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Serological testing of Singaporeans who received childhood smallpox vaccination found anti-vaccinia IgG binding and neutralizing activity indicating long-term humoral immunity. There was correlation between IgG and neutralizing titers indicating IgG could be used as a surrogate marker for humoral immunity. In 2019, Singapore experienced a case of imported monkeypox. As with smallpox, disease can be prevented through vaccination, which was mandatory for Singaporean infants until 1981. However, the degree of residual immunity in older vaccinated Singaporeans remains unknown. Sera from individuals born 1946–1984 were therefore tested and those born prior to 1981 were found to have higher anti-vaccinia IgG and neutralizing activity titers. This suggests that protective humoral immunity remains, which could reduce disease severity in an orthopoxvirus outbreak. Correlation between IgG and neutralizing titers was observed indicating that serology could be used as a surrogate marker for immunity. [ABSTRACT FROM AUTHOR]

Background: The popular statistics-based Genome-wide association studies (GWAS) have provided deep insights into the field of complex disorder genetics. However, its clinical applicability to predict disease/trait outcomes remains unclear as statistical models are not designed to make predictions. This study employs statistics-free machine-learning (ML)-optimized polygenic risk score (PRS) to complement existing GWAS and bring the prediction of disease/trait outcomes closer to clinical application. Rheumatoid Arthritis (RA) was selected as a model disease to demonstrate the robustness of ML in disease prediction as RA is a prevalent chronic inflammatory joint disease with high mortality rates, affecting adults at the economic prime. Early identification of at-risk individuals may facilitate measures to mitigate the effects of the disease. Methods: This study employs a robust ML feature selection algorithm to identify single nucleotide polymorphisms (SNPs) that can predict RA from a set of training data comprising RA patients and population control samples. Thereafter, selected SNPs were evaluated for their predictive performances across 3 independent, unseen test datasets. The selected SNPs were subsequently used to generate PRS which was also evaluated for its predictive capacity as a sole feature. Results: Through robust ML feature selection, 9 SNPs were found to be the minimum number of features for excellent predictive performance (AUC > 0.9) in 3 independent, unseen test datasets. PRS based on these 9 SNPs was significantly associated with (P < 1 × 10–16) and predictive (AUC > 0.9) of RA in the 3 unseen datasets. A RA ML-PRS calculator of these 9 SNPs was developed (https://xistance.shinyapps.io/prs-ra/) to facilitate individualized clinical applicability. The majority of the predictive SNPs are protective, reside in non-coding regions, and are either predicted to be potentially functional SNPs (pfSNPs) or in high linkage disequilibrium (r2 > 0.8) with un-interrogated pfSNPs. Conclusions: These findings highlight the promise of this ML strategy to identify useful genetic features that can robustly predict disease and amenable to translation for clinical application. [ABSTRACT FROM AUTHOR]

Purpose: In this real‐world observational study, we analyzed the effects of different drugs on the quality of life (QoL) of patients with systemic lupus erythematosus (SLE). Method: We identified patients in our prospective SLE Registry who received new medications. We measure QoL with MOS 36‐Item Short‐Form Health Survey (SF‐36), a generic health questionnaire, and SLEQOL, a disease‐specific instrument. We compared the patients' scores before and after initiation of treatment. Results: We identified 259 episodes of drug initiation in 193 SLE patients. SLEQOL registered statistically significant changes with intravenous cyclophosphamide (total score and the domains of physical functioning, activities, and self‐image), mycophenolate (total score, treatment, mood, and self‐image) and azathioprine (total score, activities, and mood), but not with cyclosporin A and hydroxychloroquine. Two SF‐36 subscales (general health and physical functioning) showed statistically significant improvement in the patients who received intravenous cyclophosphamide. Both instruments have floor effect. There was weak correlation between changes in the QoL instruments and the patient assessment of disease activity or an objective disease activity index. Conclusion: SLEQOL distinguishes the differential effects on QoL of the various drugs. Treatment with intravenous cyclophosphamide and mycophenolate impacted the highest numbers of domains of SLEQOL, followed by azathioprine, cyclosporin A, and hydroxychloroquine. SLEQOL may be a useful outcome measure in SLE clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Over-expression of common inflammatory mediators in the metabolic syndrome (MetS) and in rheumatoid arthritis (RA) may lead to mutually adverse outcomes. Aim: We investigate the prevalence of MetS in a multi-ethnic population of RA patients and its effect on clinical and patient-reported outcomes. Method: Six hundred sixty RA (561 women) patients from a public-sector specialist clinic in a hospital in Singapore were assessed for MetS according to the 2009 Joint Consensus (JC) and the 2004 National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definitions. Univariable and multivariable regression modelling were used to investigate the associations between patients' demographics with MetS and MetS with RA outcomes. Results: The prevalence of MetS in our RA cohort was 49.4% and 44.9% according to the JC and NCEP ATP III definitions, respectively. The diagnosis of MetS was largely due to hypertriglyceridemia, hypertension, and obesity. MetS was associated with older age (OR 1.06 [95% CI 1.04–1.08]), Malay ethnicity (OR 1.78 [95% CI 1.02–3.09]), or Indian ethnicity (OR 3.07 [95% CI 1.68–5.59]). No significant associations between MetS and RA outcomes were observed. RA patients with MetS are more likely to suffer from stroke and ischemic heart disease. Conclusion: The prevalence of MetS in RA patients in Singapore was almost double that in the general population. MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease. RA patients, especially those older and of Indian and Malay ethnicities, should be routinely screened for MetS. Any MetS-defining condition should be actively controlled. Key Points • Approximately half of the RA sample from the Singapore RA population can be diagnosed with MetS. • Older patients, and patients of Malay and Indian ethnicities have higher odds of MetS. • MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease. [ABSTRACT FROM AUTHOR]

