The ability to edit DNA at the nucleotide level using clustered regularly interspaced short palindromic repeats (CRISPR) systems is a relatively new investigative tool that is revolutionizing the analysis of many aspects of human health and disease, including orthopaedic disease. CRISPR, adapted for mammalian cell genome editing from a bacterial defence system, has been shown to be a flexible, programmable, scalable, and easy-to-use gene editing tool. Recent improvements increase the functionality of CRISPR through the engineering of specific elements of CRISPR systems, the discovery of new, naturally occurring CRISPR molecules, and modifications that take CRISPR beyond gene editing to the regulation of gene transcription and the manipulation of RNA. Here, the basics of CRISPR genome editing will be reviewed, including a description of how it has transformed some aspects of molecular
Involving research users in setting priorities for research is essential to ensure research outcomes are patient-centred and to maximise research value and impact. The Musculoskeletal (MSK) Disorders Research Advisory Group Versus Arthritis led a research priority setting exercise across MSK disorders. The Child Health and Nutrition Research Initiative (CHRNI) method of setting research priorities with a range of stakeholders were utilised. The MSKD RAG identified, through consensus, four research Domains: Mechanisms of Disease; Diagnosis and Impact; Living Well with MSK disorders and Successful Translation. Following ethical approval, the research priority exercise involved four stages and two surveys, to: 1) gather research uncertainties; 2) consolidate these; 3) score uncertainties using agreed criteria of importance and impact on a score of 1–10; and 4) analyse scoring, for prioritisation.Background
Methods
An institution of the authors (Center for Musculoskeletal Research) and one author (DAD) have received funding from DePuy, Inc. (Warsaw, IN). Each author certifies that his or her institution has approved the reporting of these cases, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained. This work was performed at Center for
There is ambiguity surrounding the degree of scaphoid union required to safely allow mobilization following scaphoid waist fracture. Premature mobilization could lead to refracture, but late mobilization may cause stiffness and delay return to normal function. This study aims to explore the risk of refracture at different stages of scaphoid waist fracture union in three common fracture patterns, using a novel finite element method. The most common anatomical variant of the scaphoid was modelled from a CT scan of a healthy hand and wrist using 3D Slicer freeware. This model was uploaded into COMSOL Multiphysics software to enable the application of physiological enhancements. Three common waist fracture patterns were produced following the Russe classification. Each fracture had differing stages of healing, ranging from 10% to 90% partial union, with increments of 10% union assessed. A physiological force of 100 N acting on the distal pole was applied, with the risk of refracture assessed using the Von Mises stress.Aims
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The Exeter V40 femoral stem is the most implanted stem in the National Joint Registry (NJR) for primary total hip arthroplasty (THA). In 2004, the 44/00/125 stem was released for use in ‘cement-in-cement’ revision cases. It has, however, been used ‘off-label’ as a primary stem when patient anatomy requires a smaller stem with a 44 mm offset. We aimed to investigate survival of this implant in comparison to others in the range when used in primary THAs recorded in the NJR. We analyzed 328,737 primary THAs using the Exeter V40 stem, comprising 34.3% of the 958,869 from the start of the NJR to December 2018. Our exposure was the stem, and the outcome was all-cause construct revision. We stratified analyses into four groups: constructs using the 44/00/125 stem, those using the 44/0/150 stem, those including a 35.5/125 stem, and constructs using any other Exeter V40 stem.Aims
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Open lower limb fracture is life-changing, resulting in substantial morbidity and resource demand, while inconsistent outcome-reporting hampers systematic review and meta-analysis. A core outcome set establishes consensus among key stakeholders for the recommendation of a minimum set of outcomes. This study aims to define a core outcome set for adult open lower limb fracture. Candidate outcomes were identified from a previously published systematic review and a secondary thematic analysis of 25 patient interviews exploring the lived experience of recovery from open lower limb fracture. Outcomes were categorized and sequentially refined using healthcare professional and patient structured discussion groups. Consensus methods included a multi-stakeholder two-round online Delphi survey and a consensus meeting attended by a purposive sample of stakeholders, facilitated discussion, and voting using a nominal group technique.Aims
