Aims. Surgeons commonly resect additional distal femur during primary total knee arthroplasty (TKA) to correct a flexion contracture, which leads to femoral joint line elevation. There is a paucity of data describing the effect of joint line elevation on mid-flexion stability and knee kinematics. Thus, the goal of this study was to quantify the effect of joint line elevation on mid-flexion laxity. Methods. Six computational knee models with cadaver-specific capsular and collateral ligament properties were implanted with a posterior-stabilized (PS) TKA. A 10° flexion contracture was created in each model to simulate a capsular contracture. Distal femoral resections of + 2 mm and + 4 mm were then simulated for each knee. The knee models were then extended under a standard moment. Subsequently, varus and valgus moments of 10 Nm were applied as the knee was flexed from 0° to 90° at baseline and repeated after each of the two distal resections. Coronal laxity (the sum of varus and valgus angulation with respective maximum moments) was measured throughout flexion. Results. With + 2 mm resection at 30° and 45° of flexion, mean coronal laxity increased by a mean of 3.1° (SD 0.18°) (p < 0.001) and 2.7° (SD 0.30°) (p < 0.001), respectively. With + 4 mm resection at 30° and 45° of flexion, mean coronal laxity increased by 6.5° (SD 0.56°) (p < 0.001) and 5.5° (SD 0.72°) (p < 0.001), respectively. Maximum increased coronal laxity for a + 4 mm resection occurred at a mean 15.7° (11° to 33°) of flexion with a mean increase of 7.8° (SD 0.2°) from baseline. Conclusion. With joint line elevation in primary PS TKA, coronal laxity peaks early (about 16°) with a maximum laxity of 8°. Surgeons should restore the joint line if possible; however, if joint line elevation is necessary, we recommend assessment of coronal laxity at 15° to 30° of knee flexion to assess for mid-flexion instability. Further in vivo studies are warranted to understand if this mid-flexion coronal laxity has negative clinical implications. Cite this article: Bone Joint J 2021;103-B(6 Supple A):87–93

Introduction. Surgeons commonly resect additional distal femur during primary total knee arthroplasty (TKA) to correct a flexion contracture. However, the effect of joint line proximalization on TKA kinematics is unclear. Thus, our goal was to quantify the effect of additional distal femoral resection on knee extension and mid-flexion laxity. Methods. Six computational knee models with TKA-specific capsular and collateral ligament properties were implanted with a contemporary posterior-stabilized TKA. A 10° flexion contracture was modeled to simulate a capsular contracture. Distal femoral resections of +2 mm and +4 mm were simulated for each model. The knees were then extended under standardized torque to quantify additional knee extension achieved. Subsequently, varus and valgus torques of ±10 Nm were applied as the knee was flexed from 0° to 90° at the baseline, +2 mm, and +4 mm distal resections. Coronal laxity, defined as the sum of varus and valgus angulation with respective torques, was measured at mid-flexion. Results. With +2 mm and +4 mm of distal femoral resection, the knee extended an additional 4°±0.5° and 8°±0.75°, respectively. At 30° and 45°of flexion, baseline laxity averaged 4.8° and 5.0°, respectively. At +2 mm resection, mean coronal laxity increased by 3.1° and 2.7° at 30° and 45°of flexion, respectively. At +4 mm resection, mean coronal laxity increased by 6.5° and 5.5° at 30° and 45° of flexion, respectively. Maximal increased coronal laxity for a +4 mm resection occurred at a mean 16° (range, 11–27°) of flexion with a mean increased laxity of 7.8° from baseline. Conclusion. While additional distal femoral resection in primary TKA increases knee extension, the consequent joint line elevation induces up to 8° of coronal laxity in mid-flexion in this computational model. As such, posterior capsular release prior to resecting additional distal femur to correct a flexion contracture should be considered

