Cardiac function may be compromised in patients with elevated blood cobalt levels secondary to metal-on-metal hip implants.

Aims: Elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties are a suggested risk factor for developing cardiovascular complications including cardiomyopathy. Clinical studies assessing patients with MoM hips using left ventricular ejection fraction (LVEF) have found conflicting evidence of cobalt-induced cardiomyopathy. Global longitudinal strain (GLS) is an echocardiography measurement known to be more sensitive than LVEF when diagnosing early cardiomyopathies. The extent of cardiovascular injury, as measured by GLS, in patients with elevated blood cobalt levels has not previously been examined. Methods: A total of 16 patients with documented blood cobalt ion levels above 13 µg/l (13 ppb, 221 nmol/l) were identified from a regional arthroplasty database. They were matched with eight patients awaiting hip arthroplasty. All patients underwent echocardiography, including GLS, investigating potential signs of cardiomyopathy. Results: Patients with MoM hip arthroplasties had a mean blood cobalt level of 29 µg/l (495 nmol/l) compared to 0.01 µg/l (0.2 nmol/l) in the control group. GLS readings were available for seven of the MoM cohort, and were significantly lower when compared with controls (-15.5% vs -18% (MoM vs control); p = 0.025)). Pearson correlation demonstrated that GLS significantly correlated with blood cobalt level (r = 0.8521; p < 0.001). However, there were no differences or correlations for other echocardiography measurements, including LVEF (64.3% vs 63.7% (MoM vs control); p = 0.845). Conclusion: This study supports the hypothesis that patients with elevated blood cobalt levels above 13 µg/l in the presence of a MoM hip implant may have impaired cardiac function compared to a control group of patients awaiting hip arthroplasty. It is the first study to use the more sensitive parameter of GLS to assess for any cardiac contractile dysfunction in patients with a MoM hip implant and a normal LVEF. Larger studies should be performed to determine the potential of GLS as a predictor of cardiac complications in patients with MoM arthroplasties.

Prioritization of THose aWaiting hip and knee ArthroplastY(PATHWAY): protocol for development of a stakeholder led clinical prioritization tool.

AIMS: The extended wait that most patients are now experiencing for hip and knee arthroplasty has raised questions about whether reliance on waiting time as the primary driver for prioritization is ethical, and if other additional factors should be included in determining surgical priority. Our Prioritization of THose aWaiting hip and knee ArthroplastY (PATHWAY) project will explore which perioperative factors are important to consider when prioritizing those on the waiting list for hip and knee arthroplasty, and how these factors should be weighted. The final product will include a weighted benefit score that can be used to aid in surgical prioritization for those awaiting elective primary hip and knee arthroplasty. METHODS: There will be two linked work packages focusing on opinion from key stakeholders (patients and surgeons). First, an online modified Delphi process to determine a consensus set of factors that should be involved in patient prioritization. This will be performed using standard Delphi methodology consisting of multiple rounds where following initial individual rating there is feedback, discussion, and further recommendations undertaken towards eventual consensus. The second stage will then consist of a Discrete Choice Experiment (DCE) to allow for priority setting of the factors derived from the Delphi through elicitation of weighted benefit scores. The DCE consists of several choice tasks designed to elicit stakeholder preference regarding included attributes (factors). RESULTS: The study is co-funded by the University of Aberdeen Knowledge Exchange Commission (Ref CF10693-29) and a Chief Scientist Office (CSO) Scotland Clinical Research Fellowship which runs from 08/2021 to 08/2024 (Grant ref: CAF/21/06). Approval from the University of Aberdeen Institute of Applied Health Sciences School Ethics Review Board was granted 22/03/2022 - Reference number SERB/2021/12/2210. CONCLUSION: The PATHWAY project provides the first attempt to use patient and surgeon opinions to develop a unified approach to prioritization for those awaiting hip and knee arthroplasty. Development of such a tool will provide more equitable access to arthroplasty services, as well as providing a framework for developing similar approaches in other areas of healthcare delivery.Cite this article: Bone Jt Open 2022;3(10):753-758.

