The injured anterior cruciate ligament (ACL) is thought to exhibit an impaired healing response, and attempts at surgical repair have not been successful. Connective tissue growth factor (CTGF) is reported to be associated with wound healing, probably through transforming growth factor beta 1 (TGF-β1). A rabbit ACL injury model was used to study the effect of CTGF on ligament recovery. Quantitative real-time PCR (qRT-PCR) was performed for detection of changes in RNA levels of TGF-β1, type 1 collagen (COL1), type 2 collagen (COL2), SRY-related high mobility group-box gene9 (SOX9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metallopeptidase 13 (MMP-13). Expression of related proteins was detected by Western blotting.Objectives
Methods
Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA. Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting.Objectives
Methods
Currently, there is little information about the need for peri-operative
blood transfusion in patients undergoing shoulder arthroplasty. The purpose of this study was to identify the rate of transfusion
and its predisposing factors, and to establish a blood conservation
strategy. We identified all patients who had undergone shoulder arthroplasty
at our hospital between 1 January 2011 and 31 December 2013. The
rate of transfusion was determined from the patient’s records. While
there were exceptions, patients typically underwent transfusion
if they had a level of haemoglobin of <
7.5 g/dl if asymptomatic,
<
9.0 g/dl if they had a significant cardiac history or symptoms
of dizziness or light headedness. Multivariable regression analysis was undertaken to identify
predictors of transfusion. High- and low-risk cohorts for transfusion
were identified from a receiver operating characteristic (ROC) curve.Aims
Methods
Interleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and annulus fibrosus (AF) cells and, therefore, to identify potential therapeutic and clinical benefits of recombinant human (rh)BMP-2 in intervertebral disc degeneration. Levels of IL-18 were measured in the blood of patients with intervertebral disc degenerative disease and in control patients. Human NP and AF cells were cultured in a NP cell medium and treated with IL-18 or IL-18 plus BMP-2. mRNA levels of target genes were measured by real-time polymerase chain reaction, and protein levels of aggrecan, type II collagen, SOX6, and matrix metalloproteinase 13 (MMP13) were assessed by western blot analysis.Objectives
Methods
The aims of this study were to estimate the cost of surgical
treatment of fractures of the proximal humerus using a micro-costing
methodology, contrast this cost with the national reimbursement
tariff and establish the major determinants of cost. A detailed inpatient treatment pathway was constructed using
semi-structured interviews with 32 members of hospital staff. Its
content validity was established through a Delphi panel evaluation.
Costs were calculated using time-driven activity-based costing (TDABC)
and sensitivity analysis was performed to evaluate the determinants
of costAims
Methods
Cellular movement and relocalisation are important for many physiologic properties. Local mesenchymal stem cells (MSCs) from injured tissues and circulating MSCs aid in fracture healing. Cytokines and chemokines such as Stromal cell-derived factor 1(SDF-1) and its receptor chemokine receptor type 4 (CXCR4) play important roles in maintaining mobilisation, trafficking and homing of stem cells from bone marrow to the site of injury. We investigated the differences in migration of MSCs from the femurs of young, adult and ovariectomised (OVX) rats and the effect of CXCR4 over-expression on their migration. MSCs from young, adult and OVX rats were put in a Boyden chamber to establish their migration towards SDF-1. This was compared with MSCs transfected with CXCR4, as well as MSCs differentiated to osteoblasts.Objectives
Methods
Favourable results for collarless polished tapered stems have been reported, and cement creep due to taper slip may be a contributing factor. However, the ideal cement thickness around polished stems remains unknown. We investigated the influence of cement thickness on stem subsidence and cement creep. We cemented six collarless polished tapered (CPT) stems (two stems each of small, medium and large sizes) into composite femurs that had been reamed with a large CPT rasp to achieve various thicknesses of the cement mantle. Two or three tantalum balls were implanted in the proximal cement in each femur. A cyclic loading test was then performed for each stem. The migration of the balls was measured three-dimensionally, using a micro-computed tomography (CT) scanner, before and after loading. A digital displacement gauge was positioned at the stem shoulder, and stem subsidence was measured continuously by the gauge. Final stem subsidence was measured at the balls at the end of each stem.Objectives
