Aims. The goal was to evaluate tibiofemoral knee joint kinematics during stair descent, by simulating the full stair descent motion in vitro. The knee joint kinematics were evaluated for two types of knee implants: bi-cruciate retaining and bi-cruciate stabilized. It was hypothesized that the bi-cruciate retaining implant better approximates native kinematics. Methods. The in vitro study included 20 specimens which were tested during a full stair descent with physiological muscle forces in a dynamic knee rig. Laxity envelopes were measured by applying external loading conditions in varus/valgus and internal/external direction. Results. The laxity results show that both implants are capable of mimicking the native internal/external-laxity during the controlled lowering phase. The kinematic results show that the bi-cruciate retaining implant tends to approximate the native condition better compared to bi-cruciate stabilized implant. This is valid for the internal/external rotation and the anteroposterior translation during all phases of the stair descent, and for the compression-distraction of the knee joint during swing and controlled lowering phase. Conclusion. The results show a better approximation of the native kinematics by the bi-cruciate retaining knee implant compared to the bi-cruciate stabilized knee implant for internal/external rotation and anteroposterior translation. Whether this will result in better patient outcomes remains to be investigated. Cite this article: Bone Joint Res 2023;12(4):285–293

Aims. Periprosthetic fractures (PPFs) around the knee are challenging injuries. This study aims to describe the characteristics of knee PPFs and the impact of patient demographics, fracture types, and management modalities on in-hospital mortality. Methods. Using a multicentre study design, independent of registry data, we included adult patients sustaining a PPF around a knee arthroplasty between 1 January 2010 and 31 December 2019. Univariate, then multivariable, logistic regression analyses were performed to study the impact of patient, fracture, and treatment on mortality. Results. Out of a total of 1,667 patients in the PPF study database, 420 patients were included. The in-hospital mortality rate was 6.4%. Multivariable analyses suggested that American Society of Anesthesiologists (ASA) grade, history of peripheral vascular disease (PVD), history of rheumatic disease, fracture around a loose implant, and cerebrovascular accident (CVA) during hospital stay were each independently associated with mortality. Each point increase in ASA grade independently correlated with a four-fold greater mortality risk (odds ratio (OR) 4.1 (95% confidence interval (CI) 1.19 to 14.06); p = 0.026). Patients with PVD have a nine-fold increase in mortality risk (OR 9.1 (95% CI 1.25 to 66.47); p = 0.030) and patients with rheumatic disease have a 6.8-fold increase in mortality risk (OR 6.8 (95% CI 1.32 to 34.68); p = 0.022). Patients with a fracture around a loose implant (Unified Classification System (UCS) B2) have a 20-fold increase in mortality, compared to UCS A1 (OR 20.9 (95% CI 1.61 to 271.38); p = 0.020). Mode of management was not a significant predictor of mortality. Patients managed with revision arthroplasty had a significantly longer length of stay (median 16 days; p = 0.029) and higher rates of return to theatre, compared to patients treated nonoperatively or with fixation. Conclusion. The mortality rate in PPFs around the knee is similar to that for native distal femur and neck of femur fragility fractures. Patients with certain modifiable risk factors should be optimized. A national PPF database and standardized management guidelines are currently required to understand these complex injuries and to improve patient outcomes. Cite this article: Bone Joint J 2024;106-B(2):158–165

Aims. This study aims to identify the top unanswered research priorities in the field of knee surgery using consensus-based methodology. Methods. Initial research questions were generated using an online survey sent to all 680 members of the British Association for Surgery of the Knee (BASK). Duplicates were removed and a longlist was generated from this scoping exercise by a panel of 13 experts from across the UK who provided oversight of the process. A modified Delphi process was used to refine the questions and determine a final list. To rank the final list of questions, each question was scored between one (low importance) and ten (high importance) in order to produce the final list. Results. This consensus exercise took place between December 2020 and April 2022. A total of 286 clinicians from the BASK membership provided input for the initial scoping exercise, which generated a list of 105 distinct research questions. Following review and prioritization, a longlist of 51 questions was sent out for two rounds of the Delphi process. A total of 42 clinicians responded to the first round and 24 responded to the second round. A final list of 24 research questions was then ranked by 36 clinicians. The topics included arthroplasty, infection, meniscus, osteotomy, patellofemoral, cartilage, and ligament pathologies. The management of early osteoarthritis was the highest-ranking question. Conclusion. A Delphi exercise involving the BASK membership has identified the future research priorities in knee surgery. This list of questions will allow clinicians, researchers, and funders to collaborate in order to deliver high-quality research in knee surgery and further advance the care provided to patients with knee pathology. Cite this article: Bone Joint J 2024;106-B(7):662–668

