The effect of vitamin D supplementation on outcomes following total hip or knee arthroplasty surgery: a rapid systematic review of current evidence.

Purpose: Vitamin D deficiency has been linked to poorer outcomes following hip (THR) and knee (TKR) replacement. We review the effect of peri-operative supplementation on clinical and patient-reported outcomes following THR/TKR. Methods: This study was registered with PROSPERO (CRD42021238086). Searches of electronic databases were performed from inception to March 2021. All randomised, cohort, or case-controlled studies reported in English of adults undergoing THR/TKR where vitamin D supplementation was given peri-operatively and at least one outcome was reported were included. Studies reporting on vitamin D in relation to osteoporosis and hip fracture were excluded, as were conference abstracts and those involving preclinical models. Risks of bias were performed using the RoB-2 and ROBINS-I tools. Results: Three studies comprising 413 TKR patients were identified; two were randomised controlled trials and one was a prospective cohort study. No studies meeting the inclusion criteria reported on the outcomes following THR. Supplementation was associated with a statistically significant reduction in the IL6:IL10 ratio at 24- and 48h following surgery, but no effect was noted on Western Ontario and McMaster Universities Osteoarthritis Index scores or the rates of falls. All studies were judged to be limited by bias, with heterogeneity in the supplementation dose and timing of administration, as well as the reported outcome measures used. Discussion: Further adequately powered randomised-controlled trials using vitamin D supplementation and a specific clinically relevant or patient-reported outcome measure are required to assess if pre-operative vitamin D insufficiency is a modifiable risk factor to improve outcomes following THR/TKR.

Advances in image enhancement for sarcoma surgery.

The recurrence rate of soft tissue and bone sarcomas strongly correlates to the status of the surgical margin after excision, yet excessive removal of tissue may lead to distinct, otherwise avoidable morbidity. Therefore, adequate margination of sarcomas both pre- and intra-operatively is a clinical necessity that has not yet fully been met. Current guidance for soft-tissue sarcomas recommends an ultrasound scan followed by magnetic resonance imaging (MRI). For bone sarcomas, two plane radiographs are required, followed similarly by an MRI scan. The introduction of more precise imaging modalities may reduce the morbidity associated with sarcoma surgery; the PET-CT and PET-MRI approaches in particular demonstrating high clinical efficacy. Despite advancements in the accuracy in pre-operative imaging, translation of an image to surgical margins is difficult, regularly resulting in wider resection margins than required. For soft tissue sarcomas there is currently no standard technique for image guided resections, while for bone sarcomas fluoroscopy may be used, however margins are not easily discernible during the surgical procedure. Near infra-red (NIR) fluorescence guided surgery offers an intra-operative modality through which complete tumour resection with adequate tumour-free margins may be achieved, while simultaneously minimising surgical morbidity. NIR imaging presents a potentially valuable adjunct to sarcoma surgery. Early reports indicate that it may be able to provide the surgeon with helpful information on anatomy, perfusion, lymphatic drainage, tumour margins and metastases. The use of NIR fluorochromes have also been demonstrated to be well tolerated by patients. However, prior to widespread implementation, studies related to cost-effectiveness and the development of protocols are essential. Nevertheless, NIR imaging may become ubiquitous in the future, carrying the potential to transform the surgical management of sarcoma.

Role of routine blood tests for predicting clinical outcomes in osteosarcoma patients.

BACKGROUND: This retrospective cohort study aimed to investigate whether simple routine blood tests at presentation (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), alkaline phosphatase and albumin) predict survival in patients with osteosarcoma. METHODS: Between January 1998 and February 2015, 134 patients with a histological diagnosis of osteosarcoma were treated in our unit. Of these, 79 patients with high-grade osteosarcomas were included in the study. Demographic and clinical data, and laboratory parameters obtained prior to biopsy (CRP, ESR, alkaline phosphatase and albumin levels), were obtained from patients' records. RESULTS: There were 44 males and 35 females. Univariate analysis showed that high pre-biopsy CRP ( p = 0.004), raised pre-biopsy ESR ( p = 0.010), older age ( p < 0.001), poor tumour necrosis rates (≤90%, p = 0.023) and metastasis at presentation ( p < 0.001) were poor prognostic factors. Multivariate analysis showed pre-biopsy CRP and ESR levels to be independent predictors of overall survival ( p = 0.020 and p = 0.025, respectively). Kaplan-Meier survival was significantly lower in patients with elevated CRP ( p = 0.002) and ESR ( p = 0.003). Hypoalbuminaemia and elevated alkaline phosphatase levels did not correlate with overall survival. CONCLUSION: Preoperative CRP and ESR levels may have value in building a prognostic model for patients presenting with osteosarcoma.

Blood-borne biomarkers of osteosarcoma: A systematic review.

Osteosarcoma is the most common type of primary malignant bone tumor in children and young adults. Development of clinically useful biomarkers has the potential to improve treatments. The aim of this review was to investigate the recent literature assessing the utility of biomarkers for osteosarcoma. A detailed literature search was performed, with hand searches for related research publications. The search was limited to publications in English between January 2007 and February 2017. Of 286 studies identified, 24 met the inclusion criteria. There is a wide range of osteosarcoma biomarkers identified which act as clinical prognostic factors in patient outcome.

