Controversies in orthopaedic oncology.

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting.

Challenges and solutions to system-wide use of precision oncology as the standard of care paradigm.

The personalised oncology paradigm remains challenging to deliver despite technological advances in genomics-based identification of actionable variants combined with the increasing focus of drug development on these specific targets. To ensure we continue to build concerted momentum to improve outcomes across all cancer types, financial, technological and operational barriers need to be addressed. For example, complete integration and certification of the 'molecular tumour board' into 'standard of care' ensures a unified clinical decision pathway that both counteracts fragmentation and is the cornerstone of evidence-based delivery inside and outside of a research setting. Generally, integrated delivery has been restricted to specific (common) cancer types either within major cancer centres or small regional networks. Here, we focus on solutions in real-world integration of genomics, pathology, surgery, oncological treatments, data from clinical source systems and analysis of whole-body imaging as digital data that can facilitate cost-effectiveness analysis, clinical trial recruitment, and outcome assessment. This urgent imperative for cancer also extends across the early diagnosis and adjuvant treatment interventions, individualised cancer vaccines, immune cell therapies, personalised synthetic lethal therapeutics and cancer screening and prevention. Oncology care systems worldwide require proactive step-changes in solutions that include inter-operative digital working that can solve patient centred challenges to ensure inclusive, quality, sustainable, fair and cost-effective adoption and efficient delivery. Here we highlight workforce, technical, clinical, regulatory and economic challenges that prevent the implementation of precision oncology at scale, and offer a systematic roadmap of integrated solutions for standard of care based on minimal essential digital tools. These include unified decision support tools, quality control, data flows within an ethical and legal data framework, training and certification, monitoring and feedback. Bridging the technical, operational, regulatory and economic gaps demands the joint actions from public and industry stakeholders across national and global boundaries.

The incidence, risk factors and outcomes of wound complications after preoperative radiotherapy and surgery for high grade extremity soft tissue sarcomas: A 14-year retrospective study.

OBJECTIVE: The aim of this study was to analyze the wound complication (WC) rate and to determine the risk factors for WC in patients with soft tissue sarcoma treated with preoperative radiotherapy followed by surgical resection. METHODS: Using the database of Oxford University Hospital (OUH) we retrospectively studied 126 cases of soft tissue sarcomas treated with preoperative radiotherapy and surgery between 2007 and 2021. WC were defined as minor wound complication (MiWC) not requiring surgical intervention or major wound complication (MaWC) if they received a secondary surgical intervention. Univariate and multiple regression analyses were performed using frequency of WC and MaWC as a dependent variable. RESULTS: The incidence of WC and MaWC was 43.7% (55/126) and 19% (24/126). Age (OR:1.03, 95%CI: 1.00-1.06, p = 0.016), tumor size (OR:1.11, 95%CI:1.01-1.21, p = 0.027) and tumor site namely proximal lower limb vs upper limb (OR:10.87, 95%CI 1.15-103.03, p = 0.038) were risk factors on multivariate analysis. In nested case control analysis, the incidence of MaWC was 43.6% (24/55), the mean recovery time is 143 days in patients with MaWC. Smoking increases the risk for MaWC (OR:8.32, 95%CI:1.36-49.99, p = 0.022). The time interval between surgery and wound complication reduces the risk for MaWC (OR:0.91, 95%CI:0.84-0.99, p = 0.028) in multivariate analysis. CONCLUSIONS: Age, tumor site and size are risk factors for WC requiring preoperative radiotherapy. Smoking and the time interval between surgery and wound complication are risk factors for MaWC as compared with MiWC. MaWC rate (19%) are comparable to those in postoperative radiotherapy and surgery alone.

Nomogram Predicting the Risk of Postoperative Major Wound Complication in Soft Tissue Sarcoma of the Trunk and Extremities after Preoperative Radiotherapy.

Preoperative radiotherapy increases the risk of postoperative wound complication in the treatment of soft tissue sarcoma (STS). This study aims to develop a nomogram for predicting major wound complication (MaWC) after surgery. Using the Oxford University Hospital (OUH) database, a total of 126 STS patients treated with preoperative radiotherapy and surgical resection between 2007 and 2021 were retrospectively reviewed. MaWC was defined as a wound complication that required secondary surgical intervention. Univariate and multivariate regression analyses on the association between MaWC and risk factors were performed. A nomogram was formulated and the areas under the Receiver Operating Characteristic Curves (AUC) were adopted to measure the predictive value of MaWC. A decision curve analysis (DCA) determined the model with the best discriminative ability. The incidence of MaWC was 19%. Age, tumour size, diabetes mellitus and metastasis at presentation were associated with MaWC in the univariate analysis. Age, tumour size, and metastasis at presentation were independent risk factors in the multivariate analysis. The sensitivity and specificity of the predictive model is 0.90 and 0.76, respectively. The AUC value was 0.86. The nomogram constructed in the study effectively predicts the risk of MaWC after preoperative radiotherapy and surgery for STS patients.

