Aims. Treatment of end-stage anteromedial osteoarthritis (AMOA) of the knee is commonly approached using one of two surgical strategies: medial unicompartmental knee arthroplasty (UKA) or total knee arthroplasty (TKA). In this study we aim to investigate if there is any difference in outcome for patients undergoing UKA or TKA, when treated by high-volume surgeons, in high-volume centres, using two different clinical guidelines. The two strategies are ‘UKA whenever possible’ vs TKA for all patients with AMOA. Methods. A total of 501 consecutive AMOA patients (301 UKA) operated on between 2013 to 2016 in two high-volume centres were included. Centre One employed clinical guidelines for the treatment of AMOA allowing either UKA or TKA, but encouraged UKA wherever possible. Centre Two used clinical guidelines that treated all patients with a TKA, regardless of wear pattern. TKA patients were included if they had isolated AMOA on preoperative radiographs. Data were collected from both centres’ local databases. The primary outcome measure was change in Oxford Knee Score (OKS), and the proportion of patients achieving the patient-acceptable symptom state (PASS) at one-year follow-up. The data were 1:1 propensity score matched before regression models were used to investigate potential differences. Results. The matched cohort included 400 patients (mean age 67 years (SD 9.55), 213 (53%) female, mean BMI 30.2 kg/m. 2. , 337 (84%) American Society of Anesthesiologists grade ≤ 2). We found a mean adjusted difference in change score of 3.02 points (95% confidence interval (CI) 1.41 to 4.63; p < 0.001) and a significantly larger likeliness of achieving PASS (odds ratio 3.67 (95% CI 1.73 to 8.45); p = 0.001) both in favour of the UKA strategy. Conclusion. UKA and TKA are both good strategies for treating end-stage AMOA. However, when compared as a strategy, UKA achieved larger improvements in OKS, and were more likely to reach the PASS value at one-year follow-up. Cite this article: Bone Jt Open 2022;3(5):441–447

Aims. To assess the incidence of radiological lateral osteoarthritis (OA) at 15 years after medial unicompartmental knee arthroplasty (UKA) and assess the relationship of lateral OA with symptoms and patient characteristics. Methods. Cemented Phase 3 medial Oxford UKA implanted by two surgeons since 1998 for the recommended indications were prospectively followed. A 15-year cumulative revision rate for lateral OA of 5% for this series was previously reported. A total of 163 unrevised knees with 15-year (SD 1) anterior-posterior knee radiographs were studied. Lateral joint space width (JSW. L. ) was measured and severity of lateral OA was classified as: nil/mild, moderate, and severe. Preoperative and 15-year Oxford Knee Scores (OKS) and American Knee Society Scores were determined. The effect of age, sex, BMI, and intraoperative findings was analyzed. Statistical analysis included one-way analysis of variance and Kruskal-Wallis H test, with significance set at 5%. Results. The mean age was 80.6 years (SD 8.3), with 84 females and 79 males. The mean JSW. L. was 5.6 mm (SD 1.4), and was not significantly related to age, sex, or intraoperative findings. Those with BMI > 40 kg/m. 2. had a smaller JSW. L. than those with a ‘normal’ BMI (p = 0.039). The incidence of severe and moderate lateral OA were both 4.9%. Overall, 2/142 (1.4%) of those with nil/mild lateral OA, 1/8 (13%) with moderate, and 2/8 (25%) with severe subsequently had a revision. Those with severe (mean OKS 35.6 (SD 9.3)) and moderate OA (mean OKS 35.8 (SD 10.5)) tended to have worse outcome scores than those with nil/mild (mean OKS 39.5 (SD 9.2)) but the difference was only significant for OKS-Function (p = 0.044). Conclusion. This study showed that the rate of having severe or moderate radiological lateral OA at 15 years after medial UKA was low (both 4.9%). Although patients with severe or moderate lateral OA had a lower OKS than those with nil/mild OA, their mean scores (OKS 36) would be classified as good. Cite this article: Bone Jt Open 2023;4(3):210–218