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The patient-acceptable symptom state (PASS) is a level of wellbeing, which is measured by the patient. The aim of this study was to determine if the proportion of patients who achieved an acceptable level of function (PASS) after medial unicompartmental knee arthroplasty (UKA) was different based on the status of the anterior cruciate ligament (ACL) at the time of surgery. A total of 114 patients who underwent UKA for isolated medial osteoarthritis (OA) of the knee were included in the study. Their mean age was 65 years (SD 10). No patient underwent a bilateral procedure. Those who had undergone ACL reconstruction during the previous five years were excluded. The Knee injury Osteoarthritis Outcome Score Activities of Daily Living (KOOS ADL) function score was used as the primary outcome measure with a PASS of 87.5, as described for total knee arthroplasty (TKA). Patients completed all other KOOS subscales, Lysholm score, the Western Ontario and McMaster Universities Osteoarthritis Index, and the Veterans Rand 12-item health survey score. Failure was defined as conversion to TKA.Aims
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Stiffness is a common complication after total knee arthroplasty (TKA). Pathogenesis is not understood, treatment options are limited, and diagnosis is challenging. The aim of this study was to investigate if MRI can be used to visualize intra-articular scarring in patients with stiff, painful knee arthroplasties. Well-functioning primary TKAs (n = 11), failed non-fibrotic TKAs (n = 5), and patients with a clinical diagnosis of fibrosisAims
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Introduction. To meet the demands of younger more active patients more robust pre-clinical wear testing methods are required, in order to simulate a wider range of activities. A new electromechanical simulator (Simulation Solutions, UK) with a greater range of motion, a driven abduction/adduction axis and improved input kinematic following has been developed to meet these requirements, as well as requirements of the relevant international standards. This study investigated the wear of a fixed bearing total knee replacement using this new electromechanical knee simulator, comparing with previous data from a pneumatic simulator. Materials/Methods. The wear of six Sigma CR fixed bearing TKRs (DePuy, UK) with curved moderately cross-linked polyethylene inserts (XLK) was determined in pneumatic and electromechanical Prosim knee simulators (Simulation Solutions, UK). Standard gait displacement controlled kinematics were used, with a maximum anterior-posterior displacement of either 10mm (high) or 5mm (intermediate) [1]. The output profiles from the simulators were obtained and compared to the demand input profiles. The lubricant used was 25% new-born calf serum and wear determined gravimetrically. Statistical analysis was performed using the one-way ANOVA with 95% confidence interval and significance was taken at p<0.05. Results. The electromechanical and pneumatic knee simulators both achieved the demanded maximum axial load although the pneumatic simulator did not achieve the initial peak on heel strike. The maximum delivered AP displacements from the electromechanical knee simulator were 2.8 (3.5mm input) and 9.6 (10mm input) [mm] compared to 1.7 and 9.2 [mm] from the pneumatic simulator during the stance and the swing phases respectively. The corresponding values for the IE rotation angle were ±4.9 (5 degrees input) and ±4.1 [degrees] from the electromechanical and pneumatic simulators respectively (both stance and swing phases) (Figure 1). The electromechanical knee simulator produced a mean wear rate of 2.7 ±0.9mm3/MC (mean ± 95% CI) under intermediate kinematics, compared to 2.6 ±0.9mm3/MC from the pneumatic simulator (p=0.99). The corresponding mean wear rates under high kinematics were 5.6 ± 2.3 and 6.7 ±1.5 [mm3/MC] from the electromechanical and pneumatic knee simulators respectively (p=0.59). Discussion. The wear rates from the electromechanical and pneumatic knee simulators were not significantly different. However, the output kinematic profiles followed the input kinematic profiles more closely on the electromechanical simulator than the pneumatic simulator. This electromechanical knee simulator can be used for a wider range of conditions, including high-flexion, due to it's improved capability and performance over the pneumatic simulators. Conclusion. The electromechanical knee simulator showed improved performance and capability compared to the pneumatic knee simulator, and can therefore meet higher current and future testing demands. The wear trends, from the two simulators, were however not significantly different under standard gait conditions. Acknowledgements. This research work was supported by EPSRC, Innovate UK and BBSRC [IKC Medical Technologies], the Leeds Centre of Excellence in Medical Engineering, WELMEC, funded by the Wellcome Trust and EPSRC, WT088908/Z/09/Z and the Leeds
The coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented challenges to healthcare systems worldwide. Orthopaedic departments have adopted business continuity models and guidelines for essential and non-essential surgeries to preserve hospital resources as well as protect patients and staff. These guidelines broadly encompass reduction of ambulatory care with a move towards telemedicine, redeployment of orthopaedic surgeons/residents to the frontline battle against COVID-19, continuation of education and research through web-based means, and cancellation of non-essential elective procedures. However, if containment of COVID-19 community spread is achieved, resumption of elective orthopaedic procedures and transition plans to return to normalcy must be considered for orthopaedic departments. The COVID-19 pandemic also presents a moral dilemma to the orthopaedic surgeon considering elective procedures. What is the best treatment for our patients and how does the fear of COVID-19 influence the risk-benefit discussion during a pandemic? Surgeons must deliberate the fine balance between elective surgery for a patient’s wellbeing versus risks to the operating team and utilization of precious hospital resources. Attrition of healthcare workers or Orthopaedic surgeons from restarting elective procedures prematurely or in an unsafe manner may render us ill-equipped to handle the second wave of infections. This highlights the need to develop effective screening protocols or preoperative COVID-19 testing before elective procedures in high-risk, elderly individuals with comorbidities. Alternatively, high-risk individuals should be postponed until the risk of nosocomial COVID-19 infection is minimal. In addition, given the higher mortality and perioperative morbidity of patients with COVID-19 undergoing surgery, the decision to operate must be carefully deliberated. As we ramp-up elective services and get “back to business” as orthopaedic surgeons, we have to be constantly mindful to proceed in a cautious and calibrated fashion, delivering the best care, while maintaining utmost vigilance to prevent the resurgence of COVID-19 during this critical transition period. Cite this article:
Introduction. Patella femoral joint bearings in total knee replacements have shown low wear (3.1 mm. 3. /MC) under standard gait simulator conditions. 1. However, the wear in retrieval studies have shown large variations between 1.3 to 45.2 mm. 3. /year. 2. Previous in vitro studies on the tibial femoral joint have shown wear is dependent on design, materials and kinematics. 3. . The aim of this study was to investigate the influence of the design (geometry) and shape on the wear rate of patella femoral joints in total knee replacements. Materials and Methods. The Leeds/Prosim knee simulator was used to investigate the wear of two types of commercially available patellae. The PFC Sigma cobalt chrome femoral component was coupled with 2 types of patellae buttons: round and oval dome. The UHMWPE was the same for the both types – GUR1020 GVF (gamma irradiated in vacuum and foiled packed). 25% bovine serum was used as the lubricant. The test were carried out at three conditions – high medial lateral (ML) rotations (<4°) and uncontrolled ML displacement (<4 mm), low ML rotation (<1°) and uncontrolled ML displacement (<4 mm); the physiological gait cycle; and low ML rotation and controlled ML displacement (<1.5 mm). In this abstract the two designs were tested in physiological gait condition (Figure 1). Patella ML displacement and tilt were passively controlled and measured after every 300,000 cycles. A ligament resisting force equivalent to 10 N4 was applied on the lateral side of the patella to avoid patella slip. Five samples of each design were tested for 3 million cycles at a cycle rate of 1 Hz. The wear volume was obtained gravimetrically every million cycles and presented with 95% confidence limits. Statistical significance was taken at p<0.05. Results and Discussions. The wear rate of PFC sigma round dome patella was higher (8.63 ± 3.44 mm. 3. /million cycles) compared to the PFC sigma oval dome patella (6.28 ± 3.89 mm. 3. /million cycles) (Figure 2). However, no significant difference in the wear rates was found between the two shapes (P=0.2). The low area of contact of oval dome patella (31.2% of total surface area) as compared to round dome patella (39.9%) led to low wear. 5. . The wear volume and the patellar tilt were positively correlated for oval dome and round dome patella, R. 2. > 0.9 (Figure 3). Increase in the patellar tilt resulted increase in sliding distance in perpendicular direction of polymer orientation. This led to higher wear volume. Conclusions. Wear rate decreased with change of patella shape from round dome to oval dome although not significantly. Increase in the patellar tilt resulted in increase in the wear volume. Acknowledgement. This research was supported in part by the DePuy and EPSRC. In addition, it was partially funded through WELMEC, a Centre of Excellence in Medical Engineering funded by the Wellcome Trust, under grant number WT 088908/Z/09/Z and additionally supported by the NIHR (National Institute for Health Research) as part of collaboration with the LMBRU (Leeds
