Surgery (RMH) - Research Publications

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    A phase 1b open label study of sodium selenate as a disease‐modifying treatment for behavioural variant fronto‐temporal dementia
    Vivash, LE ; Malpas, CB ; Hovens, CM ; Velakoulis, D ; O’Brien, T (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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    Extracellular vesicular lipids as biomarkers for the diagnosis of Alzheimer’s disease
    Su, H ; Rustam, YH ; Masters, CL ; Makalic, E ; McLean, C ; Hill, AF ; Barnham, KJ ; Reid, GE ; Vella, LJ (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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    Active surveillance versus enzalutamide for low-risk prostate cancer - was it really a trial we needed?
    Williams, ISC ; Perera, S ; Murphy, DG ; Corcoran, NM ; Bolton, DM ; Lawrentschuk, N (WILEY, 2022-11)
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    Low-grade prostate cancer should still be labelled cancer Comment
    Iczkowski, KA ; Molina, M ; Egevad, L ; Bostwick, DG ; van Leenders, GJLH ; La Rosa, FG ; van der Kwast, T ; Berney, DM ; Evans, AJ ; Wheeler, TM ; Leite, KRM ; Samaratunga, H ; Srigley, J ; Varma, M ; Tsuzuki, T ; Lucia, MS ; Crawford, ED ; Harris, RG ; Stricker, P ; Lawrentschuk, N ; Woo, HH ; Fleshner, NE ; Shore, ND ; Yaxley, J ; Bratt, O ; Wiklund, P ; Roberts, M ; Cheng, L ; Delahunt, B (WILEY, 2022-12)
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    Prostate-specific membrane antigen positron emission tomography/computed tomography funding grants free access to superior staging for Australian men with prostate cancer Comment
    O'Brien, JS ; McVey, A ; Kelly, BD ; Jenjitranant, P ; Buteau, J ; Hofman, MS ; Kasivisvanithan, V ; Eapen, R ; Moon, D ; Murphy, DG ; Lawrentschuk, N (WILEY, 2022-11)
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    Renal transplant injury at caesarean delivery: A cautionary tale and a plan for the future
    McCormick, CA ; de Crespigny, PC ; Suh, N ; Unterscheider, J (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.
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    Two decades of FDG-PET/CT in seminoma: exploring its role in diagnosis, surveillance and follow-up
    Conduit, C ; Koh, TT ; Hofman, MS ; Toner, GC ; Goad, J ; Lawrentschuk, N ; Tai, K-H ; Lewin, JH ; Tran, B (BMC, 2022-10-08)
    BACKGROUND: Survivors of testicular cancer may experience long-term morbidity following treatment. There is an unmet need to investigate techniques that can differentiate individuals who need additional therapy from those who do not. 2-18fluoro-deoxy-D-glucose (FDG) positron emission tomography (PET) with computerised tomography (CT) may be helpful in select settings and may be used outside of current evidence-based recommendations in real-world practice. METHODS: A institutional FDG-PET/CT database of scans performed between 2000 and 2020 for adults with testicular seminoma was interrogated. Endpoints of interest included the positive (PPV) and negative (NPV) predictive value of FDG-PET/CT for identifying active seminoma (defined by progressive radiology, response to treatment or biopsy); or no active seminoma within 24-months for patients with stage 1 and advanced seminoma. An exploratory analysis examining predictive role of SUVmax was also performed. RESULTS: 249 patients met eligibility criteria for the analysis, including 184 patients with stage 1 and 77 patients with advanced testicular seminoma. Of 193 FDG-PET/CT performed in stage 1 seminoma with available follow-up data, 79 were performed during active surveillance. 18 (23%) of these were positive, all of which had confirmed recurrent seminoma (PPV 100%). Of 45 negative FDG-PET/CT during active surveillance, 4 recurrences developed corresponding to a NPV 91%. When clinical suspicion precipitated FDG-PET/CT (n = 36): PPV 100%, NPV 86%. Of 145 FDG-PET/CT in advanced seminoma with available follow-up data, 25 (17%) were performed at baseline (within 2 months of diagnosis), 70 (48%) post-treatment for evaluation of treatment response and 50 (34%) during follow-up following prior curative treatment. 10 (14%) post-treatment FDG-PET/CT were positive corresponding to a PPV 60%. Of 46 negative FDG-PET/CT, 5 recurrences occurred (NPV 89%). During follow-up after prior curative treatment, 24 (50%) FDG-PET/CT were positive corresponding to a PPV 83%; of 20 negative FDG-PET/CT, 1 recurrence occurred, NPV 95%. When clinical suspicion indicated FDG-PET/CT (n = 36): PPV 100%, NPV 94%. CONCLUSION: FDG-PET/CT offers high PPV for identifying seminoma and accurately predicts non-recurrence across a clinically relevant 24-months. Notably, FDG-PET/CT may prevent unnecessary treatment in 45% of patients undergoing investigation for clinical suspicion of recurrence during follow-up of advanced seminoma. The use of FDG-PET/CT in selected patients now, may help prevent unnecessary treatment of people with testicular seminoma.