Aims. Joint registries classify all further arthroplasty procedures to a knee with an existing partial arthroplasty as revision surgery, regardless of the actual procedure performed. Relatively minor procedures, including bearing exchanges, are classified in the same way as major operations requiring augments and stems. A new classification system is proposed to acknowledge and describe the detail of these procedures, which has implications for risk, recovery, and health economics. Methods. Classification categories were proposed by a surgical consensus group, then ranked by patients, according to perceived invasiveness and implications for recovery. In round one, 26 revision cases were classified by the consensus group. Results were tested for inter-rater reliability. In round two, four additional cases were added for clarity. Round three repeated the survey one month later, subject to inter- and intrarater reliability testing. In round four, five additional expert partial knee arthroplasty surgeons were asked to classify the 30 cases according to the proposed revision partial knee classification (RPKC) system. Results. Four classes were proposed: PR1, where no bone-implant interfaces are affected; PR2, where surgery does not include conversion to total knee arthroplasty, for example, a second partial arthroplasty to a native compartment; PR3, when a standard primary total knee prosthesis is used; and PR4 when revision components are necessary. Round one resulted in 92% inter-rater agreement (Kendall’s W 0.97; p < 0.005), rising to 93% in round two (Kendall’s W 0.98; p < 0.001). Round three demonstrated 97% agreement (Kendall’s W 0.98; p < 0.001), with high intra-rater reliability (interclass correlation coefficient (ICC) 0.99; 95% confidence interval 0.98 to 0.99). Round four resulted in 80% agreement (Kendall’s W 0.92; p < 0.001). Conclusion. The RPKC system accounts for all procedures which may be appropriate following partial knee arthroplasty. It has been shown to be reliable, repeatable and pragmatic. The implications for patient care and health economics are discussed. Cite this article: Bone Jt Open 2021;2(8):638–645

Aims

Classifying trochlear dysplasia (TD) is useful to determine the treatment options for patients suffering from patellofemoral instability (PFI). There is no consensus on which classification system is more reliable and reproducible for the purpose of guiding clinicians’ management of PFI. There are also concerns about the validity of the Dejour Classification (DJC), which is the most widely used classification for TD, having only a fair reliability score. The Oswestry-Bristol Classification (OBC) is a recently proposed system of classification of TD, and the authors report a fair-to-good interobserver agreement and good-to-excellent intraobserver agreement in the assessment of TD. The aim of this study was to compare the reliability and reproducibility of these two classifications.

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. The primary aim of this study was to assess whether the postoperative Oxford Knee Score (OKS) demonstrated a ceiling effect at one and/or two years after total knee arthroplasty (TKA). The secondary aim was to identify preoperative independent predictors for patients that achieved a ceiling score after TKA. Methods. A retrospective cohort of 5,857 patients undergoing a primary TKA were identified from an established arthroplasty database. Patient demographics, body mass index (BMI), OKS, and EuroQoL five-dimension (EQ-5D) general health scores were collected preoperatively and at one and two years postoperatively. Logistic regression analysis was used to identify independent preoperative predictors of patients achieving postoperative ceiling scores. Receiver operating characteristic curve was used to identify a preoperative OKS that predicted a postoperative ceiling score. Results. The ceiling effect was 4.6% (n = 272) at one year which increased significantly (odds ratio (OR) 40.3, 95% confidence interval (CI) 30.4 to 53.3; p < 0.001) to 6.2% (n = 363) at two years, when defined as those with a maximal score of 48 points. However, when the ceiling effect was defined as an OKS of 44 points or more, this increased to 26.3% (n = 1,540) at one year and further to 29.8% (n = 1,748) at two years (OR 21.6, 95% CI 18.7 to 25.1; p < 0.001). A preoperative OKS of 23 or more and 22 or more were predictive of achieving a postoperative ceiling OKS at one and two years when defined as a maximal score or a score of 44 or more, respectively. Conclusion. The postoperative OKS demonstrated a small ceiling effect when defined by a maximal score, but when defined by a postoperative OKS of 44 or more the ceiling effect was moderate and failed to meet standards. The preoperative OKS was an independent predictor of achieving a ceiling score. Cite this article: Bone Joint J 2020;102-B(11):1519–1526