Aims. The use of high tibial osteotomy (HTO) to delay total knee arthroplasty (TKA) in young patients with osteoarthritis (OA) and constitutional deformity remains debated. The aim of this study was to compare the long-term outcomes of TKA after HTO compared to TKA without HTO, using the time from the index OA surgery as reference (HTO for the study group, TKA for the control group). Methods. This was a case-control study of consecutive patients receiving a posterior-stabilized TKA for OA between 1996 and 2010 with previous HTO. A total of 73 TKAs after HTO with minimum ten years’ follow-up were included. Cases were matched with a TKA without previous HTO for age at the time of the HTO. All revisions were recorded. Kaplan-Meier survivorship analysis was performed using revision of metal component as the endpoint. The Knee Society Score, range of motion, and patient satisfaction were assessed. Results. Mean follow-up was 13 years (SD 3) after TKA in both groups. The 20-year Kaplan-Meier survival estimate was 98.6% in TKA post-HTO group (HTO as timing reference) and 81.4% in control group (TKA as timing reference) (p = 0.030). There was no significant difference in clinical outcomes, radiological outcomes, and complications at the last follow-up. Conclusion. At the same delay from index surgery (HTO or TKA), a strategy of HTO followed by TKA had superior knee survivorship compared to early TKA at long term in young patients. Level of evidence: III. Cite this article: Bone Jt Open 2023;4(2):62–71

Aims

To compare time dependent functional improvement for patients with medial, respectively lateral knee osteoarthritis (OA) after treatment with opening wedge osteotomy relieving the pressure on the osteoarthritic part of the knee.

Aims. Hereditary haemochromatosis is a genetic disorder that is caused by several known mutations in the human homeostatic iron regulator protein (HFE) gene. Abnormal accumulation of iron causes a joint disease that resembles osteoarthritis (OA), but appears at a relatively younger age and is accompanied by cirrhosis, diabetes, and injury to other organs. Increased serum transferrin saturation and ferritin levels are known markers of haemochromatosis with high positive predictive values. Methods. We have retrospectively analyzed the iron studies of a cohort of 2,035 patients undergoing knee joint arthroplasty due to OA. Results. No patients had HFE gene C282Y, S65C, or H63D mutations testing. In total, 18 patients (2.96%) of the male cohort and 51 (3.58%) of the female cohort had pathologically increased ferritin levels that may be indicative of haemochromatosis. Seven patients (0.34%) had serum transferrin saturation above 45%. Conclusion. The awareness for the diagnosis of this disorder in Orthopaedics is low and needs improvement. Osteoarthritic patients undergoing knee arthroplasty should be routinely screened for haemochromatosis by iron studies and referred to genetic testing when needed. Level of evidence: Level III - Retrospective cohort study. Cite this article: Bone Jt Open 2021;2(12):1062–1066

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This study investigated the effects of transcatheter arterial embolization (TAE) on pain, function, and quality of life in people with early-stage symptomatic knee osteoarthritis (OA) compared to a sham procedure.

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Once knee arthritis and deformity have occurred, it is currently not known how to determine a patient’s constitutional (pre-arthritic) limb alignment. The purpose of this study was to describe and validate the arithmetic hip-knee-ankle (aHKA) algorithm as a straightforward method for preoperative planning and intraoperative restoration of the constitutional limb alignment in total knee arthroplasty (TKA).

Aims. With up to 40% of patients having patellofemoral joint osteoarthritis (PFJ OA), the two arthroplasty options are to replace solely the patellofemoral joint via patellofemoral arthroplasty (PFA), or the entire knee via total knee arthroplasty (TKA). The aim of this study was to assess postoperative success of second-generation PFAs compared to TKAs for patients treated for PFJ OA using patient-reported outcome measures (PROMs) and domains deemed important by patients following a patient and public involvement meeting. Methods. MEDLINE, EMBASE via OVID, CINAHL, and EBSCO were searched from inception to January 2022. Any study addressing surgical treatment of primary patellofemoral joint OA using second generation PFA and TKA in patients aged above 18 years with follow-up data of 30 days were included. Studies relating to OA secondary to trauma were excluded. ROB-2 and ROBINS-I bias tools were used. Results. A total of nine studies were included, made up of four randomized controlled trials (domain 1) and five cohort studies (domain 2). PROMs and knee function specific scores developed for reporting TKA were unable to detect any difference between PFA and TKA. There was no significant difference in complications between PFA and TKA. PFAs were found to have a better postoperative range of motion. Conclusion. TKA and PFA are both viable options for patients with primary PFJ OA. Over time, we have seen an emphasis on patient satisfaction and better quality of life. Recommending sacrificing healthy medial and lateral compartments to treat patellofemoral joint arthritis should be given further thought. Cite this article: Bone Jt Open 2023;4(12):948–956

