Aging, Immunology, Postoperative Complications, Surgery
Conditions
Keywords
Frailty, Neuro-Degenerative Disease, innate immunity, immunphenotyping
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.
Interventions
None listed
Sponsors
University of Bonn
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
80 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peri-interventional (surgical and non-surgical interventional) all-cause mortality rate on day 30 | 30 days | Number of patients with death from any cause |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| Unplanned intensive care unit admission | 30 days | Number of patients |
| Unplanned intubation after intervention | 30 days | Number of patients |
| 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 surgical side infection | 30 days | Number of patients |
| Ventilator dependency >48 h | 48 hours | duration of mechanical ventilation |
| 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 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 |
Countries
Germany
Contacts
Primary ContactChristian Bode, MD
Outcome results
None listed