Chronic inflammatory events have been associated to almost every chronic disease, including cardiovascular-, neurodegenerative- and autoimmune- diseases, cancer, and host-implant rejection. Given the toll of chronic inflammation in healthcare and socioeconomical costs developing strategies to resolve and control chronic states of inflammation remain a priority for the significant benefit of patients. Macrophages (Mφ) hold a central role both in the initiation and resolution of inflammatory events, assuming different functional profiles. The outstanding features of Mφ counting with the easy access to tissues, and the extended networking make Mφ excellent candidates for precision therapy. Moreover, sophisticated macrophage-oriented systems could offer innovative immune-regulatory alternatives to effectively regulate chronic environments that traditional pharmacological agents cannot provide. We propose magnetically assisted systems for balancing Mφ functions at the injury site. This platform combines polymers, inflammatory miRNA antagonists and magnetically responsive nanoparticles to stimulate Mφ functions towards pro-regenerative phenotypes. Strategies with magnetically assisted systems include contactless presentation of immune-modulatory molecules, cell internalization of regulatory agents for functional programming via magnetofection, and multiple payload delivery and release. Overall, Mφ-oriented systems stimulated pro-regenerative functions of Mφ supporting magnetically assisted theranostic nanoplatforms for precision therapies, envisioning safer and more effective control over the distribution of sensitive nanotherapeutics for the treatments of chronical inflammatory conditions. Acknowledgements: ERC CoG MagTendon No.772817; FCT Doctoral Grant SFRD/BD/144816/2019, and TERM. RES Hub (Norte-01-0145-FEDER-022190)

The principal of “function priority, early rehabilitation, and return to sports” is now the goal for sports injury rehabilitation. Neuromuscular electrical stimulation for anterior cruciate ligament (ACL) reconstruction is a rising procedure for early rehabilitation. This paper systematically assessed the effects of neuromuscular electrical stimulation on postoperative ACL reconstruction to provide guidance for physiotherapist and patient when designing a suitable rehabilitation protocol. To evaluate the interventional outcomes of neuromuscular electrical stimulation following ACL reconstruction, we searched PubMed, EMbase, the Cochrane Library, Web of Science and CNKI to collect all randomized controlled trials (RCTs) comparing the effects with neuromuscular electrical stimulation and without intervention on rehabilitation after ACL reconstruction up to January 30, 2022. Two investigators independently performed literature screening, data extraction, bias assessment of risk, and used RevMan 5.3 software to conduct a meta-analysis. A total of six RCTs were included, and the results showed that the use of neuromuscular electrical stimulation after anterior cruciate ligament reconstruction significantly improved the International Knee Documentation Committee (IKDC) scores (MD 6.33, 95% CI [-0.43, 12.22]; I2 = 66%; p = 0.040), the Lysholm score (MD 7.94, 95% CI [6.49, 9.39]; I2 = 89%; p < 0.001), and the range of motion (ROM) (MD 9.99, 95% CI [7.97, 12.02]; I2 = 81%; p < 0.001) in the knees when compared to the control group without using neuromuscular electrical stimulation. Existing evidence show that neuromuscular electrical stimulation is beneficial for early rehabilitation after ACL reconstruction. The use of neuromuscular electrical stimulation is encouraged in the design of rehabilitation protocol. However, due to the limited number of RCT studies and the small sample size, further multi-center RCTs with more participants are needed for a higher-level evidence