Aims. The aim of this study was to investigate differences in pain, range of movement function and satisfaction at three months and one year after total knee arthroplasty (TKA) in patients with an oblique pattern of kinematic graph of the knee and those with a varus pattern. Patients and Methods. A total of 91 patients who underwent TKA were included in this retrospective study. Patients (59 women and 32 men with mean age of 68.7 years; 38.6 to 88.4) were grouped according to kinematic graphs which were generated during navigated TKA and the outcomes between the groups were compared. Results. The graphs were varus in 50 patients (55%), oblique in 19 (21%), neutral in 17 (18.5%) and valgus in five (5.5%). After adjustment for pre-operative scores and gender, compared with patients with varus knee kinematics, patients with an oblique kinematic graph had a poorer outcome with lower Knee Society scores at three months (9.2 points, p = 0.038). Conclusion. We found four distinct kinematic graphs in knees and that patients with an oblique graph have a poorer outcome in the short-term after TKA. Cite this article: Bone Joint J 2016;98-B:1471–8

Aims. The aim of this consensus was to develop a definition of post-operative fibrosis of the knee. Patients and Methods. An international panel of experts took part in a formal consensus process composed of a discussion phase and three Delphi rounds. Results. Post-operative fibrosis of the knee was defined as a limited range of movement (ROM) in flexion and/or extension, that is not attributable to an osseous or prosthetic block to movement from malaligned, malpositioned or incorrectly sized components, metal hardware, ligament reconstruction, infection (septic arthritis), pain, chronic regional pain syndrome (CRPS) or other specific causes, but due to soft-tissue fibrosis that was not present pre-operatively. Limitation of movement was graded as mild, moderate or severe according to the range of flexion (90° to 100°, 70° to 89°, < 70°) or extension deficit (5° to 10°, 11° to 20°, > 20°). Recommended investigations to support the diagnosis and a strategy for its management were also agreed. Conclusion. The development of standardised, accepted criteria for the diagnosis, classification and grading of the severity of post-operative fibrosis of the knee will facilitate the identification of patients for inclusion in clinical trials, the development of clinical guidelines, and eventually help to inform the management of this difficult condition. Cite this article: Bone Joint J 2016;98-B:1479–88

Osteochondritis Dissecans (OCD) is a condition for which the aetiology remains unknown. It affects subchondral bone and secondarily its overlying cartilage and is mostly found in the knee. It can occur in adults, but is generally identified when growth remains, when it is referred to as juvenile OCD. As the condition progresses, the affected subchondral bone separates from adjacent healthy bone, and can lead to demarcation and separation of its associated articular cartilage. Any symptoms which arise relate to the stage of the disease. Early disease without separation of the lesion results in pain. Separation of the lesion leads to mechanical symptoms and swelling and, in advanced cases, the formation of loose bodies. Early identification of OCD is essential as untreated OCD can lead to the premature degeneration of the joint, whereas appropriate treatment can halt the disease process and lead to healing. Establishing the stability of the lesion is a key part of providing the correct treatment. Stable lesions, particularly in juvenile patients, have greater propensity to heal with non-surgical treatment, whereas unstable or displaced lesions usually require surgical management. This article discusses the aetiology, clinical presentation and prognosis of OCD in the knee. It presents an algorithm for treatment, which aims to promote healing of native hyaline cartilage and to ensure joint congruity. Take home message: Although there is no clear consensus as to the best treatment of OCD, every attempt should be made to retain the osteochondral fragment when possible as, with a careful surgical technique, there is potential for healing even in chronic lesions. Cite this article: Bone Joint J 2016;98-B:723–9

