Surgery (RMH) - Research Publications
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ItemEpidemiology of pregnant patients with major trauma in Victoria(WILEY, 2021-06-23)OBJECTIVE: Trauma is one of the most common contributors to maternal and foetal morbidity and mortality. The aim of the present study was to describe the characteristics and outcomes of major trauma in pregnant patients using a population-based registry. METHODS: Registry-based study using data from the Victorian State Trauma Registry (VSTR), a population-based database of all hospitalised major trauma (death due to injury, Injury Severity Score [ISS] ≥12, admission to an intensive care unit [ICU] for more than 24 h and requiring mechanical ventilation for at least part of their ICU stay or urgent surgery) in Victoria, Australia, from 1 July 2007 to 30 June 2019. Pregnant patients with major trauma were identified on the VSTR. We summarised patient data using descriptive statistics. RESULTS: Over the 12-year study period, there were 63 pregnant major trauma patients. Fifty-two (82.5%) patients sustained injuries resulting from road transport collisions. The maternal survival rate was 98.4% and the foetal survival rate was 88.9%. Thoracic injury was the most common injury (25/63), followed by abdominal injury (23/63). Eighty-six percent of the third trimester patients (19/22) were transported directly to a major trauma service with capacity for definitive care of the pregnancy. CONCLUSION: The present study demonstrated road transport injury was the most common mechanism of injury and both maternal survival rates and foetal survival rates were high. This information is essential for trauma care system planning and public health initiatives to improve the clinical management and outcomes of pregnant women with major trauma.
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ItemCancer stem cell marker DCLK1 reprograms small extracellular vesicles toward migratory phenotype in gastric cancer cells(WILEY, 2021-05-28)Doublecortin-like kinase 1 (DCLK1) is a putative cancer stem cell marker, a promising diagnostic and prognostic maker for malignant tumors and a proposed driver gene for gastric cancer (GC). DCLK1 overexpression in a majority of solid cancers correlates with lymph node metastases, advanced disease and overall poor-prognosis. In cancer cells, DCLK1 expression has been shown to promote epithelial-to-mesenchymal transition (EMT), driving disruption of cell-cell adhesion, cell migration and invasion. Here, we report that DCLK1 influences small extracellular vesicle (sEV/exosome) biogenesis in a kinase-dependent manner. sEVs isolated from DCLK1 overexpressing human GC cell line MKN1 (MKN1OE -sEVs), promote the migration of parental (non-transfected) MKN1 cells (MKN1PAR ). Quantitative proteome analysis of MKN1OE -sEVs revealed enrichment in migratory and adhesion regulators (STRAP, CORO1B, BCAM, COL3A, CCN1) in comparison to MKN1PAR -sEVs. Moreover, using DCLK1-IN-1, a specific small molecule inhibitor of DCLK1, we reversed the increase in sEV size and concentration in contrast to other EV subtypes, as well as kinase-dependent cargo selection of proteins involved in EV biogenesis (KTN1, CHMP1A, MYO1G) and migration and adhesion processes (STRAP, CCN1). Our findings highlight a specific role of DCLK1-kinase dependent cargo selection for sEVs and shed new light on its role as a regulator of signaling in gastric tumorigenesis.