Objectives. The goal of this study was to determine whether intra-articular administration of the potentially anti-fibrotic agent decorin influences the expression of genes involved in the fibrotic cascade, and ultimately leads to less contracture, in an animal model. Methods. A total of 18 rabbits underwent an operation on their right knees to form contractures. Six limbs in group 1 received four intra-articular injections of decorin; six limbs in group 2 received four intra-articular injections of bovine serum albumin (BSA) over eight days; six limbs in group 3 received no injections. The contracted limbs of rabbits in group 1 were biomechanically and genetically compared with the contracted limbs of rabbits in groups 2 and 3, with the use of a calibrated joint measuring device and custom microarray, respectively. Results. There was no statistical difference in the flexion contracture angles between those limbs that received intra-articular decorin versus those that received intra-articular BSA (66° vs 69°; p = 0.41). Likewise, there was no statistical difference between those limbs that received intra-articular decorin versus those who had no injection (66° vs 72°; p = 0.27). When compared with BSA, decorin led to a statistically significant increase in the mRNA expression of 12 genes (p < 0.01). In addition, there was a statistical change in the mRNA expression of three genes, when compared with those without injection. . Conclusions. In this model, when administered intra-articularly at eight weeks, 2 mg of decorin had no significant effect on joint contractures. However, our genetic analysis revealed a significant alteration in several fibrotic genes. Cite this article: Bone Joint Res 2014;3:82–8

Aims. As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA). Methods. Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections. Results. Experimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced. Conclusion. This study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies. Cite this article: Bone Joint Res 2023;12(1):58–71

Aims. The impact of a diaphyseal femoral deformity on knee alignment varies according to its severity and localization. The aims of this study were to determine a method of assessing the impact of diaphyseal femoral deformities on knee alignment for the varus knee, and to evaluate the reliability and the reproducibility of this method in a large cohort of osteoarthritic patients. Methods. All patients who underwent a knee arthroplasty from 2019 to 2021 were included. Exclusion criteria were genu valgus, flexion contracture (> 5°), previous femoral osteotomy or fracture, total hip arthroplasty, and femoral rotational disorder. A total of 205 patients met the inclusion criteria. The mean age was 62.2 years (SD 8.4). The mean BMI was 33.1 kg/m. 2. (SD 5.5). The radiological measurements were performed twice by two independent reviewers, and included hip knee ankle (HKA) angle, mechanical medial distal femoral angle (mMDFA), anatomical medial distal femoral angle (aMDFA), femoral neck shaft angle (NSA), femoral bowing angle (FBow), the distance between the knee centre and the top of the FBow (DK), and the angle representing the FBow impact on the knee (C’KS angle). Results. The FBow impact on the mMDFA can be measured by the C’KS angle. The C’KS angle took the localization (length DK) and the importance (FBow angle) of the FBow into consideration. The mean FBow angle was 4.4° (SD 2.4; 0 to 12.5). The mean C’KS angle was 1.8° (SD 1.1; 0 to 5.8). Overall, 84 knees (41%) had a severe FBow (> 5°). The radiological measurements showed very good to excellent intraobserver and interobserver agreements. The C’KS increased significantly when the length DK decreased and the FBow angle increased (p < 0.001). Conclusion. The impact of the diaphyseal femoral deformity on the mechanical femoral axis is measured by the C’KS angle, a reliable and reproducible measurement. Cite this article: Bone Jt Open 2023;4(4):262–272

