Surgery (RMH) - Research Publications

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    "Iodide mumps" after angioplasty
    Chuen, J ; Roberts, N ; Lovelock, M ; King, B ; Beiles, B ; Frydman, G (Elsevier, 2000-02-01)
    Vascular surgeons are increasingly performing endo- vascular fluoroscopy-guided procedures. We report a rare complication of radiographic contrast exposure (iodide-induced sialadenitis or “iodide mumps”), which has significance in the postoperative observation and management of patients after these procedures.
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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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    Vascular endothelial growth factor d is dispensable for development of the lymphatic system
    Baldwin, ME ; Halford, MA ; Roufail, S ; Williams, RA ; Hibbs, ML ; Grail, D ; Kubo, H ; Stacker, SA ; Achen, MG (AMER SOC MICROBIOLOGY, 2005-03)
    Vascular endothelial growth factor receptor 3 (Vegfr-3) is a tyrosine kinase that is expressed on the lymphatic endothelium and that signals for the growth of the lymphatic vessels (lymphangiogenesis). Vegf-d, a secreted glycoprotein, is one of two known activating ligands for Vegfr-3, the other being Vegf-c. Vegf-d stimulates lymphangiogenesis in tissues and tumors; however, its role in embryonic development was previously unknown. Here we report the generation and analysis of mutant mice deficient for Vegf-d. Vegf-d-deficient mice were healthy and fertile, had normal body mass, and displayed no pathologic changes consistent with a defect in lymphatic function. The lungs, sites of strong Vegf-d gene expression during embryogenesis in wild-type mice, were normal in Vegf-d-deficient mice with respect to tissue mass and morphology, except that the abundance of the lymphatics adjacent to bronchioles was slightly reduced. Dye uptake experiments indicated that large lymphatics under the skin were present in normal locations and were functional. Smaller dermal lymphatics were similar in number, location, and function to those in wild-type controls. The lack of a profound lymphatic phenotype in Vegf-d-deficient mice suggests that Vegf-d does not play a major role in lymphatic development or that Vegf-c or another, as-yet-unknown activating Vegfr-3 ligand can compensate for Vegf-d during development.
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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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