Publications by authors named "Kenneth Chan"

People with severe-mental-illness (SMI), often defined as "schizophrenia-spectrum disorders and bipolar disorder", have increased premature mortality and elevated prevalence of diabetes compared with general population. Evidence indicated that one-third of their premature death was from cardiovascular diseases (CVD), with risk conferred by diabetes. Although earlier studies have examined SMI-associated diabetes-related outcomes, findings were inconsistent and not systematically evaluated.

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Aims: Coronary Computed Tomography Angiography (CCTA) is a first line investigation for chest pain in patients with suspected obstructive coronary artery disease (CAD). However, many acute cardiac events occur in the absence of obstructive CAD. We assessed the lifetime cost-effectiveness of integrating a novel artificial intelligence-enhanced image analysis algorithm (AI-Risk) that stratifies the risk of cardiac events by quantifying coronary inflammation, combined with the extent of coronary artery plaque and clinical risk factors, by analysing images from routine CCTA.

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Importance: Previous studies showed that 42% to 50% of patients with locally advanced hepatocellular carcinoma (HCC) achieved complete remission (CR) after combined locoregional therapy (LRT) plus immunotherapy (IO). However, data on predictors of CR and long-term clinical outcomes without surgery and after discontinuation of IO are lacking.

Objective: To assess the long-term clinical outcomes among patients with unresectable HCC who achieved CR after LRT-IO and were placed on a watch-and-wait protocol.

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Background: Left ventricular (LV) hypertrophy occurs in both aortic stenosis (AS) and systemic hypertension (HTN) in response to wall stress. However, differentiation of hypertrophy due to these 2 etiologies is lacking. The aim was to study the 3-dimensional geometric remodeling pattern in severe AS pre- and postsurgical aortic valve replacement and to compare with HTN and healthy controls.

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Background & Aims: Combined F-fluorodeoxyglucose (FDG) and C-acetate (dual-tracer) positron-emission tomography/computed tomography (PET/CT) is being increasingly performed for the management of hepatocellular carcinoma (HCC), although its role is not well defined. Therefore, we evaluated its effectiveness in (i) staging, (ii) characterization of indeterminate lesions on conventional imaging, and (iii) detection of HCC in patients with unexplained elevations in serum alpha-fetoprotein (AFP) levels.

Methods: We retrospectively assessed 525 consecutive patients from three tertiary centers between 2014 and 2020.

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Background: The predictive value of programmed death-ligand 1 (PD-L1) expression in nasopharyngeal cancer (NPC) patients receiving immune checkpoint inhibitors (ICIs) remains controversial. This study aimed to evaluate the optimal threshold of PD-L1 expression in predicting the efficacy of ICIs in patients with recurrent or metastatic (R/M) NPC.

Methods: A meta-analysis was performed by retrieving relevant literature from PubMed, EMBASE, and Cochrane Library databases.

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With the enormous progress in the field of cardiovascular imaging in recent years, computed tomography (CT) has become readily available to phenotype atherosclerotic coronary artery disease. New analytical methods using artificial intelligence (AI) enable the analysis of complex phenotypic information of atherosclerotic plaques. In particular, deep learning-based approaches using convolutional neural networks (CNNs) facilitate tasks such as lesion detection, segmentation, and classification.

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Background: Pediatric-type diffuse high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (IHG) but also in other pHGG and are associated with devastating morbidity and mortality.

Methods: To identify new treatment options, we established and characterized two novel orthotopic mouse models harboring distinct MET fusions.

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Background: Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD.

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Article Synopsis
  • The study compares the effectiveness and safety of combining stereotactic body radiotherapy (SBRT) with immunotherapy versus SBRT alone in patients with unresectable hepatocellular carcinoma.
  • Results show that the combination therapy (SBRT-IO) led to significantly improved overall survival rates and response compared to SBRT alone, with higher rates of complete and partial responses among patients.
  • Despite some cases of severe side effects from immunotherapy, the combination treatment demonstrated better outcomes, suggesting that further research through randomized trials is needed.
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Background: Locally advanced nasopharyngeal cancer (NPC) patients undergoing radiotherapy are at risk of treatment failure, particularly locoregional recurrence. To optimize the individual radiation dose, we hypothesize that the genomic adjusted radiation dose (GARD) can be used to correlate with locoregional control.

Methods: A total of 92 patients with American Joint Committee on Cancer / International Union Against Cancer stage III to stage IVB recruited in a randomized phase III trial were assessed (NPC-0501) (NCT00379262).

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is an antimicrobial-resistant bacterium that has no vaccine approved for human use. Additionally, it has been identified by the World Health Organization as a priority pathogen for novel vaccines and therapeutic development. We previously developed a synthetic mimic of the A-band polysaccharide tip that showed promise in terms of immunogenicity for use as a glycoconjugate vaccine.

