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Cyclophosphamide is an important immunosuppressive agent in the treatment of many rheumatic diseases. Urticaria and anaphylaxis to intravenous cyclophosphamide (i.v. CYC) have been reported in patients with haematological and solid organ malignancies. This is the first report in the rheumatology literature of a type I hypersensitivity reaction following monthly i.v. CYC. An 18-year-old girl with systemic lupus erythematosus (SLE) developed generalized urticaria (without concomitant angioedema or anaphylaxis) following i.v. CYC. She had previously developed life-threatening angioedema following a respiratory tract infection. She successfully completed regular pulse i.v. CYC with pre-medication with anti-histamine. In the absence of a severe type I hypersensitivity reaction and other suitable immunosuppressive agents, i.v. CYC may be safely continued with pre-medication and careful monitoring during each infusion. [ABSTRACT FROM AUTHOR]

Singapore managed the COVID-19 pandemic in the past three years and gleaned valuable lessons on patient management when the public healthcare system was inundated with COVID-19 patients. There were several initiatives, which included setting up of community treatment facilities to help hospitals manage in-patient loads that did not require acute monitoring, leveraging telemedicine, and developing heuristics to sort patients based on their clinical disposition to various care pathways and to effectively manage patients of different medical needs. These initiatives were implemented in the second year of the epidemic in 2021 and did not include the dormitory-based migrant workers and migrant workers in the construction, maritime and production sectors who were under the care of the Assurance, Care and Engagement Group (ACE) in the Ministry of Manpower that had its own set of treatment management measures. The different care pathways ensured that patients received appropriate levels of care and allowed healthcare facilities to focus on more acute cases. In 2022 alone, 23,159 patients were discharged from community treatment facilities against the background of 1.9 million COVID-19 patients. These initiatives would not be possible without the oversight of an advisory board comprising senior leadership from the healthcare clusters and the Ministry of Health to align clinical governance with medical policies, and prompt and immense support from medical specialist panels. The strong public-private partnership forged in the process was instrumental in the successful operation of community facilities and implementation of patient care protocols, coupled with harnessing information technology and leveraging on emerging data to refine care protocols.

Introduction: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are used in the diagnosis and prognostication of rheumatoid arthritis (RA). We wanted to determine the specific contributions of RF and ACPA to the biological nature of RA and whether they act synergistically., Methods: We identified 731 patients from our prospective multi-ethnic RA cohort and categorised them into four groups: ACPA-positive, RF-positive, doubly positive and doubly negative. We compared the demographics, Disease Activity Score-28, Health Assessment Questionnaire score, quality of life using Short Form 36 and the use of prednisolone and disease-modifying antirheumatic drugs (DMARDs) of these patient groups., Results: Four hundred and ninety-one patients (67.2%) were ACPA+RF+, 54 (7.4%) were ACPA+RF-, 82 (11.2%) were ACPA-RF+ and 104 (14.2%) were ACPA-RF-. Mean disease duration before the study entry was not different in the four groups. Patients with older age of onset were less likely to be positive for RF and ACPA. Fewer ACPA+RF+ patients were in remission compared to those in the other groups (P < 0.05). Erythrocyte sedimentation rate (ESR) was higher at study entry in the ACPA+RF+ group (40.4 mm/h vs. 30.6-30.9 mm/h, P < 0.05). Prednisolone and number of DMARDs used were higher in the ACPA+RF+ group compared to the doubly negative group. There were no differences in the functional status and quality of life., Conclusions: RA patients who were positive for both ACPA and RF had lower remission rate, higher baseline ESR and required more corticosteroid and DMARD treatment compared to those who were singly positive or doubly negative. Being doubly positive confers a worse outcome to RA patients., Competing Interests: None

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., (© 2023. The Author(s).)