Aims. Outcomes of current operative treatments for arthrofibrosis after total knee arthroplasty (TKA) are not consistently positive or predictable. Pharmacological in vivo studies have focused mostly on prevention of arthrofibrosis. This study used a rabbit model to evaluate intra-articular (IA) effects of celecoxib in treating contracted knees alone, or in combination with capsular release. Methods. A total of 24 rabbits underwent contracture-forming surgery with knee immobilization followed by remobilization surgery at eight weeks. At remobilization, one cohort underwent capsular release (n = 12), while the other cohort did not (n = 12). Both groups were divided into two subcohorts (n = 6 each) – one receiving IA injections of celecoxib, and the other receiving injections of vehicle solution (injections every day for two weeks after remobilization). Passive extension angle (PEA) was assessed in live rabbits at 10, 16, and 24 weeks, and disarticulated limbs were analyzed for capsular stiffness at 24 weeks. Results. IA celecoxib resulted in greater mean PEA at ten weeks (69.6° (SD 4.6) vs 45.2° (SD 9.6), p = 0.004), 16 weeks (109.8° (SD 24.2) vs 60.9° (SD10.9), p = 0.004), and 24 weeks (101.0° (SD 8.0) vs 66.3° (SD 5.8), p = 0.004). Capsular stiffness was significantly reduced with IA celecoxib (2.72 Newton per cm (N·cm)/° (SD 1.04), p = 0.008), capsular release (2.41 N·cm/° (SD 0.80), p = 0.008), and capsular release combined with IA celecoxib (3.56 N·cm/° (SD 0.99), p = 0.018) relative to IA vehicle (6.09 N·cm/° (SD 1.64)). Conclusion. IA injections of a celecoxib led to significant improvements in passive extension angles, with reduced capsular stiffness, when administered to rabbit knees with established experimental contracture. Celecoxib was superior to surgical release, and the combination of celecoxib and a surgical release did not provide any additional value. Cite this article: Bone Joint Res 2022;11(1):32–39

Abstract. Introduction. Total knee replacement (TKR) in patients with skeletal dysplasia is technically challenging surgery due to deformity, joint contracture, and associated co-morbidities. The aim of this study is to follow up patients with skeletal dysplasia following a TKR. Methodology. We retrospectively reviewed 22 patients with skeletal dysplasia who underwent 31 TKRs at our institution between 2006 and 2022. Clinical notes, operative records and radiographic data were reviewed. Results. Achondroplasia was the most common skeletal dysplasia (8), followed by Chondrodysplasia punctata (7) and Spondyloepiphyseal dysplasia (5). There were fourteen men and eight women with mean age of 51 years (28 to 73). The average height of patients was 1.4 metres (1.16–1.75) and the mean weight was 64.8 Kg (34.3–100). The mean follow up duration was 68.32 months (1–161). Three patients died during follow up. Custom implants were required in twelve patients (38.71%). Custom jigs were utilised in six patients and two patients underwent robotic assisted surgery. Hinged TKR was used in seventeen patients (54.84%), posterior stabilised TKR in nine patients (29.03%), and cruciate retaining TKR in five patients (16.13%). One patient underwent a patella resurfacing for persistent anterior knee pain and another had an intra-operative medial tibial plateau fracture which was managed with fixation. No revisions occurred during the follow up period. Conclusion. Despite the technical challenges and complexity of TKR within this unique patient group, we demonstrate good implant survivorship during the study period. Cross sectional imaging is recommended preoperatively for precise planning and templating

