Publications by authors named "William Chan"

Purpose: Patients with Cardiogenic shock (CS) admitted to intensive care units (ICUs) have high mortality rates. We aimed to investigate the changes patient characteristics and outcomes over time among patients admitted to the ICU with CS.

Methods: Retrospective study utilizing a large bi-national ICU database from 2003 to 2022.

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Objectives: Diffuse alveolar hemorrhage (DAH) is a life-threatening complication of systemic lupus erythematosus and small vessel vasculitis. We previously showed that neutrophil extracellular traps (NETs) were associated with the pathogenesis of pristane-induced DAH and demonstrated that neutrophil NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome assembly participated in NET generation under sterile stimulation. We investigated whether NLRP3 inflammasome assembly in neutrophils may drive pulmonary NETosis in a mouse model of pristane-induced DAH.

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Article Synopsis
  • The study aimed to explore how different emergency medical service (EMS) providers around the world use vasoactive medications, including their guidelines and treatment goals.
  • A survey sent to EMS medical directors in March 2022 received responses from 25 out of 108 directors, revealing that most had guidelines for vasoactive agents.
  • Epinephrine was the most commonly chosen first-line medication for shock, especially in cases of cardiogenic shock and post-cardiac arrest, highlighting the variability in international EMS practices and the need for more research on optimal prehospital treatment.
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In patients with previous coronary artery bypass graft surgery (CABG) requiring subsequent percutaneous coronary intervention (PCI), there is uncertainty whether bypass grafts or native coronary arteries should be targeted. We analyzed data from 2,764 patients with previous CABG in the Melbourne Interventional Group registry (2005 to 2018), divided into 2 groups: those who underwent PCI in a native vessel (n = 1,928) and those with PCI in a graft vessel (n = 836). Patients with a graft vessel PCI were older, had more high-risk clinical characteristics (previous myocardial infarction, heart failure, ejection fraction <50%, renal impairment, peripheral and cerebrovascular disease), and had high-risk procedural features (American College of Cardiology and American Heart Association types B2/C lesions).

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Article Synopsis
  • The study investigates long-term survival outcomes for patients with severe ischaemic cardiomyopathy who underwent either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) due to a lack of recent trial data.
  • Using records from Australian and New Zealand cardiac registries between 2005 and 2018, researchers analyzed data from 2042 patients, with 1451 treated by CABG and 591 by PCI, adjusting for various risk factors.
  • Results showed CABG patients had significantly lower long-term mortality compared to those who received PCI, although there were no differences in in-hospital mortality; however, CABG was associated with a higher risk of peri-procedural strokes and a longer hospital stay
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Ubiquitin (Ub) is a post-translational modification that largely controls proteostasis through mechanisms spanning transcription, translation, and notably, protein degradation. Ub conjugation occurs through a hierarchical cascade of three enzyme classes (E1, E2, and E3s) involving >1000 proteins that regulate the ubiquitination of proteins. The E2 Ub-conjugating enzymes are the midpoint, yet their cellular roles remain under-characterized, partly due to a lack of inhibitors.

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Background: Guidelines and international appropriate use criteria increasingly endorse non-invasive stress testing to evaluate patients with suspected chronic coronary disease (CCD). We sought to review the real-world utilisation of non-invasive stress testing and investigate whether their use prior to PCI associates with outcomes in patients with CCD.

Methods: Consecutive patients from a multicentre registry who underwent PCI for CCD between 2006 and 2018 were included.

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Background: Nocturnal hemodialysis (nHD) restores the attenuated brachial artery vasodilator responsiveness of patients receiving conventional intermittent hemodialysis (iHD). Its impact on coronary vasodilatation is unknown.

Methods: We evaluated 25 patients on hemodialysis who fulfilled transplant criteria: 15 on iHD (4-hour sessions, 3 d/wk) and 10 on nHD (≈40 h/wk over 8-10-hour sessions) plus 6 control participants.

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Article Synopsis
  • - The study analyzed the impact of COVID-19 lockdown on emergency medical service (EMS) usage and percutaneous coronary intervention (PCI) in Australia, observing an increase in EMS calls for acute coronary syndrome (ACS) during lockdown compared to other periods.
  • - The number of daily PCI cases remained stable across all periods, including during lockdown, while the median time from door to procedure for ACS was shorter during lockdown, indicating efficient response despite the pandemic.
  • - Lockdown also correlated with lower odds of major adverse cardiovascular and cerebrovascular events (MACCE) within 30 days following treatment, suggesting a potentially positive impact on patient outcomes during that time.
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NLRP3 inflammasome has been implicated in neutrophil polarization and extrusion of neutrophil extracellular traps (NETs) in vitro and facilitates secretion of Il1-beta (IL-1β). Permanent ligation of the left anterior descending artery was used to induce MI in WT and NLRP3 mice as well as in NLRP3 recipient mice transfused with either WT or NLRP3 neutrophils. NLRP3 deficiency reduced infarct size to roughly a third of WT heart injury and preserved left ventricular (LV) function at 12 h after MI as assessed by echocardiography and triphenyltetrazolium chloride staining of live tissue.