Aims. The aim of this study was to describe the pattern of revision indications for unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) and any change to this pattern for UKA patients over the last 20 years, and to investigate potential associations to changes in surgical practice over time. Methods. All primary knee arthroplasty surgeries performed due to primary osteoarthritis and their revisions reported to the Danish Knee Arthroplasty Register from 1997 to 2017 were included. Complex surgeries were excluded. The data was linked to the National Patient Register and the Civil Registration System for comorbidity, mortality, and emigration status. TKAs were propensity score matched 4:1 to UKAs. Revision risks were compared using competing risk Cox proportional hazard regression with a shared γ frailty component. Results. Aseptic loosening (loosening) was the most common revision indication for both UKA (26.7%) and TKA (29.5%). Pain and disease progression accounted for 54.6% of the remaining UKA revisions. Infections and instability accounted for 56.1% of the remaining TKA revision. The incidence of revision due to loosening or pain decreased over the last decade, being the second and third least common indications in 2017. There was a decrease associated with fixation method for pain (hazard ratio (HR) 0.40; 95% confidence interval (CI) 0.17 to 0.94) and loosening (HR 0.29; 95% CI 0.10 to 0.81) for cementless compared to cemented, and units UKA usage for pain (HR 0.67, 95% CI 0.50 to 0.91), and loosening (HR 0.51; 95% CI 0.37 to 0.70) for high usage. Conclusion. The overall revision patterns for UKA and TKA for the last 20 years are comparable to previous published patterns. We found large changes to UKA revision patterns in the last decade, and with the current surgical practice, revision due to pain or loosening are significantly less likely. Cite this article: Bone Jt Open 2023;4(12):923–931

Aims. The aim of this study was to describe and compare joint-specific and generic health-related quality of life outcomes of the first versus second knee in patients undergoing staged bilateral total knee arthroplasty (BTKA) for osteoarthritis. Methods. This retrospective cohort study used Australian national arthroplasty registry data from January 2013 to January 2021 to identify participants who underwent elective staged BTKA with six to 24 months between procedures. The primary outcome was Oxford Knee Score (OKS) at six months postoperatively for the first TKA compared to the second TKA, adjusted for age and sex. Secondary outcomes compared six-month EuroQol five-dimension five-level (EQ-5D-5L) domain scores, EQ-5D index scores, and the EQ visual analogue scale (EQ-VAS) between knees at six months postoperatively. Results. The cohort included 635 participants (1,270 primary procedures). Preoperative scores were worse in the first knee compared to the second for all instruments; however, comparing the first knee at six months postoperatively with the second knee at six months postoperatively, the mean between-knee difference was minimal for OKS (-0.8 points; 95% confidence interval (CI) -1.4 to -0.2), EQ-VAS (3.3; 95% CI 1.9 to 4.7), and EQ-5D index (0.09 points; 95% CI 0.07 to 0.12). Outcomes for the EQ-5D-5L domains ‘mobility’, ‘usual activities’, and ‘pain/discomfort’ were better following the second TKA. Conclusion. At six months postoperatively, there were no clinically meaningful differences between the first and second TKA in either the joint-specific or overall generic health-related quality of life outcomes. However, individual domain scores assessing mobility, pain, and usual activities were notably higher after the second TKA, likely reflecting the cumulative improvement in quality of life after both knees have been replaced. Cite this article: Bone Jt Open 2024;5(3):202–209

