Surgery (RMH) - Research Publications
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ItemIL-10 in glioma(Springer Nature [academic journals on nature.com], 2021-08-04)The prognosis for patients with glioblastoma (GBM), the most common and malignant type of primary brain tumour, is very poor, despite current standard treatments such as surgery, radiotherapy and chemotherapy. Moreover, the immunosuppressive tumour microenvironment hinders the development of effective immunotherapies for GBM. Cytokines such as interleukin-10 (IL-10) play a major role in modulating the activity of infiltrating immune cells and tumour cells in GBM, predominantly conferring an immunosuppressive action; however, in some circumstances, IL-10 can have an immunostimulatory effect. Elucidating the function of IL-10 in GBM is necessary to better strategise and improve the efficacy of immunotherapy. This review discusses the immunostimulatory and immunosuppressive roles of IL-10 in the GBM tumour microenvironment while considering IL-10-targeted treatment strategies. The molecular mechanisms that underlie the expression of IL-10 in various cell types are also outlined, and how this resulting information might provide an avenue for the improvement of immunotherapy in GBM is explored.
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ItemNo Preview AvailableA phase 1b open label study of sodium selenate as a disease‐modifying treatment for behavioural variant fronto‐temporal dementia(Wiley, 2021-12)Abstract Background Hyperphosphorylated tau is a pathological hallmark of ∼45% of behavioural variant frontotemporal dementia (bvFTD). For this reason, hyperphosphorylated tau represents a promising treatment target for this population. Sodium selenate stimulates the PP2A enzyme, which directly dephosphorylates hyperphosphorylated tau. This Phase 1b, open‐labelled, study investigated sodium selenate as a disease‐modifying treatment for patients with bvFTD. Method Twelve patients with bvFTD were treated with sodium selenate (15mg tds) for twelve months. Participants underwent a cognitive and behavioural battery, MRI, lumbar puncture and safety assessments at screening, baseline, and at regular intervals following treatment commencement. Adverse events were monitored via diary cards between clinic visits. Result All 12 patients completed the study. Safety analysis found that sodium selenate was safe and well tolerated, with no study withdrawals. Commonly reported mild‐moderate adverse events were nail changes (n=6), muscles aches (n=4), headache, fatigue, hair loss and fall (n=3). Five patients reduced their dose to 10mg tds due to adverse events. No treatment‐related serious adverse events occurred. Analyses of efficacy data are ongoing. A mixed‐effects analysis showed an overall small but significant decline on cognition and behaviour, including total NUCOG score (b=‐0.18, 95% CI=‐0.28–0.08) Cambridge Behavioural Index (b=0.32, 95% CI=0.18‐0.46) and Carer Burden Scale score (b=0.1, 95% CI = 0.02‐0.18). Percentage change in whole‐brain volume from baseline to week 52 ranged from ‐0.26% to ‐6.51% (n=7 >‐1.8%, n=4 <‐1.8%). Plasma tau levels (n=6) did not change from baseline (3.73±0.26pg/mL) to week 52 (4.66±0.24pg/mL). CSF tau also showed no change from baseline (167.8±11.2pg/mL) to week 52 (156.1±2.49pg/mL). Although not significant, the directional changes are in line with the proposed mechanism of sodium selenate. Exploratory analyses of “responders” (brain volume change >‐1.8%, n=7) found no change in NUCOG total score (b=‐0.03, 95% CI ‐0.14‐0.07) or CBS score (b=‐0.05, 95% CI ‐0.04‐0.13) over time. Conclusion Sodium selenate is safe and well tolerated in patients with bvFTD. Exploratory analyses indicate it may reduce atrophy and halt cognitive decline in a subset of bvFTD patients. Sodium selenate should be further investigated as a potential treatment for bvFTD, and biomarkers to identify the subset of “responder” patients explored.
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ItemNo Preview AvailableExtracellular vesicular lipids as biomarkers for the diagnosis of Alzheimer’s disease(Wiley, 2021-12-31)An increasing number of studies have revealed that dysregulated lipid homeostasis is associated with the pathological processes that lead to Alzheimer’s disease (AD). If changes in key lipid species could be detected in the periphery, it would advance our understanding of the disease and facilitate biomarker discovery. Global lipidomic profiling of sera/blood however has proved challenging with limited disease or tissue specificity. Small extracellular vesicles (EV) in the central nervous system, can pass the blood-brain barrier and enter the periphery, carrying a subset of lipids that could reflect lipid homeostasis in brain. This makes EVs uniquely suited for peripheral biomarker exploration.
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ItemLow-grade prostate cancer should still be labelled cancer Comment(WILEY, 2022-12)
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ItemRenal transplant injury at caesarean delivery: A cautionary tale and a plan for the future(WILEY, 2022-04)Pregnancy following renal transplantation is increasingly common. Overall pregnancy outcomes are favourable; however, specific transplant-related risks do exist. In particular, the risk of caesarean delivery is much higher in renal transplant recipients when compared to the general obstetric population. This is owing to the necessity for preterm delivery in cases of severe and early-onset pre-eclampsia and/or fetal growth restriction. We describe two recent cases of renal transplant injury at caesarean delivery at our institution, a tertiary/quaternary obstetric service, which highlight the potential operative risks associated with abdominal surgery. We propose a standardised approach in the care of transplant recipients undergoing caesarean delivery which is aimed at minimising harm and increasing patient safety.