Objectives. Salubrinal is a synthetic agent that elevates phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) and alleviates stress to the endoplasmic reticulum. Previously, we reported that in chondrocytes, Salubrinal attenuates expression and activity of matrix metalloproteinase 13 (MMP13) through downregulating nuclear factor kappa B (NFκB) signalling. We herein examine whether Salubrinal prevents the degradation of articular cartilage in a mouse model of osteoarthritis (OA). Methods. OA was surgically induced in the left knee of female mice. Animal groups included age-matched sham control, OA placebo, and OA treated with Salubrinal or Guanabenz. Three weeks after the induction of OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At three and six weeks, the femora and tibiae were isolated and the sagittal sections were stained with Safranin O. Results. Salubrinal suppressed the progression of OA by downregulating p-NFκB p65 and MMP13. Although Guanabenz elevates the phosphorylation level of eIF2α, it did not suppress the progression of OA. Conclusions. Administration of Salubrinal has chondroprotective effects in arthritic joints. Salubrinal can be considered as a potential therapeutic agent for alleviating symptoms of OA. Cite this article: Bone Joint Res 2015;4:84–92

Treatment for osteoarthritis (OA) has traditionally focused on joint replacement for end-stage disease. An increasing number of surgical and pharmaceutical strategies for disease prevention have now been proposed. However, these require the ability to identify OA at a stage when it is potentially reversible, and detect small changes in cartilage structure and function to enable treatment efficacy to be evaluated within an acceptable timeframe. This has not been possible using conventional imaging techniques but recent advances in musculoskeletal imaging have been significant. In this review we discuss the role of different imaging modalities in the diagnosis of the earliest changes of OA. The increasing number of MRI sequences that are able to non-invasively detect biochemical changes in cartilage that precede structural damage may offer a great advance in the diagnosis and treatment of this debilitating condition. Cite this article: Bone Joint J 2013;95-B:738–46

Aims. The aetiologies of common degenerative spine, hip, and knee pathologies are still not completely understood. Mechanical theories have suggested that those diseases are related to sagittal pelvic morphology and spinopelvic-femoral dynamics. The link between the most widely used parameter for sagittal pelvic morphology, pelvic incidence (PI), and the onset of degenerative lumbar, hip, and knee pathologies has not been studied in a large-scale setting. Methods. A total of 421 patients from the Cohort Hip and Cohort Knee (CHECK) database, a population-based observational cohort, with hip and knee complaints < 6 months, aged between 45 and 65 years old, and with lateral lumbar, hip, and knee radiographs available, were included. Sagittal spinopelvic parameters and pathologies (spondylolisthesis and degenerative disc disease (DDD)) were measured at eight-year follow-up and characteristics of hip and knee osteoarthritis (OA) at baseline and eight-year follow-up. Epidemiology of the degenerative disorders and clinical outcome scores (hip and knee pain and Western Ontario and McMaster Universities Osteoarthritis Index) were compared between low PI (< 50°), normal PI (50° to 60°), and high PI (> 60°) using generalized estimating equations. Results. Demographic details were not different between the different PI groups. L4 to L5 and L5 to S1 spondylolisthesis were more frequently present in subjects with high PI compared to low PI (L4 to L5, OR 3.717; p = 0.024 vs L5 to S1 OR 7.751; p = 0.001). L5 to S1 DDD occurred more in patients with low PI compared to high PI (OR 1.889; p = 0.010), whereas there were no differences in L4 to L5 DDD among individuals with a different PI. The incidence of hip OA was higher in participants with low PI compared to normal (OR 1.262; p = 0.414) or high PI (OR 1.337; p = 0.274), but not statistically different. The incidence of knee OA was higher in individuals with a high PI compared to low PI (OR 1.620; p = 0.034). Conclusion. High PI is a risk factor for development of spondylolisthesis and knee OA. Low pelvic incidence is related to DDD, and may be linked to OA of the hip. Level of Evidence: 1b. Cite this article: Bone Joint J 2020;102-B(9):1261–1267

Aims

The evidence base within trauma and orthopaedics has traditionally favoured quantitative research methodologies. Qualitative research can provide unique insights which illuminate patient experiences and perceptions of care. Qualitative methods reveal the subjective narratives of patients that are not captured by quantitative data, providing a more comprehensive understanding of patient-centred care. The aim of this study is to quantify the level of qualitative research within the orthopaedic literature.