Aims. Distal femoral resection in conventional total knee arthroplasty (TKA) utilizes an intramedullary guide to determine coronal alignment, commonly planned for 5° of valgus. However, a standard 5° resection angle may contribute to malalignment in patients with variability in the femoral anatomical and mechanical axis angle. The purpose of the study was to leverage deep learning (DL) to measure the femoral mechanical-anatomical axis angle (FMAA) in a heterogeneous cohort. Methods. Patients with full-limb radiographs from the Osteoarthritis Initiative were included. A DL workflow was created to measure the FMAA and validated against human measurements. To reflect potential intramedullary guide placement during manual TKA, two different FMAAs were calculated either using a line approximating the entire diaphyseal shaft, and a line connecting the apex of the femoral intercondylar sulcus to the centre of the diaphysis. The proportion of FMAAs outside a range of 5.0° (SD 2.0°) was calculated for both definitions, and FMAA was compared using univariate analyses across sex, BMI, knee alignment, and femur length. Results. The algorithm measured 1,078 radiographs at a rate of 12.6 s/image (2,156 unique measurements in 3.8 hours). There was no significant difference or bias between reader and algorithm measurements for the FMAA (p = 0.130 to 0.563). The FMAA was 6.3° (SD 1.0°; 25% outside range of 5.0° (SD 2.0°)) using definition one and 4.6° (SD 1.3°; 13% outside range of 5.0° (SD 2.0°)) using definition two. Differences between males and females were observed using definition two (males more valgus; p < 0.001). Conclusion. We developed a rapid and accurate DL tool to quantify the FMAA. Considerable variation with different measurement approaches for the FMAA supports that patient-specific anatomy and surgeon-dependent technique must be accounted for when correcting for the FMAA using an intramedullary guide. The angle between the mechanical and anatomical axes of the femur fell outside the range of 5.0° (SD 2.0°) for nearly a quarter of patients. Cite this article: Bone Jt Open 2024;5(2):101–108

Aims. Accurate identification of the ankle joint centre is critical for estimating tibial coronal alignment in total knee arthroplasty (TKA). The purpose of the current study was to leverage artificial intelligence (AI) to determine the accuracy and effect of using different radiological anatomical landmarks to quantify mechanical alignment in relation to a traditionally defined radiological ankle centre. Methods. Patients with full-limb radiographs from the Osteoarthritis Initiative were included. A sub-cohort of 250 radiographs were annotated for landmarks relevant to knee alignment and used to train a deep learning (U-Net) workflow for angle calculation on the entire database. The radiological ankle centre was defined as the midpoint of the superior talus edge/tibial plafond. Knee alignment (hip-knee-ankle angle) was compared against 1) midpoint of the most prominent malleoli points, 2) midpoint of the soft-tissue overlying malleoli, and 3) midpoint of the soft-tissue sulcus above the malleoli. Results. A total of 932 bilateral full-limb radiographs (1,864 knees) were measured at a rate of 20.63 seconds/image. The knee alignment using the radiological ankle centre was accurate against ground truth radiologist measurements (inter-class correlation coefficient (ICC) = 0.99 (0.98 to 0.99)). Compared to the radiological ankle centre, the mean midpoint of the malleoli was 2.3 mm (SD 1.3) lateral and 5.2 mm (SD 2.4) distal, shifting alignment by 0.34. o. (SD 2.4. o. ) valgus, whereas the midpoint of the soft-tissue sulcus was 4.69 mm (SD 3.55) lateral and 32.4 mm (SD 12.4) proximal, shifting alignment by 0.65. o. (SD 0.55. o. ) valgus. On the intermalleolar line, measuring a point at 46% (SD 2%) of the intermalleolar width from the medial malleoli (2.38 mm medial adjustment from midpoint) resulted in knee alignment identical to using the radiological ankle centre. Conclusion. The current study leveraged AI to create a consistent and objective model that can estimate patient-specific adjustments necessary for optimal landmark usage in extramedullary and computer-guided navigation for tibial coronal alignment to match radiological planning. Cite this article: Bone Jt Open 2022;3(10):767–776