Objectives: The Montreal Cognitive Assessment (MoCA) is an increasingly used screening tool for cognitive impairment. The aim of this study was to examine how MoCA performed in identifying cognitive impairment (CI) domains in SLE patients compared with formal standardized neuropsychological testing (NPT). Factors related to SLE disease, immunologic and psychological state associated with CI were also explored., Methods: This cross-sectional study recruited 50 SLE patients without overt neuropsychiatric manifestations from April 2017 to May 2018. The patients were evaluated with MoCA, formal NPT and the Depression, Anxiety, and Stress Scales (DASS) 42-item self-report questionnaire. Values of sensitivity and specificity were computed for different cut-offs of MoCA within each cognitive domain of NPT and descriptive analysis was used to identify the factors affecting cognitive function., Results: The median score for MoCA was 27.5 (range 22-30). Using a MoCA cutoff of <26, 18 (36%) were identified to have CI using NPT compared to 8 (16%) using MoCA. The most frequently affected cognitive domain was executive functioning with 15 affected patients. Sensitivities and specificities of the MoCA range from 50% to 100% and 5.7% to 16.7%, respectively, across cognitive domains. A lower MoCA cutoff of <25 improve sensitivity of identifying impairment in executive functioning from 60% to 80%. In univariate analysis, DASS scores, disease activity, presence of antiphospholipid antibodies, presence of concurrent autoimmune disease, current, and cumulative corticosteroid therapy did not predict cognitive performance., Conclusion: MoCA may be a useful screening tool to identify the most frequently affected cognitive domain which is executive functioning using a lower cutoff of <25 in SLE patients without overt neuropsychiatric manifestations.

Objective: To develop a hypothesis-free model that best predicts response to MTX drug in RA patients utilizing biologically meaningful genetic feature selection of potentially functional single nucleotide polymorphisms (pfSNPs) through robust machine learning (ML) feature selection methods., Methods: MTX-treated RA patients with known response were divided in a 4:1 ratio into training and test sets. From the patients' exomes, potential features for classifier prediction were identified from pfSNPs and non-genetic factors through ML using recursive feature elimination with cross-validation incorporating the random forest classifier. Feature selection was repeated on random subsets of the training cohort, and consensus features were assembled into the final feature set. This feature set was evaluated for predictive potential using six ML classifiers, first by cross-validation within the training set, and finally by analysing its performance with the unseen test set., Results: The final feature set contains 56 pfSNPs and five non-genetic factors. The majority of these pfSNPs are located in pathways related to RA pathogenesis or MTX action and are predicted to modulate gene expression. When used for training in six ML classifiers, performance was good in both the training set (area under the curve: 0.855-0.916; sensitivity: 0.715-0.892; and specificity: 0.733-0.862) and the unseen test set (area under the curve: 0.751-0.826; sensitivity: 0.581-0.839; and specificity: 0.641-0.923)., Conclusion: Sensitive and specific predictors of MTX response in RA patients were identified in this study through a novel strategy combining biologically meaningful and machine learning feature selection and training. These predictors may facilitate better treatment decision-making in RA management., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© 2021. International League of Associations for Rheumatology (ILAR).)

