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The Bone & Joint Journal
Vol. 97-B, Issue 11 | Pages 1512 - 1518
1 Nov 2015
Courtney PM Melnic CM Gutsche J Hume EL Lee G

Older patients with multiple medical co-morbidities are increasingly being offered and undergoing total joint arthroplasty (TJA). These patients are more likely to require intensive care support, following surgery. We prospectively evaluated the need for intensive care admission and intervention in a consecutive series of 738 patients undergoing elective hip and knee arthroplasty procedures. The mean age was 60.6 years (18 to 91; 440 women, 298 men. Risk factors, correlating with the need for critical care intervention, according to published guidelines, were analysed to identify high-risk patients who would benefit from post-operative critical care monitoring. A total of 50 patients (6.7%) in our series required critical care level interventions during their hospital stay. Six independent multivariate clinical predictors were identified (p < 0.001) including a history of congestive heart failure (odds ratio (OR) 24.26, 95% confidence interval (CI) 9.51 to 61.91), estimated blood loss >  1000 mL (OR 17.36, 95% CI 5.36 to 56.19), chronic obstructive pulmonary disease (13.90, 95% CI 4.78 to 40.36), intra-operative use of vasopressors (OR 8.10, 95% CI 3.23 to 20.27), revision hip arthroplasty (OR 2.71, 95% CI 1.04 to 7.04) and body mass index > 35 kg/m2 (OR 2.70, 95% CI 123 to 5.94). The model was then validated against an independent, previously published data set of 1594 consecutive patients. The use of this risk stratification model can be helpful in predicting which high-risk patients would benefit from a higher level of monitoring and care after elective TJA and aid hospitals in allocating precious critical care resources.

Cite this article: Bone Joint J 2015;97-B:1512–18.


Bone & Joint Research
Vol. 7, Issue 1 | Pages 58 - 68
1 Jan 2018
Portal-Núñez S Ardura JA Lozano D Martínez de Toda I De la Fuente M Herrero-Beaumont G Largo R Esbrit P

Objectives

Oxidative stress plays a major role in the onset and progression of involutional osteoporosis. However, classical antioxidants fail to restore osteoblast function. Interestingly, the bone anabolism of parathyroid hormone (PTH) has been shown to be associated with its ability to counteract oxidative stress in osteoblasts. The PTH counterpart in bone, which is the PTH-related protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like region and the C-terminal domain.

Methods

We examined and compared the antioxidant capacity of PTHrP (1-37) with the C-terminal PTHrP domain comprising the 107-111 epitope (osteostatin) in both murine osteoblastic MC3T3-E1 cells and primary human osteoblastic cells.


The Bone & Joint Journal
Vol. 98-B, Issue 1 | Pages 14 - 20
1 Jan 2016
Zywiel MG Cherian JJ Banerjee S Cheung AC Wong F Butany J Gilbert C Overgaard C Syed K Jacobs JJ Mont MA

As adverse events related to metal on metal hip arthroplasty have been better understood, there has been increased interest in toxicity related to the high circulating levels of cobalt ions. However, distinguishing true toxicity from benign elevations in cobalt levels can be challenging. The purpose of this review is to examine the use of cobalt alloys in total hip arthroplasty, to review the methods of measuring circulating cobalt levels, to define a level of cobalt which is considered pathological and to review the pathophysiology, risk factors and treatment of cobalt toxicity. To the best of our knowledge, there are 18 published cases where cobalt metal ion toxicity has been attributed to the use of cobalt-chromium alloys in hip arthroplasty. Of these cases, the great majority reported systemic toxic reactions at serum cobalt levels more than 100 μg/L. This review highlights some of the clinical features of cobalt toxicity, with the goal that early awareness may decrease the risk factors for the development of cobalt toxicity and/or reduce its severity.

Take home message: Severe adverse events can arise from the release of cobalt from metal-on-metal arthroplasties, and as such, orthopaedic surgeons should not only be aware of the presenting problems, but also have the knowledge to treat appropriately.

Cite this article: Bone Joint J 2016;98-B:14–20.


Aims

The aim of this study was to examine the efficacy and safety of multiple boluses of intravenous (IV) tranexamic acid (TXA) on the hidden blood loss (HBL) and inflammatory response following primary total hip arthroplasty (THA).

