Exome Sequencing of Chinese Patients With Anticitrullinated Protein Antibody-Positive Rheumatoid Arthritis in Singapore.

Objective: More than 130 susceptibility loci for rheumatoid arthritis (RA) have been identified with genome-wide association studies. To investigate the genetic predisposition of Chinese patients to anticitrullinated protein antibody (ACPA)-positive RA, we carried out an exome sequencing study.

Methods: Patients were recruited from 3 major public hospitals in Singapore: Tan Tock Seng Hospital (TTSH), Singapore General Hospital, and the National University Hospital.

Dampened Inflammation and Improved Survival After CXCL5 Administration in Murine Lupus via Myeloid and Neutrophil Pathways.

Objective: To determine the efficacy of CXCL5 administration in lupus-prone MRL/lpr (Fas ) mice and elucidate its working mechanisms.

Methods: CXCL5 expression in blood (obtained from SLE patients and Fas mice) and major internal organs (obtained from Fas mice) was examined by Luminex, real-time polymerase chain reaction, and immunofluorescent staining analyses. Pharmacokinetic studies were performed in Fas mice and healthy Institute of Cancer Research mice.

Physical activity in patients with axial spondyloarthritis in a multi-ethnic south-east Asian country.

Background: Patients with axial spondyloarthritis (axSpA) may experience spinal stiffness and pain, leading to reduced physical function and quality of life. Despite the benefits of physical activity (PA) and exercise, previous studies have demonstrated lower levels of PA among patients with axSpA. This study aims to examine the patterns of PA among patients with axSpA compared to the general population in a multi-ethnic Asian country.

Ethnic differences in the prevalence, socioeconomic and health related risk factors of knee pain and osteoarthritis symptoms in older Malaysians.

Knee pain is often underreported, underestimated and undertreated. This study was conducted to estimate the prevalence, burden and further identify socioeconomic factors influencing ethnic differences in knee pain and symptoms of OA among older adults aged 55 years and over in Greater Kuala Lumpur (the capital city of Malaysia). The sample for the Malaysian Elders Longitudinal Research (MELoR) was selected using stratified random sampling, by age and ethnicity from the electoral rolls of three parliamentary constituencies.

2018 update of the APLAR recommendations for treatment of rheumatoid arthritis.

Aim: To update recommendations based on current best evidence concerning the treatment of rheumatoid arthritis (RA), focusing particularly on the role of targeted therapies, to inform clinicians on new developments that will impact their current practice.

Materials And Methods: A search of relevant literature from 2014 to 2016 concerning targeted therapies in RA was conducted. The RA Update Working Group evaluated the evidence and proposed updated recommendations using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach, to describe the quality of evidence and strength of recommendations.

Oxidative stress impairs energy metabolism in primary cells and synovial tissue of patients with rheumatoid arthritis.

Background: In this study, we examined the effect of oxidative stress on cellular energy metabolism and pro-angiogenic/pro-inflammatory mechanisms of primary rheumatoid arthritis synovial fibroblast cells (RASFC) and human umbilical vein endothelial cells (HUVEC).

Methods: Primary RASFC and HUVEC were cultured with the oxidative stress inducer 4-hydroxy-2-nonenal (4-HNE), and extracellular acidification rate, oxygen consumption rate, mitochondrial function and pro-angiogenic/pro-inflammatory mechanisms were assessed using the Seahorse analyser, complex I-V activity assays, random mutation mitochondrial capture assays, enzyme-linked immunosorbent assays and functional assays, including angiogenic tube formation, migration and invasion. Expression of angiogenic growth factors in synovial tissue (ST) was assessed by IHC in patients with rheumatoid arthritis (RA) undergoing arthroscopy before and after administration of tumour necrosis factor inhibitors (TNFi).

Clinical and economic implications of upper gastrointestinal adverse events in Asian rheumatological patients on long-term non-steroidal anti-inflammatory drugs.

Aim: To determine the incidence and direct costs of NSAID-induced upper GI adverse events in Malaysian rheumatology patients.

Methods: A retrospective, multi-centre, cohort study of rheumatology patients on long-term NSAIDs was conducted. Clinical data of patients treated between 2010 and 2013 were collected for a 24-month follow-up period.