Background: Major challenges in large scale genetic association studies include not only the identification of causative single nucleotide polymorphisms (SNPs), but also accounting for SNP-SNP interactions. This study thus proposes a novel feature engineering approach integrating potentially functional coding haplotypes (pfcHap) with machine-learning (ML) feature selection to identify biologically meaningful, possibly causative genetic factors, that take into consideration potential SNP-SNP interactions within the pfcHap, to best predict for methotrexate (MTX) response in rheumatoid arthritis (RA) patients., Methods: Exome sequencing from 349 RA patients were analysed, of which they were split into training and unseen test set. Inferred pfcHaps were combined with 30 non-genetic features to undergo ML recursive feature elimination with cross-validation using the training set. Predictive capacity and robustness of the selected features were assessed using six popular machine learning models through a train set cross-validation and evaluated in an unseen test set., Findings: Significantly, 100 features (95 pfcHaps, 5 non-genetic factors) were identified to have good predictive performance (AUC: 0.776-0.828; Sensitivity: 0.656-0.813; Specificity: 0.684-0.868) across all six ML models in an unseen test dataset for the prediction of MTX response in RA patients., Interpretation: Majority of the predictive pfcHap SNPs were predicted to be potentially functional and some of the genes in which the pfcHap resides in were identified to be associated with previously reported MTX/RA pathways., Funding: Singapore Ministry of Health's National Medical Research Council (NMRC) [NMRC/CBRG/0095/2015; CG12Aug17; CGAug16M012; NMRC/CG/017/2013]; National Cancer Center Research Fund and block funding Duke-NUS Medical School.; Singapore Ministry of Education Academic Research Fund Tier 2 grant MOE2019-T2-1-138., Competing Interests: Declaration of Competing Interest CGL, KPL, CCK, SSC, AJWL, and LJL declare that they have a pending Coversheet IP application., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: We evaluated the impact of type 2 diabetes mellitus (T2DM) on RA treatment and outcomes in a longitudinal RA cohort., Methods: We analysed data collected in the period 2001-2013 involving 583 RA patients, including demographics, diabetes diagnosis, clinical features, treatment, ACR functional class, HAQ, and quality-of-life measurement using the Short-Form 36., Results: Seventy-seven (13.2%) of the RA patients had T2DM. DAS28 was not different in patients with T2DM at 5 years post-RA diagnosis. Fewer T2DM patients received MTX than those without T2DM (51% vs 80%, P < 0.001). Using univariate analysis, T2DM patients were more likely to experience poorer outcomes in terms of ACR functional status ( P = 0.009), joint surgery ( P = 0.007), knee arthroplasty ( P < 0.001) and hospital admissions ( P = 0.006). Multivariate regression analyses showed more knee arthroplasty ( P = 0.047) in patients with T2DM., Conclusion: Fewer patients with T2DM received MTX compared with those without T2DM. Patients with RA and T2DM were at higher risk of knee arthroplasty than RA patients without T2DM., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: This study aims to uncover variants of large effect size and allele frequency below 5% by sequencing all extant genes associated with rheumatoid arthritis (RA) in a homogeneous patient cohort., Patients and Methods: This retrospective study was conducted between January 2001 and December 2017. We selected Chinese RA patients positive for anti-citrullinated peptide antibody (ACPA). All the 128 known candidate genes identified through genome-wide association studies were sequenced in 48 RA patients (15 males, 33 females; mean age 53.32±8.98 years; range, 32 to 75 years) and 45 controls (11 males, 34 females; mean age 32.18±9.54; range, 21 to 57 years). The exonic regions of these genes were sequenced. The resultant data were analyzed for association using single variant association and pathway-based association enrichment tests. The genetic burden due to low-frequency variants was assessed with the C-alpha test. The candidate variants that showed significant association were validated in a larger cohort of 500 RA cases (71 males, 429 females; mean age 48.6±12.2 years; range, 24 to 92 years) and 500 controls (66 males, 434 females; mean age 32.3±10.1 years; range, 21 to 73 years)., Results: Thirty-nine variants in 21 genes were identified using single variant association analysis and C-alpha test, with stepwise filtering. Among these, the missense variant in interleukin-6 signal transducer (IL-6ST) 5:55260065 (p.Cys47Phe) was significantly associated with RA in Chinese patients in Singapore., Conclusion: Our results suggest that a mutation in IL-6ST (5:55260065) confers risk of RA in Chinese patients in Singapore., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2021, Turkish League Against Rheumatism.)

Feature selection (marker gene selection) is widely believed to improve clustering accuracy, and is thus a key component of single cell clustering pipelines. Existing feature selection methods perform inconsistently across datasets, occasionally even resulting in poorer clustering accuracy than without feature selection. Moreover, existing methods ignore information contained in gene-gene correlations. Here, we introduce DUBStepR (Determining the Underlying Basis using Stepwise Regression), a feature selection algorithm that leverages gene-gene correlations with a novel measure of inhomogeneity in feature space, termed the Density Index (DI). Despite selecting a relatively small number of genes, DUBStepR substantially outperformed existing single-cell feature selection methods across diverse clustering benchmarks. Additionally, DUBStepR was the only method to robustly deconvolve T and NK heterogeneity by identifying disease-associated common and rare cell types and subtypes in PBMCs from rheumatoid arthritis patients. DUBStepR is scalable to over a million cells, and can be straightforwardly applied to other data types such as single-cell ATAC-seq. We propose DUBStepR as a general-purpose feature selection solution for accurately clustering single-cell data., (© 2021. The Author(s).)