Aim: This study was undertaken to determine the incidence and patterns of malignancies in rheumatoid arthritis (RA) patients in our cohort. Methods: Between 2001 and 2013, we analyzed 1117 patients in the prospective Tan Tock Seng Hospital (TTSH) RA Registry. Patients who developed malignancies after the onset of RA were identified from this registry. Age‐ and sex‐adjusted standardized incidence ratios (SIRs) were calculated to compare observed to expected numbers of malignancies based on data from the Singapore Cancer Registry. Results: Out of 19 839 person‐years of follow‐up, 132 incident malignancies were diagnosed during the observation period. There were 114 (86.4%) solid‐organ tumors and 18 (13.6%) hematological malignancies. The SIR (95% confidence interval) for all malignancies combined was 1.28 (0.88‐1.87) for males and 1.21 (1.00‐1.46) for females. Compared to the general population, we found a 4‐ to 5‐fold increase in lymphoma among our RA patients compared to the general population (SIR 5.05 [1.90‐13.46] for males and 3.75 [1.95‐7.20] for females). The SIR of lung malignancy in male RA patients is 2.36 (1.23‐4.53) and SIR of cervical malignancy in female RA patients is 3.72 (2.20‐6.23). Conclusion: There is a trend toward an overall increased malignancy risk in our RA patients compared to the general population. Specifically, there is an increased risk of lymphomas in all RA patients, lung malignancy in male patients, and cervical malignancy in female patients, compared to the general population. [ABSTRACT FROM AUTHOR]

Objective To describe the demographic characteristics, clinical features, functional status and quality of life of elderly-onset ( EORA) and young-onset ( YORA) rheumatoid arthritis ( RA) patients in an Asian cohort. Methods We studied all RA patients in our prospective disease registry, utilizing baseline data. EORA was defined as disease onset at 60 years or older. We collected data from January 2001 to December 2012. Results There were 1206 patients in our cohort, of which 178 (14.8%) had EORA, with a mean age of onset of 66.7 ± 5.6 years. There were more males in the EORA than YORA group (23.0% vs. 14.7%, P = 0.005). EORA patients were diagnosed sooner after symptom onset and had a higher number of comorbidities (median 2 [inter-quartile range 1-3] vs. 1 (0-2), P < 0.001). They were less likely to be rheumatoid factor positive, had higher erythrocyte sedimentation rate values and lower hemoglobin concentrations. There was no significant difference in joint counts, Disease Activity Score of 28 joints activity score and prevalence of radiographic erosions. Though EORA patients had worse Health Assessment Questionnaire scores and poorer functional status than YORA ones, they had lower pain scores and higher scores in the general health and mental component summary of the Short Form-36. EORA patients received significantly lower numbers of disease-modifying anti-rheumatic drugs. Conclusions EORA and YORA patients had different demographic characteristics. Although they had similar disease activities, EORA patients received less intensive treatment. EORA patients had a higher number of RA-related co-morbidities and poorer physical functioning but they coped better emotionally and mentally. [ABSTRACT FROM AUTHOR]