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ItemEfficacy of the novel, innovative, single-use grasper integrated flexible cystoscope for ureteral stent removal: a systematic review(WILEY, 2021-05-24)BACKGROUND: We aimed to define the published impact, efficacy, cost-effectiveness and precise role of the Isiris-α device: the world's first sterile, single-use grasper integrated flexible cystoscope (SUGIFC) for ureteral stent removal. METHODS: After PROSPERO registration (CRD42021228755), the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were utilized. The search terms "Grasper Integrated Flexible Cystoscope," and "Isiris," within the following databases: PubMed, Scopus, Cochrane Library, Web of Science and EMBASE were searched. RESULTS: In this review, a cumulative total experience (10 publications) included 970 "SUGIFC" procedures (755 patients). However, only 366/970 procedures were actually used for "ureteral stent removal," with the remainder being surveillance cystoscopy only (603/970) or foreign body retrieval (1/970). Procedure-related and device failures in planned "removal of ureteral stents," was reported in 8/366 (346 patients) and 1/366 (346 patients), respectively. The cost-benefit utilizing the SUGIFC device is advantageous compared to "in-theatre" stent removals and favours less busy centres where maintenance, repair and replacement costs are more relevant. Other listed benefits include shorter stent indwelling times, shorter procedure duration, lower rates of bacteriuria and urinary tract infections, fewer emergency department visits and lower readmission rates. Technical limitations include the absence of an independent working channel, a narrower visual field and the lack of image universality since the monitor is device-specific. CONCLUSION: The SUGIFC device needs to be outweighed against local costs and individual health systems. Its application in ambulatory ureteral stent removal may become significant due to the accessibility and convenience that it offers the attending urologist.
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ItemUptake of bone-modifying agents in patients with HER2+ metastatic breast cancer with bone metastases - prospective data from a multi-site Australian registry.(Wiley, 2021-05-18)BACKGROUND: International practice guidelines recommend administration of bone-modifying agents (BMA) in metastatic breast cancer (MBC) patients with bone metastases to reduce skeletal-related events (SRE). Optimal delivery of BMA in routine clinical practice, including agent selection and prescribing intervals, remains unclear. AIM: To describe real-world practice of Australian breast oncologists. METHODS: Prospective data from February 2015 to July 2020 on BMA delivery to MBC patients with bone metastases was analysed from Treatment of Advanced Breast Cancer in the Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Australian Patient (TABITHA), a multi-site Australian HER2+ MBC registry. RESULTS: Of 333 HER2+ MBC patients, 171 (51%) had bone metastases at diagnosis, with a mean age of 58.1 years (range, 32-87). One hundred and thirty (76%) patients received a BMA, with 90 (69%) receiving denosumab and 40 (31%) receiving a bisphosphonate. Patients who received a BMA were more likely to have received concurrent first-line systemic anti-HER2 therapy (95% vs 83%; P = 0.04), to present with bone-only metastases at diagnosis (24% vs 7%; P = 0.02) and less likely to have visceral metastases (51% vs 71%; P = 0.03). Ten of 40 (25%) bisphosphonate patients and 45 of 90 (50%) denosumab patients received their BMA at the recommended 4-weekly interval. Prescribing intervals varied over time. Adverse events reported were consistent with clinical trial data. CONCLUSION: Three-quarters of Australian HER2+ MBC patients with bone metastases receive a BMA, often at different schedules than guidelines recommend. Further studies, including all MBC subtypes, are warranted to better understand clinicians' prescribing rationale and potential consequences of current prescribing practice on SRE incidence.
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ItemQuality-of-life outcomes after operative management of primary and secondary lymphoedema: a systematic review.(Wiley, 2021-12)BACKGROUND: Lymphoedema is an incurable and progressive disease that affects not only physical function but overall quality of life. Surgical treatment options for the management of lymphoedema are being increasingly performed. This study aims to review post-operative health-related quality of life (HRQOL) following surgical treatment of lymphoedema. METHODS: A systematic search of the PubMed and Medline databases was performed from the date of their inception until September 2018 to evaluate HRQOL following different surgical options for the treatment of lymphoedema. RESULTS: One hundred and thirteen articles were identified. Twenty-one articles were included in the final review, comprising a total of 736 patients. HRQOL improvements appear to be sustained for at least 6-12 months post-operatively. In particular, major benefits were noted in the domains based around physical functioning. Patient satisfaction similarly mirrors HRQOL improvements, following an initial dip in the immediate post-operative period. CONCLUSION: All surgical treatment modalities for the management of lymphoedema confer significant HRQOL improvements across a diverse range of health domains, with this critical outcome of surgery an important pre-operative consideration. Recommendations for ongoing research are suggested.