The mediating role of psychological symptoms on falls risk among older adults with osteoarthritis.

The purpose of this study was to investigate the role of fear of falling (FoF) and psychological symptoms in explaining the relationship between osteoarthritis (OA) symptom severity and falls. Individuals aged ≥65 years with ≥2 falls or ≥1 injurious fall over the past 12 months were included in the falls group, while volunteers aged ≥65 years with no history of falls over 12 months were recruited as controls. The presence of lower extremity OA was determined radiologically and clinically.

Effect of Modified Otago Exercises on Postural Balance, Fear of Falling, and Fall Risk in Older Fallers With Knee Osteoarthritis and Impaired Gait and Balance: A Secondary Analysis.

Background: Osteoarthritis (OA) is considered an established risk factor for falls. Published studies evaluating secondary falls prevention strategies among individuals with OA are limited.

Objective: To evaluate the effect of a personalized home-based exercise program to improve postural balance, fear of falling, and falls risk in older fallers with knee OA and gait and balance problems.

Synovial Immunophenotype and Anti-Citrullinated Peptide Antibodies in Rheumatoid Arthritis Patients: Relationship to Treatment Response and Radiologic Prognosis.

Objective: Serum anti-citrullinated peptide antibodies (ACPAs) may be present before the development of rheumatoid arthritis (RA) and may be predictive of more severe, erosive disease. This study was undertaken to examine the synovial tissue immunophenotype according to ACPA status in patients with RA, as well as the response to treatment and erosion status.

Methods: Consecutive RA patients were prospectively recruited and underwent clinical and serologic assessments before and after treatment.

Precision medicine in pediatric rheumatology.

Purpose Of Review: Precision medicine is the tailoring of medical care to subcategories of disease. In pediatric rheumatology, these subcategories must first be defined by their specific molecular immunological profiles, and then the effects of growth and puberty, developmental immunological changes, and differences in treatment options and adherence considered when designing therapeutic strategies. In the present review, we summarize the unmet needs in pediatric rheumatology before such precision medical care can be effectively delivered to affected patients.

Influence of hip and knee osteoarthritis on dynamic postural control parameters among older fallers.

Objective: To compare the relationship between postural control and knee and hip osteoarthritis in older adults with and without a history of falls.

Methods: Fallers were those with ≥ 2 falls or 1 injurious fall over 12 months. Non-fallers were volunteers with no falls in the past year.

High-resolution oesophageal manometry and 24-hour impedance-pH study in systemic sclerosis patients: association with clinical features, symptoms and severity.

Objectives: To evaluate the associations between objectively measured gastroesophageal involvement using high-resolution manometry and 24- hour impedance-pH study, and clinical presentations in systemic sclerosis (SSc) patients.

Methods: This cross-sectional study was conducted in University of Malaya Medical Centre (UMMC) with 31 consecutive SSc patients recruited into this study. Clinical symptoms of gastroesophageal involvement, high-resolution impedance-manometry and 24-hour impedance-pH monitoring were assessed.

Mild Joint Symptoms Are Associated with Lower Risk of Falls than Asymptomatic Individuals with Radiological Evidence of Osteoarthritis.

Osteoarthritis (OA) exacerbates skeletal muscle functioning, leading to postural instability and increased falls risk. However, the link between impaired physical function, OA and falls have not been elucidated. We investigated the role of impaired physical function as a potential mediator in the association between OA and falls.

APLAR rheumatoid arthritis treatment recommendations.

Aims: Rheumatoid arthritis is a chronic inflammatory condition that affects approximately 1% of the world's population. There are a wide number of guidelines and recommendations available to support the treatment of rheumatoid arthritis; however, the evidence used for these guidelines is predominantly based on studies in Caucasian subjects and may not be relevant for rheumatoid arthritis patients in the Asia-Pacific region. Therefore, the Asia Pacific League of Associations for Rheumatology established a Steering Committee in 2013 to address this issue.

Cryptococcal meningitis and SLE: a diagnostic and therapeutic challenge.

