Dataset Information

Association of circulating gene expression signatures with stiffness following total knee arthroplasty for osteoarthritis: a pilot study.

ABSTRACT: A subset of patients undergoing total knee arthroplasty (TKA) for knee osteoarthritis develop debilitating knee stiffness (reduced range of motion) for poorly understood reasons. Dysregulated inflammatory and immune responses to surgery correlate with reduced surgical outcomes, but the dysregulated gene signatures in patients with stiffness after TKA are poorly defined. As a consequence, we are limited in our ability to identify patients at risk of developing poor surgical outcomes and develop preventative approaches. In this pilot study we aimed to identify perioperative blood gene signatures in patients undergoing TKA for knee osteoarthritis and its association with early surgical outcomes, specifically knee range of motion. To do this, we integrated clinical outcomes collected at 6 weeks after surgery with transcriptomics analyses in blood samples collected immediately before surgery and at 24 h after surgery. We found that patients with stiffness at 6 weeks after surgery have a more variable and attenuated circulating gene expression response immediately after surgery. Our results suggest that patients with stiffness following TKA may have distinct gene expression signatures detectable in peripheral blood in the immediate postoperative period.

SUBMITTER: Kirksey MA

PROVIDER: S-EPMC9314445 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Association of circulating gene expression signatures with stiffness following total knee arthroplasty for osteoarthritis: a pilot study.

Kirksey Meghan A MA Lessard Samantha G SG Khan Marjan M Birch George A GA Oliver David D Singh Purva P Rotundo Valeria V Sideris Alexandra A Gonzalez Della Valle Alejandro A Parks Michael L ML Sculco Peter K PK Otero Miguel M

Scientific reports 20220725 1

A subset of patients undergoing total knee arthroplasty (TKA) for knee osteoarthritis develop debilitating knee stiffness (reduced range of motion) for poorly understood reasons. Dysregulated inflammatory and immune responses to surgery correlate with reduced surgical outcomes, but the dysregulated gene signatures in patients with stiffness after TKA are poorly defined. As a consequence, we are limited in our ability to identify patients at risk of developing poor surgical outcomes and develop p ...[more]

PMID: 35879399

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Project description:BackgroundAfter total knee arthroplasty (TKA), patients' physical activity (PA) levels at 6 months are lower than those of healthy subjects. Few studies have investigated the factors associated with PA at 6 months after TKA by objectively measuring preoperative and postoperative PA intensity using an accelerometer and knee function using a goniometer and dynamometer. The purpose of this study was to determine the factors associated with PA levels at 6 months after TKA based on objective data.MethodsEighty-two patients (mean [SD] age 74.5 [6.4] years) with moderate-to-severe knee osteoarthritis (OA) who were scheduled for TKA at the Nagoya Orthopaedic and Joint Replacement Clinic from July 2018 to July 2019 were enrolled in this longitudinal study. All patients underwent evaluations of knee function, including range-of-motion and knee-extension muscle strength; knee pain; performance in the timed up-and-go test; and accelerometer-measured PA both preoperatively and 6 months postoperatively. Factors associated with PA at 6 months after TKA were assessed using a hierarchical multiple linear regression analysis adjusted for age, sex, body mass index, and presence of diabetes mellitus.ResultsA higher average daily step count at 6 months after TKA was significantly associated with greater preoperative knee-extension muscle strength on the operated side (β = 0.155, p = 0.028) as well as a higher preoperative average daily step count (β = 0.834, p < 0.001). Furthermore, average daily time spent in moderate-to-vigorous-intensity PA postoperatively was significantly associated only with time spent in moderate-to-vigorous-intensity PA preoperatively (β = 0.723, p < 0.001).ConclusionThese findings indicate that a higher preoperative daily step count and greater preoperative knee-extension muscle strength on the operated side may be associated with a higher daily step count at 6 months after TKA. Factors associated with PA differed by the PA intensity level. Rehabilitation and interventions for psychosocial factors before TKA beginning when mild knee OA first occurs are expected to lead to increased PA in TKA patients.

Project description:BackgroundIndividuals who undergo total knee arthroplasty (TKA) for treatment of knee osteoarthritis often experience suboptimal outcomes. Investigation of neuromuscular control strategies in these individuals may reveal factors that contribute to these functional deficits. The purpose of this pilot study was to determine the relationship between patient function and modular control during gait before and after TKA.MethodsElectromyography data from 36 participants (38 knees) were collected from 8 lower extremity muscles on the TKA-involved limb during ≥5 over-ground walking trials before (n = 30), 6-months after (n = 26), and 24-months after (n = 13) surgery. Muscle modules were estimated using non-negative matrix factorization. The number of modules was determined from 500 resampled trials.ResultsA higher number of modules was related to better performance-based and patient-reported function before and 6-months after surgery. Participants with organization similar to healthy, age-matched controls trended toward better function 24-months after surgery, though these results were not statistically significant. We also observed plasticity in the participants' modular control strategies, with 100% of participants who were present before and 24-months after surgery (10/10) demonstrating changes in the number of modules and/or organization of at least 1 module.ConclusionsThis pilot work suggests that functional improvements following TKA may initially present as increases in the number of modules recruited during gait. Subsequent improvements in function may present as improved module organization.NoteworthyThis work is the first to characterize motor modules in TKA both before and after surgery and to demonstrate changes in the number and organization of modules over the time course of recovery, which may be related to changes in patient function. The plasticity of modular control following TKA is a key finding which has not been previously documented and may be useful in predicting or improving surgical outcomes through novel rehabilitation protocols.

Dataset Information

Association of circulating gene expression signatures with stiffness following total knee arthroplasty for osteoarthritis: a pilot study.

Publications

Association of circulating gene expression signatures with stiffness following total knee arthroplasty for osteoarthritis: a pilot study.

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