Objective: Disease activity indices for rheumatoid arthritis (RA) are important in clinical practice and research. Although they are closely correlated, they are not in good agreement. We derived formulae to convert values from one of the four 28-joint count indices (disease activity score using erythrocyte sedimentation rate [DAS28-ESR], disease activity score using C-reactive protein [DAS28-CRP], clinical disease activity index [CDAI], and simple disease activity index [SDAI]) to any of the others., Methods: We obtained data from 175 patients from our RA registry with concurrent CRP and ESR and established the nature of relationships between the indices using these data. Subsequently, we developed empiric conversion formulae. Furthermore, we developed new cutoff values for classifying disease activity to minimize the disparity among indices, using an iterative method., Results: The relationships between DAS28-ESR and DAS28-CRP and between SDAI and CDAI were approximately linear; the others were quadratic. Quadratic equations approximated the relationship between DAS, SDAI, and CDAI, whereas natural logarithms function approximated the relationship between DAS28-ESR and DAS28-CRP. Patients are frequently categorized into inconsistent disease activity states with any two indices, with the disparity ranging from 9.7% to 40.6%. The new cutoff values were developed to minimize the discrepant activity state categorization, reducing the disparity range to 6.3%-32.6%., Conclusion: We derived empiric formulae that connect DAS28-ESR, DAS28-CRP, SDAI, and CDAI. Moreover, we developed new cutoff values to minimize the discrepant activity state categorization with different indices.

