Publications by authors named "Anselm Mak"

Patients with autoimmune inflammatory rheumatic diseases (AIIRD) are potentially at a higher risk of contracting the SARS-CoV-2 virus and have poorer outcomes of the infection as a result of their immunocompromised state due to the nature of the underlying autoimmune conditions and immunosuppressant use. mRNA-based vaccines provide a novel approach to establishing immunity against SARS-CoV-2. However, the implications of toll-like receptors (TLRs), type I interferon (IFN) and pro-inflammatory cytokines raise concerns on disease severity and inefficient immune response following mRNA vaccination.

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Background: Transplantation of CD34 hematopoietic stem and progenitor cells (HSPC) into immunodeficient mice is an established method to generate humanized mice harbouring a human immune system. Different sources and methods for CD34 isolation have been employed by various research groups, resulting in customized models that are difficult to compare. A more detailed characterization of CD34 isolates is needed for a better understanding of engraftable hematopoietic and potentially non-hematopoietic cells.

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Objective: This international task force aimed to provide healthcare professionals and persons living with systemic lupus erythematosus (SLE) with consensus-based recommendations for physical activity and exercise in SLE.

Methods: Based on evidence from a systematic literature review and expert opinion, 3 overarching principles and 15 recommendations were agreed on by Delphi consensus.

Results: The overarching principles highlight the importance of shared decision-making and the need to explain the benefits of physical activity to persons living with SLE and other healthcare providers.

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Objective: Patients with systemic lupus erythematosus (SLE) have increased risk of premature atherosclerosis but the exact mechanisms remains unclear. Flow-mediated dilatation (FMD) is an established non-invasive assessment of vascular endothelial function. Lipoprotein subfractions may be better predictors of FMD than conventional cholesterol measurements.

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Unlabelled: We recently reported that messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination was associated with flares in 9% of patients with systemic lupus erythematosus (SLE). Herein, we focused our analysis on patients from a multi-ethnic Southeast Asian lupus cohort with the intention of identifying distinct phenotypes associated with increased flares after mRNA COVID-19 vaccination.

Methods: Six hundred and thirty-three SLE patients from eight public healthcare institutions were divided into test and validation cohorts based on healthcare clusters.

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Objective: To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA).

Methods: A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first.

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Objective: To study whether multimodal brain MRI comprising permeability and perfusion measures coupled with machine learning can predict neurocognitive function in young patients with SLE without neuropsychiatric manifestations.

Methods: SLE patients and healthy controls (HCs) (≤40 years of age) underwent multimodal structural brain MRI that comprised voxel-based morphometry (VBM), magnetization transfer ratio (MTR) and dynamic contrast-enhanced (DCE) MRI in this cross-sectional study. Neurocognitive function assessed by Automated Neuropsychological Assessment Metrics was reported as the total throughput score (TTS).

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Background: Studies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias.

Methods: A national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first.

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Article Synopsis
  • An international survey was conducted among patients with Systemic Lupus Erythematosus (SLE) to evaluate their access to and trust in health information sources before and during the COVID-19 pandemic.
  • Results showed a decline in the use of lupus specialists and family physicians as information sources, while access to news and social media increased during the pandemic.
  • A significant portion of respondents (17.2%) experienced negative effects from the information they obtained through news and social media, with various demographics influencing their information-seeking behaviors and experiences.
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Central nervous system (CNS) involvement of systemic lupus erythematosus (SLE), termed neuropsychiatric SLE (NPSLE), is a major and debilitating manifestation of the disease. While patients with SLE mostly complain of common neuropsychological symptoms such headache and mild mood disorders that may not even be technically attributed to SLE, many SLE patients present with life-threatening NPSLE syndromes such as cerebrovascular disease, seizures and psychosis that are equally challenging in terms of early diagnosis and therapy. While we are just beginning to unravel some mysteries behind the immunologic basis of NPSLE, advancements in the mechanistic understanding of the complex pathogenic processes of NPSLE have been emerging through recent murine and human studies.