Patients and Methods

A total of 150 patients were allocated randomly to receive a single bolus of 20 mg/kg IV TXA before the incision (group A), a single bolus followed by a second bolus of 1 g IV-TXA three hours later (group B) or a single bolus followed by two boluses of 1 g IV-TXA three and six hours later (group C). All patients were treated using a standard peri-operative enhanced recovery protocol. Primary outcomes were HBL and the level of haemoglobin (Hb) as well as the levels of C-reactive protein (CRP) and interleukin-6 (IL-6) as markers of inflammation. Secondary outcomes included the length of stay in hospital and the incidence of venous thromboembolism (VTE).


Bone & Joint 360
Vol. 6, Issue 4 | Pages 23 - 25
1 Aug 2017


Bone & Joint Research
Vol. 6, Issue 3 | Pages 186 - 193
1 Mar 2017
Choi YJ Lee YS Lee HW Shim DM Seo SW

Objectives

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.

Methods

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.


Bone & Joint 360
Vol. 5, Issue 4 | Pages 40 - 41
1 Aug 2016


Bone & Joint Research
Vol. 5, Issue 11 | Pages 569 - 576
1 Nov 2016
Akahane M Shimizu T Kira T Onishi T Uchihara Y Imamura T Tanaka Y

Objectives

To assess the structure and extracellular matrix molecule expression of osteogenic cell sheets created via culture in medium with both dexamethasone (Dex) and ascorbic acid phosphate (AscP) compared either Dex or AscP alone.

Methods

Osteogenic cell sheets were prepared by culturing rat bone marrow stromal cells in a minimal essential medium (MEM), MEM with AscP, MEM with Dex, and MEM with Dex and AscP (Dex/AscP). The cell number and messenger (m)RNA expression were assessed in vitro, and the appearance of the cell sheets was observed after mechanical retrieval using a scraper. β-tricalcium phosphate (β-TCP) was then wrapped with the cell sheets from the four different groups and subcutaneously implanted into rats.


Bone & Joint Research
Vol. 5, Issue 12 | Pages 610 - 618
1 Dec 2016
Abubakar AA Noordin MM Azmi TI Kaka U Loqman MY

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.


The Bone & Joint Journal
Vol. 97-B, Issue 6 | Pages 847 - 852
1 Jun 2015
Nakamura T Matsumine A Asanuma K Matsubara T Sudo A

The aim of this study was to determine whether the high-sensitivity modified Glasgow prognostic score (Hs-mGPS) could predict the disease-specific survival and oncological outcome in adult patients with non-metastatic soft-tissue sarcoma before treatment. A total of 139 patients treated between 2001 and 2012 were retrospectively reviewed. The Hs-mGPS varied between 0 and 2. Patients with a score of 2 had a poorer disease-specific survival than patients with a score of 0 (p < 0.001). The estimated five-year rate of disease-specific survival for those with a score of 2 was 0%, compared with 85.4% (95% CI 77.3 to 93.5) for those with a score of 0. Those with a score of 2 also had a poorer disease-specific survival than those with a score of 1 (75.3%, 95% CI 55.8 to 94.8; p < 0.001). Patients with a score of 2 also had a poorer event-free rate than those with a score of 0 (p < 0.001). Those with a score of 2 also had a poorer event-free survival than did those with a score of 1 (p = 0.03). A multivariate analysis showed that the Hs-mGPS remained an independent predictor of survival and recurrence. The Hs-mGPS could be a useful prognostic marker in patients with a soft-tissue sarcoma.

Cite this article: Bone Joint J 2015; 97-B:847–52.


Bone & Joint Research
Vol. 5, Issue 5 | Pages 162 - 168
1 May 2016
Athanasou NA

Pathological assessment of periprosthetic tissues is important, not only for diagnosis, but also for understanding the pathobiology of implant failure. The host response to wear particle deposition in periprosthetic tissues is characterised by cell and tissue injury, and a reparative and inflammatory response in which there is an innate and adaptive immune response to the material components of implant wear. Physical and chemical characteristics of implant wear influence the nature of the response in periprosthetic tissues and account for the development of particular complications that lead to implant failure, such as osteolysis which leads to aseptic loosening, and soft-tissue necrosis/inflammation, which can result in pseudotumour formation. The innate response involves phagocytosis of implant-derived wear particles by macrophages; this is determined by pattern recognition receptors and results in expression of cytokines, chemokines and growth factors promoting inflammation and osteoclastogenesis; phagocytosed particles can also be cytotoxic and cause cell and tissue necrosis. The adaptive immune response to wear debris is characterised by the presence of lymphoid cells and most likely occurs as a result of a cell-mediated hypersensitivity reaction to cell and tissue components altered by interaction with the material components of particulate wear, particularly metal ions released from cobalt-chrome wear particles.