'Face time' for the first time: Video communication between relatives and junior doctors in the COVID-19 pandemic.

Working on a COVID-19 ward presents a number of challenges to staff, with communication between families, patients and staff being highlighted as a key challenge. Novel methods are needed to overcome the barriers presented by COVID-19, with many turning to technology to offer solutions. Recognising these challenges as an area for improvement on our own ward, we sought to introduce new methods of communication to improve patient, relative and staff understanding and wellbeing. Through our own experiences and a discussion of the literature on this topic, we have identified some key themes which we believe can assist in the development of communication strategies in the developing pandemic.

To scan or not to scan - D-dimers and computed tomography pulmonary angiography in the era of COVID-19.

The COVID-19 pandemic has had many ramifications on healthcare delivery and practice. As part of this, utilising biomarkers to risk stratify patients has become increasingly popular. During the COVID-19 pandemic the use of D-dimer has increased due to the evidence of COVID-19 induced thrombo-embolic disease. We evaluated the use of D-dimer on all hospital admissions during the peak of the pandemic and evaluated its sensitivity in diagnosing pulmonary embolic disease (PE). Patients without COVID-19 infection were as likely to have evidence of PE as their COVID-positive counterparts. However, the sensitivity of a D-dimer was higher in COVID-positive patients at a lower D-dimer level (>1,500 µg/L, sensitivity 81%, specificity 70%) than in those without clinical, immunological or radiological evidence of COVID-19 infection (D-dimer >2,000 µg/L, sensitivity 80%, specificity 76%). These data suggest higher D-dimer thresholds should be considered for the exclusion of pulmonary emboli.

Design and establishment of a cancer registry: a literature review.

BACKGROUND: Establishment of a cancer registry is a complex process that requires substantial resources and careful planning. There are numerous resources available to provide guidance for this, which include guidelines and frameworks of varying quality. It is the authors' goal to identify evidence-based recommendations within the literature to help guide the process of designing a new registry with optimal efficiency, workability and data use. The objective of this study is to examine the primary literature for evidence-based recommendations on how to design and establish a cancer registry, with a focus on literature which analyses the performance and usefulness of already established registries or guidelines. METHODS: An electronic search was completed in MEDLINE, CINAHL, EMCARE, SCOPUS and the Cochrane Database of Systematic Reviews. Recommendations were extracted from the identified articles and collated as themes. RESULTS: Nine articles of varying quality were included in the review. Recommendations obtained from the literature included broad themes of the importance of clinician involvement, establishment of clear data definitions, number of variables used, inbuilt strategies to improve quality and completeness of data, considerations of costs, an 'opt-out' strategy for ethics and privacy and flexibility of the system. CONCLUSION: This review concluded that there is a large gap in the primary literature for evidence-based recommendations on the design and establishment of cancer registries. The included articles established a small scope of relevant themes, which were largely non-specific. This area of deficiency provides an opportunity for future research, which would further strengthen the quality of current or new guidelines in cancer registry establishment.

Influence of vagal control on sex-related differences in left ventricular mechanics and hemodynamics.

Left ventricular (LV) twist mechanics differ between men and women during acute physiological stress, which may be partly mediated by sex differences in autonomic control. While men appear to have greater adrenergic control of LV twist, the potential contribution of vagal modulation to sex differences in LV twist remains unknown. Therefore, the present study examined the role of vagal control on sex differences in LV twist during graded lower body negative pressure (LBNP) and supine cycling. On two separate visits, LV mechanics were assessed using two-dimensional speckle-tracking echocardiography in 18 men (22 ± 2 yr) and 17 women (21 ± 4 yr) during -40- and -60-mmHg LBNP and 25% and 50% of peak supine cycling workload with and without glycopyrrolate (vagal blockade). LV twist was not different at baseline but was greater in women during -60 mmHg in both control (women: 16.0 ± 3.4° and men: 12.9 ± 2.3°, P = 0.004) and glycopyrrolate trials (women: 17.7 ± 5.9° and men: 13.9 ± 3.3°, P < 0.001) due to greater apical rotation during control (women: 11.9 ± 3.6° and men: 7.8 ± 1.5°, P < 0.001) and glycopyrrolate (women: 11.6 ± 4.9° and men: 7.1 ± 3.6°, P = 0.009). These sex differences in LV twist consistently coincided with a greater LV sphericity index (i.e., ellipsoid geometry) in women compared with men. In contrast, LV twist did not differ between the sexes during exercise with or without glycopyrrolate. In conclusion, women have augmented LV twist compared with men during large reductions to preload, even during vagal blockade. As such, differences in vagal control do not appear to contribute to sex differences in the LV twist responses to physiological stress, but they may be related to differences in ventricular geometry. NEW & NOTEWORTHY This is the first study to specifically examine the role of vagal autonomic control on sex-related differences in left ventricular (LV) mechanics. Contrary to our hypothesis, vagal control does not appear to primarily determine sex differences in LV mechanical or hemodynamic responses to acute physiological stress. Instead, differences in LV geometry may be a more important contributor to sex differences in LV mechanics.