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ItemMinimally invasive ileal ureter replacement: Comparative analysis of robot-assisted laparoscopic versus conventional laparoscopic surgery.(Wiley, 2021-06)BACKGROUND: This study is an initial comparative analysis of perioperative and intermediate-term functional outcomes between patients who underwent robot-assisted laparoscopic (RALS) or conventional laparoscopic surgery (LS). MATERIALS AND METHODS: A total of 25 patients who underwent ileal ureter replacement (10 RALS and 15 LS) were followed by functional cine magnetic resonance urography (MRU) combined with a modified Whitaker test. Also, the characteristics, perioperative data and functional outcomes of the patients were compared. RESULTS: The estimated blood loss, postoperative hospital stay and time to oral intake were significantly lower in the RALS group. At the median 14-month follow-up, all the patients showed improved renal function and were symptom-free, with no signs of leakage or stenosis observed by cine MRU combined with a modified Whitaker test. CONCLUSIONS: RALS with an extracorporeal bowel resection is feasible and appears to be safe, with quick postoperative recovery and encouraging outcomes.
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ItemNeuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein IgG associated disorder: A comprehensive neuro-ophthalmic review(WILEY, 2021-01-10)Neuromyelitis optica spectrum disorder (NMOSD) is an antibody-mediated inflammatory disease of the central nervous system that involves the optic nerves, spinal cord, and often other specific brain regions such as area postrema of the medulla. NMOSD was formerly classified as a variant of multiple sclerosis (MS), given the similar symptomatology and relapsing course but is now considered to have distinct clinical, paraclinical, immunological and prognostic features. The discovery of aquaporin 4 (AQP4) immunoglobulin G (IgG) has improved the ability to diagnose NMOSD. AQP4-IgG targets the astrocytic AQP4 water channel leading to complement activation and increased blood-brain barrier permeability. Accurate and early diagnosis is crucial as timely treatment may result in mitigation of long-term disability. Myelin oligodendrocyte glycoprotein (MOG)-IgG associated disorder (MOGAD) is a distinct nosologic entity, which has been more recently described. Its clinical spectrum partly overlaps that of seronegative NMOSD and MS. Although it is considered to have fewer relapses and better prognosis than NMOSD, the clinical course and outcome of MOGAD has not been fully characterized.
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ItemBullying, harassment and sexual discrimination among ophthalmologists in Australia and New Zealand(WILEY, 2021-01-10)BACKGROUND: Discrimination, bullying and sexual harassment (DBSH) impact the psychological well-being of doctors and contribute to poor health outcomes. The Royal Australian and New Zealand College of Ophthalmologists (RANZCO) commissioned independent surveys to evaluate DBSH among members/trainees. METHODS: Anonymous online surveys by Best Practice Australia were undertaken in 2015 and 2018. Cross-sectional analysis was prevalence of perceived DBSH, rates of reporting, intervention and resolution undertaken. Response rate was 50% (658/1319) in 2015 and 40% (557/1401) in 2018. In both surveys, 29% were female. This is representative of the distribution of the RANZCO members. RESULTS: In a 2015 survey, 37.6% of respondents experienced DBSH, with prevalence being the highest for females (62.3%; N = 104 cf males 27.7%; N = 167) and trainees (49.2%; N = 61). In 2018, 49.2% of respondents reported DBSH with rates low for all forms of DBSH (22%-29%). Sexual harassment was reported by 12% and the least discussed or reported. Respondents strategy for taking action included draw on personal support network (25-43%), official complaints to supervisors (16-22%), human resources (2%-10%) and RANZCO (0%-6%). Reasons for not taking action included fear of impact of future career options (54.1%-60.7%), fear of victimization (35.7%-50.4%) and afraid of not being believed (31.9%-52.4%). Satisfactory resolution rates were 6% to 25%. A majority of respondents (77%) were positive about RANZCO initiatives. CONCLUSIONS: DBSH is commonly reported by RANZCO members with female ophthalmologists more than two times more likely to experience any one of the four behaviours, three times more likely to experience discrimination and six times for sexual harassment. Fear of compromising personal and career progression contribute to low levels of reporting.