Indeterminate nodules in osteosarcoma: what's the follow-up?

BACKGROUND: Indeterminate pulmonary nodules in patients diagnosed with osteosarcoma present a challenge for accurate staging and prognosis. The aim of this study was to explore the significance of this finding. METHODS: A retrospective cohort study of 120 patients with osteosarcoma was performed in the North East of England. Chest computed tomographies (CTs) at presentation were reviewed and the incidence of 'indeterminate' nodules recorded. Follow-up scans were reviewed and survival as well as prognostic features were analysed. RESULTS: 25% of our cohort presented with indeterminate nodules. Of these, 33% were subsequently confirmed as metastases, the majority within a year. Kaplan-Meier survival analysis showed that patients with indeterminate nodules fared better than those with frank metastatic disease, and similar to those who presented with a normal chest CT. We found no radiographic features that predicted survival. CONCLUSIONS: Indeterminate nodules remain a clinical and diagnostic dilemma. Close monitoring of patients is advised during the first year from presentation, and there is potential for indeterminate nodules to develop into frank metastases later than five years from presentation.

The effect of operating lights on laminar flow: an experimental study using neutrally buoyant helium bubbles.

AIMS: The interaction between surgical lighting and laminar airflow is poorly understood. We undertook an experiment to identify any effect contemporary surgical lights have on laminar flow and recommend practical strategies to limit any negative effects. MATERIALS AND METHODS: Neutrally buoyant bubbles were introduced into the surgical field of a simulated setup for a routine total knee arthroplasty in a laminar flow theatre. Patterns of airflow were observed and the number of bubbles remaining above the surgical field over time identified. Five different lighting configurations were assessed. Data were analysed using simple linear regression after logarithmic transformation. RESULTS: In the absence of surgical lights, laminar airflow was observed, bubbles were cleared rapidly and did not accumulate. If lights were placed above the surgical field laminar airflow was abolished and bubbles rose from the surgical field to the lights then circulated back to the surgical field. The value of the decay parameter (slope) of the two setups differed significantly; no light (b = -1.589) versus one light (b = -0.1273, p < 0.001). Two lights touching (b = -0.1191) above the surgical field had a similar effect to that of a single light (p = 0. 2719). Two lights positioned by arms outstretched had a similar effect (b = -0.1204) to two lights touching (p = 0.998) and one light (p = 0.444). When lights were separated widely (160 cm), laminar airflow was observed but the rate of clearance of the bubbles remained slower (b = -1.1165) than with no lights present (p = 0.004). CONCLUSION: Surgical lights have a significantly negative effect on laminar airflow. Lights should be positioned as far away as practicable from the surgical field to limit this effect. Cite this article: Bone Joint J 2017;99-B:1061-6.

Myxofibrosarcoma of the extremity and trunk: a multidisciplinary approach leads to good local rates of LOCAL control.

AIMS: Myxofibrosarcomas (MFSs) are malignant soft-tissue sarcomas characteristically presenting as painless slowly growing masses in the extremities. Locally infiltrative growth means that the risk of local recurrence is high. We reviewed our experience to make recommendations about resection strategies and the role of the multidisciplinary team in the management of these tumours. PATIENTS AND METHODS: Patients with a primary or recurrent MFS who were treated surgically in our unit between 1997 and 2012 were included in the study. Clinical records and imaging were reviewed. A total of 50 patients with a median age of 68.4 years (interquartile range 61.6 to 81.8) were included. There were 35 men; 49 underwent surgery in our unit. RESULTS: The lower limb was the most common site (32/50, 64%). The mean size of the tumours was 8.95 cm (1.5 to 27.0); 26 (52%) were French Fédération Nationale des Centres de Lutte Contre le Cancer grade III. A total of 21 (43%) had positive margins after the initial excision; 11 underwent further excision. Histology showed microscopic spread of up to 29 mm beyond macroscopic tumour. Local recurrence occurred in seven patients (14%) at a mean of 21 months (3 to 33) and 15 (30%) developed metastases at a mean of 17 months (3 to 30) post-operatively. CONCLUSION: High rates of positive margins and the need for further excision makes this tumour particularly suited to management by multidisciplinary surgical teams. Microscopic tumour can be present up to 29 mm from the macroscopic tumour in fascially-based tumours. Cite this article: Bone Joint J 2016;98-B:1682-8.

Long-term in vitro maintenance of clonal abundance and leukaemia-initiating potential in acute lymphoblastic leukaemia.

