Charcot neuroarthropathy is a rare but serious complication of diabetes, causing progressive destruction of the bones and joints of the foot leading to deformity, altered biomechanics and an increased risk of ulceration. Management is complicated by a lack of consensus on diagnostic criteria and an incomplete understanding of the pathogenesis. In this review, we consider recent insights into the development of Charcot neuroarthropathy. It is likely to be dependent on several interrelated factors which may include a genetic pre-disposition in combination with diabetic neuropathy. This leads to decreased neuropeptides (nitric oxide and calcitonin gene-related peptide), which may affect the normal coupling of bone formation and resorption, and increased levels of Receptor activator of nuclear factor kappa-B ligand, potentiating osteoclastogenesis. Repetitive unrecognized trauma due to neuropathy increases levels of pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumour necrosis factor α) which could also contribute to increased bone resorption, in combination with a pre-inflammatory state, with increased autoimmune reactivity and a profile of monocytes primed to transform into osteoclasts - cluster of differentiation 14 (CD14). Increased blood glucose and loss of circulating Receptor for Advanced Glycation End-Products (AGLEPs), leading to increased non-enzymatic glycation of collagen and accumulation of AGLEPs in the tissues of the foot, may also contribute to the pathological process. An understanding of the relative contributions of each of these mechanisms and a final common pathway for the development of Charcot neuroarthropathy are still lacking.
Increasing innovation in rapid prototyping (RP)
and additive manufacturing (AM), also known as 3D printing, is bringing
about major changes in translational surgical research. This review describes the current position in the use of additive
manufacturing in orthopaedic surgery. Cite this article:
Studies reporting specifically on squeaking in total hip arthroplasty have focused on cementless, and not on hybrid, fixation. We hypothesised that the cement mantle of the femur might have a damping effect on the sound transmitted through the metal stem. The objective of this study was to test the effect of cement on sound propagation along different stem designs and under different fixation conditions. An Objectives
Methods
Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from
The objectives of this study were: 1) to examine osteophyte formation, subchondral bone advance, and bone marrow lesions (BMLs) in osteoarthritis (OA)-prone Hartley guinea pigs; and 2) to assess the disease-modifying activity of an orally administered phosphocitrate ‘analogue’, Carolinas Molecule-01 (CM-01). Young Hartley guinea pigs were divided into two groups. The first group (n = 12) had drinking water and the second group (n = 9) had drinking water containing CM-01. Three guinea pigs in each group were euthanized at age six, 12, and 18 months, respectively. Three guinea pigs in the first group were euthanized aged three months as baseline control. Radiological, histological, and immunochemical examinations were performed to assess cartilage degeneration, osteophyte formation, subchondral bone advance, BMLs, and the levels of matrix metalloproteinse-13 (MMP13) protein expression in the knee joints of hind limbs.Objectives
Methods
Recently, high failure rates of metal-on-metal (MOM) hip implants have raised concerns of cobalt toxicity. Adverse reactions occur to cobalt nanoparticles (CoNPs) and cobalt ions (Co2+) during wear of MOM hip implants, but the toxic mechanism is not clear. To evaluate the protective effect of zinc ions (Zn2+), Balb/3T3 mouse fibroblast cells were pretreated with 50 μM Zn2+ for four hours. The cells were then exposed to different concentrations of CoNPs and Co2+ for four hours, 24 hours and 48 hours. The cell viabilities, reactive oxygen species (ROS) levels, and inflammatory cytokines were measured.Objectives
Methods
‘Big data’ is a term for data sets that are so
large or complex that traditional data processing applications are
inadequate. Billions of dollars have been spent on attempts to build predictive
tools from large sets of poorly controlled healthcare metadata.
Companies often sell reports at a physician or facility level based
on various flawed data sources, and comparative websites of ‘publicly
reported data’ purport to educate the public. Physicians should
be aware of concerns and pitfalls seen in such data definitions,
data clarity, data relevance, data sources and data cleaning when
evaluating analytic reports from metadata in health care. Cite this article:
Osteoarthritis (OA) is characterised by articular cartilage degradation. MicroRNAs (miRNAs) have been identified in the development of OA. The purpose of our study was to explore the functional role and underlying mechanism of miR-138-5p in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage. Human articular cartilage was obtained from patients with and without OA, and chondrocytes were isolated and stimulated by IL-1β. The expression levels of miR-138-5p in cartilage and chondrocytes were both determined. After transfection with miR-138-5p mimics, allele-specific oligonucleotide (ASO)-miR-138-5p, or their negative controls, the messenger RNA (mRNA) levels of aggrecan (ACAN), collagen type II and alpha 1 (COL2A1), the protein levels of glycosaminoglycans (GAGs), and both the mRNA and protein levels of matrix metalloproteinase (MMP)-13 were evaluated. Luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot were performed to explore whether Forkhead Box C1 (FOCX1) was a target of miR-138-5p. Further, we co-transfected OA chondrocytes with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 and then stimulated with IL-1β to determine whether miR-138-5p-mediated IL-1β-induced cartilage matrix degradation resulted from targeting FOXC1.Objectives
Materials and Methods
Adverse reaction to wear and corrosion debris
is a cause for concern in total hip arthroplasty (THA). Modular junctions
are a potential source of such wear products and are associated
with secondary pseudotumour formation. We present a consecutive series of 17 patients treated at our
unit for this complication following metal-on-highly cross-linked
polyethylene (MoP) THA. We emphasise the risk of misdiagnosis as
infection, and present the aggregate laboratory results and pathological
findings in this series. The clinical presentation was pain, swelling or instability.