We have investigated whether shape of the knee can predict the clinical outcome of patients after an anterior cruciate ligament rupture. We used statistical shape modelling to measure the shape of the knee joint of 182 prospectively followed patients on lateral and Rosenberg view radiographs of the knee after a rupture of the anterior cruciate ligament. Subsequently, we associated knee shape with the International Knee Documentation Committee subjective score at two years follow-up. The mean age of patients was 31 years (21 to 51), the majority were male (n = 121) and treated operatively (n = 135). We found two modes (shape variations) that were significantly associated with the subjective score at two years: one for the operatively treated group (p = 0.002) and one for the non-operatively treated group (p = 0.003). Operatively treated patients who had higher subjective scores had a smaller intercondylar notch and a smaller width of the intercondylar eminence. Non-operatively treated patients who scored higher on the subjective score had a more pyramidal intercondylar notch as opposed to one that was more dome-shaped. We conclude that the shape of the femoral notch and the intercondylar eminence is predictive of clinical outcome two years after a rupture of the anterior cruciate ligament. Cite this article: Bone Joint J 2014;96-B:737–42

The lateral compartment is predominantly affected in approximately 10% of patients with osteoarthritis of the knee. The anatomy, kinematics and loading during movement differ considerably between medial and lateral compartments of the knee. This in the main explains the relative protection of the lateral compartment compared with the medial compartment in the development of osteoarthritis. The aetiology of lateral compartment osteoarthritis can be idiopathic, usually affecting the femur, or secondary to trauma commonly affecting the tibia. Surgical management of lateral compartment osteoarthritis can include osteotomy, unicompartmental knee replacement and total knee replacement. This review discusses the biomechanics, pathogenesis and development of lateral compartment osteoarthritis and its management. Cite this article: Bone Joint J 2013;95-B:436–44

We retrospectively reviewed the records of 1150 computer-assisted total knee replacements and analysed the clinical and radiological outcomes of 45 knees that had arthritis with a pre-operative recurvatum deformity. The mean pre-operative hyperextension deformity of 11° (6° to 15°), as measured by navigation at the start of the operation, improved to a mean flexion deformity of 3.1° (0° to 7°) post-operatively. A total of 41 knees (91%) were managed using inserts ≤ 12.5 mm thick, and none had mediolateral laxity > 2 mm from a mechanical axis of 0° at the end of the surgery. At a mean follow-up of 26.4 months (13 to 48) there was significant improvement in the mean Knee Society, Oxford knee and Western Ontario and McMaster Universities Osteoarthritis Index scores compared with the pre-operative values. The mean knee flexion improved from 105° (80° to 125°) pre-operatively to 131° (120° to 145°), and none of the limbs had recurrent recurvatum. These early results show that total knee replacement using computer navigation and an algorithmic approach for arthritic knees with a recurvatum deformity can give excellent radiological and functional outcomes without recurrent deformity

Aims. To present our experience of using a combination of intra-articular osteotomy and external fixation to treat different deformities of the knee. Patients and Methods. A total of six patients with a mean age of 26.5 years (15 to 50) with an abnormal hemi-joint line convergence angle (HJLCA) and mechanical axis deviation (MAD) were included. Elevation of a tibial hemiplateau or femoral condylar advancement was performed and limb lengthening with correction of residual deformity using a circular or monolateral Ilizarov frame. Results. At a mean follow-up of 2.8 years (1.5 to 4.1), the mean HJLCA improved from 15.6° (10° to 23°) pre-operatively to 0.4° (0° to 2°). The mean MAD improved from 70.0 mm (20.1 to 118.5) pre-operatively to 9.1 mm (3 to 15). The mean tibiofemoral angle improved from 31.0° (8° to 54°) pre-operatively to 4.9° (2° to 8°). The mean limb-length discrepancy decreased from 6.3 cm (2.9 to 13.6) pre-operatively to 1.1 cm (0 to 5). All osteotomies and distraction zones healed without complications. Conclusion. The use of intra-articular corrective osteotomies combined with the Ilizarov technique allowed correction of deformities of the knee joint with satisfactory HJLCA and overall mechanical axis in six patients with a good functional and cosmetic outcome in the short term. Cite this article: Bone Joint J 2017;99-B:204–10