INTRODUCTION. Ceramic-on-ceramic hip replacements have generated great interest in recent years due to substantial improvements in manufacturing techniques and material properties. 1. Microseparation conditions that could occur due to several clinical factors such as head offset deficiency, medialised cup combined with laxity of soft tissue resulting in a translation malalignment, have been shown to cause edge loading, replicate clinically relevant wear mechanisms. 2,3. and increase the wear of ceramic-on-ceramic bearings. 3,4. The aim of this study was to investigate the influence of increasing the femoral head size on the wear of ceramic-on-ceramic bearings under several clinically relevant simulator conditions. MATERIALS AND METHODS. The wear of size 28mm and 36mm ceramic-on-ceramic bearings (BIOLOX® Delta, CeramTec, Germany) was determined under different in vitro conditions using the Leeds II hip simulator. For each size bearing, two clinical cup inclination angles were considered, 55° (n=3) and 65° (n=3) for the 28mm bearing and 45° (n=3) and 65° (n=3) for the 36mm bearing. The first two (28mm study) or three (36mm study) million cycles ran under standard gait conditions and a subsequent three million cycles ran under microseparation conditions. A standard gait cycle included a twin peak load (300N–3000N), extension/flexion (−15°/+30°) and internal/external rotation (±10°). Microseparation. 3. was achieved by applying a 0.4–0.5mm medial displacement to the cup relative to the head during the swing phase of the standard gait cycle resulting in edge loading at heel strike. The lubricant was 25% (v/v) new-born calf serum which was changed approximately every 333,000 cycles. The wear volume was ascertained through gravimetric analysis every million cycles. One way ANOVA was performed (significance: p<0.05), and 95% confidence limits were calculated. RESULTS AND DISCUSSION. The mean wear rate under standard gait conditions was 0.05mm. 3. / million cycles for the 28mm bearings and significantly lower (p=0.003) for the 36mm bearings (Figure 1) which could be due to improved lubrication regime. The wear of ceramic-on-ceramic bearings was not influenced by the increase in cup inclination angle for either bearing size (Figure 1). The introduction of microseparation into the gait cycle resulted in stripe wear on the femoral head with a corresponding wear area at the rim of the acetabular cup and significantly higher wear rates of the ceramic-on-ceramic bearings (Figure 2). The wear rate of BIOLOX® Delta bearings under microseparation conditions was still low (<0.25mm. 3. /million cycles) compared to the third generation alumina ceramic-on-ceramic bearings (1.84mm. 3. /million cycles). 4. under the same adverse conditions. Under microseparation conditions, the wear rate of size 36mm bearings was significantly higher (p=0.004) than that for size 28mm bearings. This was thought to be due to the larger contact area for the larger bearings and deprived lubrication under edge loading conditions. For both bearing sizes, the combination of both steep cup inclination angles and microseparation conditions did not increase the wear rates any further compared to microseparation conditions alone (Figure 3). This study shows the importance of surgical positioning of the femoral head and acetabular cup and the importance of testing new bearing materials and designs using these adverse simulator methods. ACKNOWLEDGEMENT. This study was supported by the Furlong Research Charitable Foundation (FRCF) and the National Institute of Health Research (NIHR) as part of a collaboration with the Leeds
INTRODUCTION. Retrieval and clinical studies of metal-on-metal (MoM) bearings have associated increased wear. 1. and elevated patient ion levels. 2. with steep cup inclination angles and edge loading conditions. The University of Leeds have previously developed a hip simulator method that has been validated against retrievals and shown to replicate clinically relevant wear rates and wear mechanisms. 3,4. This method involves introducing lateral microseparation to represent adverse joint laxity and offset deficiency. This study aimed to investigate the effect of microseparation representing translational malpostion, and increased cup inclination angle, representing rotational malposition, in isolation and combined on the wear of different sizes (28 and 36mm) MoM bearing in total hip replacement (THRs). MATERIALS AND METHODS. The wear of size 28mm and 36mm MoM THRs bearings was determined under different in vitro conditions using the Leeds II hip simulator. For each size bearing, two clinical cup inclination angles were considered, 45° (n=3) and 65° (n=3). The first three million cycles were run under standard gait conditions and subsequently three million cycles were run under microseparation conditions. Standard gait cycles included a twin peak load (300N–3000N), extension/flexion (−15°/+30°) and internal/external rotation (±10°). Microseparation. 