Aims. To map literature on prognostic factors related to outcomes of revision total knee arthroplasty (rTKA), to identify extensively studied factors and to guide future research into what domains need further exploration. Methods. We performed a systematic literature search in MEDLINE, Embase, and Web of Science. The search string included multiple synonyms of the following keywords: "revision TKA", "outcome" and "prognostic factor". We searched for studies assessing the association between at least one prognostic factor and at least one outcome measure after rTKA surgery. Data on sample size, study design, prognostic factors, outcomes, and the direction of the association was extracted and included in an evidence map. Results. After screening of 5,660 articles, we included 166 studies reporting prognostic factors for outcomes after rTKA, with a median sample size of 319 patients (30 to 303,867). Overall, 50% of the studies reported prospectively collected data, and 61% of the studies were performed in a single centre. In some studies, multiple associations were reported; 180 different prognostic factors were reported in these studies. The three most frequently studied prognostic factors were reason for revision (213 times), sex (125 times), and BMI (117 times). Studies focusing on functional scores and patient-reported outcome measures as prognostic factor for the outcome after surgery were limited (n = 42). The studies reported 154 different outcomes. The most commonly reported outcomes after rTKA were: re-revision (155 times), readmission (88 times), and reinfection (85 times). Only five studies included costs as outcome. Conclusion. Outcomes and prognostic factors that are routinely registered as part of clinical practice (e.g. BMI, sex, complications) or in (inter)national registries are studied frequently. Studies on prognostic factors, such as functional and sociodemographic status, and outcomes as healthcare costs, cognitive and mental function, and psychosocial impact are scarce, while they have been shown to be important for patients with osteoarthritis. Cite this article: Bone Jt Open 2023;4(5):338–356

Aims. The aim of this study was to report patient and clinical outcomes following robotic-assisted total knee arthroplasty (RA-TKA) at multiple institutions with a minimum two-year follow-up. Methods. This was a multicentre registry study from October 2016 to June 2021 that included 861 primary RA-TKA patients who completed at least one pre- and postoperative patient-reported outcome measure (PROM) questionnaire, including Forgotten Joint Score (FJS), Knee Injury and Osteoarthritis Outcomes Score for Joint Replacement (KOOS JR), and pain out of 100 points. The mean age was 67 years (35 to 86), 452 were male (53%), mean BMI was 31.5 kg/m. 2. (19 to 58), and 553 (64%) cemented and 308 (36%) cementless implants. Results. There were significant improvements in PROMs over time between preoperative, one- to two-year, and > two-year follow-up, with a mean FJS of 17.5 (SD 18.2), 70.2 (SD 27.8), and 76.7 (SD 25.8; p < 0.001); mean KOOS JR of 51.6 (SD 11.5), 85.1 (SD 13.8), and 87.9 (SD 13.0; p < 0.001); and mean pain scores of 65.7 (SD 20.4), 13.0 (SD 19.1), and 11.3 (SD 19.9; p < 0.001), respectively. There were eight superficial infections (0.9%) and four revisions (0.5%). Conclusion. RA-TKA demonstrated consistent clinical results across multiple institutions with excellent PROMs that continued to improve over time. With the ability to achieve target alignment in the coronal, axial, and sagittal planes and provide intraoperative real-time data to obtain balanced gaps, RA-TKA demonstrated excellent clinical outcomes and PROMs in this patient population. Cite this article: Bone Jt Open 2022;3(7):589–595

Aims. The aims of this study were: 1) to describe extended restricted kinematic alignment (E-rKA), a novel alignment strategy during robotic-assisted total knee arthroplasty (RA-TKA); 2) to compare residual medial compartment tightness following virtual surgical planning during RA-TKA using mechanical alignment (MA) and E-rKA, in the same set of osteoarthritic varus knees; 3) to assess the requirement of soft-tissue releases during RA-TKA using E-rKA; and 4) to compare the accuracy of surgical plan execution between knees managed with adjustments in component positioning alone, and those which require additional soft-tissue releases. Methods. Patients who underwent RA-TKA between January and December 2022 for primary varus osteoarthritis were included. Safe boundaries for E-rKA were defined. Residual medial compartment tightness was compared following virtual surgical planning using E-rKA and MA, in the same set of knees. Soft-tissue releases were documented. Errors in postoperative alignment in relation to planned alignment were compared between patients who did (group A) and did not (group B) require soft-tissue releases. Results. The use of E-rKA helped restore all knees within the predefined boundaries, with appropriate soft-tissue balancing. E-rKA compared with MA resulted in reduced residual medial tightness following surgical planning, in full extension (2.71 mm (SD 1.66) vs 5.16 mm (SD 3.10), respectively; p < 0.001), and 90° of flexion (2.52 mm (SD 1.63) vs 6.27 mm (SD 3.11), respectively; p < 0.001). Among the study population, 156 patients (78%) were managed with minor adjustments in component positioning alone, while 44 (22%) required additional soft-tissue releases. The mean errors in postoperative alignment were 0.53 mm and 0.26 mm among patients in group A and group B, respectively (p = 0.328). Conclusion. E-rKA is an effective and reproducible alignment strategy during RA-TKA, permitting a large proportion of patients to be managed without soft-tissue releases. The execution of minor alterations in component positioning within predefined multiplanar boundaries is a better starting point for gap management than soft-tissue releases. Cite this article: Bone Jt Open 2024;5(8):628–636