This randomised trial evaluated the outcome of a single design of unicompartmental arthroplasty of the knee (UKA) with either a cemented all-polyethylene or a metal-backed modular tibial component. A total of 63 knees in 45 patients (17 male, 28 female) were included, 27 in the all-polyethylene group and 36 in the metal-backed group. The mean age was 57.9 years (39.6 to 76.9). At a mean follow-up of 6.4 years (5 to 9.9), 11 all-polyethylene components (41%) were revised (at a mean of 5.8 years; 1.4 to 8.0) post-operatively and two metal-backed components were revised (at one and five years). One revision in both groups was for unexplained pain, one in the metal-backed group was for progression of osteoarthritis. The others in the all-polyethylene group were for aseptic loosening. The survivorship at seven years calculated by the Kaplan–Meier method for the all-polyethylene group was 56.5% (95% CI 31.9 to 75.2, number at risk 7) and for the metal-backed group was 93.8% (95% CI 77.3 to 98.4, number at risk 16) This difference was statistically significant (p <  0.001). At the most recent follow-up, significantly better mean Western Ontario and McMaster Universities Arthritis Index Scores were found in the all-polyethylene group (13.4 vs 23.0, p = 0.03) but there was no difference in the mean Knee injury and Osteoarthritis Outcome scores (68.8; 41.4 to 99.0 vs 62.6; 24.0 to 100.0), p = 0.36). There were no significant differences for range of movement (p = 0.36) or satisfaction (p = 0.23). This randomised study demonstrates that all-polyethylene components in this design of fixed bearing UKA had unsatisfactory results with significantly higher rates of failure before ten years compared with the metal-back components. Cite this article: Bone Joint J 2015;97-B:786–92

The success of total knee replacement (TKR) depends on optimal soft-tissue balancing, among many other factors. The objective of this study is to correlate post-operative anteroposterior (AP) translation of a posterior cruciate ligament-retaining TKR with clinical outcome at two years. In total 100 patients were divided into three groups based on their AP translation as measured by the KT-1000 arthrometer. Group 1 patients had AP translation < 5 mm, Group 2 had AP translation from 5 mm to 10 mm, and Group 3 had AP translation >  10 mm. Outcome assessment included range of movement of the knee, the presence of flexion contractures, hyperextension, knee mechanical axes and functional outcome using the Knee Society score, Oxford knee score and the Short-Form 36 questionnaire. At two years, patients in Group 2 reported significantly better Oxford knee scores than the other groups (p = 0.045). A positive correlation between range of movement and AP translation was noted, with patients in group 3 having the greatest range of movement (mean flexion: 117.9° (106° to 130°)) (p < 0.001). However, significantly more patients in Group 3 developed hyperextension > 10° (p = 0.01). In this study, the best outcome for cruciate-ligament retaining TKR was achieved in patients with an AP translation of 5 mm to 10 mm

We systematically reviewed the published literature on the complications of closing wedge high tibial osteotomy for the treatment of unicompartmental osteoarthritis of the knee. Publications were identified using the Cochrane Library, MEDLINE, EMBASE and CINAHL databases up to February 2012. We assessed randomised (RCTs), controlled group clinical (CCTs) trials, case series in publications associated with closing wedge osteotomy of the tibia in patients with osteoarthritis of the knee and finally a Cochrane review. Many of these trials included comparative studies (opening wedge versus closing wedge) and there was heterogeneity in the studies that prevented pooling of the results