Methods
The October 2015 Shoulder &
Elbow Roundup360 looks at: Culture time important in propionibacterium acnes; Microvascularisation of the cuff footprint; Degenerative cuff tears: evidence for repair; Middle ground in distal humeral fractures?; Haste needed in elbow heterotopic ossification; Iatrogenic frozen shoulder; Salvage of failed humeral fixation
This study aimed to explore the role of miR-320a in the pathogenesis of osteoarthritis (OA). Human cartilage cells (C28/I2) were transfected with miR-320a or antisense oligonucleotides (ASO)-miR-320a, and treated with IL-1β. Subsequently the expression of collagen type II alpha 1 (Col2α1) and aggrecan (ACAN), and the concentrations of sulfated glycosaminoglycans (sGAG) and matrix metallopeptidase 13 (MMP-13), were assessed. Luciferase reporter assay, qRT-PCR, and Western blot were performed to explore whether pre-B-cell leukemia Homeobox 3 (PBX3) was a target of miR-320a. Furthermore, cells were co-transfected with miR-320a and PBX3 expressing vector, or cells were transfected with miR-320a and treated with a nuclear factor kappa B (NF-κB) antagonist MG132. The changes in Col2α1 and ACAN expression, and in sGAG and MMP-13 concentrations, were measured again. Statistical comparisons were made between two groups by using the two-tailed paired Objectives
Methods
This study aims to assess first, whether mutations in the epidermal
growth factor receptor (EGFR) and Kirsten rat sarcoma (kRAS) genes
are associated with overall survival (OS) in patients who present
with symptomatic bone metastases from non-small cell lung cancer
(NSCLC) and secondly, whether mutation status should be incorporated into
prognostic models that are used when deciding on the appropriate
palliative treatment for symptomatic bone metastases. We studied 139 patients with NSCLC treated between 2007 and 2014
for symptomatic bone metastases and whose mutation status was known.
The association between mutation status and overall survival was
analysed and the results applied to a recently published prognostic
model to determine whether including the mutation status would improve
its discriminatory power.Aims
Patients and Methods
To assess the clinical and cost-effectiveness of a virtual fracture clinic (VFC) model, and supplement the literature regarding this service as recommended by The National Institute for Health and Care Excellence (NICE) and the British Orthopaedic Association (BOA). This was a retrospective study including all patients (17 116) referred to fracture clinics in a London District General Hospital from May 2013 to April 2016, using hospital-level data. We used interrupted time series analysis with segmented regression, and direct before-and-after comparison, to study the impact of VFCs introduced in December 2014 on six clinical parameters and on local Clinical Commissioning Group (CCG) spend. Student’s Objectives
Methods
Joint replacement of the hip and knee remain
very satisfactory operations. They are, however, expensive. The
actual manufacturing of the implant represents only 30% of the final
cost, while sales and marketing represent 40%. Recently, the patents
on many well established and successful implants have expired. Companies
have started producing and distributing implants that purport to
replicate existing implants with good long-term results. The aims of this paper are to assess the legality, the monitoring
and cost saving implications of such generic implants. We also assess
how this might affect the traditional orthopaedic implant companies. Cite this article:
To present our experience of using a combination of intra-articular
osteotomy and external fixation to treat different deformities of
the knee. A total of six patients with a mean age of 26.5 years (15 to
50) with an abnormal hemi-joint line convergence angle (HJLCA) and
mechanical axis deviation (MAD) were included. Elevation of a tibial
hemiplateau or femoral condylar advancement was performed and limb
lengthening with correction of residual deformity using a circular
or monolateral Ilizarov frame.Aims
Patients and Methods
The present study describes a novel technique for revitalising allogenic intrasynovial tendons by combining cell-based therapy and mechanical stimulation in an Specifically, canine flexor digitorum profundus tendons were used for this study and were divided into the following groups: (1) untreated, unprocessed normal tendon; (2) decellularised tendon; (3) bone marrow stromal cell (BMSC)-seeded tendon; and (4) BMSC-seeded and cyclically stretched tendon. Lateral slits were introduced on the tendon to facilitate cell seeding. Tendons from all four study groups were distracted by a servohydraulic testing machine. Tensile force and displacement data were continuously recorded at a sample rate of 20 Hz until 200 Newton of force was reached. Before testing, the cross-sectional dimensions of each tendon were measured with a digital caliper. Young’s modulus was calculated from the slope of the linear region of the stress-strain curve. The BMSCs were labeled for histological and cell viability evaluation on the decellularized tendon scaffold under a confocal microscope. Gene expression levels of selected extracellular matrix tendon growth factor genes were measured. Results were reported as mean ± SD and data was analyzed with one-way ANOVAs followed by Tukey’s post hoc multiple-comparison test.Objectives