An international Consensus Group has by a Delphi approach identified the topic of host factors affecting pin site infection to be one of the top 10 priorities in external fixator management. The aim of this study was to report the frequency of studies reporting on specific host factors as a significant association with pin site infection. Host factors to be assessed was: age, smoking, BMI and any comorbidity, diabetes, in particular. The intention was an ethological review, data was extracted if feasible, however no meta-analysis was performed. A systematic literature search was performed according to the PRISMA-guidelines. The protocol was registered before data extraction in PROSPERO. The search string was based on the PICO criterias. A logic grid with key concept and index terms was made. A search string was built assisted by a librarian. The literature search was executed in three electronic bibliographic databases, including Embase MEDLINE (1111 hits) and CINAHL (2066 hits) via Ovid and Cochrane Library CENTRAL (387 hits). Inclusion criteria: external fixation, >1 pin site infection, host factor of interest, peer-reviewed journal. Exclusion criteria: Not written in English, German, Danish, Swedish, or Norwegian, animal or cadaveric studies, location on head, neck, spine, cranium or thorax, editorials or conference abstract. The screening process was done using Covidence. A total of 3564 titles found. 3162 excluded by title and abstract screening. 140 assessed for full text eligibility. 11 studies included for data extraction. The included studies all had a retrospective design. Three identified as case-control studies. Generally the included studies was assessed to have a high risk of bias. A significant associations between pin site infection for following host factors: a) increased HbA1C level in diabetic patients; b) congestive heart failure in diabetic patients; c) less co-morbidity; d) preoperative osteomyelitis was found individually. This systematic literature search identified a surprisingly low number of studies examining for risk of pin site infection and host factors. Thus, this review most of all serves to demonstrate a gap of evidence about correlation between host factors and risk of pin site infection, and further studies are warranted

The World Health Organisation (WHO) has included low back pain in its list of twelve priority diseases. Notably, Degenerative disc disease (DDD) presents a large, unmet medical need which results in a disabling loss of mechanical function. Today, no efficient therapy is available. Chronic cases often receive surgery, which may lead to biomechanical problems and accelerated degeneration of adjacent segments. Our consortium partners have developed and studied mesenchymal stem cell-based, regenerative therapies trials. In previous phase 2 trial, patients exhibited rapid and progressive improvement of functional and pain indexes after 1 year with no significant side effects. To develop the world's first rigorously proven, effective treatment of DDD, EUROSPINE aims to assess, via a multicentre, randomized, controlled, phase 2b clinical trial including 112 patients with DDD, the efficacy of an allogenic intervertebral mesenchymal stem cell (MSC)-based therapy. This innovative therapy aims to rapidly and sustainably (at least 24 months) reduce pain and disability. In addition, the consortium aims to provide new knowledge on immune response & safety associated with allogeneic BM-MSC intradiscal injection. This simple procedure would be cost-effective, minimally invasive, and standardised. At the end of the RESPINE trial, we aim to propose a broadly available and clinically applicable treatment for DDD, marketed by European SMEs

Sarcopenia is a progressive and generalized skeletal muscle disorder that involves loss of muscle mass and function. It is associated with increased adverse outcomes including falls, functional decline, frailty and mortality and affects 65% of people over the age of 65 more than half of people aged 80 and above. The factors that cause and worsen sarcopenia are categorised into two groups. The primary aetiological factor is ageing and the secondary factors include disease, physical inactivity, and poor nutrition. Sarcopenia is considered to be ‘primary' (or age-related) when no other specific cause is evident. However, a number of ‘secondary' factors may be present in addition to ageing. Sarcopenia can occur secondary to a systemic or inflammatory disease, including malignancy and organ failure. Physical inactivity is one of the major contributors to the development of sarcopenia, whether due to a sedentary lifestyle or to disease related immobility or disability. Furthermore, sarcopenia can develop as a result of inadequate protein consumption. Biomarkers are objective and quantifiable characteristics of physiological and pathophysiological processes. Biomarkers can be used to predict the development of sarcopenia in older susceptible adults and enable early interventions that can reduce the risk of physical disability, the co-morbidities associated with the loss of muscle mass and the poor health outcomes that result from sarcopenia. Non-invasive imaging technologies can be used as biomarkers to detect loss of skeletal muscle mass in sarcopenia include bone densitometry, computed tomography, ultrasound and magnetic resonance imaging. However, imaging requires sophisticated and expensive equipment that is not available in a resource poor setting. Therefore, markers of skeletal muscle strength and fitness and soluble biochemical markers in blood may be used as alternative biomarkers. Studies on sarcopenia have identified numerous soluble biochemical biomarkers. These biomarkers can be divided into two groups: “muscle-specific” and “non-muscle-specific” biomarkers. Since sarcopenia is associated with rapid skeletal muscle wasting, the skeletal muscle-specific isoform of troponin T may be considerate a useful biomarker of sarcopenia, since high troponin levels in blood are an expression of muscle wasting. Peptides derived from collagen type VI turnover may be potential biomarkers of sarcopenia. We have recently conducted a systematic review to summarize the data from recent mass-spectrometry based proteomic studies of the secretome of skeletal muscle cells in response to disease, exercise or metabolic stress in order to identify the proteins involved in muscle breakdown. Developing robust in vitro models for the study of sarcopenia using primary muscle cells is a high priority as is exploiting the in vitro models to understand catabolic and inflammatory processes and molecular mechanisms involved in sarcopenia. Co-cultures with adipose-derived and other cells may be used to screen for small molecules and biologicals capable of inhibiting the catabolic and inflammatory pathways involved in sarcopenia. This presentation reviews recent progress in this area and outlines opportunities for future research on sarcopenia

Tourniquets have been used for many years during total knee arthroplasty (TKA). With a growing demand for TKA in recent years, tourniquet use has been surrounded by ongoing controversy due to many conflicting advantages and disadvantages of tourniquet use. Quantifying the case for or against tourniquet use in TKA, in terms of patient focused outcomes, is a priority. This meta-analysis analysed, the never before assessed, impact of tourniquet use during TKA on post-operative pain. We completed a systematic review and meta-analysis using PRISMA reporting guidelines to assess the impact of tourniquet use on patients post-TKA. Post-operative pain was the primary outcome. Secondary outcomes were post-operative range of motion (ROM) and length of stay (LOS). The initial search yielded 230 studies, of which 14 met the inclusion criteria. A post-operative increase in pain and reduction in ROM when using a tourniquet appeared significantly more likely when compared to no tourniquet use during TKA, yet with no overall difference in post-operative LOS. Subgroup meta-analysis demonstrated a trend that favoured the half-course tourniquet for reduced post-operative pain in patients when compared to full tourniquet use during TKA. This systematic review and meta-analysis concluded that the after-effects of tourniquet use in TKA patients and its impact on post-operative pain and ROM are indeed significant. We recommend further randomized controlled trials (RCTs) focusing on TKA patient outcomes of post-operative pain and ROM. Conflict of interest: The authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript

Evaluation of different biomaterials is being performed with various methods trying to simulate the closest hostile-like in vitro environments. However the complexity of the conditions usually limits practically feasible combination of most relevant chemical, biological, biomechanical parameters in one single test. Many biomaterials and tissue engineering developments rely on high-throughput screening to multiply number of specimens and thus to gather sufficient data. The price to be paid for these methods is limited number of physical readouts, increased inter-specimens scatter, and unavoidable spatial constrains driving the conditions away of the clinical scenarios. For orthopaedic biomaterials this is of a particular concern, as implantation site conditions cannot be squeezed too much without lost of natural-mimicking stimuli. Here we are presenting another approach based on high-output screening of biomaterials, which is based on the strategy of raising the number of readouts obtainable from every specimen at more clinically-relevant conditions. On the contrary to common methods like ISO 10993 or simplified biomechanical tests, the biomaterials enhanced simulation testing (BEST) evaluates specimens without pre-selected biomaterial model, assessing the whole specimen as would happen in the implantation site. Besides reducing the risk of improper conclusions caused by wrong material model choice, the data processing with non-local method intrinsically includes the test history bypassing common challenges usually seen with hereditary integration. For properly designed experiment, readouts might include invariant moduli, viscous stiffness, fluidity, fluid permittivity and diffusivity (without need for pressure-driven separate tests), fluid source, effective channel size, and swelling pressure (if swelling is present) in addition to conventional biomechanical parameters. New solutions in advanced and consistent evaluations for biomaterials allow better risks control, shorten lead development time and costs, and compliant with 3R-strategy (2010/63/EC) and new regulatory requirements (2012/0266/COD in EU and FY2017 regulatory priorities by FDA). The approach shown is able to combine scientifically based tests with multi-purpose protocols to secure patient safety by screening of biomaterials under proper conditions. The authors thank Finnish Agency for Innovations (Tekes) for providing partial financial support

The Cochrane Collaboration has produced five new reviews relevant to bone and joint surgery since the publication of the last Cochrane Corner These reviews are relevant to a wide range of musculoskeletal specialists, and include reviews in Morton’s neuroma, scoliosis, vertebral fractures, carpal tunnel syndrome, and lower limb arthroplasty.

Background. Around 1% of patients who have hip replacement have deep prosthetic joint infection afterwards. Infection is treated with antibiotics and revision surgery. We aimed to characterise the impact of deep joint infection and its treatment, to identify treatment preferences, and to describe surgeons' treatment decisions. Methods. In a qualitative study in the UK we interviewed 19 patients who had infection after hip replacement and 12 orthopaedic surgeons specialising in infection. Face-to-face interviews with patients explored experience of infection, treatment and recovery. Interviews with surgeons explored treatment decisions. With consent, interviews were audio-recorded, transcribed and anonymised. Once imported into QSR NVivo software, data were analysed using constant comparison. Results. Patients with deep joint infection described mobility loss, pain, loss of valued activities, changes to home environments/moving into care, negative impact on personal relationships and financial strain. Physical and psychological trauma was associated with revision surgery and antibiotic treatment. Patients had strong preferences for treatment options, emphasising impact of surgery, side effects of antibiotics and duration of treatment as key considerations. Although eradication of infection was important, patients felt that reducing impact of treatment was high priority and identified a need for more support. Surgeons' treatment decisions focused on patient characteristics and nature of infection to prioritise eradication of infection. During patients' recovery surgeons' were concerned about possible return of infection and patients' mobility and function. Conclusion. Infection after joint replacement causes physical and psychological trauma. Balancing patients' preferences for reducing impact of treatment with surgeons' emphasis on eradication of infection should be an important consideration in care. There is also need to develop new interventions to support patients with infection. Level of evidence. Level 3 – Qualitative Research. Funding statement. This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (grant number: RP-PG-1210-12005). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Ethics. This study has been given a favourable opinion for conduct in the NHS by the National Research Ethics Service Committee South West – Exeter 14/SW/0072

Background. Although the aetiology of chronic low back pain (CLBP) is unknown, it is suggested that several subgroups among CLBP-patients might be identified who are likely to benefit from different interventions. The results of these interventions might be improved by matching interventions to patient characteristics. Purpose. The purpose of this longitudinal study is to determine which subgroup of CLBP-patients benefits most from the short, intensive pain management program of RealHealth_NL. Methods. A prospective cohort of 524 selected consecutive CLBP-patients was followed. Potential predictive indicators included demographic characteristics, functional disability, experienced pain and cognitive behavioural factors as measured at pre-treatment assessment. The outcome is defined as one year improvement in functional disability. A successful outcome is a value as seen in healthy populations. The two-week residential program is in line with recommendations in international guidelines, based on cognitive behavioural principles and delivered in collaboration with orthopedic spine surgeons. Results. Multivariate logistic regression revealed pre-treatment being employed (OR 3.609 [95%CI 1.795–7.256]), and functional disability (OR 0.943 [95%CI 0.921–0.965]) as significant predictive factors of a successful outcome in functional disability at one year follow-up. Conclusion. The results imply that CLBP-patients, who are employed, and less disabled at pre-treatment assessment, who participated in the RealHealth_NL program, are consistently associated with one year follow-up improvement of functional disability toward normal values. A small set of indicators is more easily identified and addressed and CLBP-patients who are more likely to benefit from the program could be given a higher entry priority. Conflict of Interest: J O'Dowd owns shares in RealHealth_NL; Research Development & Education independent research organisation; Sint Maartenskliniek health care provider and referral organisation. Source of funding: None. This abstract has not been previously published in whole or substantial part nor has it been presented previously at a national meeting

Background. Fractured neck of femurs cause substantial morbidity and mortality in elderly patients and represent a huge financial burden to the NHS. Hip fracture patients are generally malnourished on admission, often having poor nutritional inpatient intake, hindering recovery and increasing chances of “unfavourable outcome.” Nutritional care is included in intercollegiate guidelines for management of fractured neck of femur patients, but is nutrition a management priority in clinical practice?. Study Aim. To evaluate protein and energy intake of acute fractured neck of femur patients depending on admission MMSE, and compare these to department of health targets. Method. 40 acute fractured neck of femur admissions were recruited between December 08-March 09 and put into three groups depending on admission MMSE. Initial nutrition screening information (mid-arm circumference, grip strength, MUST score) was recorded and through food charts daily kcal and protein intake were calculated for a three day period. Results. 100% of patients recruited were high risk of malnutrition on admission. Overall average daily calorie intake over 3 days was 385.9 kCal, average protein intake was 14.1g. Intake for each group was well below recommended target intake of 1810kCal and 46.5g, p<0.05. Discussion. On admission all 40 patients included were classified high risk for malnutrition, therefore in need of dietetic and nutritional intervention. Two patients received dietician input and oral supplementation. Recorded nutritional intake was very low, well below target nutrient intakes for this population even before extra requirement due to the stress response is accounted for. Whilst there is a paucity of hard evidence linking poor nutrition to clinical outcome, this is likely to be detrimental to rehabilitation from surgery. Conclusion. Despite attempted adherence to NICE nutrition guidance, involving screening tools, care plans and protected mealtimes; acutely unwell, malnourished patients are not receiving their basic nutritional requirements

Summary. Cognitive testing scores do not correlate with physical braking performance. Psychological questioning shows patients are more dependent on driving than a control group. Introduction. Returning to driving after surgery is a multifaceted issue. There are the medical aspects to consider- whether the patient is medically fit to drive. The term ‘medically fit to drive’ can encompass a range of issues which fall to doctors to solve, including the psychological and mental wellbeing. Groups whose governance involves patients or driving do not issue sound advice for patients or doctors to follow. Investigation of aspects affecting a driver's ability to control their vehicle in a safe manner could go towards providing an evidence base for guidance to be issued in the future. Methods. A custom force assessment rig was used to gather peak force and reaction time measurements from a group of patients waiting for, or having undergone lower limb surgery. A bespoke questionnaire that investigated patient's attitudes towards returning to driving; their behaviours and concerns was issued. Other mobility questions were also issued to these patients, including the lower extremity functional scale (LEFS). The final tests (Stroop task, tower of Hanoi, and the opposite worlds test [OWT]) were aimed at assessing a patient's neurological function, in an attempt to investigate the effect of post-operative cognitive dysfunction (POCD) on driving ability. These data were compared against a control cohort. Results. No significant differences were observed in the physical results between cohorts. However, significant differences between the control cohort and patient cohort were observed in a number of tests. The tower of Hanoi was the only significantly different neurological test (p=0.027). The Stroop task and OWT were not significantly different (p=0.103, p=0.131 respectively). There were significant differences in many of the psychological and mobility questions posed (reliance on driving [p<0.001], keenness to return [p=0.014], anxiety about being unable to drive [p=0.019], depression at being unable to drive [p=0.011], worries that driving would cause them pain [p<0.001], and confidence in using public transport [p=0.002]). Activity rankings also had a significant difference, with driving becoming a higher priority in the patient group (p=0.002). There were no significant differences between cohorts in physical testing, but LEFS was significantly different (p<0.001). There was no significant correlation between physical testing and neurological function, so we cannot prove nor disprove that neurological deficits affect physical function. Psychological variables and physical function did not correlate, but LEFS was correlated to a number of psychological variables. Conclusions. Due to the insignificance of correlations between neurological function tests and physical function, further work is recommended to conclusively determine whether there is a link or not. Different and/or additional neurological test batteries should be also considered, for example the CANTAB. Future studies should stratify cohorts based on surgical indication. Extension of the psychological research could identify the most popular goals or activities for those returning from surgery, potentially creating targets for the rehabilitation process

Objectives

The aim of this study was to systematically review the literature on measurement of muscle strength in patients with femoroacetabular impingement (FAI) and other pathologies and to suggest guidelines to standardise protocols for future research in the field.

Trauma and orthopaedics is the largest of the surgical specialties and yet attracts a disproportionately small fraction of available national and international funding for health research. With the burden of musculoskeletal disease increasing, high-quality research is required to improve the evidence base for orthopaedic practice. Using the current research landscape in the United Kingdom as an example, but also addressing the international perspective, we highlight the issues surrounding poor levels of research funding in trauma and orthopaedics and indicate avenues for improving the impact and success of surgical musculoskeletal research.

Cite this article: Bone Joint J 2014; 96-B:1578–85.

In vivo animal experimentation has been one of the cornerstones of biological and biomedical research, particularly in the field of clinical medicine and pharmaceuticals. The conventional in vivo model system is invariably associated with high production costs and strict ethical considerations. These limitations led to the evolution of an ex vivo model system which partially or completely surmounted some of the constraints faced in an in vivo model system. The ex vivo rodent bone culture system has been used to elucidate the understanding of skeletal physiology and pathophysiology for more than 90 years. This review attempts to provide a brief summary of the historical evolution of the rodent bone culture system with emphasis on the strengths and limitations of the model. It encompasses the frequency of use of rats and mice for ex vivo bone studies, nutritional requirements in ex vivo bone growth and emerging developments and technologies. This compilation of information could assist researchers in the field of regenerative medicine and bone tissue engineering towards a better understanding of skeletal growth and development for application in general clinical medicine.

Cite this article: A. A. Abubakar, M. M. Noordin, T. I. Azmi, U. Kaka, M. Y. Loqman. The use of rats and mice as animal models in ex vivo bone growth and development studies. Bone Joint Res 2016;5:610–618. DOI: 10.1302/2046-3758.512.BJR-2016-0102.R2.

Objectives

To assess the sensitivity and specificity of self-reported osteoporosis compared with dual energy X-ray absorptiometry (DXA) defined osteoporosis, and to describe medication use among participants with the condition.

We have evaluated four different fixation techniques for the reconstruction of a standard Mason type-III fracture of the radial head in a sawbone model. The outcome measurements were the quality of the reduction, and stability.

A total of 96 fractures was created. Six surgeons were involved in the study and each reconstructed 16 fractures with 1.6 mm fine-threaded wires (Fragment Fixation System (FFS)), T-miniplates, 2 mm miniscrews and 2 mm Kirschner (K-) wires; four fractures being allocated to each method using a standard reconstruction procedure.

The quality of the reduction was measured after definitive fixation. Biomechanical testing was performed using a transverse plane shear load in two directions to the implants (parallel and perpendicular) with respect to ultimate failure load and displacement at 50 N.

A significantly better quality of reduction was achieved using the FFS wires (Tukey’s post hoc tests, p < 0.001) than with the other devices with a mean step in the articular surface and the radial neck of 1.04 mm (sd 0.96) for the FFS, 4.25 mm (sd 1.29) for the miniplates, 2.21 mm (sd 1.06) for the miniscrews and 2.54 mm (sd 0.98) for the K-wires. The quality of reduction was similar for K-wires and miniscrews, but poor for miniplates.

The ultimate failure load was similar for the FFS wires (parallel, 196.8 N (sd 46.8), perpendicular, 212.5 N (sd 25.6)), miniscrews (parallel, 211.8 N (sd 47.9), perpendicular, 208.0 N (sd 65.9)) and K-wires (parallel, 200.4 N (sd 54.5), perpendicular, 165.2 N (sd 37.9)), but significantly worse (Tukey’s post hoc tests, p < 0.001) for the miniplates (parallel, 101.6 N (sd 43.1), perpendicular, 122.7 N (sd 40.7)). There was a significant difference in the displacement at 50 N for the miniplate (parallel, 4.8 mm (sd 2.8), perpendicular, 4.8 mm (sd 1.7)) vs FFS (parallel, 2.1 mm (sd 0.8), perpendicular, 1.9 mm (sd 0.7)), miniscrews (parallel, 1.8 mm (sd 0.5), perpendicular, 2.3 mm (sd 0.8)) and K-wires (parallel, 2.2 mm (sd 1.8), perpendicular, 2.4 mm (sd 0.7; Tukey’s post hoc tests, p < 0.001)).

The fixation of a standard Mason type-III fracture in a sawbone model using the FFS system provides a better quality of reduction than that when using conventional techniques. There was a significantly better stability using FFS implants, miniscrews and K-wires than when using miniplates.