Aim We sought to evaluate the relationship of urine levels of soluble cellular adhesion molecules s VCAM-1 (vascular) and s ICAM-1 (intercellular) in systemic lupus erythematosus ( SLE) patients with or without lupus nephritis, and to explore their correlation with renal disease activity. Methods Paired serum and urine samples of 121 Asian SLE patients, and urine samples of 19 normal healthy controls were collected. Demographic data, disease activity and damage scores, and selected laboratory parameters, including levels of anti-double stranded DNA antibody, complements C3, C4, and creatinine were captured. Renal disease activity was scored with renal SLE Activity Measure revised (r SLAM- R). Serum and urine s VCAM-1 and s ICAM-1 levels were assayed by enzyme-linked immunosorbent assay. Results Urinary s VCAM-1 and s ICAM-1 were elevated in SLE patients compared to controls. Significantly higher levels of urine s VCAM-1 found in patients with active lupus nephritis correlated with r SLAM- R. In addtion, significantly more patients with active lupus nephritis had detectable levels of urine s ICAM-1, but no correlation with renal activity was observed. Conclusion Urinary s VCAM-1 may serve as a potential biomarker for early diagnosis of lupus nephritis as levels correlated with even mild abnormalities of urine sediment. In addition, both urine s VCAM-1 and s ICAM-1 levels may be useful in identifying patients at risk of lupus nephritis. [ABSTRACT FROM AUTHOR]

Background Alcohol intake is inversely related to rheumatoid arthritis (RA) disease incidence and severity. Resveratrol, a safe, well-described plant-derived compound, possesses anti-inflammation and immuneregulatory properties and is present in red wine. As such, it could mediate anti-inflammatory properties of the latter and offer novel therapeutic utility in is own right. Objective To evaluate the therapeutic effect of resveratrol on collagen-induced arthritis (CIA) and its putative immune modulation in mice. Methods CIA was induced in DBA1 mice by immunisation with collagen II. Different doses of resveratrol were administered before or after the development of CIA. The levels of antibody and cytokines in serum or in draining lymph node (DLN) lymphocyte culture supernatants were measured by ELISA and Th17 cell development in DLN was monitored by flow cytometry. Results Either prophylactic or therapeutic administration of resveratrol attenuated clinical parameters and bone erosion in CIA mice. The arthritis-protective effects were associated with markedly reduced serum levels of pro-inflammatory cytokines and collagen-specific, but not total, IgG, and with reduced numbers of Th17 cells and the production of IL-17 in DLN. Conclusion Resveratrol modulates inflammatory arthritis in rodents by selectively suppressing key cellular and humoral responses necessary for disease development. This may partly explain the protective effects of red wine but importantly may offer a novel, effective and safe pathway whereby novel agents could be developed to treat RA. [ABSTRACT FROM AUTHOR]

We describe a 35-year-old Chinese woman with Behçet disease complicated by recurrent gastrointestinal flares. During admission for acute lower abdominal pain, a computed tomographic scan of the abdomen showed thrombosis of the left ovarian vein. She was treated with increased immunosuppressant and oral anticoagulant. Although she was not compliant to oral anticoagulant with her international normalized ratio frequently subtherapeutic, her symptoms abated and the thrombosis resolved. There has been only 1 reported case of a patient with Behçet disease presenting with postpartum ovarian vein thrombosis and pulmonary embolism and no reported case of Behçet disease with ovarian vein thrombosis occurring outside pregnancy and the puerperium. Ovarian vein thrombosis is a rare cause of abdominal pain that should be considered in patients with Behçet disease.

Objectives: This study aimed to identify potential blood-derived biomarkers distinguishing patients with ankylosing spondylitis from those with mechanical low back pain., Methods: Serum and synovial fluid samples from our cohorts were assayed by using enzyme-linked immunosorbent assay for the following inflammatory biomarkers: interleukin (IL)-1α, IL-6, IL-8, IL-17, IL-23, monocyte chemotactic protein (MCP)-1, macrophage inflammatory proteins (MIP)-1α, MIP-1β, tumor necrosis factor-α (TNF-α), interferon-α (IFN-α), IFN-β, metalloproteinase (MMP-3), and bone morphogenetic protein 7 (BMP-7)., Results: After screening, a panel of serum and synovial fluid samples with a series of potential biomarkers, cytokines including IL-6, IL-8, MMP-3, and MCP-1 were selected for additional testing because they exhibited higher concentrations than paired serum samples in the synovial fluid. Sera obtained from 50 patients with ankylosing spondylitis and 27 patients with mechanical low back pain were measured for these biomarkers., Conclusions: The MCP-1 serum was identified as a biomarker candidate, distinguishing ankylosing spondylitis from mechanical low back pain with a sensitivity of 96% and a specificity of 83.3%.