Aims. To compare patients undergoing total knee arthroplasty (TKA) with ≤ 80° range of movement (ROM) operated with a 2 mm increase in the flexion gap with matched non-stiff patients with at least 100° of preoperative ROM and balanced flexion and extension gaps. Methods. In a retrospective cohort study, 98 TKAs (91 patients) with a preoperative ROM of ≤ 80° were examined. Mean follow-up time was 53 months (24 to 112). All TKAs in stiff knees were performed with a 2 mm increased flexion gap. Data were compared to a matched control group of 98 TKAs (86 patients) with a mean follow-up of 43 months (24 to 89). Knees in the control group had a preoperative ROM of at least 100° and balanced flexion and extension gaps. In all stiff and non-stiff knees posterior stabilized (PS) TKAs with patellar resurfacing in combination with adequate soft tissue balancing were used. Results. Overall mean ROM in stiff knees increased preoperatively from 67° (0° to 80°) to 114° postoperatively (65° to 135°) (p < 0.001). Mean knee flexion improved from 82° (0° to 110°) to 115° (65° to 135°) and mean flexion contracture decreased from 14° (0° to 50°) to 1° (0° to 10°) (p < 0.001). The mean Knee Society Score (KSS) improved from 34 (0 to 71) to 88 (38 to 100) (p < 0.001) and the KSS Functional Score from 43 (0 to 70) to 86 (0 to 100). Seven knees (7%) required manipulations under anaesthesia (MUA) and none of the knees had flexion instability. The mean overall ROM in the control group improved from 117° (100° to 140°) to 123° (100° to 130°) (p < 0.001). Mean knee flexion improved from 119° (100° to 140°) to 123° (100° to 130°) (p < 0.001) and mean flexion contracture decreased from 2° (0° to 15°) to 0° (0° to 5°) (p < 0.001). None of the knees in the control group had flexion instability or required MUA. The mean KSS Knee Score improved from 48 (0 to 80) to 94 (79 to 100) (p < 0.001) and the KSS Functional Score from 52 (5 to 100) to 95 (60 to 100) (p < 0.001). Mean improvement in ROM (p < 0.001) and KSS Knee Score (p = 0.017) were greater in knees with preoperative stiffness compared with the control group, but the KSS Functional Score improvement was comparable (p = 0.885). Conclusion. TKA with a 2 mm increased flexion gap provided a significant improvement of ROM in knees with preoperative stiffness. While the improvement in ROM was greater, the absolute postoperative ROM was less than in matched non-stiff knees. PS TKA with patellar resurfacing and a 2 mm increased flexion gap, in combination with adequate soft tissue balancing, provides excellent ROM and knee function when stiffness of the knee had been present preoperatively. Cite this article: Bone Joint J 2020;102-B(4):426–433

Aims. Alternative alignment concepts, including kinematic and restricted kinematic, have been introduced to help improve clinical outcomes following total knee arthroplasty (TKA). The purpose of this study was to evaluate the clinical results, along with patient satisfaction, following TKA using the concept of restricted kinematic alignment. Methods. A total of 121 consecutive TKAs performed between 11 February 2018 to 11 June 2019 with preoperative varus deformity were reviewed at minimum one-year follow-up. Three knees were excluded due to severe preoperative varus deformity greater than 15°, and a further three due to requiring revision surgery, leaving 109 patients and 115 knees to undergo primary TKA using the concept of restricted kinematic alignment with advanced technology. Patients were stratified into three groups based on the preoperative limb varus deformity: Group A with 1° to 5° varus (43 knees); Group B between 6° and 10° varus (56 knees); and Group C with varus greater than 10° (16 knees). This study group was compared with a matched cohort of 115 TKAs and 115 patients using a neutral mechanical alignment target with manual instruments performed from 24 October 2016 to 14 January 2019. Results. Mean overall patient satisfaction for the entire cohort was 4.7 (SE 0.1) on a 5-point Likert scale, with 93% being either very satisfied or satisfied compared with a Likert of 4.3 and patient satisfaction of 81% in the mechanical alignment group (p < 0.001 and p < 0.006 respectively). At mean follow-up of 17 months (11 to 27), the mean overall Likert, Knee Injury and Osteoarthritis Outcome Score for Joint Replacement, Western Ontario and McMaster Universities Osteoarthritis Index, Forgotten Joint Score, and Knee Society Knee and Function Scores were significantly better in the kinematic group than in the neutral mechanical alignment group. The most common complication in both groups was contracture requiring manipulation under anaesthesia, involving seven knees (6.1%) in the kinematic group and nine knees (7.8%) in the mechanical alignment group. Conclusion. With the advent of advanced technology, and the ability to obtain accurate bone cuts, the target limb alignment, and soft-tissue balance within millimetres, using a restricted kinematic alignment concept demonstrated excellent patient satisfaction following primary TKA. Longer-term analysis is required as to the durability of this method. Cite this article: Bone Joint J 2021;103-B(6 Supple A):59–66