Cite this article: Professor N. A. Athanasou. The pathobiology and pathology of aseptic implant failure. Bone Joint Res 2016;5:162–168. DOI: 10.1302/2046-3758.55.BJR-2016-0086.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 9 | Pages 1201 - 1209
1 Sep 2011
Peng K Hsu W Shih H Hsieh C Huang T Hsu RW Chang P

In this study of 41 patients, we used proteomic, Western blot and immunohistochemical analyses to show that several reactive oxygen species scavenging enzymes are expressed differentially in patients with primary osteoarthritis and those with non-loosening and aseptic loosening after total hip replacement (THR). The patients were grouped as A (n = 16, primary THR), B (n = 10, fixed THR but requiring revision for polyethylene wear) and C (n = 15, requiring revision due to aseptic loosening) to verify the involvement of the identified targets in aseptic loosening. When compared with Groups A and B, Group C patients exhibited significant up-regulation of transthyretin and superoxide dismutase 3, but down-regulation of glutathione peroxidase 2 in their hip synovial fluids. Also, higher levels of superoxide dismutase 2 and peroxiredoxin 2, but not superoxide dismutase 1, catalase and glutathione perioxidase 1, were consistently detected in the hip capsules of Group C patients.

We propose that dysregulated reactive oxygen species-related enzymes may play an important role in the pathogenesis and progression of aseptic loosening after THR.


The Bone & Joint Journal
Vol. 98-B, Issue 2 | Pages 271 - 277
1 Feb 2016
Sørensen MS Gerds TA Hindsø K Petersen MM

Aims

The purpose of this study was to develop a prognostic model for predicting survival of patients undergoing surgery owing to metastatic bone disease (MBD) in the appendicular skeleton.

Methods

We included a historical cohort of 130 consecutive patients (mean age 64 years, 30 to 85; 76 females/54 males) who underwent joint arthroplasty surgery (140 procedures) owing to MBD in the appendicular skeleton during the period between January 2003 and December 2008. Primary cancer, pre-operative haemoglobin, fracture versus impending fracture, Karnofsky score, visceral metastases, multiple bony metastases and American Society of Anaesthesiologist’s score were included into a series of logistic regression models. The outcome was the survival status at three, six and 12 months respectively. Results were internally validated based on 1000 cross-validations and reported as time-dependent area under the receiver-operating characteristic curves (AUC) for predictions of outcome.


Bone & Joint 360
Vol. 4, Issue 4 | Pages 30 - 31
1 Aug 2015

The August 2015 Oncology Roundup360 looks at: Glasgow prognostic score in soft-tissue sarcoma; Denosumab in giant cell tumour; Timing, complications and radiotherapy; Pigmented villonodular synovitis and arthroscopy; PATHFx: estimating survival in pathological cancer; Prosthetic lengthening of short stumps; Chondrosarcoma and pathological fracture


Bone & Joint 360
Vol. 3, Issue 5 | Pages 10 - 12
1 Oct 2014

The October 2014 Hip & Pelvis Roundup360 looks at: functional acetabular orientation; predicting re-admission following THR; metal ions and resurfacing; lipped liners increase stability; all anaesthetics equal in hip fracture surgery; revision hip surgery in very young patients; and uncemented hips.


The Bone & Joint Journal
Vol. 96-B, Issue 10 | Pages 1312 - 1318
1 Oct 2014
Ibrahim MS Raja S Khan MA Haddad FS

We report the five year outcomes of a two-stage approach for infected total hip replacement. This is a single-surgeon experience at a tertiary centre where the more straightforward cases are treated using single-stage exchange. This study highlights the vital role of the multidisciplinary team in managing these cases.