An unusual presentation of metastatic melanoma in the shoulder.

A 72-year-old lady underwent a Copeland hemiarthoplasty of the shoulder for rotator cuff arthropathy with a good functional outcome. Her past medical history included previous management of a malignant melanoma. Several years following arthroplasty surgery, she acutely developed signs and symptoms of prosthetic joint infection. The present case report describes the metastatic spread of malignant melanoma mimicking that of prosthetic sepsis.

Quantification of the heterogeneity of prognostic cellular biomarkers in ewing sarcoma using automated image and random survival forest analysis.

Driven by genomic somatic variation, tumour tissues are typically heterogeneous, yet unbiased quantitative methods are rarely used to analyse heterogeneity at the protein level. Motivated by this problem, we developed automated image segmentation of images of multiple biomarkers in Ewing sarcoma to generate distributions of biomarkers between and within tumour cells. We further integrate high dimensional data with patient clinical outcomes utilising random survival forest (RSF) machine learning. Using material from cohorts of genetically diagnosed Ewing sarcoma with EWSR1 chromosomal translocations, confocal images of tissue microarrays were segmented with level sets and watershed algorithms. Each cell nucleus and cytoplasm were identified in relation to DAPI and CD99, respectively, and protein biomarkers (e.g. Ki67, pS6, Foxo3a, EGR1, MAPK) localised relative to nuclear and cytoplasmic regions of each cell in order to generate image feature distributions. The image distribution features were analysed with RSF in relation to known overall patient survival from three separate cohorts (185 informative cases). Variation in pre-analytical processing resulted in elimination of a high number of non-informative images that had poor DAPI localisation or biomarker preservation (67 cases, 36%). The distribution of image features for biomarkers in the remaining high quality material (118 cases, 104 features per case) were analysed by RSF with feature selection, and performance assessed using internal cross-validation, rather than a separate validation cohort. A prognostic classifier for Ewing sarcoma with low cross-validation error rates (0.36) was comprised of multiple features, including the Ki67 proliferative marker and a sub-population of cells with low cytoplasmic/nuclear ratio of CD99. Through elimination of bias, the evaluation of high-dimensionality biomarker distribution within cell populations of a tumour using random forest analysis in quality controlled tumour material could be achieved. Such an automated and integrated methodology has potential application in the identification of prognostic classifiers based on tumour cell heterogeneity.

Maus-tratos contra idosos: atualização dos estudos brasileiros / Abuse against elderly: uptade of the brazilian studies

O envelhecimento populacional trouxe consigo temas emergentes como os maus-tratos contra idosos, que em decorrência de seu caráter biopsicossocial, aspira por investigações mais profundas e soluções urgentes. A pouca disseminação das informações sobre maus-tratos aos idosos contribui para a perpetuação da violência e, frente a este cenário, o presente estudo objetivou realizar uma atualização ampla da literatura através da caracterização dos tipos de violência, do perfil do agressor e vítima, principais locais de ocorrência, indicadores, epidemiologia, instrumentos de detecção e propostas de resolução com base nos dados dos últimos anos de pesquisa científica (2001 a 2008). No desenvolvimento desta produção, nos deparamos com a escassez de dados epidemiológicos atualizados que expressem a verdadeira dimensão estatística do problema, além da ausência de exploração científica minuciosa das diversas faces da violência contra o idoso. Sendo assim, este possui, também, o intuito de enfatizar a necessidade de futuras produções científicas abordando a presente questão visto que, por meio do maior entendimento e desenvolvimento de pesquisas acerca do assunto, serão ampliadas as condições para prevenção, autuação e condutas adequadas, tanto por parte de órgãos e profissionais, que sejam ou não da área da saúde, quanto pelos próprios idosos que necessitam de maior respaldo de orientação.