Aims

The aim of this study was to surveil whether the standard operating procedure created for the NHS Golden Jubilee sufficiently managed COVID-19 risk to allow safe resumption of elective orthopaedic surgery.

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Orthopaedic infection is a potentially serious complication of elective and emergency trauma and orthopaedic procedures, with a high associated burden of morbidity and cost. Optimization of vitamin D levels has been postulated to be beneficial in the prevention of orthopaedic infection. This study explores the role of vitamin D in orthopaedic infection through a systematic review of available evidence.

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Bone demonstrates good healing capacity, with a variety of strategies being utilized to enhance this healing. One potential strategy that has been suggested is the use of stem cells to accelerate healing.

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This study aimed to identify patients receiving total hip arthroplasty (THA) for trauma during the peak of the COVID-19 pandemic in the UK and quantify the risks of contracting SARS-CoV-2 virus, the proportion of patients requiring treatment in an intensive care unit (ICU), and rate of complications including mortality.

Aims

Medical comorbidities are a critical factor in the decision-making process for operative management and risk-stratification. The Hierarchical Condition Categories (HCC) risk adjustment model is a powerful measure of illness severity for patients treated by surgeons. The HCC is utilized by Medicare to predict medical expenditure risk and to reimburse physicians accordingly. HCC weighs comorbidities differently to calculate risk. This study determines the prevalence of medical comorbidities and the average HCC score in Medicare patients being evaluated by neurosurgeons and orthopaedic surgeon, as well as a subset of academic spine surgeons within both specialities, in the USA.

It is unusual, if not unique, for three major research papers concerned with the management of the fractured neck of femur (FNOF) to be published in a short period of time, each describing large prospective randomized clinical trials. These studies were conducted in up to 17 countries worldwide, involving up to 80 surgical centers and include large numbers of patients (up to 2,900) with FNOF. Each article investigated common clinical dilemmas; the first paper comparing total hip arthroplasty versus hemiarthroplasty for FNOF, the second as to whether ‘fast track’ care offers improved clinical outcomes and the third, compares sliding hip with multiple cancellous hip screws. Each paper has been deemed of sufficient quality and importance to warrant publication in The Lancet or the New England Journal of Medicine. Although ‘premier’ journals, they only occationally contain orthopaedic studies and thus may not be routinely read by the busy orthopaedic/surgical clinician of any grade. It is therefore our intention with this present article to accurately summarize and combine the results of all three papers, presenting, in our opinion, the most important clinically relevant facts.

Cite this article: Bone Joint Open 2020;1-6:198–202.

Aims

The aim of this study was to determine the impact of the severity of anaemia on postoperative complications following total hip arthroplasty (THA) and total knee arthroplasty (TKA).

Aims

The Precice intramedullary limb-lengthening system has demonstrated significant benefits over external fixation lengthening methods, leading to a paradigm shift in limb lengthening. This study compares outcomes following antegrade and retrograde femoral lengthening in both adolescent and adult patients.

Drug therapy forms an integral part of the management of many orthopaedic conditions. However, many medicines can produce serious adverse reactions if prescribed inappropriately, either alone or in combination with other drugs. Often these hazards are not appreciated. In response to this, the European Union recently issued legislation regarding safety measures which member states must adopt to minimise the risk of errors of medication.

In March 2014 the Medicines and Healthcare products Regulatory Agency and NHS England released a Patient Safety Alert initiative focussed on errors of medication. There have been similar initiatives in the United States under the auspices of The National Coordinating Council for Medication Error and The Joint Commission on the Accreditation of Healthcare Organizations. These initiatives have highlighted the importance of informing and educating clinicians.

Here, we discuss common drug interactions and contra-indications in orthopaedic practice. This is germane to safe and effective clinical care.

Cite this article: Bone Joint J 2015;97-B:434–41.

There has been an in increase in the availability of effective biological agents for the treatment of rheumatoid arthritis as well as a shift towards early diagnosis and management of the inflammatory process. This article explores the impact this may have on the place of orthopaedic surgery in the management of patients with rheumatoid arthritis.

Cite this article: Bone Joint J 2014;96-B:1287–9

We evaluated the top 13 journals in trauma and orthopaedics by impact factor and looked at the longer-term effect regarding citations of their papers.

All 4951 papers published in these journals during 2007 and 2008 were reviewed and categorised by their type, subspecialty and super-specialty. All citations indexed through Google Scholar were reviewed to establish the rate of citation per paper at two, four and five years post-publication. The top five journals published a total of 1986 papers. Only three (0.15%) were on operative orthopaedic surgery and none were on trauma. Most (n = 1084, 54.5%) were about experimental basic science. Surgical papers had a lower rate of citation (2.18) at two years than basic science or clinical medical papers (4.68). However, by four years the rates were similar (26.57 for surgery, 30.35 for basic science/medical), which suggests that there is a considerable time lag before clinical surgical research has an impact.

We conclude that high impact journals do not address clinical research in surgery and when they do, there is a delay before such papers are cited. We suggest that a rate of citation at five years post-publication might be a more appropriate indicator of importance for papers in our specialty.

Cite this article: Bone Joint J 2014;96-B:414–19.

Non-tuberculous mycobacterial (NTM) infection of the musculoskeletal tissue is a rare disease. An early and accurate diagnosis is often difficult because of the indolent clinical course and difficulty of isolating pathogens. Our goal was to determine the clinical features of musculoskeletal NTM infection and to present the treatment outcomes. A total of 29 patients (nine females, 20 males between 34 and 85 years old, mean age 61.7 years; 34 to 85) with NTM infection of the musculoskeletal system between 1998 to 2011 were identified and their treatment retrospectively analysed. Microbiological studies demonstrated NTM in 29 patients: the isolates were Mycobacterium intracellulare in six patients, M. fortuitum in three, M. abscessus in two and M. marinum in one. In the remaining patients we failed to identify the species. The involved sites were the hand/wrist in nine patients the knee in five patients, spine in four patients, foot in two patients, elbow in two patients, shoulder in one, ankle in two patients, leg in three patients and multiple in one patient. The mean interval between the appearance of symptoms and diagnosis was 20.8 months (1.5 to 180). All patients underwent surgical treatment and antimicrobial medication according to our protocol for chronic musculoskeletal infection: 20 patients had NTM-specific medication and nine had conventional antimicrobial therapy. At the final follow-up 22 patients were cured, three failed to respond to treatment and four were lost to follow-up. Identifying these diseases due the initial non-specific presentation can be difficult. Treatment consists of surgical intervention and adequate antimicrobial therapy, which can result in satisfactory outcomes.

Cite this article: Bone Joint J 2014;96-B:1561–5.

High-quality randomised controlled trials (RCTs) evaluating surgical therapies are fundamental to the delivery of evidence-based orthopaedics. Orthopaedic clinical trials have unique challenges; however, when these challenges are overcome, evidence from trials can be definitive in its impact on surgical practice. In this review, we highlight several issues that pose potential challenges to orthopaedic investigators aiming to perform surgical randomised controlled trials. We begin with a discussion on trial design issues, including the ethics of sham surgery, the importance of sample size, the need for patient-important outcomes, and overcoming expertise bias. We then explore features surrounding the execution of surgical randomised trials, including ethics review boards, the importance of organisational frameworks, and obtaining adequate funding.

Cite this article: Bone Joint Res 2014;3:161–8.

Hyaline articular cartilage has been known to be a troublesome tissue to repair once damaged. Since the introduction of autologous chondrocyte implantation (ACI) in 1994, a renewed interest in the field of cartilage repair with new repair techniques and the hope for products that are regenerative have blossomed. This article reviews the basic science structure and function of articular cartilage, and techniques that are presently available to effect repair and their expected outcomes.

We report the results of six trauma and orthopaedic projects to Kenya in the last three years. The aims are to deliver both a trauma service and teaching within two hospitals; one a district hospital near Mount Kenya in Nanyuki, the other the largest public hospital in Kenya in Mombasa. The Kenya Orthopaedic Project team consists of a wide range of multidisciplinary professionals that allows the experience to be shared across those specialties. A follow-up clinic is held three months after each mission to review the patients. To our knowledge there are no reported outcomes in the literature for similar projects.

A total of 211 operations have been performed and 400 patients seen during the projects. Most cases were fractures of the lower limb; we have been able to follow up 163 patients (77%) who underwent surgical treatment. We reflect on the results so far and discuss potential improvements for future missions.

We performed a systematic review and meta-analysis to compare the efficacy of intermittent mechanical compression combined with pharmacological thromboprophylaxis, against either mechanical compression or pharmacological prophylaxis in preventing deep-vein thrombosis (DVT) and pulmonary embolism in patients undergoing hip or knee replacement. A total of six randomised controlled trials, evaluating a total of 1399 patients, were identified. In knee arthroplasty, the rate of DVT was reduced from 18.7% with anticoagulation alone to 3.7% with combined modalities (risk ratio (RR) 0.27, p = 0.03; number needed to treat: seven). There was moderate, albeit non-significant, heterogeneity (I² = 42%). In hip replacement, there was a non-significant reduction in DVT from 8.7% with mechanical compression alone to 7.2% with additional pharmacological prophylaxis (RR 0.84) and a significant reduction in DVT from 9.7% with anticoagulation alone to 0.9% with additional mechanical compression (RR 0.17, p < 0.001; number needed to treat: 12), with no heterogeneity (I² = 0%). The included studies had insufficient power to demonstrate an effect on pulmonary embolism.

We conclude that the addition of intermittent mechanical leg compression augments the efficacy of anticoagulation in preventing DVT in patients undergoing both knee and hip replacement. Further research on the role of combined modalities in thromboprophylaxis in joint replacement and in other high-risk situations, such as fracture of the hip, is warranted.

Osteoporosis is common and the health and financial cost of fragility fractures is considerable. The burden of cardiovascular disease has been reduced dramatically by identifying and targeting those most at risk. A similar approach is potentially possible in the context of fragility fractures. The World Health Organization created and endorsed the use of FRAX, a fracture risk assessment tool, which uses selected risk factors to calculate a quantitative, patient-specific, ten-year risk of sustaining a fragility fracture. Treatment can thus be based on this as well as on measured bone mineral density. It may also be used to determine at-risk individuals, who should undergo bone densitometry. FRAX has been incorporated into the national osteoporosis guidelines of countries in the Americas, Europe, the Far East and Australasia. The United Kingdom National Institute for Health and Clinical Excellence also advocates its use in their guidance on the assessment of the risk of fragility fracture, and it may become an important tool to combat the health challenges posed by fragility fractures.

The most frequent cause of failure after total hip replacement in all reported arthroplasty registries is peri-prosthetic osteolysis. Osteolysis is an active biological process initiated in response to wear debris. The eventual response to this process is the activation of macrophages and loss of bone.

Activation of macrophages initiates a complex biological cascade resulting in the final common pathway of an increase in osteolytic activity. The biological initiators, mechanisms for and regulation of this process are beginning to be understood. This article explores current concepts in the causes of, and underlying biological mechanism resulting in peri-prosthetic osteolysis, reviewing the current basic science and clinical literature surrounding the topic.

This study was undertaken to evaluate the safety and efficacy of retrievable inferior vena cava filters in high-risk orthopaedic patients. A total of 58 patients had a retrievable inferior vena cava filter placed as an adjunct to chemical and mechanical prophylaxis, most commonly for a history of previous deep-vein thrombosis or pulmonary embolism, polytrauma, or expected prolonged immobilisation. In total 56 patients (96.6%) had an uncomplicated post-operative course. Two patients (3.4%) died in the peri-operative period for unrelated reasons.

Of the 56 surviving patients, 50 (89%) were available for follow-up. A total of 32 filters (64%) were removed without complication at a mean of 37.8 days (4 to 238) after placement. There were four filters (8%) which were retained because of thrombosis at the filter site, and four (8%) were retained because of incorporation of the filter into the wall of the inferior vena cava. In ten cases (20%) the retrievable filter was left in place to continue as primary prophylaxis. No patient had post-removal thromboembolic complications.

