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Bone & Joint Research
Vol. 5, Issue 8 | Pages 347 - 352
1 Aug 2016
Nuttall J Evaniew N Thornley P Griffin A Deheshi B O’Shea T Wunder J Ferguson P Randall RL Turcotte R Schneider P McKay P Bhandari M Ghert M

Objectives. The diagnosis of surgical site infection following endoprosthetic reconstruction for bone tumours is frequently a subjective diagnosis. Large clinical trials use blinded Central Adjudication Committees (CACs) to minimise the variability and bias associated with assessing a clinical outcome. The aim of this study was to determine the level of inter-rater and intra-rater agreement in the diagnosis of surgical site infection in the context of a clinical trial. Materials and Methods. The Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial CAC adjudicated 29 non-PARITY cases of lower extremity endoprosthetic reconstruction. The CAC members classified each case according to the Centers for Disease Control (CDC) criteria for surgical site infection (superficial, deep, or organ space). Combinatorial analysis was used to calculate the smallest CAC panel size required to maximise agreement. A final meeting was held to establish a consensus. Results. Full or near consensus was reached in 20 of the 29 cases. The Fleiss kappa value was calculated as 0.44 (95% confidence interval (CI) 0.35 to 0.53), or moderate agreement. The greatest statistical agreement was observed in the outcome of no infection, 0.61 (95% CI 0.49 to 0.72, substantial agreement). Panelists reached a full consensus in 12 of 29 cases and near consensus in five of 29 cases when CDC criteria were used (superficial, deep or organ space). A stable maximum Fleiss kappa of 0.46 (95% CI 0.50 to 0.35) at CAC sizes greater than three members was obtained. Conclusions. There is substantial agreement among the members of the PARITY CAC regarding the presence or absence of surgical site infection. Agreement on the level of infection, however, is more challenging. Additional clinical information routinely collected by the prospective PARITY trial may improve the discriminatory capacity of the CAC in the parent study for the diagnosis of infection. Cite this article: J. Nuttall, N. Evaniew, P. Thornley, A. Griffin, B. Deheshi, T. O’Shea, J. Wunder, P. Ferguson, R. L. Randall, R. Turcotte, P. Schneider, P. McKay, M. Bhandari, M. Ghert. The inter-rater reliability of the diagnosis of surgical site infection in the context of a clinical trial. Bone Joint Res 2016;5:347–352. DOI: 10.1302/2046-3758.58.BJR-2016-0036.R1


Bone & Joint Research
Vol. 11, Issue 10 | Pages 715 - 722
10 Oct 2022
Matsuyama Y Nakamura T Yoshida K Hagi T Iino T Asanuma K Sudo A

Aims

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.

Methods

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.


Bone & Joint Research
Vol. 4, Issue 9 | Pages 154 - 162
1 Sep 2015

Objective. Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. . Methods. We performed a pilot international multi-centre RCT. We used central randomisation to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. . Results. We screened 96 patients and enrolled 60 participants (44 men and 16 women) across 21 sites from four countries over 24 months (mean 2.13 participants per site per year, standard deviation 2.14). One participant was lost to follow-up and one withdrew consent. Complete data were obtained for 98% of eligible patients at two weeks, 83% at six months, and 73% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol. . Conclusions. It is feasible to conduct a definitive multi-centre RCT of post-operative antibiotic regimens in patients with bone sarcomas, but further expansion of our collaborative network will be critical. We have demonstrated an ability to coordinate in multiple countries, enrol participants, maintain protocol adherence, and minimise losses to follow-up. Cite this article: Bone Joint Res;4:154–162


Bone & Joint Research
Vol. 9, Issue 11 | Pages 821 - 826
1 Nov 2020
Hagi T Nakamura T Kita K Iino T Asanuma K Sudo A

Aims

Tocilizumab, an interleukin-6 (IL-6) receptor (IL-6R) targeting antibody, enhances the anti-tumour effect of conventional chemotherapy in preclinical models of cancer. We investigated the anti-tumour effect of tocilizumab in osteosarcoma (OS) cell lines.

Methods

We used the 143B, HOS, and Saos-2 human OS cell lines. We first analyzed the IL-6 gene expression and IL-6Rα protein expression in OS cells using reverse transcription real time quantitative-polymerase chain reaction (RT-qPCR) analysis and western blotting, respectively. We also assessed the effect of tocilizumab on OS cells using proliferation and invasion assay.


Bone & Joint Research
Vol. 6, Issue 10 | Pages 577 - 583
1 Oct 2017
Sallent A Vicente M Reverté MM Lopez A Rodríguez-Baeza A Pérez-Domínguez M Velez R

Objectives

To assess the accuracy of patient-specific instruments (PSIs) versus standard manual technique and the precision of computer-assisted planning and PSI-guided osteotomies in pelvic tumour resection.

Methods

CT scans were obtained from five female cadaveric pelvises. Five osteotomies were designed using Mimics software: sacroiliac, biplanar supra-acetabular, two parallel iliopubic and ischial. For cases of the left hemipelvis, PSIs were designed to guide standard oscillating saw osteotomies and later manufactured using 3D printing. Osteotomies were performed using the standard manual technique in cases of the right hemipelvis. Post-resection CT scans were quantitatively analysed. Student’s t-test and Mann–Whitney U test were used.


Bone & Joint Research
Vol. 6, Issue 5 | Pages 307 - 314
1 May 2017
Rendon JS Swinton M Bernthal N Boffano M Damron T Evaniew N Ferguson P Galli Serra M Hettwer W McKay P Miller B Nystrom L Parizzia W Schneider P Spiguel A Vélez R Weiss K Zumárraga JP Ghert M

Objectives

As tumours of bone and soft tissue are rare, multicentre prospective collaboration is essential for meaningful research and evidence-based advances in patient care. The aim of this study was to identify barriers and facilitators encountered in large-scale collaborative research by orthopaedic oncological surgeons involved or interested in prospective multicentre collaboration.

Methods

All surgeons who were involved, or had expressed an interest, in the ongoing Prophylactic Antibiotic Regimens in Tumour Surgery (PARITY) trial were invited to participate in a focus group to discuss their experiences with collaborative research in this area. The discussion was digitally recorded, transcribed and anonymised. The transcript was analysed qualitatively, using an analytic approach which aims to organise the data in the language of the participants with little theoretical interpretation.


Bone & Joint Research
Vol. 1, Issue 10 | Pages 272 - 280
1 Oct 2012
De Mattos CBR Binitie O Dormans JP

Pathological fractures in children can occur as a result of a variety of conditions, ranging from metabolic diseases and infection to tumours. Fractures through benign and malignant bone tumours should be recognised and managed appropriately by the treating orthopaedic surgeon. The most common benign bone tumours that cause pathological fractures in children are unicameral bone cysts, aneurysmal bone cysts, non-ossifying fibromas and fibrous dysplasia. Although pathological fractures through a primary bone malignancy are rare, these should be recognised quickly in order to achieve better outcomes. A thorough history, physical examination and review of plain radiographs are crucial to determine the cause and guide treatment. In most benign cases the fracture will heal and the lesion can be addressed at the time of the fracture, or after the fracture is healed. A step-wise and multidisciplinary approach is necessary in caring for paediatric patients with malignancies. Pathological fractures do not have to be treated by amputation; these fractures can heal and limb salvage can be performed when indicated.