Surgical smoke: how an issue in healthcare fits a planetary health framework.

AIM: The smoke generated from electrocautery machines may be harmful to health. Healthcare in general, and surgery in particular, has a large environmental footprint. The aims of this study were to discover what healthcare workers thought about the problem of electrocautery smoke, the idea of a surgical smoke-free policy, and to formulate ideas on how the matter could be approached in an environmentally and socially responsible way. METHOD: Operating room personnel in a tertiary referral hospital were invited to complete a survey about electrocautery smoke: perceived risks, current exposure, and measures to minimise exposure. Quantitative data were analysed in a generalised linear model, and qualitative data by reflexive thematic analysis within a constructivist theoretical framework. RESULTS: The survey response rate was 463/1234 (38%). Most supported a smoke-free policy (89%). Support for a policy was positively correlated with the perceived risk of electrocautery smoke (p<0.001. Support was lower amongst males (p<0.05). Themes from the qualitative analysis developed around nature, society and technology. A framework was developed consisting of earth and its ecosystems, human health, governance, economics, society, and the interconnected of these systems. CONCLUSION: Although smoke-free policies form part of the solution to electrocautery smoke, they are not the whole solution. Healthcare issues, in this case the issue of electrocautery smoke, could be tackled within a planetary health healthcare framework, promoting a systems approach. Applicability of the framework requires confirmation by further research.

PDGF-R inhibition induces glioblastoma cell differentiation via DUSP1/p38MAPK signalling.

Glioblastoma (GBM) is the most common and fatal primary brain tumour in adults. Considering that resistance to current therapies leads to limited response in patients, new therapeutic options are urgently needed. In recent years, differentiation therapy has been proposed as an alternative for GBM treatment, with the aim of bringing cancer cells into a post-mitotic/differentiated state, ultimately limiting tumour growth. As an integral component of cancer development and regulation of differentiation processes, kinases are potential targets of differentiation therapies. The present study describes how the screening of a panel of kinase inhibitors (KIs) identified PDGF-Rα/ß inhibitor CP-673451 as a potential differentiation agent in GBM. We show that targeting PDGF-Rα/ß with CP-673451 in vitro triggers outgrowth of neurite-like processes in GBM cell lines and GBM stem cells (GSCs), suggesting differentiation into neural-like cells, while reducing proliferation and invasion in 3D hyaluronic acid hydrogels. In addition, we report that treatment with CP-673451 improves the anti-tumour effects of temozolomide in vivo using a subcutaneous xenograft mouse model. RNA sequencing and follow-up proteomic analysis revealed that upregulation of phosphatase DUSP1 and consecutive downregulation of phosphorylated-p38MAPK can underlie the pro-differentiation effect of CP-673451 on GBM cells. Overall, the present study identifies a potential novel therapeutic option that could benefit GBM patients in the future, through differentiation of residual GSCs post-surgery, with the aim to limit recurrence and improve quality of life.

Bilateral Wilms' tumour: An international comparison of treatments and outcomes.

INTRODUCTION: Wilms' tumour is the most common childhood renal malignancy, with 5-10% of cases presenting bilaterally 1. However, there is currently no consensus between centres on optimal management of bilateral Wilms' tumours. This is an international multi-centre case series comparing management and outcomes of bilateral Wilms' tumours between low-income centres (LIC) and high-income centres (HIC). METHODS: Patients with bilateral Wilms' tumour were identified from four tertiary referral centres internationally. Data were collected on baseline characteristics, disease status, treatment used and clinical outcomes. Results were compared between individual centres as well as between groups of low-income centres (LIC) and high-income centres (HIC). RESULTS: Data were collected for forty patients. Most patients received preoperative chemotherapy (n = 38, 95%). The most common surgical procedures were bilateral nephron-sparing surgery (n = 10, 25%) and nephrectomy with partial nephrectomy (n = 20, 50%). Ten-year survival after treatment was as follows: LIC's n = 13 (65%); HIC's n = 20 (100%) (p = 0.01). DISCUSSION: Ten-year survival was significantly higher in HIC's. Our results show this may be caused by patient factors such as later presentation with more advanced disease in low-income centres. This comparative case series is the first to report on a large number of cases from multiple international centres, and to compare key outcomes.

Cell-derived extracellular vesicles can be used as a biomarker reservoir for glioblastoma tumor subtyping.

Glioblastoma (GBM) is one of the most aggressive solid tumors for which treatment options and biomarkers are limited. Small extracellular vesicles (sEVs) produced by both GBM and stromal cells are central in the inter-cellular communication that is taking place in the tumor bulk. As tumor sEVs are accessible in biofluids, recent reports have suggested that sEVs contain valuable biomarkers for GBM patient diagnosis and follow-up. The aim of the current study was to describe the protein content of sEVs produced by different GBM cell lines and patient-derived stem cells. Our results reveal that the content of the sEVs mirrors the phenotypic signature of the respective GBM cells, leading to the description of potential informative sEV-associated biomarkers for GBM subtyping, such as CD44. Overall, these data could assist future GBM in vitro studies and provide insights for the development of new diagnostic and therapeutic methods as well as personalized treatment strategies.