Methods
We wished to investigate the influence of metal debris exposure
on the subsequent immune response and resulting soft-tissue injury
following metal-on-metal (MoM) hip arthroplasty. Some reports have
suggested that debris generated from the head-neck taper junction
is more destructive than equivalent doses from metal bearing surfaces. We investigated the influence of the source and volume of metal
debris on chromium (Cr) and cobalt (Co) concentrations in corresponding
blood and hip synovial fluid samples and the observed agglomerated
particle sizes in excised tissues using multiple regression analysis
of prospectively collected data. A total of 199 explanted MoM hips
(177 patients; 132 hips female) were analysed to determine rates
of volumetric wear at the bearing surfaces and taper junctions. Aims
Patients and Methods
We investigated the effects on fracture healing of two up-regulators of inducible nitric oxide synthase (iNOS) in a rat model of an open femoral osteotomy: tadalafil, a phosphodiesterase inhibitor, and the recently reported nutraceutical, COMB-4 (consisting of L-citrulline, Paullinia cupana, ginger and muira puama), given orally for either 14 or 42 days. Unilateral femoral osteotomies were created in 58 male rats and fixed with an intramedullary compression nail. Rats were treated daily either with vehicle, tadalafil or COMB-4. Biomechanical testing of the healed fracture was performed on day 42. The volume, mineral content and bone density of the callus were measured by quantitative CT on days 14 and 42. Expression of iNOS was measured by immunohistochemistry.Objectives
Materials and Methods
After an injury, the biological reattachment of tendon to bone is a challenge because healing takes place between a soft (tendon) and a hard (bone) tissue. Even after healing, the transition zone in the enthesis is not completely regenerated, making it susceptible to re-injury. In this study, we aimed to regenerate Achilles tendon entheses (ATEs) in wounded rats using a combination of kartogenin (KGN) and platelet-rich plasma (PRP). Wounds created in rat ATEs were given three different treatments: kartogenin platelet-rich plasma (KGN-PRP); PRP; or saline (control), followed by histological and immunochemical analyses, and mechanical testing of the rat ATEs after three months of healing.Objectives
Methods
Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect.
The PROximal Fracture of the Humerus Evaluation by Randomisation
(PROFHER) randomised clinical trial compared the operative and non-operative
treatment of adults with a displaced fracture of the proximal humerus
involving the surgical neck. The aim of this study was to determine
the long-term treatment effects beyond the two-year follow-up. Of the original 250 trial participants, 176 consented to extended
follow-up and were sent postal questionnaires at three, four and
five years after recruitment to the trial. The Oxford Shoulder Score
(OSS; the primary outcome), EuroQol 5D-3L (EQ-5D-3L), and any recent
shoulder operations and fracture data were collected. Statistical
and economic analyses, consistent with those of the main trial were
applied.Aims
Patients and Methods
The aim of this study was to compare the Push Ortho Thumb Brace
CMC and a custom-made orthosis in the treatment of patients with
primary osteoarthritis of the carpometacarpal joint of the thumb.
Our outcome measures were pain scores, tests of hand function, patient
satisfaction and patient preference. A multicentre crossover randomised controlled trial was conducted
which included 63 patients (44 women) with primary osteoarthritis
of the carpometacarpal joint of the thumb. Of these, 59 patients
with a mean age of 60.1 years (standard deviation 8.2), completed
the study. Patients used both orthoses for two weeks with a two-week washout
period in-between. Pain was measured on a 10-cm visual analogue
scale. Hand function was assessed using the Jebsen Taylor Hand Function
test, Nine Hole Peg Test, key grip, pinch grip and Functional Index
for Hand Osteoarthritis. Patient preference was assessed using the
Dutch version of the Quebec User Evaluation of Satisfaction with
Assistive Technology score.Aims
Patients and Methods