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Title: Muscle factors and demographic characteristics affecting early functional outcome following total knee arthroplasty
Author: Griffin, Maurice Thomas Adam
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2020
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Primary total knee arthroplasty (TKA) for end-stage osteoarthritis (OA) is a surgical procedure with a long history of successful outcomes. However, one fifth of patients report dissatisfaction with the outcome of surgery which results from a combination of factors including poor functional improvement. This research examined the functional elements of recovery, with a focus on the role of skeletal muscle. The pain of OA normally limits activity; if the pain is relieved by TKA, any disuse atrophy associated with the OA has been reported in some patients to improve postoperatively with an eventual strengthening. Quadriceps muscle group strength is correlated with activities of daily living (ADLs). Myogenesis is complex but facilitated by muscle precursor stem cells; mainly muscle satellite cells. An individual’s skeletal muscle phenotype contributes to their physical recovery following surgery. Many factors have been reported as individually influencing skeletal muscle phenotype, but patient specific clinical data is lacking to evaluate these. In this study, these factors were examined in a primary TKA population to test the hypothesis that specific preoperative and perioperative muscle factors and patient background characteristics affect outcome, with the aim of indicating which patients might benefit from targeted treatment. Seventy-two patients listed for primary TKA were recruited to a single centre longitudinal observational cohort study. The participants underwent preoperative interview and assessment, provided a quadriceps skeletal muscle sample at time of surgery and completed a range of functional assessments and outcome reports during their recovery until 12 months following their operations. Muscle biopsies were analysed to determine morphometric and gene expression levels for each patient. Immunofluorescence histology identified muscle fibre type profiles, and quantitative real-time polymerase chain reaction (qPCR) determined relative translational profiles for myogenic, inflammatory, and senescent gene markers. GeNorm methodology identified 3 reference targets as optimal, and EIF4A2, UBC, and GAPDH were noted as the most stable (M=0.55) within the target superficial vastus medialis skeletal muscle tissue in the TKA cohort population. Patient functional performance was evaluated in outpatient hospital research clinics using a battery of functional tests in tandem with patient reported outcome measures (PROMs) tools. Patient function was also evaluated in a sub-cohort in the community setting using activity monitoring devices. Different temporal trends were observed between functional measurements. Substantial variation was observed in the response trajectory of functional metrics. Patients perceived that they meaningfully improved earlier than was observed through directly measured functional performance. Compared to preoperative values, by 12 weeks post-op, patients had achieved 82% of final (12 months post-op) PROM score, 63% of final leg power, 63% of final ADL performance, and 5% of final daily step count. The values further increased by 6 months post-op with PROM score increase at 92% of final score, leg power at 94% final, ADL at 116% final, and daily step count at 110% of final value. These findings highlighted the utility of using a combination of diverse metrics to evaluate patient functional outcome and showed that patient evaluated outcome alone may not fully represent early functional outcome. They also emphasise the critical nature of the follow up time points chosen for clinical trials. Patient background characteristics (demographic, health, and lifestyle factors) were contrasted with patient functional performance and skeletal muscle phenotype using univariate and exploratory multivariate regression modelling. Relationships were identified between patient preoperative baseline factors and post-surgical outcomes, with an observed R2 range of 0.14-0.31 (p≤0.05). Associations were found between background characteristics and physiological phenotypes at time of surgery (R2 0.11- 0.29, p≤0.06). Influences were identified from perioperative physiology on early or primary end-point surgical outcomes, with distinct contributions from certain molecular profiles and skeletal muscle fibre phenotypes (R2 0.09-0.24, p < 0.05). Models constructed using patient preoperative function combined with preoperative PROMs parameters provided the strongest prediction of surgical primary functional outcomes (R2 0.28-0.73, p≤0.006). The results provided new insights into the relationship between functional metrics during early recovery post-TKA. The study identified a variety of demographic and muscle related factors which significantly affect patient early surgical outcomes in primary TKA populations.
Supervisor: Simpson, Hamish ; Hamilton, David ; Brzeszczynska, Joanna Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: muscle ; arthritis ; orthopaedics ; outcomes ; muscle satellite cells ; myogenesis ; knee ; arthroplasty ; function ; musculoskeletal ; PROMs ; inflammation ; senescence ; histology ; molecular biology ; physiology ; knee replacement