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The observations that traditional cardiovascular disease (CVD) risk factors fail to fully account for the excessive cardiovascular mortality in patients with systemic lupus erythematosus (SLE) compared with the general population have prompted in-depth investigations of non-traditional, SLE-related risk factors that contribute to cardiovascular complications in patients with SLE. Of the various perturbations of vascular physiology, endothelial dysfunction, which is believed to occur in the earliest step of atherosclerosis, has been extensively investigated for its contribution to CVD risk in SLE. Endothelial progenitor cells (EPCs), which play a crucial part in vascular repair, neovascularization and maintenance of endothelial function, are quantitatively and functionally reduced in patients with SLE.

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The phenotypic and functional complexities of T cells engender complicated and often confusing concepts as to how T cells ignite, accelerate and brake the inflammatory processes involved in systemic lupus erythematosus (SLE), let alone the plasticity of T cells that takes place under different immunological contexts. Nevertheless, being one of the prime survival factors of T cells, interleukin (IL)-2 plays a potentially critical role in many immunological scenarios during the pathophysiological process of SLE. Here, the pathophysiology of lupus T cells and current, as well as ongoing, therapeutic approaches of SLE that involve low-dose IL-2 administration will be highlighted.

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Dysregulation of type I interferons (IFNs) has been implicated in the pathogenesis of systemic lupus erythematosus (SLE) since the late 1970s. The majority of SLE patients demonstrate evidence of type I IFN pathway activation; however, studies attempting to address the relationship between type I IFN signature and SLE disease activity have yielded conflicting results. In addition to type I IFNs, type II and III IFNs may overlap and also contribute to the IFN signature.

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Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of immunotherapy. Unlike other immune-related adverse events, CRS triggered by immune checkpoint inhibitors (ICIs) is not well described. The clinical characteristics and course of 25 patients with ICI-induced CRS from 2 tertiary hospitals were abstracted retrospectively from the medical records and analyzed.

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Objectives: To determine the association between neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) with disease activity and flares in an inception cohort of patients with systemic lupus erythematosus (SLE) using a prospective study design.

Methods: Consecutive adult patients (age≥21) who fulfilled the 1997 American College of Rheumatology (ACR) or the 2012 Systemic Lupus International Collaboration Clinic Classification (SLICC) Criteria for SLE were followed every 3 months, with SLE disease activity assessed by using SLEDAI-2K, and disease flares defined and captured by the SELENA-SLEDAI Flare Index (SFI). NLR and PLR were computed from the automated machine-counted blood count differentials.

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Objectives: Systemic lupus erythematosus (SLE) in Asians is a unique patient group that has been thought to present with more severe organ involvement in comparison to their non-Asian counterparts. We set out to perform a meta-analysis to compare clinical manifestations between ancestries, with a focus on Southeast Asian ethnicities and gender.

Materials And Methods: A cross-sectional study was performed in conjunction with a meta-analysis to identify differences in prevalences of SLE clinical manifestations.

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Objective: The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI.

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Article Synopsis
  • - The study investigates the link between glucocorticoid (GC) exposure and the risk of irreversible organ damage in patients with systemic lupus erythematosus (SLE), emphasizing the importance of managing GC use effectively.
  • - Researchers conducted a literature review and analyzed 49 studies involving over 16,000 SLE patients to assess how different levels of GC exposure correlate with specific organ damage outcomes over an average follow-up of about 105 months.
  • - Findings revealed that higher daily GC doses were connected to increased occurrences of cardiovascular issues, osteoporosis with fractures, and osteonecrosis, suggesting the need for careful management of GC therapy in SLE patients to balance treatment benefits and potential harm.
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Objective: Small fiber neuropathy (SFN) is clinically and etiologically heterogeneous. Although autoimmunity has been postulated to be pathophysiologically important in SFN, few autoantibodies have been described. We aimed to identify autoantibodies associated with idiopathic SFN (iSFN) by a novel high-throughput protein microarray platform that captures autoantibodies expressed in the native conformational state.

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