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Article Synopsis
  • - The study examined patients with acute coronary syndrome (ACS) lacking standard modifiable risk factors (SMuRFs) like diabetes and smoking to assess their prevalence and health outcomes compared to those with SMuRFs.
  • - Out of nearly 19,000 patients, 14.4% were classified as SMuRF-less, experiencing more severe initial cardiac events but showing similar 30-day mortality rates as patients with SMuRFs.
  • - Over a median follow-up of 7 years, SMuRF-less patients had a 13% lower long-term mortality risk, indicating they might have better outcomes over time despite their acute presentations.
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Huntington's disease (HD) arises from expanded CAG repeats in exon 1 of the () gene. The resultant misfolded HTT protein accumulates within neuronal cells, negatively impacting their function and survival. Ultimately, HTT accumulation results in cell death, causing the development of HD.

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Background: Invasive CFT is the gold standard for diagnosing coronary vasomotor dysfunction in patients with ANOCA. Most institutions recommend only testing the left coronary circulation. Therefore, it is unknown whether testing multiple coronary territories would increase diagnostic yield.

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Objectives: We aimed to assess the healthcare costs and impact on the economy at large arising from emergency medical services (EMS) treated non-traumatic shock.

Design: We conducted a population-based cohort study, where EMS-treated patients were individually linked to hospital-wide and state-wide administrative datasets. Direct healthcare costs (Australian dollars, AUD) were estimated for each element of care using a casemix funding method.

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Background: Clinical outcomes of patients with renal transplant (RT) undergoing percutaneous coronary intervention (PCI) remain poorly elucidated.

Method: Between 2014 and 2021, data were analysed for the following three groups of patients undergoing PCI enrolled in a multicentre Australian registry: (1) RT recipients (n=226), (2) patients on dialysis (n=992), and (3) chronic kidney disease (CKD) patients (estimated glomerular filtration rate [eGFR], 30‒60 mL/min per 1.73 m) without previous RT (n=15,534).

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Background: Suboptimal coronary reperfusion (no reflow) is common in acute coronary syndrome percutaneous coronary intervention (PCI) and is associated with poor outcomes. We aimed to develop and externally validate a clinical risk score for angiographic no reflow for use following angiography and before PCI.

Methods: We developed and externally validated a logistic regression model for prediction of no reflow among adult patients undergoing PCI for acute coronary syndrome using data from the Melbourne Interventional Group PCI registry (2005-2020; development cohort) and the British Cardiovascular Interventional Society PCI registry (2006-2020; external validation cohort).

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Objectives: To determine the influence of presenting electrocardiographic (ECG) changes on prognosis in acute coronary syndrome cardiogenic shock (ACS-CS) patients undergoing percutaneous coronary angiography (PCI).

Background: The effect of initial ECG changes such as ST-elevation myocardial infarction (STEMI) versus non-STEMI among patients ACS-CS on prognosis remains unclear.

Methods: We analysed data from consecutive patients with ACS-CS enrolled in the Victorian Cardiac Outcomes registry between 2014 and 2020.

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Background: The Impella (Abiomed, Danvers, MA, USA) temporary percutaneous left ventricular assist device is increasingly used as mechanical circulatory support in patients with acute myocardial infarction-cardiogenic shock (AMICS) or those undergoing high-risk protected percutaneous coronary intervention (PCI). The optimal weaning regimen remains to be defined.

Method: We implemented a structured weaning protocol in a series of 10 consecutive patients receiving Impella support for protected PCI or AMICS treated with PCI in a high volume non-cardiac surgery centre.

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Background: Unfractionated heparin (UFH) is the preferred anticoagulant agent in percutaneous coronary intervention (PCI) procedures for minimising the risk of thrombotic complications. Because of the narrow therapeutic range of UFH, some society guidelines have advocated the use of the activated clotting time (ACT) test to monitor anticoagulation intensity during PCI to reduce thrombotic and bleeding complications. We aimed to assess the current practice of UFH prescription and its monitoring in Australia and New Zealand (ANZ).

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Background: Undifferentiated carcinomas of the pancreas with osteoclast-like giant cells (UCPOGC) are rare pancreatic neoplasms that account for less than 1% of all pancreatic malignancies. This case report of a 54-year-old male with metastatic UCPOGC adds to the existing literature and further ascertains the clinical and imaging features, treatment options, and prognosis of this rare entity.

Case Presentation: We present the detailed clinical course of a 54-year-old Asian male patient with UCPOGC, with focus on the relevant clinical features and imaging findings that are characteristic of this disease entity.

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The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor and a substrate protein of a Cullin 4B E3 ligase complex responsible for diverse cellular processes. In the lung, this receptor is responsible for the bioactivation of benzo[a]pyrene during tumorigenesis. Realizing that the AHR function is affected by its expression level, we are interested in the degradation mechanism of AHR in the lung.

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Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality worldwide. Even with excellent control of low-density lipoprotein cholesterol (LDL-C) levels, adverse cardiovascular events remain a significant clinical problem worldwide, including among those without any traditional ASCVD risk factors. It is necessary to identify novel sources of residual risk and to develop targeted strategies that address them.

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