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The ferritin-lymphocyte ratio (FLR) is a novel inflammatory biomarker for the assessment of acute COVID-19 patients. However, the prognostic value of FLR for predicting adverse clinical outcomes in COVID-19 remains unclear, which hinders its clinical translation. We characterised the prognostic value of FLR in COVID-19 patients, as compared to established inflammatory markers.

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CRB-65 (onfusion; espiratory rate ≥ 30/min; lood pressure ≤ 90/60 mmHg; age ≥ years) is a risk score for prognosticating patients with COVID-19 pneumonia. However, a significant proportion of COVID-19 patients have normal chest X-rays (CXRs). The influence of CXR abnormalities on the prognostic value of CRB-65 is unknown, limiting its wider applicability.

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Background: The strategy of dual blockade of TGF-β and PD-L1 pathways has not been previously tested in platinum-refractory recurrent or metastatic nasopharyngeal cancer (R/M NPC) patients. This study aimed to evaluate the safety and efficacy of bintrafusp alfa in refractory R/M NPC patients.

Methods: In this single-arm, single-centre phase II clinical trial, 38 histologically confirmed R/M NPC patients were enrolled and administered with bintrafusp alfa every 2 weeks.

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Article Synopsis
  • - This study focuses on identifying the cellular origins of common childhood brain tumors (ependymoma, pilocytic astrocytoma, and medulloblastoma) using a human cerebellar atlas, which offers a more accurate reference than previous methods that compared human tumors to mouse tissues.
  • - Using a large dataset of normal and tumor-specific gene expressions, the researchers suggest that different brain tumors can arise from various progenitor cells in the cerebellum and have distinct lineage origins.
  • - The findings indicate that tumors may consist of cells resembling different types from a specific developmental lineage, highlighting the complexity of tumor origins and suggesting potential therapeutic strategies based on identified tumor-specific genes.
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Article Synopsis
  • The lymphocyte-CRP ratio (LCR) is a potential biomarker for predicting adverse outcomes in COVID-19 patients, but its effectiveness compared to traditional inflammatory markers is still unclear.
  • In a study of 413 COVID-19 inpatients, LCR showed similar predictive power to CRP for mortality and combined adverse outcomes, while outperforming other markers like lymphocyte and platelet counts.
  • Patients with a low LCR (below 58) had significantly poorer survival rates, indicating LCR's importance, but further research is needed to enhance its clinical application.
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Increasingly, safety-critical systems include artificial intelligence and machine learning components (i.e., learning-enabled components (LECs)).

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Article Synopsis
  • Assessing the risk of inpatient mortality in COVID-19 patients is crucial for clinical decision-making, focusing on the role of high sensitivity cardiac troponin T (hs-cTnT) as a biomarker indicating worse prognosis.
  • A study conducted on 191 COVID-19 patients found that 65% had elevated hs-cTnT levels, correlating with significantly worse survival rates and increased mortality risk.
  • The findings suggest that hs-cTnT could be particularly useful for ruling out inpatient mortality, which could lead to better management practices and potential early discharge for patients with normal levels.
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Background: Abnormal global longitudinal strain (GLS) has been independently associated with adverse cardiac outcomes in both obstructive and nonobstructive hypertrophic cardiomyopathy.

Objectives: The goal of this study was to understand predictors of abnormal GLS from baseline data from the National Heart, Lung, and Blood Institute (NHLBI) Hypertrophic Cardiomyopathy Registry (HCMR).

Methods: The study evaluated comprehensive 3-dimensional left ventricular myocardial strain from cine cardiac magnetic resonance in 2,311 patients from HCMR using in-house validated feature-tracking software.

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Background: The synergy between locoregional therapies and immune checkpoint inhibitors has not been investigated as conversion therapy for unresectable hepatocellular carcinoma. We aimed to investigate the activity of sequential transarterial chemoembolisation (TACE) and stereotactic body radiotherapy followed by avelumab (an anti-PD-L1 drug) for locally advanced, unresectable hepatocellular carcinoma.

Methods: START-FIT was a single-arm, phase 2 trial in patients with locally advanced hepatocellular carcinoma who were not suitable for curative treatment, conducted in two hospitals in Hong Kong and one in Shenzhen, China.

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Archaeosomes, composed of sulfated lactosyl archaeol (SLA) glycolipids, have been proven to be an effective vaccine adjuvant in multiple preclinical models of infectious disease or cancer. They have classically been prepared using a thin-film hydration method with an average particle size of 100-200 nm. In this study, we developed methods to generate SLA archaeosomes at different sizes, i.

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Background: Genome-wide association studies have discovered a link between genetic variants on human chromosome 15q26.1 and increased coronary artery disease (CAD) susceptibility; however, the underlying pathobiological mechanism is unclear. This genetic locus contains the (FES proto-oncogene, tyrosine kinase) gene encoding a cytoplasmic protein-tyrosine kinase involved in the regulation of cell behavior.

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