A total of 125 patients (51 male, 74 female) with a mean age of 68 years (42 to 78) were reviewed prospectively. Functional status was assessed using the Harris hip score (HHS). The mean HHS improved from 38 (6 to 78.5) pre-operatively to 81.2 (33 to 98) post-operatively. Staphylococcus species were isolated in 85 patients (68%).

The rate of control of infection was 96% at five years. In all, 19 patients died during the period of the study. This represented a one year mortality of 0.8% and an overall mortality of 15.2% at five years. No patients were lost to follow-up.

We report excellent control of infection in a series of complex patients and infections using a two-stage revision protocol supported by a multidisciplinary approach. The reason for the high rate of mortality in these patients is not known.

Cite this article: Bone Joint J 2014;96-B:1312–18


Bone & Joint Research
Vol. 3, Issue 9 | Pages 273 - 279
1 Sep 2014
Vasiliadis ES Kaspiris A Grivas TB Khaldi L Lamprou M Pneumaticos SG Nikolopoulos K Korres DS Papadimitriou E

Objectives

The aim of this study was to examine whether asymmetric loading influences macrophage elastase (MMP12) expression in different parts of a rat tail intervertebral disc and growth plate and if MMP12 expression is correlated with the severity of the deformity.

Methods

A wedge deformity between the ninth and tenth tail vertebrae was produced with an Ilizarov-type mini external fixator in 45 female Wistar rats, matched for their age and weight. Three groups were created according to the degree of deformity (10°, 30° and 50°). A total of 30 discs and vertebrae were evaluated immunohistochemically for immunolocalisation of MMP12 expression, and 15 discs were analysed by western blot and zymography in order to detect pro- and active MMP12.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 5 | Pages 693 - 700
1 May 2007
Ishii I Mizuta H Sei A Hirose J Kudo S Hiraki Y

We have investigated in vitro the release kinetics and bioactivity of fibroblast growth factor-2 (FGF-2) released from a carrier of fibrin sealant. In order to evaluate the effects of the FGF-2 delivery mechanism on the repair of articular cartilage, full-thickness cylindrical defects, 5 mm in diameter and 4 mm in depth, which were too large to undergo spontaneous repair, were created in the femoral trochlea of rabbit knees. These defects were then filled with the sealant.

Approximately 50% of the FGF-2 was released from the sealant within 24 hours while its original bioactivity was maintained. The implantation of the fibrin sealant incorporating FGF-2 successfully induced healing of the surface with hyaline cartilage and concomitant repair of the subchondral bone at eight weeks after the creation of the defect.

Our findings suggest that this delivery method for FGF-2 may be useful for promoting regenerative repair of full-thickness defects of articular cartilage in humans.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 3 | Pages 414 - 417
1 Mar 2011
Knox D Murray G Millar M Hamilton D Connor M Ferdinand RD Jones GA

Anthrax is extremely rare in the western world but is endemic to areas of south and central Asia. In early 2010 an outbreak was identified in heroin-injecting intravenous drug users in the United Kingdom and Europe. Afghanistan is currently the principal source of heroin which reaches the United Kingdom. When anthrax occurs, cutaneous disease accounts for over 95% of cases. At least 47 cases with 13 deaths have been confirmed so far. We present three cases presenting during this time with marked swelling, one resulting in compartment syndrome but all with an absence of the expected cutaneous appearances.

We suggest that rather than cutaneous anthrax, these patients represent a new subcutaneous presentation of anthrax.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 12 | Pages 1700 - 1702
1 Dec 2010
Simon DA Taylor T Bayley G Lalonde K

Systemic capillary leak syndrome, or the Clarkson syndrome, is an extremely rare condition in which increased capillary permeability results in a massive shift of fluid into the extravascular space. This is followed rapidly by hypotensive shock, haemoconcentration, and, potentially, substantial oedema of the limbs resulting in an acute compartment syndrome. It is important for orthopaedic surgeons to be aware of this syndrome as our medical colleagues, who initially care for these patients, are less familiar with the diagnosis and the need for emergency management of the associated compartment syndrome should it develop. There have been fewer than 100 cases of this entity reported.

This case report is the first to describe the subsequent development of a compartment syndrome in all four limbs. Clinical vigilance and continuous monitoring of intracompartmental pressure is necessary in these patients in order to help reduce limb-threatening complications.