4. was achieved by applying a 0.4–0.5mm medial displacement to the cup relative to the head during the swing phase of the standard gait cycle resulting in edge loading at heel strike. The lubricant was 25% (v/v) new-born calf serum. The wear volume was determined through gravimetric analysis every million cycles. One way ANOVA was performed (significance: p<0.05), and 95% confidence limits were calculated. RESULTS. Under standard gait conditions, the 28mm MoM bearing showed head-rim contact and increased wear rate with increased cup inclination angle but the 36mm bearing did not show any increase in wear. Microseparation and edge loading increased the wear rate of MoM bearings for all cup inclination angle conditions and bearing sizes (Figure 1). DISCUSSION. With the larger size bearings, head-rim contact occurred at a steeper cup inclination angle (>65°) providing an advantage over smaller bearings. Under standard gait conditions, where head-rim contact did not occur, wear was low, due to mixed lubrication and wear reduction through a protein boundary film. However, edge loading of the cup, with elevated stress, caused excess damage and wear. This effect was more dominant with microseparation conditions to that of head-rim contact due to increased cup inclination angle alone. Under microseparation conditions, there were no significant differences in the wear rates of the 28mm and the 36mm size bearings. However, the wear rates obtained in this study for 28mm and 36mm bearings were significantly lower than those obtained for size 39mm surface replacement MoM bearings (8.99 mm. 3. /million cycles) tested under the same adverse conditions. 5. . CONCLUSION. This study shows the importance of acetabular cup design and correct surgical positioning of the femoral head and acetabular cup and restoration of offset and cup centre. ACKNOWLEDGEMENT. This study was supported by the Furlong Research Charitable Foundation (FRCF) and the National Institute of Health Research (NIHR) as part of a collaboration with the Leeds
The traditional biomedical model of managing musculoskeletal problems, such as low back pain (LBP), tends to be pathology driven, in which the aim is to locate an objectively identified disturbance. Appropriate treatment is conceptualised as a physical intervention that will compensate for or correct the identified disturbance. There is growing appreciation of the need to consider other factors, e.g. the meaning of the problem to the patient and professional, his/her experiences, cognitions, motivations and preferences. Improving the understanding about the beliefs and expectations of patients and health professionals is fundamental, since a better understanding of these factors, and any mismatch between professionals and patients, will facilitate improved management. A multidisciplinary group of researchers (chiropractor, GP, osteopath, physiotherapist, psychologist, sociologist) have developed a collaborative research programme to investigate the decision-making processes in the care of patients with musculoskeletal pain. The programme uses mixed methods, including systematic reviews, survey research, focus groups and semi-structured interviews with patients and practitioners. Three studies have already started: patient and health professional beliefs and expectations for the causes and treatment of chronic musculoskeletal pain. 1) Funded by the ARC, the purpose is to develop an understanding of the relationships between the different, professional and lay, theoretical frameworks used to diagnose and treat chronic musculoskeletal pain, and how these affect care. 2) Clinicians cognitions in apparently ineffective treatment of low back pain: funded by the ESRC, the purpose is to identify the reasons clinicians continue to treat LBP in the absence of improvement. Research on risk factors for the transition from acute to chronic LBP has concentrated on patient characteristics (psychological and social). It is possible that clinicians’ behaviour, advice and even treatment contribute to maintaining the problem indirectly. 3) Overcoming barriers to evidence-based practice (EBP) in LBP management in the physical therapy professions; funded by the Department of Physiotherapy Studies, Keele University, this study aims to explore the perceptions of physiotherapists, chiropractors and osteopaths, about the opportunities and threats of taking an EBP approach to LBP management and identify methods by which implementation of evidence can be facilitated. This collaboration is the first of its kind and was developed through shared interests in the decision-making processes in the healthcare of people with musculoskeletal pain. We are keen to share the ideas and work in progress with the wider