We assessed the effect of mental disability on the outcome of total knee replacement (TKR) and investigated whether mental health improves post-operatively. Outcome data were prospectively recorded over a three-year period for 962 patients undergoing primary TKR for osteoarthritis. Pre-operative and one year Short-Form (SF)-12 scores and Oxford knee scores (OKS) were obtained. The mental component of the SF-12 was stratified into four groups according to level of mental disability (none ≥ 50, mild 40 to 49, moderate 30 to 39, severe < 30). Patients with any degree of mental disability had a significantly greater subjective physical disability according to the SF-12 (p = 0.06) and OKS (p < 0.001). The improvement in the disease-specific score (OKS) was not affected by a patient’s mental health (p = 0.33). In contrast, patients with mental disability had less of an improvement in their global physical health (SF-12) (p < 0.001). However, patients with any degree of mental disability had a significant improvement in their mental health post-operatively (p < 0.001). Despite a similar improvement in their disease-specific scores and improvement in their mental health, patients with mental disability were significantly more likely to be dissatisfied with their TKR at one year (p = 0.001). Patients with poor mental health do benefit from improvements in their mental health and knee function after TKR, but also have a higher rate of dissatisfaction. Cite this article: Bone Joint J 2013;95-B:360–6

This review considers the surgical treatment of displaced fractures involving the knee in elderly, osteoporotic patients. The goals of treatment include pain control, early mobilisation, avoidance of complications and minimising the need for further surgery. Open reduction and internal fixation (ORIF) frequently results in loss of reduction, which can result in post-traumatic arthritis and the occasional conversion to total knee replacement (TKR). TKR after failed internal fixation is challenging, with modest functional outcomes and high complication rates. TKR undertaken as treatment of the initial fracture has better results to late TKR, but does not match the outcome of primary TKR without complications. Given the relatively infrequent need for late TKR following failed fixation, ORIF is the preferred management for most cases. Early TKR can be considered for those patients with pre-existing arthritis, bicondylar femoral fractures, those who would be unable to comply with weight-bearing restrictions, or where a single definitive procedure is required

Objectives. An important measure for the diagnosis and monitoring of knee osteoarthritis is the minimum joint space width (mJSW). This requires accurate alignment of the x-ray beam with the tibial plateau, which may not be accomplished in practice. We investigate the feasibility of a new mJSW measurement method from stereo radiographs using 3D statistical shape models (SSM) and evaluate its sensitivity to changes in the mJSW and its robustness to variations in patient positioning and bone geometry. Materials and Methods. A validation study was performed using five cadaver specimens. The actual mJSW was varied and images were acquired with variation in the cadaver positioning. For comparison purposes, the mJSW was also assessed from plain radiographs. To study the influence of SSM model accuracy, the 3D mJSW measurement was repeated with models from the actual bones, obtained from CT scans. Results. The SSM-based measurement method was more robust (consistent output for a wide range of input data/consistent output under varying measurement circumstances) than the conventional 2D method, showing that the 3D reconstruction indeed reduces the influence of patient positioning. However, the SSM-based method showed comparable sensitivity to changes in the mJSW with respect to the conventional method. The CT-based measurement was more accurate than the SSM-based measurement (smallest detectable differences 0.55 mm versus 0. 82 mm, respectively). Conclusion. The proposed measurement method is not a substitute for the conventional 2D measurement due to limitations in the SSM model accuracy. However, further improvement of the model accuracy and optimisation technique can be obtained. Combined with the promising options for applications using quantitative information on bone morphology, SSM based 3D reconstructions of natural knees are attractive for further development. Cite this article: E. A. van IJsseldijk, E. R. Valstar, B. C. Stoel, R. G. H. H. Nelissen, N. Baka, R. van’t Klooster, B. L. Kaptein. Three dimensional measurement of minimum joint space width in the knee from stereo radiographs using statistical shape models. Bone Joint Res 2016;320–327. DOI: 10.1302/2046-3758.58.2000626