Solid, cystic and mixed soft-tissue lesions were noted on imaging
and confirmed intra-operatively. Corrosion at the head–neck junction
was noted in all cases. No bacteria were isolated on multiple pre-
and intra-operative samples yet the mean erythrocyte sedimentation
rate was 49 (9 to 100) and C-reactive protein 32 (0.6 to 106) and
stromal polymorphonuclear cell counts were noted in nine cases. Adverse soft–tissue reactions can occur in MoP THA owing to corrosion
products released from the head–neck junction. The diagnosis should
be carefully considered when investigating pain after THA. This
may avoid the misdiagnosis of periprosthetic infection with an unidentified
organism and mitigate the unnecessary management of these cases
with complete single- or two-stage exchange. Cite this article:
Implant-related infection is one of the most devastating complications in orthopaedic surgery. Many surface and/or material modifications have been developed in order to minimise this problem; however, most of the We describe a method for the study of bacterial adherence in the presence of preosteoblastic cells. For this purpose we mixed different concentrations of bacterial cells from collection and clinical strains of staphylococci isolated from implant-related infections with preosteoblastic cells, and analysed the minimal concentration of bacteria able to colonise the surface of the material with image analysis.Objectives
Methods
We have designed a prospective study to evaluate
the usefulness of prolonged incubation of cultures from sonicated
orthopaedic implants. During the study period 124 implants from
113 patients were processed (22 osteosynthetic implants, 46 hip
prostheses, 54 knee prostheses, and two shoulder prostheses). Of
these, 70 patients had clinical infection; 32 had received antibiotics
at least seven days before removal of the implant. A total of 54 patients
had sonicated samples that produced positive cultures (including
four patients without infection). All of them were positive in the
first seven days of incubation. No differences were found regarding
previous antibiotic treatment when analysing colony counts or days
of incubation in the case of a positive result. In our experience, extending
incubation of the samples to 14 days does not add more positive
results for sonicated orthopaedic implants (hip and knee prosthesis
and osteosynthesis implants) compared with a conventional seven-day incubation
period. Cite this article:
Eukaryotic translation initiation factor 3 (eIF3) is a multi-subunit complex that plays a critical role in translation initiation. Expression levels of eIF3 subunits are elevated or decreased in various cancers, suggesting a role for eIF3 in tumorigenesis. Recent studies have shown that the expression of the eIF3b subunit is elevated in bladder and prostate cancer, and eIF3b silencing inhibited glioblastoma growth and induced cellular apoptosis. In this study, we investigated the role of eIF3b in the survival of osteosarcoma cells. To investigate the effect of eIF3b on cell viability and apoptosis in osteosarcoma cells, we first examined the silencing effect of eIF3b in U2OS cells. Cell viability and apoptosis were examined by the Cell Counting Kit-8 (CCK-8) assay and Western blot, respectively. We also performed gene profiling to identify genes affected by eIF3b silencing. Finally, the effect of eIF3b on cell viability and apoptosis was confirmed in multiple osteosarcoma cell lines.Objectives
Methods
Joint-preserving surgery of the hip (JPSH) has evolved considerably
and now includes a number of procedures, including arthroscopy,
surgical dislocation, and redirectional osteotomies of the femur
and acetabulum. There are a number of different factors which lead
to failure of JPSH. Consequently, it is of interest to assess the
various modes of failure in order to continue to identify best practice
and the indications for these procedures. Using a retrospective observational study design, we reviewed
1013 patients who had undergone JPSH by a single surgeon between
2005 and 2015. There were 509 men and 504 women with a mean age
of 39 years (16 to 78). Of the 1013 operations, 783 were arthroscopies,
122 surgical dislocations, and 108 peri-acetabular osteotomies (PAO).
We analysed the overall failure rates and modes of failure. Re-operations
were categorised into four groups: Mode 1 was arthritis progression
or organ failure leading to total hip arthroplasty (THA); Mode 2
was an Incorrect diagnosis/procedure; Mode 3 resulted from malcorrection
of femur (type A), acetabulum (type B), or labrum (type C) and Mode 4
resulted from an unintended consequence of the initial surgical
intervention.Aims
Patients and Methods
The number of arthroplasties being undertaken
is expected to grow year on year, and periprosthetic joint infections will
be an increasing socioeconomic burden. The challenge to prevent
and eradicate these infections has resulted in the emergence of
several new strategies, which are discussed in this review. Cite this article:
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
The June 2015 Oncology Roundup360 looks at: Infection in megaprosthesis; Impressive results for mid femoral reconstruction; Revered teaching or old myth? Femoral neck protection in metastatic disease; Megaprosthesis about the knee; Malignant transformation in multiple hereditary exostoses; Fracture of intercalary bone allograft; Comorbidity and outcomes in sarcoma; A worrying turn? Use of denosumab for giant cell tumour of bone
