timeFrame: 30 days
measure: Analysis of the new-onset surgical side infection
timeFrame: 30 days
measure: Ventilator dependency >48 h
timeFrame: 48 hours
measure: Analysis of the new-onset thrombosis
timeFrame: 30 days
measure: all cause mortality
timeFrame: 12 month
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: University Hospital Bonn
Study officials:
affiliation: mark.coburn@ukbonn.de
name: Mark Coburn, Prof
role: STUDY_CHAIR
References: