Adenosine, lidocaine, and Mg2+ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.Aims
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This study aimed to investigate the estimated change in primary and revision arthroplasty rate in the Netherlands and Denmark for hips, knees, and shoulders during the COVID-19 pandemic in 2020 (COVID-period). Additional points of focus included the comparison of patient characteristics and hospital type (2019 vs COVID-period), and the estimated loss of quality-adjusted life years (QALYs) and impact on waiting lists. All hip, knee, and shoulder arthroplasties (2014 to 2020) from the Dutch Arthroplasty Register, and hip and knee arthroplasties from the Danish Hip and Knee Arthroplasty Registries, were included. The expected number of arthroplasties per month in 2020 was estimated using Poisson regression, taking into account changes in age and sex distribution of the general Dutch/Danish population over time, calculating observed/expected (O/E) ratios. Country-specific proportions of patient characteristics and hospital type were calculated per indication category (osteoarthritis/other elective/acute). Waiting list outcomes including QALYs were estimated by modelling virtual waiting lists including 0%, 5% and 10% extra capacity.Aims
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To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs). Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 106 ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed.Aims
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The aim of this study was to compare the cost-effectiveness of surgical fixation with Kirschner (K-)wire ersus moulded casting after manipulation of a fracture of the distal radius in an operating theatre setting. An economic evaluation was conducted based on data collected from the Distal Radius Acute Fracture Fixation Trial 2 (DRAFFT2) multicentre randomized controlled trial in the UK. Resource use was collected at three, six, and 12 months post-randomization using trial case report forms and participant-completed questionnaires. Cost-effectiveness was reported in terms of incremental cost per quality-adjusted life year (QALY) gained from an NHS and personal social services perspective. Sensitivity analyses were conducted to examine the robustness of cost-effectiveness estimates, and decision uncertainty was handled using confidence ellipses and cost-effectiveness acceptability curves.Aims
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The aim of this study was to longitudinally compare the clinical and radiological outcomes of anatomical total shoulder arthroplasty (aTSA) up to long-term follow-up, when using cemented keel, cemented peg, and hybrid cage peg glenoid components and the same humeral system. We retrospectively analyzed a multicentre, international clinical database of a single platform shoulder system to compare the short-, mid-, and long-term clinical outcomes associated with three designs of aTSA glenoid components: 294 cemented keel, 527 cemented peg, and 981 hybrid cage glenoids. Outcomes were evaluated at 4,746 postoperative timepoints for 1,802 primary aTSA, with a mean follow-up of 65 months (24 to 217).Aims
Methods
This study aimed to evaluate the effectiveness of the induced membrane technique for treating infected bone defects, and to explore the factors that might affect patient outcomes. A comprehensive search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases between 1 January 2000 and 31 October 2021. Studies with a minimum sample size of five patients with infected bone defects treated with the induced membrane technique were included. Factors associated with nonunion, infection recurrence, and additional procedures were identified using logistic regression analysis on individual patient data.Aims
Methods
Ankle fractures are common, mainly affecting adults aged 50 years and over. To aid recovery, some patients are referred to physiotherapy, but referral patterns vary, likely due to uncertainty about the effectiveness of this supervised rehabilitation approach. To inform clinical practice, this study will evaluate the effectiveness of supervised versus self-directed rehabilitation in improving ankle function for older adults with ankle fractures. This will be a multicentre, parallel-group, individually randomized controlled superiority trial. We aim to recruit 344 participants aged 50 years and older with an ankle fracture treated surgically or non-surgically from at least 20 NHS hospitals. Participants will be randomized 1:1 using a web-based service to supervised rehabilitation (four to six one-to-one physiotherapy sessions of tailored advice and prescribed home exercise over three months), or self-directed rehabilitation (provision of advice and exercise materials that participants will use to manage their recovery independently). The primary outcome is participant-reported ankle-related symptoms and function six months after randomization, measured by the Olerud and Molander Ankle Score. Secondary outcomes at two, four, and six months measure health-related quality of life, pain, physical function, self-efficacy, exercise adherence, complications, and resource use. Due to the nature of the interventions, participants and intervention providers will be unblinded to treatment allocation.Aims
Methods
This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night. In this study, a titanium rod was implanted in the medullary cavity of one femoral metaphysis in OVX rats, and then the rats were randomly divided into four groups: Sham group (Sham, n = 10), OVX rat group (OVX, n = 10), melatonin day treatment group (OVX + MD, n = 10), and melatonin night treatment group (OVX + MN, n = 10). The OVX + MD and OVX + MN rats were treated with 30 mg/kg/day melatonin at 9 am and 9 pm, respectively, for 12 weeks. At the end of the research, the rats were killed to obtain bilateral femora and blood samples for evaluation.Aims
Methods
The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold. Female Sprague Dawley (SD) rats were used to establish a rat model of BCP, and the messenger RNA (mRNA) and protein expression of ionized calcium binding adaptor molecule 1 (IBA1) and cyclin D1 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. The proliferation of spinal microglia was detected by immunohistochemistry. The pain behaviour test was assessed by quantification of spontaneous flinches, limb use, and guarding during forced ambulation, mechanical paw withdrawal threshold, and thermal paw withdrawal latency.Aims
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The rationale for exacting restoration of skeletal anatomy after unstable ankle fracture is to improve outcomes by reducing complications from malunion; however, current definitions of malunion lack confirmatory clinical evidence. Radiological (absolute radiological measurements aided by computer software) and clinical (clinical interpretation of radiographs) definitions of malunion were compared within the Ankle Injury Management (AIM) trial cohort, including people aged ≥ 60 years with an unstable ankle fracture. Linear regressions were used to explore the relationship between radiological malunion (RM) at six months and changes in function at three years. Function was assessed with the Olerud-Molander Ankle Score (OMAS), with a minimal clinically important difference set as six points, as per the AIM trial. Piecewise linear models were used to investigate new radiological thresholds which better explain symptom impact on ankle function.Aims
Methods
Ankle fracture is one of the most common musculoskeletal injuries sustained in the UK. Many patients experience pain and physical impairment, with the consequences of the fracture and its management lasting for several months or even years. The broad aim of ankle fracture treatment is to maintain the alignment of the joint while the fracture heals, and to reduce the risks of problems, such as stiffness. More severe injuries to the ankle are routinely treated surgically. However, even with advances in surgery, there remains a risk of complications; for patients experiencing these, the associated loss of function and quality of life (Qol) is considerable. Non-surgical treatment is an alternative to surgery and involves applying a cast carefully shaped to the patient’s ankle to correct and maintain alignment of the joint with the key benefit being a reduction in the frequency of common complications of surgery. The main potential risk of non-surgical treatment is a loss of alignment with a consequent reduction in ankle function. This study aims to determine whether ankle function, four months after treatment, in patients with unstable ankle fractures treated with close contact casting is not worse than in those treated with surgical intervention, which is the current standard of care. This trial is a pragmatic, multicentre, randomized non-inferiority clinical trial with an embedded pilot, and with 12 months clinical follow-up and parallel economic analysis. A surveillance study using routinely collected data will be performed annually to five years post-treatment. Adult patients, aged 60 years and younger, with unstable ankle fractures will be identified in daily trauma meetings and fracture clinics and approached for recruitment prior to their treatment. Treatments will be performed in trauma units across the UK by a wide range of surgeons. Details of the surgical treatment, including how the operation is done, implant choice, and the recovery programme afterwards, will be at the discretion of the treating surgeon. The non-surgical treatment will be close-contact casting performed under anaesthetic, a technique which has gained in popularity since the publication of the Ankle Injury Management (AIM) trial. In all, 890 participants (445 per group) will be randomly allocated to surgical or non-surgical treatment. Data regarding ankle function, QoL, complications, and healthcare-related costs will be collected at eight weeks, four and 12 months, and then annually for five years following treatment. The primary outcome measure is patient-reported ankle function at four months from treatment.Aims
Methods
There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Aims
Methods
We have previously developed a radiographic technique, the oblique posterior condylar view, for assessment of the posterior aspect of the femoral condyles after total knee arthroplasty. The purpose of this study was to confirm the validity of this radiographic view based upon intra-operative findings at revision total knee arthroplasty. Lateral and oblique posterior condylar views were performed for 11 knees prior to revision total knee arthroplasty, and radiolucent lines or osteolysis of the posterior aspect of the femoral condyles were identified. These findings were compared with the intra-operative appearance of the posterior aspects of the femoral condyles.
A substantial fraction of patients undergoing knee arthroplasty (KA) or hip arthroplasty (HA) do not achieve an improvement as high as the minimal clinically important difference (MCID), i.e. do not achieve a meaningful improvement. Using three patient-reported outcome measures (PROMs), our aim was: 1) to assess machine learning (ML), the simple pre-surgery PROM score, and logistic-regression (LR)-derived performance in their prediction of whether patients undergoing HA or KA achieve an improvement as high or higher than a calculated MCID; and 2) to test whether ML is able to outperform LR or pre-surgery PROM scores in predictive performance. MCIDs were derived using the change difference method in a sample of 1,843 HA and 1,546 KA patients. An artificial neural network, a gradient boosting machine, least absolute shrinkage and selection operator (LASSO) regression, ridge regression, elastic net, random forest, LR, and pre-surgery PROM scores were applied to predict MCID for the following PROMs: EuroQol five-dimension, five-level questionnaire (EQ-5D-5L), EQ visual analogue scale (EQ-VAS), Hip disability and Osteoarthritis Outcome Score-Physical Function Short-form (HOOS-PS), and Knee injury and Osteoarthritis Outcome Score-Physical Function Short-form (KOOS-PS).Aims
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The aim of this study was to examine the implant accuracy of custom-made partial pelvis replacements (PPRs) in revision total hip arthroplasty (rTHA). Custom-made implants offer an option to achieve a reconstruction in cases with severe acetabular bone loss. By analyzing implant deviation in CT and radiograph imaging and correlating early clinical complications, we aimed to optimize the usage of custom-made implants. A consecutive series of 45 (2014 to 2019) PPRs for Paprosky III defects at rTHA were analyzed comparing the preoperative planning CT scans used to manufacture the implants with postoperative CT scans and radiographs. The anteversion (AV), inclination (IC), deviation from the preoperatively planned implant position, and deviation of the centre of rotation (COR) were explored. Early postoperative complications were recorded, and factors for malpositioning were sought. The mean follow-up was 30 months (SD 19; 6 to 74), with four patients lost to follow-up.Aims
Methods
Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated.Aims
Methods
The primary aim of this study was to determine the ten-year outcome following surgical treatment for femoroacetabular impingement (FAI). We assessed whether the evolution of practice from open to arthroscopic techniques influenced outcomes and tested whether any patient, radiological, or surgical factors were associated with outcome. Prospectively collected data of a consecutive single-surgeon cohort, operated for FAI between January 2005 and January 2015, were retrospectively studied. The cohort comprised 393 hips (365 patients; 71% male (n = 278)), with a mean age of 34.5 years (SD 10.0). Over the study period, techniques evolved from open surgical dislocation (n = 94) to a combined arthroscopy-Hueter technique (HA + Hueter; n = 61) to a pure arthroscopic technique (HA; n = 238). Outcome measures of interest included modes of failures, complications, reoperation, and patient-reported outcome measures (PROMs). Demographic, radiological, and surgical factors were tested for possible association with outcome.Aims
Methods
Traditionally, total hip arthroplasty (THA) templating has been performed on anteroposterior (AP) pelvis radiographs. Recently, additional AP hip radiographs have been recommended for accurate measurement of the femoral offset (FO). To verify this claim, this study aimed to establish quantitative data of the measurement error of the FO in relation to leg position and X-ray source position using a newly developed geometric model and clinical data. We analyzed the FOs measured on AP hip and pelvis radiographs in a prospective consecutive series of 55 patients undergoing unilateral primary THA for hip osteoarthritis. To determine sample size, a power analysis was performed. Patients’ position and X-ray beam setting followed a standardized protocol to achieve reproducible projections. All images were calibrated with the KingMark calibration system. In addition, a geometric model was created to evaluate both the effects of leg position (rotation and abduction/adduction) and the effects of X-ray source position on FO measurement.Aims
Methods
Adult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 107 colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling.Aims
Methods
Accurate identification of the ankle joint centre is critical for estimating tibial coronal alignment in total knee arthroplasty (TKA). The purpose of the current study was to leverage artificial intelligence (AI) to determine the accuracy and effect of using different radiological anatomical landmarks to quantify mechanical alignment in relation to a traditionally defined radiological ankle centre. Patients with full-limb radiographs from the Osteoarthritis Initiative were included. A sub-cohort of 250 radiographs were annotated for landmarks relevant to knee alignment and used to train a deep learning (U-Net) workflow for angle calculation on the entire database. The radiological ankle centre was defined as the midpoint of the superior talus edge/tibial plafond. Knee alignment (hip-knee-ankle angle) was compared against 1) midpoint of the most prominent malleoli points, 2) midpoint of the soft-tissue overlying malleoli, and 3) midpoint of the soft-tissue sulcus above the malleoli.Aims
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