Driving reaction time following periacetabular osteotomy.

INTRODUCTION: Periacetabular osteotomy (PAO) is increasingly being used to treat young adults with symptomatic hip dysplasia. Currently there is a lack of evidence to guide return to driving after this procedure. This study aimed to identify the length of time required after a Periacetabular Osteotomy procedure before a patient can safely return to driving. METHODS: All patients undergoing PAO were assessed for suitability for the study. Inclusion criteria were: currently driving with a valid licence; and being able to attend follow-up assessment. Baseline driving reaction time was assessed using a driving simulator preoperatively. The simulation was repeated 5 times for each patient and reaction times recorded (Thinking time, Action time and Total reaction time for braking at 30 mph). The driving simulation was repeated using the same methods at 6 weeks and 12 weeks postoperatively. Pre- and postoperative times were compared. RESULTS: 26 patients were included (24 females, 2 males) with a mean age of 32 (range 19-50) years. The mean preoperative times were: Thinking time 0.48, Action time 0.21, Total time 0.69 seconds. At 6 weeks postoperatively, mean Action time increased to 0.26 seconds (p = 0.012) and mean Total time increased to 0.78 seconds (p = 0.013). By 12 weeks post procedure, there was no significant difference in reaction times compared to baseline (mean Thinking time 0.47 seconds, Action time 0.23, Total time 0.72; p > 0.05). CONCLUSIONS: Most patients may not be safe to drive at 6 weeks following PAO procedures but should be safe to drive at 12 weeks postoperatively. Individual patient factors should also be taken into consideration.

Nanovibrational stimulation inhibits osteoclastogenesis and enhances osteogenesis in co-cultures.

Models of bone remodelling could be useful in drug discovery, particularly if the model is one that replicates bone regeneration with reduction in osteoclast activity. Here we use nanovibrational stimulation to achieve this in a 3D co-culture of primary human osteoprogenitor and osteoclast progenitor cells. We show that 1000 Hz frequency, 40 nm amplitude vibration reduces osteoclast formation and activity in human mononuclear CD14+ blood cells. Additionally, this nanoscale vibration both enhances osteogenesis and reduces osteoclastogenesis in a co-culture of primary human bone marrow stromal cells and bone marrow hematopoietic cells. Further, we use metabolomics to identify Akt (protein kinase C) as a potential mediator. Akt is known to be involved in bone differentiation via transforming growth factor beta 1 (TGFß1) and bone morphogenetic protein 2 (BMP2) and it has been implicated in reduced osteoclast activity via Guanine nucleotide-binding protein subunit α13 (Gα13). With further validation, our nanovibrational bioreactor could be used to help provide humanised 3D models for drug screening.

Nanovibrational Stimulation of Mesenchymal Stem Cells Induces Therapeutic Reactive Oxygen Species and Inflammation for Three-Dimensional Bone Tissue Engineering.

There is a pressing clinical need to develop cell-based bone therapies due to a lack of viable, autologous bone grafts and a growing demand for bone grafts in musculoskeletal surgery. Such therapies can be tissue engineered and cellular, such as osteoblasts, combined with a material scaffold. Because mesenchymal stem cells (MSCs) are both available and fast growing compared to mature osteoblasts, therapies that utilize these progenitor cells are particularly promising. We have developed a nanovibrational bioreactor that can convert MSCs into bone-forming osteoblasts in two- and three-dimensional, but the mechanisms involved in this osteoinduction process remain unclear. Here, to elucidate this mechanism, we use increasing vibrational amplitude, from 30 nm (N30) to 90 nm (N90) amplitudes at 1000 Hz and assess MSC metabolite, gene, and protein changes. These approaches reveal that dose-dependent changes occur in MSCs' responses to increased vibrational amplitude, particularly in adhesion and mechanosensitive ion channel expression and that energetic metabolic pathways are activated, leading to low-level reactive oxygen species (ROS) production and to low-level inflammation as well as to ROS- and inflammation-balancing pathways. These events are analogous to those that occur in the natural bone-healing processes. We have also developed a tissue engineered MSC-laden scaffold designed using cells' mechanical memory, driven by the stronger N90 stimulation. These mechanistic insights and cell-scaffold design are underpinned by a process that is free of inductive chemicals.

Obesity is associated with higher complication rates in revision total hip arthroplasty.

We examined differences in complication rates between obese and non-obese patients undergoing revision total hip arthroplasty. Sixty-five patients with a BMI ≥30 kg/m2 and 54 patients with a BMI of <30 kg/m2 were identified. Obese patients were 2.5 times more likely to suffer a complication than non-obese (38.4% cf 14.8%, p = 0.02). Obese patients were more likely to experience dislocation, leg length discrepancy, fracture, implant loosening, infection and pulmonary embolus. The obese group had a significantly higher revision rate (12.3% cf 1.8%, p = 0.039). Obese patients should be counselled pre-operatively on their elevated risk.

Confined Sandwichlike Microenvironments Tune Myogenic Differentiation.

Sandwichlike (SW) cultures are engineered as a multilayer technology to simultaneously stimulate dorsal and ventral cell receptors, seeking to mimic cell adhesion in three-dimensional (3D) environments in a reductionist manner. The effect of this environment on cell differentiation was investigated for several cell types cultured in standard growth media, which promotes proliferation on two-dimensional (2D) surfaces and avoids any preferential differentiation. First, murine C2C12 myoblasts showed specific myogenic differentiation. Human mesenchymal stem cells (hMSCs) of adipose and bone marrow origin, which can differentiate toward a wider variety of lineages, showed again myodifferentiation. Overall, this study shows myogenic differentiation in normal growth media for several cell types under SW conditions, avoiding the use of growth factors and cytokines, i.e., solely by culturing cells within the SW environment. Mechanistically, it provides further insights into the balance between integrin adhesion to the dorsal substrate and the confinement imposed by the SW system.

Delays in diagnosis are associated with poorer outcomes in adult hip dysplasia.

Background and Aims Developmental dysplasia of the hip is a common cause of osteoarthritis. Periacetabular osteotomy can restore femoral head coverage; however, it is reserved for patients with minimal articular degeneration. We examined the relationship between delays in diagnosis and outcomes. Methods We identified patients presenting to a hip specialist with a new diagnosis of hip dysplasia. The time taken between patients presenting to their general practitioner and attending the young adult hip clinic was established. Patients were stratified into Early, Moderate and Late Referral groups. Hip and SF-12 questionnaires were completed. Radiographs were graded according to the Tönnis classification system and the outcome following hip specialist review documented. Results Fifty-one patients were identified. Mean time from attending a general practitioner to review at the young adult hip clinic was 40.4 months. Lower hip and SF-12 scores, and higher radiological osteoarthritis grades were found in the Moderate and Late Referral groups. A higher proportion of the Moderate and Late Referral group underwent total hip arthroplasty rather than periacetabular osteotomy. Conclusion Delays in referring a patient to a hip specialist are associated with poorer outcomes. We propose pelvic radiographs are requested early by general practitioners to allow prompt diagnosis and referral to a hip specialist.

Nanotopography controls cell cycle changes involved with skeletal stem cell self-renewal and multipotency.

In culture isolated bone marrow mesenchymal stem cells (more precisely termed skeletal stem cells, SSCs) spontaneously differentiate into fibroblasts, preventing the growth of large numbers of multipotent SSCs for use in regenerative medicine. However, the mechanisms that regulate the expansion of SSCs, while maintaining multipotency and preventing fibroblastic differentiation are poorly understood. Major hurdles to understanding how the maintenance of SSCs is regulated are (a) SSCs isolated from bone marrow are heterogeneous populations with different proliferative characteristics and (b) a lack of tools to investigate SSC number expansion and multipotency. Here, a nanotopographical surface is used as a tool that permits SSC proliferation while maintaining multipotency. It is demonstrated that retention of SSC phenotype in culture requires adjustments to the cell cycle that are linked to changes in the activation of the mitogen activated protein kinases. This demonstrates that biomaterials can offer cross-SSC culture tools and that the biological processes that determine whether SSCs retain multipotency or differentiate into fibroblasts are subtle, in terms of biochemical control, but are profound in terms of determining cell fate.

Noise production in ceramic-on-ceramic total hip arthroplasty is associated with lower patient satisfaction and hip scores.

BACKGROUND: Ceramic-on-ceramic total hip arthroplasties (THA) are commonly implanted. We investigated the incidence of noise in ceramic-on-ceramic and determined any association with patient satisfaction and hip scores. METHODS: We recruited 140 THA. Questionnaires were completed to assess the incidence and frequency of noise, and satisfaction level. Hip and SF-12 scores were recorded. RESULTS: Forty-two patients (30%) were aware of noise production. Patients with noise production had lower satisfaction, mean hip and SF-12 scores than those with silent hips. CONCLUSION: Given the high incidence of noise in ceramic-on-ceramic THA, patients should be counselled on this risk pre-operatively.

Fracture of an Exeter 'cement in cement' revision stem: a case report.

The 'cement in cement' technique for revision hip arthroplasty has become popular in recent years, particularly in relation to polished taper stems. Since 2006 a short Exeter stem with 44 mm offset has been available specifically for this purpose. We report a fracture of such a stem in the absence of trauma 5 years after the revision procedure. The patient had a BMI of 27.8 and the proximal cement mantle gave good support to the stem. The fracture initiated and propagated from the introducer hole on the shoulder of the prosthesis. Macroscopically there was no defect in this area. This may be an unusual case of fatigue failure.

Posterior dislocation of the elbow as an unusual presentation after a total hip replacement: a case report.

INTRODUCTION: Posterior dislocation of the elbow is usually associated with trauma to the joint with a reported incidence of 3%to 6%. Chronic instability is usually symptomatic following the initial injury. CASE PRESENTATION: We report a case of posterior dislocation of the elbow occurring in a patient while using her arm to lift herself using a monkey pole on the second day following a total hip replacement. The dislocation was reduced under sedation in the ward. There were no signs or symptoms suggesting any joint hypermobility syndrome in the patient. Follow up 4 months following the injury revealed a complete recovery in the range of motion and a pain free elbow. There were no signs and symptoms of any instability. CONCLUSION: This is the first time such a case is reported in the literature. It certainly demonstrates that even in the absence of instability a patient can be predisposed to low energy dislocation of the elbow.

Expression of nitric oxide synthase and transforming growth factor-beta in crush-injured tendon and synovium.

This study examined the expression of inducible nitric oxide synthase (iNOS) and transforming growth factor-beta (TGF-beta) in macrophage infiltrates within crush-injured digital flexor tendon and synovium of control rats and rats treated with N(G)-nitro-1-arginine methyl ester (L-NAME) (5 mg/kg). Release of TGF-beta from organ cultures of tendon, muscle, and synovium, and the effects of L-NAME treatment (in vitro and in vivo), on adhesion of peritoneal macrophages to epitenon monolayers were also investigated. The results showed that during normal tendon healing the levels of TGF-beta are high at first and gradually decrease after 3 weeks of injury to slightly above control uninjured levels. However, when L-NAME was administered at the time of injury, the macrophage infiltrates were expressing high levels of TGF-beta even at 5 weeks after the injury, with no evidence of reduction. In the standard injury, iNOS activity was greatest at the acute phase of the inflammatory response and then gradually returned to normal. Treatment with L-NAME, however, resulted in inhibition of iNOS activity at 3 days and a reduction in the activity at the later time points examined after injury. We also found greatly increased levels of adhesion of peritoneal macrophages from L-NAME-treated rats to epitenon monolayers in vitro, which reflect a chronic imbalance in expression of TGF-beta, which is overexpressed, and nitric oxide, which is underexpressed. The results of the current study show that formation of nitric oxide is an important event in the course of tendon healing since its inhibition results in chronic inflammation and fibrosis due to an imbalance in TGF-beta expression in vivo.