Aging, Immunosenescence
Conditions
Keywords
Knee arthroplasty, Elderly, Immune functioning, Monocytes
Brief summary
The goal of this observational study is to determine changes in immune functioning after total knee replacement surgery in elderly. The study population consists of 14 patients aged 65 years or over undergoing primary total knee replacement surgery. Immune functioning will be assessed at multiple timepoints before and after surgery (i.e., ± 6 weeks before, and 1 day, 1 week, ± 2 weeks, and ± 6 weeks after surgery). Each patient will serve as his/her own control. Immune functioning will primarily be assessed by determining the change from baseline in monocyte-derived TNFα production at 1 week after surgery. Changes in monocyte responsiveness are considered indicative for changes in immune functioning. As secondary objective, additional parameters of immune functioning will be assessed. In addition, the course of immune functioning following total knee replacement surgery will be investigated. Burden and potential risks for the patient are estimated to be minor. During the study, 5 blood samples of 20 mL will be collected over a period of ± 12 weeks, resulting in a total blood draw of 100 mL. During surgery a sample of synovial fluid (± 2 mL) will be taken from surgical waste. Before and after surgery patients will report their pain medication intake and the presence of cold and flu-like symptoms in a diary. Patients do not directly benefit from the study.
Detailed description
The world population is progressively aging. As humans age, their immune system becomes weaker through a process called immunosenescence. This age-related decline in immune functioning results in an increased susceptibility to infections. Elderly with chronic diseases or elderly who have experienced an incident, such as fall-related trauma or surgery, are particularly vulnerable to these infections, likely due to immunosuppression resulting from such an immune challenge. Currently, there are no standard interventions used to improve immune functioning in these immune-suppressed elderly. However, before the potential of such interventions can be explored, postoperative immune suppression in elderly first needs to be demonstrated. The goal of this prospective ex vivo study is therefore to determine changes in immune functioning after total knee replacement surgery in elderly. The study population consists of 14 patients (classified as ASA II or ASA III) aged 65 years or over, diagnosed with osteoarthritis, undergoing primary total knee replacement surgery under general anesthesia. Immune functioning will be assessed at multiple timepoints before and after surgery (i.e., ± 6 weeks before, and 1 day, 1 week, ± 2 weeks, and ± 6 weeks after surgery). Each patient will serve as his/her own control. Immune functioning will primarily be assessed by determining the change from baseline in monocyte-derived TNFα production at 1 week after surgery. TNFα production will be measured after ex vivo stimulation of whole blood with inflammatory stimuli and normalized for monocyte count. Changes in monocyte responsiveness are considered indicative for changes in immune functioning. As secondary objective, additional parameters of immune functioning will be assessed. In addition, the course of immune functioning following total knee replacement surgery will be investigated. Burden and potential risks for the patient are estimated to be minor. During the study, 5 blood samples of 20 mL will be collected over a period of ± 12 weeks, resulting in a total blood draw of 100 mL. Blood sampling will be combined with regular care visits, with the exception of one occasion where blood sampling will be performed at home. Patients could experience mild pain by the venipuncture, which occasionally leads to lightheadedness, fainting and hematoma. During surgery a sample of synovial fluid (± 2 mL) will be taken from surgical waste. Before and after surgery patients will report their pain medication intake and the presence of cold and flu-like symptoms in a diary. Patients do not directly benefit from the study.
Interventions
PROCEDUREKnee arthroplasty
At multiple timepoints (i.e., ± 6 weeks before, and 1 day, 1 week, ± 2 weeks, and ± 6 weeks after surgery) before and after total knee replacement surgery blood will be collected to assess immune functioning
Sponsors
Wageningen University and Research
Gelderse Vallei Hospital
Wageningen University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Planned for primary total knee replacement surgery * Aged 65 years or over * Diagnosed with osteoarthritis * ASA Physical Status Classification of II or III * Willing to donate a blood sample at 5 different timepoints * Able to give written informed consent
Exclusion criteria
* Daily use of high doses NSAIDs within the 14 days before inclusion: Defined as higher than maintenance dose in the farmacotherapeutisch kompas. For example: acetylsalicylic acid \> 4 g/day; diclofenac \> 75 mg/day; naproxen \> 500 mg/day; ibuprofen\> 1600 mg/day; celecoxib \> 200 mg/day * Use of systemic corticosteroids * Use of antibiotics within the 14 days before inclusion * Current diagnosis of cancer * Diagnosed with a primary immunodeficiency disorder (e.g., Severe Combined Immunodeficiency (SCID), Common Variable Immune Deficiency (CVID), X-linked agammaglobulinemia, selective immunoglobulin A deficiency, chronic granulomatous disease) * Vaccination (e.g., immunization against COVID-19, influenza, pneumonia, and travel-related infections) within the 14 days before inclusion and during the study period * Current participation in other scientific research
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Monocyte-derived TNFa production | Change from baseline at 1 week after surgery | TNFα production after ex vivo stimulation of whole blood with inflammatory stimuli corrected for monocyte count |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PBMC (peripheral blood mononuclear cell)-derived cytokine production | Change from baseline at 1 day after surgery | Cytokine production after ex vivo stimulation of PBMCs with inflammatory stimuli |
| PBMC-derived cytokine production | Change from baseline at 1 week after surgery | Cytokine production after ex vivo stimulation of PBMCs with inflammatory stimuli |
| Composition of immune cell populations | Change from baseline at 1 day after surgery | Composition of immune cell populations (white blood cell count and differential) in whole blood |
| Monocyte-derived cytokine production | Change from baseline at 1 day after surgery | Cytokine production after ex vivo stimulation of whole blood with inflammatory stimuli and corrected for monocyte count |
| Phagocytic function of monocytes | Change from baseline at 1 day after surgery | Phagocytic function of monocytes as measured by the uptake of fluorescent particles |
| Monocyte HLA-DR expression | Change from baseline at 1 day after surgery | Monocyte HLA-DR expression as measured with fluorescent antibodies |
| Synovial inflammation | During surgery | Synovial inflammation as scored by the surgeon (yes/no) |
| Systemic inflammation | Change from baseline at 1 day after surgery | Systemic inflammation as measured by circulating cytokines, chemokines, acute phase proteins, oxylipins, and markers of intestinal function |
Other
| Measure | Time frame | Description |
|---|---|---|
| Amount of blood loss | During surgery | Amount of blood loss |
| Body Mass Index | Baseline | Body Mass Index |
| Cold and flu-like symptoms | In the 6 weeks after surgery | Cold and flu-like symptoms in a diary |
| Analgesic therapies | 1 week before surgery | Amount of analgesic therapies recorded in a pain medication diary |
| American Society of Anesthesiologists (ASA) classification | Baseline | ASA classification |
| Kellgren-Lawrence classification | Baseline | Kellgren-Lawrence classification |
| Knee function and pain | Baseline | Knee function and pain as measured by the Oxford Knee Score (OKS) |
| Physical function | Baseline | Physical function as measure by the Knee injury and Osteoarthritis Outcome Score - Physical Function Short Form (KOOS-PS) |
| Quality of Life (QoL) | Baseline | QoL as measured by EQ-5D |
| Pain as measured by the Numeric Pain Rating Scale (NPRS) | Baseline | Pain as measured by the NPRS |
| Mobility | Baseline | Timed Up and Go (TUG) test |
| Duration of surgery | During surgery | Duration of surgery |
Countries
Netherlands
Outcome results
None listed