A retrievable inferior vena cava filter, as an adjunct to chemical and mechanical prophylaxis, was a safe and effective means of reducing the acute risk of pulmonary embolism in this high-risk group of patients. Although most filters were removed without complications, thereby avoiding the long-term complications that have plagued permanent indwelling filters, a relatively high percentage of filters had to be left in situ.

We examined the usefulness of neutrophil CD64 expression in detecting local musculoskeletal infection and the impact of antibiotics on its expression. Of 141 patients suspected of musculoskeletal infection, 46 were confirmed by microbiological culture to be infected and 95 had infection excluded. The median CD64 count of patients with localised infection was 2230 molecules per cell (interquartile range (IQR) 918 to 4592) and that of the patients without infection was 937 molecules per cell (IQR 648 to 1309) (p < 0.001). The level of CD64 correlated with the CRP level in patients with infection, but not in those without infection (r = 0.59, p < 0.01). Receiver operator characteristic curve analysis revealed that CD64 was a good predictor of local infection. When the patients were subdivided into two groups based on the administration of antibiotics at the time of CD64 sampling, the sensitivity for detecting infection was better in those who had not received antibiotics.

These results suggest that measurement of CD64 expression is a useful marker for local musculoskeletal infection.

The risk of venous thromboembolism in patients following arthroplasty may be reduced by continuing chemical thromboprophylaxis for up to 35 days post-operatively. This prospective cohort study investigated the compliance of 40 consecutive consenting patients undergoing lower limb arthroplasty with self-administration of a recommended subcutaneous chemotherapeutic agent for six weeks after surgery. Compliance was assessed by examination of the patient for signs of injection, number of syringes used, and a self-report diary at the end of the six-week period. A total of 40 patients, 15 men and 25 women, were recruited. One woman was excluded because immediate post-operative complications prevented her participation. Self-administration was considered feasible in 87% of patients (95% confidence interval (CI) 76 to 98) at the time of discharge. Among this group of 34 patients, 29 (85%) were compliant (95% CI 73 to 97). Patients can learn to self-administer subcutaneous injections of thromboprophylaxis, and compliance with extended prophylaxis to six weeks is good.

We present seven patients with recurrent haemarthroses after total knee arthroplasty, caused by an inherent platelet function defect. These patients developed painful knee swelling, persistent bleeding and/or wound breakdown, a platelet factor 3 availability defect being identified in all cases. Surgical exploration, with joint debridement, lavage and synovectomy, was performed in four patients who did not improve with conservative therapy. Histopathological examination of synovium revealed a focal synovial reaction with histiocytic infiltration, and occasional foreign-body giant cells. One patient required an early revision because of aseptic loosening of their tibial component. The condition was treated by single-donor platelet transfusions with good results. The diagnosis, management, and relevance of this disorder are discussed.

In order to assess current opinions on the long-term outcome after primary total hip replacement, we performed a multicentre, cross-sectional survey in 22 centres from 12 European countries. Different patient characteristics were categorised into ‘decreases chances’, ‘does not affect chances’, and ‘increases chances’ of a favourable long-term outcome, by 304 orthopaedic surgeons and 314 referring practitioners. The latter were less likely to associate age older than 80 years and obesity with a favourable outcome than orthopaedic surgeons (p < 0.001 and p = 0.006, respectively) and more likely to associate age younger than 50 years with a favourable outcome (p = 0.006). Comorbidity, rheumatoid arthritis, and poor bone quality were thought to be associated with a decreased chance of a favourable outcome. We found important differences in the opinions regarding long-term outcome after total hip replacement within and between referring practitioners and orthopaedic surgeons. These are likely to affect access to and the provision of total hip replacement.

Injury to the sciatic nerve is one of the more serious complications of acetabular fracture and traumatic dislocation of the hip, both in the short and long term. We have reviewed prospectively patients, treated in our unit, for acetabular fractures who had concomitant injury to the sciatic nerve, with the aim of predicting the functional outcome after these injuries.

Of 136 patients who underwent stabilisation of acetabular fractures, there were 27 (19.9%) with neurological injury. At initial presentation, 13 patients had a complete foot-drop, ten had weakness of the foot and four had burning pain and altered sensation over the dorsum of the foot. Serial electromyography (EMG) studies were performed and the degree of functional recovery was monitored using the grading system of the Medical Research Council. In nine patients with a foot-drop, there was evidence of a proximal acetabular (sciatic) and a distal knee (neck of fibula) nerve lesion, the double-crush syndrome.

At the final follow-up, clinical examination and EMG studies showed full recovery in five of the ten patients with initial muscle weakness, and complete resolution in all four patients with sensory symptoms (burning pain and hyperaesthesia). There was improvement of functional capacity (motor and sensory) in two patients who presented initially with complete foot-drop. In the remaining 11 with foot-drop at presentation, including all nine with the double-crush lesion, there was no improvement in function at a mean follow-up of 4.3 years.

We have prospectively studied the outcome of infections associated with implants which were retained and treated using a standardised antimicrobial protocol. Over a period of four years, we studied 24 consecutive patients who had symptoms of infection for less than one year, a stable implant, no sinus tract and a known pathogen which was susceptible to recommended antimicrobial agents. The infections involved hip prostheses (14), knee prostheses (5), an internal fixation device (4), and an ankle prosthesis (1).

Twenty patients had a successful outcome at a median follow-up of 3.7 years (1.8 to 4.7); four had failure of the implant after a median follow-up of 1.2 years (0.3 to 2.5). The probability of survival without failure of treatment was 96% at one year (95% confidence interval (CI) 88 to 100), 92% at two years (95% CI 80 to 100) and 86% at three years (95% CI 72 to 100).

Patients with a short-term infection but with a stable implant, no sinus tract and a known pathogen may be successfully treated by retention of the implant and the use of a standardised regimen of antimicrobial treatment.

The Control of Infection Committee at a specialist orthopaedic hospital prospectively collected data on all episodes of bacteriologically-proven deep infection arising after primary hip and knee replacements over a 15-year period from 1987 to 2001.

There were 10 735 patients who underwent primary hip or knee replacement. In 34 of 5947 hip replacements (0.57%) and 41 of 4788 knee replacements (0.86%) a deep infection developed. The most common infecting micro-organism was coagulase-negative staphylococcus, followed by Staphylococcus aureus, enterococci and streptococci. Of the infecting organisms, 72% were sensitive to routine prophylactic antimicrobial agents.

Of the infections, 29% (22) arose in the first three months following surgery, 35% between three months and one year (26), and 36% (27) after one year. Most cases were detected early and treated aggressively, with eradication of the infection in 96% (72). There was no significant change in the infection rate or type of infecting micro-organism over the course of this study.

These results set a benchmark, and importantly emphasise that only 64% of peri-prosthetic infections arise within one year of surgery. These results also illustrate the advantages of conducting joint replacement surgery in the isolation of a specialist hospital.

Post-discharge surveillance of surgical site infection is necessary if accurate rates of infection following surgery are to be available. We undertook a prospective study of 376 knee and hip replacements in 366 patients in order to estimate the rate of orthopaedic surgical site infection in the community. The inpatient infection was 3.1% and the post-discharge infection rate was 2.1%. We concluded that the use of telephone interviews of patients to identify the group at highest risk of having a surgical site infection (those who think they have an infection) with rapid follow-up by a professional trained to diagnose infection according to agreed criteria is an effective method of identifying infection after discharge from hospital.

Bone-marrow oedema can occur both in isolation and in association with necrosis of bone, but it has not been shown whether each respond to the same methods of treatment.

We treated 16 patients with isolated oedema and 17, in which it was associated with necrosis of the proximal femur, with the prostacyclin derivative iloprost, which has been shown to be effective in the idiopathic form. The Harris hip score, the range of movement, the extent of the oedema as measured by MRI, pain on a visual analogue scale and patient satisfaction were recorded before and subsequent to treatment.

In both groups, we were able to show a significant improvement (p < 0.001) in these observations during the period of follow-up indicating that iloprost will produce clinical improvement in both circumstances.