Introduction. The Center for Medicare and Medicaid Services (CMS) is faced with a challenge of decreasing the cost of care for total knee arthroplasty (TKA), but must make efforts to prevent patient selection bias in the process. Currently, no appropriate modifier codes exist for primary TKA based on case complexity. We sought to determine differences in perioperative parameters for patients with “complex” primary TKA with the hypothesis that they would require increased cost of care, prolonged care times, and have worse postoperative outcome metrics. Methods. We performed a single center retrospective review from 2015 to 2018 of all primary TKA. Patient demographics, medial proximal tibial angle (mPTA), lateral distal femoral angle (lDFA), flexion contracture, cost of care, and early postoperative outcomes were collected. ‘Complex’ patients were defined as those requiring stems or augments, and multivariable logistic regression analysis and propensity score matching were performed to evaluate perioperative outcomes. Results. 1046 primary TKA were studied and 84 patients (8.3%) were classified as “complex”. For this cohort, surgery duration was greater (117 vs 82 minutes; p<0.001), cost of care excessive (p<0.001), and patients had a greater likelihood for 90-day hospital return. Deviation of mPTA and lDFA was significantly greater preoperatively before and after propensity score matching. Cutpoint analysis demonstrated that preoperative mPTA <83o or >91o, lDFA <84o or >90o, flexion contracture >10o, and BMI > 35.7 were associated with ‘Complex’ procedures. Conclusions. Complex primary TKA may be identifiable preoperatively and are associated prolonged operative time, excess hospital cost of care and increased 90-day hospital returns. This should be considered in future reimbursement models to prevent patient selection bias, and a complexity modifier is warranted

Aims. Aseptic loosening of the tibial component is a frequent cause of failure in primary total knee arthroplasty (TKA). Management options include an isolated tibial revision or full component revision. A full component revision is frequently selected by surgeons unfamiliar with the existing implant or who simply wish to “start again”. This option adds morbidity compared with an isolated tibial revision. While isolated tibial revision has a lower morbidity, it is technically more challenging due to difficulties with exposure and maintaining prosthetic stability. This study was designed to compare these two reconstructive options. Methods. Patients undergoing revision TKA for isolated aseptic tibial loosening between 2012 and 2017 were identified. Those with revision implants or revised for infection, instability, osteolysis, or femoral component loosening were excluded. A total of 164 patients were included; 88 had an isolated tibial revision and 76 had revision of both components despite only having a loose tibial component. The demographics and clinical and radiological outcomes were recorded. Results. The patient demographics were statistically similar in the two cohorts. The median follow-up was 3.5 years (interquartile range (IQR) 1 to 12.5). Supplementary femoral metaphyseal fixation was required in five patients in the full revision cohort. There was a higher incidence of radiological tibial loosening in the full component revision cohort at the final follow-up (8 (10.5%) vs 5 (5.7%); p = 0.269). Three patients in the full component revision cohort developed instability while only one in the isolated tibial cohort did. Three patients in the full revision cohort developed a flexion contracture greater than 5° while none in the isolated tibial cohort did. Conclusion. Isolated tibial revision for aseptic tibial loosening has statistically similar clinical and radiological outcomes at a median follow-up of 3.5 years, when compared with full component revision. Substantial bone loss can occur when removing a well-fixed femoral component necessitating a cone or sleeve. Femoral component revision for isolated tibial loosening can frequently be avoided provided adequate ligamentous stability can be obtained. Cite this article: Bone Joint J 2020;102-B(6 Supple A):123–128

Aims. The aim of this study was to examine the results of revision total knee arthroplasty (TKA) undertaken for stiffness in the absence of sepsis or loosening. Patients and Methods. We present the results of revision surgery for stiff TKA in 48 cases (35 (72.9%) women and 13 (27.1%) men). The mean age at revision surgery was 65.5 years (42 to 83). All surgeries were performed by a single surgeon. Stiffness was defined as an arc of flexion of < 70° or a flexion contracture of > 15°. The changes in the range of movement (ROM) and the Western Ontario and McMasters Osteoarthritis index scores (WOMAC) were recorded. Results. At a mean follow up of 59.9 months (12 to 272) there was a mean improvement in arc of movement of 45.0°. Mean flexion improved from 54.4° (5° to 100°) to 90° (10° to 125°) (p <  0.05) and the mean flexion contracture decreased from 12.0° (0° to 45°) to 3.5° (0° to 25°) (p < 0.05). The mean WOMAC scores improved for pain, stiffness and function. In patients with extreme stiffness we describe a novel technique, which we have called the ‘sloppy’ revision. This entails downsizing the polyethylene insert by 4 mm and using a more constrained liner to retain stability. Conclusion. To our knowledge, this is the largest series of revision surgeries for stiffness reported in the literature where infection and loosening have been excluded. . Take home message: Whilst revision surgery is technically demanding, improvements in ROM and outcome can be achieved, particularly when the revision is within two years of the primary surgery. Cite this article: Bone Joint J 2016;98-B:622–7