Aims. An algorithm to determine the constitutional alignment of the lower limb once arthritic deformity has occurred would be of value when undertaking kinematically aligned total knee arthroplasty (TKA). The purpose of this study was to determine if the arithmetic hip-knee-ankle angle (aHKA) algorithm could estimate the constitutional alignment of the lower limb following development of significant arthritis. Methods. A matched-pairs radiological study was undertaken comparing the aHKA of an osteoarthritic knee (aHKA-OA) with the mechanical HKA of the contralateral normal knee (mHKA-N). Patients with Grade 3 or 4 Kellgren-Lawrence tibiofemoral osteoarthritis in an arthritic knee undergoing TKA and Grade 0 or 1 osteoarthritis in the contralateral normal knee were included. The aHKA algorithm subtracts the lateral distal femoral angle (LDFA) from the medial proximal tibial angle (MPTA) measured on standing long leg radiographs. The primary outcome was the mean of the paired differences in the aHKA-OA and mHKA-N. Secondary outcomes included comparison of sex-based differences and capacity of the aHKA to determine the constitutional alignment based on degree of deformity. Results. A total of 51 radiographs met the inclusion criteria. There was no significant difference between aHKA-OA and mHKA-N, with a mean angular difference of −0.4° (95% SE −0.8° to 0.1°; p = 0.16). There was no significant sex-based difference when comparing aHKA-OA and mHKA-N (mean difference 0.8°; p = 0.11). Knees with deformities of more than 8° had a greater mean difference between aHKA-OA and mHKA-N (1.3°) than those with lesser deformities (-0.1°; p = 0.009). Conclusion. This study supports the arithmetic HKA algorithm for prediction of the constitutional alignment once arthritis has developed. The algorithm has similar accuracy between sexes and greater accuracy with lesser degrees of deformity. Cite this article: Bone Joint Open 2020;1-7:339–345

Aims. This study aims to evaluate a new home medical stretching device called the Self Treatment Assisted Knee (STAK) tool to treat knee arthrofibrosis. Methods. 35 patients post-major knee surgery with arthrofibrosis and mean range of movement (ROM) of 68° were recruited. Both the STAK intervention and control group received standard physiotherapy for eight weeks, with the intervention group additionally using the STAK at home. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Oxford Knee Scores (OKS) were collected at all timepoints. An acceptability and home exercise questionnaire capturing adherence was recorded after each of the interventions. Results. Compared to the control group, the STAK intervention group made significant gains in mean ROM (30° versus 8°, p < 0.0005), WOMAC (19 points versus 3, p < 0.0005), and OKS (8 points versus 3, p < 0.0005). The improvements in the STAK group were maintained at long-term follow-up. No patients suffered any complications relating to the STAK, and 96% of patients found the STAK tool ‘perfectly acceptable’. Conclusion. The STAK tool is effective in increasing ROM and reducing pain and stiffness. Patients find it acceptable and adherence to treatment was high. This study indicates that the STAK tool would be of benefit in clinical practice and may offer a new, cost-effective treatment for arthrofibrosis. Cite this article: Bone Joint Open 2020;1-8:465–473

Aims

Unicompartmental knee arthroplasty (UKA) is the preferred treatment for anterior medial knee osteoarthritis (OA) owing to the rapid postoperative recovery. However, the risk factors for UKA failure remain controversial.

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Revision total knee arthroplasty (rTKA) is a technically challenging and costly procedure. It is well-documented that primary TKA (pTKA) have better survivorship than rTKA; however, we were unable to identify any studies explicitly investigating previous rTKA as a risk factor for failure following rTKA. The purpose of this study is to compare the outcomes following rTKA between patients undergoing index rTKA and those who had been previously revised.

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This prospective study reports longitudinal, within-patient, patient-reported outcome measures (PROMs) over a 15-year period following cemented single radius total knee arthroplasty (TKA). Secondary aims included reporting PROMs trajectory, 15-year implant survival, and patient attrition from follow-up.