Cryptococcal meningitis is a rare occurrence in systemic lupus erythematosus (SLE). The risk factors of developing this infection are duration of SLE, intensity of glucocorticoid use, and SLE-related intrinsic immune abnormalities. Early recognition and prompt initiation of antifungals can prevent complications and improve survival.

Physical therapies for improving balance and reducing falls risk in osteoarthritis of the knee: a systematic review.

Introduction: osteoarthritis (OA) of knee has been reported as a risk factor for falls and reduced balance in the elderly. This systematic review evaluated the effectiveness of physical therapies in improving balance and reducing falls risk among patients with knee OA.

Methods: a computerised search was performed to identify relevant studies up to November 2013.

Clinical and autoantibody profile in systemic sclerosis: baseline characteristics from a West Malaysian cohort.

Aim: To evaluate the clinical and antibody profile of systemic sclerosis (SSc) in a Malaysian cohort.

Methods: Consecutive patients with SSc in University Malaya Medical Centre from March to November 2012 were included in this study. In addition to clinical characterization, all subjects underwent autoantibody testing using Euroline immunoblot assay.

Open label randomized controlled trial assessing the efficacy of mycophenolate sodium against other conventional immunosuppressive agents in active systemic lupus erythematosus patients without renal involvement.

Aim: Mycophenolate is an immunosuppressive agent which has been used in systemic lupus erythematosus (SLE) patients who have failed conventional therapy. However, the use of mycophenolate sodium in extra-renal SLE involvement has yet to be established. This study aimed to assess the efficacy of mycophenolate sodium in extra-renal SLE.

Osteoarthritis and falls in the older person.

Osteoarthritis and falls are common conditions affecting older individuals which are associated with disability and escalating health expenditure. It has been widely assumed that osteoarthritis is an established risk factor for falls in older people. The relationship between osteoarthritis and falls has, quite surprisingly, not been adequately elucidated, and published reports have been conflicting.

Glycosylation status of serum in inflammatory arthritis in response to anti-TNF treatment.

Objective: Glycosylation is the most common post-translational modification and is altered in disease. The typical glycosylation change in patients with inflammatory arthritis (IA) is a decrease in galactosylation levels on IgG. The aim of this study is to evaluate the effect of anti-TNF therapy on whole serum glycosylation from IA patients and determine whether these alterations in the glycome change upon treatment of the disease.

Periarticular bone gain at proximal interphalangeal joints and changes in bone turnover markers in response to tumor necrosis factor inhibitors in rheumatoid and psoriatic arthritis.

Objective: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are characterized by periarticular bone erosion; periarticular bone formation is a feature in PsA. The effect of anti-tumor necrosis factor-α (TNF-α) on periarticular bone remodeling is unclear in both diseases. Our aim was to assess the response of bone turnover markers (BTM) and hand bone mineral density (BMD) to anti-TNF over 3 years in RA and PsA.

Notch-1 mediates hypoxia-induced angiogenesis in rheumatoid arthritis.

Objective: To examine the effect of hypoxia on Notch-1 signaling pathway components and angiogenesis in inflammatory arthritis.

Methods: The expression and regulation of Notch-1, its ligand delta-like protein 4 (DLL-4) and downstream signaling components (hairy-related transcription factor 1 [HRT-1], HRT-2), and hypoxia-inducible factor 1α (HIF-1α) under normoxic and hypoxic conditions (1-3%) were assessed in synovial tissue specimens from patients with inflammatory arthritis and controls and in human dermal microvascular endothelial cells (HDMECs) by immunohistology, dual immunofluorescence staining (Notch-1/factor VIII), Western blotting, and real-time polymerase chain reaction. In vivo synovial tissue oxygen levels (tissue PO2) were measured under direct visualization at arthroscopy.

IL-17A expression is localised to both mononuclear and polymorphonuclear synovial cell infiltrates.

Introduction: This study examines the expression of IL-17A-secreting cells within the inflamed synovium and the relationship to in vivo joint hypoxia measurements.

Methods: IL-17A expression was quantified in synovial tissue (ST), serum and synovial fluid (SF) by immunohistochemistry and MSD-plex assays. IL-6 SF and serum levels were measured by MSD-plex assays.