Fixed flexion deformities are common in osteoarthritic knees that are indicated for total knee arthroplasty. The lack of full extension at the knee results in a greater force of quadriceps contracture and energy expenditure. It also results in slower walking velocity and abnormal gait mechanics, overloading the contralateral limb. Residual flexion contractures after TKA have been associated with poorer functional scores and outcomes. Although some flexion contractures may resolve with time after surgery, a substantial percentage will become permanent. Therefore, it is essential to correct fixed flexion deformities at the time of TKA, and be vigilant in the post-operative course to maintain the correction. Surgical techniques to address pre-operative flexion contractures include: adequate bone resection, ligament releases, removal of posterior osteophytes, and posterior capsular releases. Post-operatively, extension can be maintained with focused physiotherapy, a specially modified continuous passive motion machine, a contralateral heel lift, and splinting

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

We report the results of a prospective study of the surgical release of 45 knee flexion contractures in 28 patients with myelomeningocele. The neurosegmental level was thoracic in ten patients, L1/2 in one, L3/4 in 11, and L5/S1 in six. In walkers the indication for surgery was a fixed flexion contracture impeding walking, and in non-walking patients it was a flexion contracture impeding transfers or sitting balance, or likely to do so with increasing deformity. The mean age at surgery was 6.4 years (3 to 21) and the mean period of follow-up 13 years (4 to 20). The mean knee flexion contracture before surgery was 39° (25 to 70) which improved to 5° at maximum correction and to 13° at latest follow-up. We conclude that surgical release of knee flexion contractures in myelomeningocele improves gait in all children who walk, particularly those with low lumbar lesions. Recurrence of knee flexion contractures after surgical release is most common in those with thoracic lesions who do not achieve independent walking

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Knowledge on total knee arthroplasties (TKAs) in patients with a history of poliomyelitis is limited. This study compared implant survivorship and clinical outcomes among affected and unaffected limbs in patients with sequelae of poliomyelitis undergoing TKAs.

The term mid-flexion instability has entered the orthopaedic literature as a concept, but has not been confirmed as a distinct clinical entity. The term is used freely, sometimes as a synonym for flexion instability. However, the terms need to be clearly separated. A cadaver study published in 1990 associated joint line elevation with decreased stability at many angles of flexion, but that model was not typical of clinical scenarios. The literature is considered and it is proposed that the more common entity of an uncorrected flexion contracture after a measured resection arthroplasty technique is more likely to produce clinical findings that suggest instability mid-flexion. It is proposed that the clinical scenario encountered is generalised instability, with the appearance of stability in full extension from tight posterior structures. This paper seeks to clarify whether mid-flexion instability exists as an entity distinct from other commonly recognised forms of instability. Cite this article: Bone Joint J 2016;98-B(1 Suppl A):84–8

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The aim of this study was to evaluate whether achieving medial joint opening, as measured by the change in the joint line convergence angle (∆JLCA), is a better predictor of clinical outcomes after high tibial osteotomy (HTO) compared with the mechanical axis deviation, and to find individualized targets for the redistribution of load that reflect bony alignment, joint laxity, and surgical technique.

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This study compared patient-reported outcomes of three total knee arthroplasty (TKA) designs from one manufacturer: one cruciate-retaining (CR) design, and two cruciate-sacrificing designs, anterior-stabilized (AS) and posterior-stabilized (PS).

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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.