Lack of suitable in vitro culture conditions for primary acute lymphoblastic leukaemia (ALL) cells severely impairs their experimental accessibility and the testing of new drugs on cell material reflecting clonal heterogeneity in patients. We show that Nestin-positive human mesenchymal stem cells (MSCs) support expansion of a range of biologically and clinically distinct patient-derived ALL samples. Adherent ALL cells showed an increased accumulation in the S phase of the cell cycle and diminished apoptosis when compared with cells in the suspension fraction. Moreover, surface expression of adhesion molecules CD34, CDH2 and CD10 increased several fold. Approximately 20% of the ALL cells were in G0 phase of the cell cycle, suggesting that MSCs may support quiescent ALL cells. Cellular barcoding demonstrated long-term preservation of clonal abundance. Expansion of ALL cells for >3 months compromised neither feeder dependence nor cancer initiating ability as judged by their engraftment potential in immunocompromised mice. Finally, we demonstrate the suitability of this co-culture approach for the investigation of drug combinations with luciferase-expressing primograft ALL cells. Taken together, we have developed a preclinical platform with patient-derived material that will facilitate the development of clinically effective combination therapies for ALL.

Impact of Weekend Physiotherapy Service on the Cost Effectiveness of Elective Orthopaedic Hip and Knee Arthroplasty.

We performed a prospective correlational study to evaluate the efficiency and cost effectiveness of weekend physiotherapy in accelerating rehabilitation, reducing hospital stay as well as hospital costs for joint arthroplasty patients in a busy Scottish district general hospital. Patients that underwent elective hip (470) and knee (321) arthroplasty were analysed over a 12 month period. A four month period with weekend physiotherapy provision was arranged to ascertain its effectiveness on the length of stay and the achievement of set physiotherapy milestones. Data collected included length of stay and progression in a defined set of physiotherapy milestones. The relationship between time to discharge, mobilisation with sticks, straight leg raise, 90º knee flexion and cost effectiveness of service were used to determine the correlation, and analysis of the interactions of these factors separately. Our Outcome data demonstrate a statistical significance for the time to mobilisation with two sticks for hip (p=0.0030) and knee (p= 0.0037) arthroplasty patients. There was a trend towards earlier discharge times for all patients receiving weekend physiotherapy, but this was not statistically significant. We conclude that the provision of a continuous programme of weekend physiotherapy for all arthroplasty patients has the potential benefit of a quicker rehabilitation that would results in a cost saving.

The orthopaedic research scene and strategies to improve it.

Trauma and orthopaedics is the largest of the surgical specialties and yet attracts a disproportionately small fraction of available national and international funding for health research. With the burden of musculoskeletal disease increasing, high-quality research is required to improve the evidence base for orthopaedic practice. Using the current research landscape in the United Kingdom as an example, but also addressing the international perspective, we highlight the issues surrounding poor levels of research funding in trauma and orthopaedics and indicate avenues for improving the impact and success of surgical musculoskeletal research.

Consultant and trainee attitudes towards supervision of operative procedures in the UK and Ireland.

The e-logbook is used to monitor progression through training and to assess training within teaching units. We document consultant and trainee opinions with regards to supervision status, and to inform guidelines for trainees and trainers using the e-logbook. A questionnaire was sent to consultants and trainees in the UK and Ireland. Eight theatre scenarios were described and respondents were asked to state what they felt was the appropriate supervision status for the trainee. Significantly more consultants in the UK use the e-logbook than those based in Ireland (58.5%:14.5%). There were differences in consensus response to the scenarios between consultants and trainees, and between Irish and UK based surgeons. We have documented the opinions of consultants and trainees from across the UK and Ireland with regards to supervision status for trainees under certain theatre situations. This information should support formal guidelines for all users of the logbook.

Improving the peer review process in orthopaedic journals.

The peer review process for the evaluation of manuscripts for publication needs to be better understood by the orthopaedic community. Improving the degree of transparency surrounding the review process and educating orthopaedic surgeons on how to improve their manuscripts for submission will help improve both the review procedure and resultant feedback, with an increase in the quality of the subsequent publications. This article seeks to clarify the peer review process and suggest simple ways in which the quality of submissions can be improved to maximise publication success. Cite this article: Bone Joint Res 2013;2:245-7.

Identification of the pathogenic pathways in osteoarthritic hip cartilage: commonality and discord between hip and knee OA.

OBJECTIVE: To define for the first time the transcriptomes of normal and end-stage osteoarthritis (OA) hip cartilage. MATERIALS AND METHODS: RNA was isolated from cartilage within 2h of joint replacement surgery. Gene expression was analyzed using Agilent GeneSpring GX 11 following hybridization to Illumina Human HT-12 V3 microarrays. Real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to validate the expression of six genes identified by microarray as differentially expressed. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) were used to investigate enriched functions or canonical pathways amongst differentially expressed genes respectively. RESULTS: In total we identified 998 differentially expressed genes (fold change ≥ ±1.5, P-value ≤ 0.01) between neck of femur fracture (NOF) (n = 10) and OA hip (n = 9) patient cartilage. These differentially expressed genes were enriched within 71 canonical pathways. A comparison between a comparable knee dataset(20) only identified 229 genes similarly differentially expressed although remarkably 34 canonical pathways overlapped between experiments. CONCLUSIONS: This study is the first to report a comprehensive gene expression analysis of human hip OA cartilage compared to control (NOF) cartilage at the whole-genome level. Our differential gene expression dataset shows excellent correlation with similar defined studies using comparable tissue but reveals discord between hip and knee OA at the individual gene status but with commonality with regards the molecular pathways involved.