Objective: Urinary tract endometriosis involves the bladder and/or the ureters and is present in approximately 1% of women with endometriosis [1]. Bladder endometriosis is the most frequent type of urinary tract endometriosis, occurring in about 70% to 85% of cases [2,3]. Bladder endometriosis is defined as the presence of endometrial glands and stroma in the detrusor muscle. Surgically, there are 2 ways of excising this disease. The first is by transurethral bladder resection of the tumor, and the second is laparoscopic/robotic/open partial cystectomy of the bladder endometriosis. Because the nodule develops from the outer layer of the bladder wall toward the inner layer, complete excision of the endometriotic lesion is virtually unachievable with transurethral resection surgery. There is also a high risk of bladder perforation [4-8]. Partial cystectomy of the bladder runs a risk of excising normal bladder tissues because it is difficult to ascertain the margins of the bladder nodule. However, we found the best method to deal with bladder endometriosis is a combined approach whereby the margins of the bladder nodule are cut via a cystoscopy and then excision of the bladder nodule is done laparoscopically. This particular technique is presented here with an accompanying video., Design: Excision of bladder endometriosis by first delineating the tumor via cystoscopy and simultaneously excising the nodule laparoscopically SETTING: Mahkota Medical Centre, Melaka, Malaysia., Intervention: Here we describe a simultaneous cystoscopic and laparoscopic excision of bladder endometriosis. The patient was first seen in 2005 at age 19 years with an endometrioma. She was single (virgo intacta) at that time. She underwent a laparoscopic cystectomy. Postoperatively, she received 3 doses of monthly gonadotropin-releasing hormone (GnRH) analogue injection. She was last seen in 2006 and was well. She conceived spontaneously after that and delivered 2 babies spontaneously in 2007 and 2010 in another city. She consulted me again in April 2016 complaining of dysuria, dysmenorrhea, and inability to hold her urine. She had consulted a urologist 6 months earlier. Cystoscopy performed by the urologist showed bladder endometriosis. No further surgery was performed, and she was given GnRH analogues for 6 months. However, her symptoms persisted after completion of the GnRH analogue. Examination and ultrasound showed a large bladder nodule measuring 4.17 × 2.80 cm. Intravenous urogram showed stricture in the upper right ureter. She underwent a combined urology and gynecology surgery to excise the bladder nodule. Informed consent was obtained from the patient, and the local institutional board provided the approval. The surgery was performed with the patient in the dorsosacral position. A Verres needle was inserted into the abdomen at the umbilicus, and carbon dioxide insufflation was performed. A 10-mm trocar was inserted in the umbilicus, and a 3-dimensional laparoscope (Aesculup-BBraun Einstein Vision; BBraun, Melsungen AG, Germany) was inserted to view the pelvis. Three 5-mm trocars were inserted, 1 on the right side and 2 on the left side of the abdomen. A RUMI (CooperSurgical, Trumbull, CT) uterine manipulator was placed into the uterine cavity. Laparoscopy showed no adhesions in the upper and mid-abdomen. The appendix and the intestines looked normal. Both the ovaries and fallopian tubes were normal. Uterine insufflation with methylene blue showed that both tubes were patent. There was dense endometriosis between the bladder and fundus of the uterus. The omentum was also adherent to the site of the endometriosis. There were endometriotic nodules on the left uterosacral ligaments and the peritoneum in the wall in the pouch of Douglas. The omentum was released, and laparoscopic adhesiolysis was performed. Both the paravesical spaces lateral to the nodule were dissected out. The bladder was released from the uterus with some difficulty. The peritoneal endometriosis in the Pouch of Douglas and the nodules in the left uterosacral ligament were excised. Cystoscopy was performed and stents were first placed in both ureters. The nodule was found to be in the central position, and the margins were about 2 cm from both the ureteral orifices. The nodule was seen protruding into the bladder containing bluish lesions. Demarcation of the bladder endometriosis was done using a resectoscope. Using a needle electrode, a deep circular incision was made around the bladder nodule and into the detrusor muscle. Cystoscopic perforation of the bladder was done and was seen laparoscopically. The bladder endometriotic nodule was completely excised laparoscopically after the demarcation line created via the cystoscopy. Stay sutures were first placed at the superior and inferior edges of the defect. The bladder was repaired continuously in 1 layer using polyglactin 3-0 sutures. The nodule was placed in a bag cut into smaller pieces and removed through the umbilical incision. At the end of the surgery a cystoscopy was perform to check the integrity of the suture. The pelvis was then washed. A bladder catheter was placed. The trocars were then removed under vision, and the rectus sheath was closed using polyglactin 1 suture. The skin incisions were closed. The operation time was 2 hours. The patient received antibiotics for 10 days. She was discharged with a catheter in place on day 3. She underwent a cystogram on day 10 of the surgery, and the bladder was found to be intact. The catheter was then removed. She was seen 6 weeks after the surgery and was well without any symptoms. The ureteric catheters were removed. Histopathology confirmed bladder endometriosis. Five months later she conceived spontaneously and delivered her third child naturally in June 2017. She was seen after her delivery and was advised to take oral contraceptive pills continuously or an intrauterine contraceptive device to prevent recurrence of the endometriosis. She took the oral contraceptive pills for 3 months and then refused any further treatment. She was last seen in February 2019 and was well without any symptoms., Conclusion: In bladder endometriosis a combined approach with the urologist can assist in safely excising deep bladder endometriosis without removal of normal bladder tissue. Stents placed in the ureter assist in avoiding injury to the ureters. Demarcating the endometriotic nodule by the urologist through the bladder and excising the bladder nodule laparoscopically is both safe and effective., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

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., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = -0·436, P < 0·01), levels of anti-dsDNA antibody (r = -0·347, P < 0·02) and BAFF (r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies., (© 2017 British Society for Immunology.)

Studies have shown that the genetic risk factors for rheumatoid arthritis (RA) differ substantially between Asian and Caucasian populations. Even among Asian populations, the genetic contributions of NLRP1, PTPN22 and PADI4 have been controversial. Consequently, we sought to address these separate findings and determine whether any of these proposed risk variants are associated with RA susceptibility, onset, DAS activity and erosion in a Singaporean Chinese cohort. We genotyped five SNPs within NLRP1 (rs878329 and rs6502867), PTPN22 (rs2488457 and rs6665194), and PADI4 (rs2240340) in 500 anti-cyclic citrullinated peptide antibody-positive (ACPA) patients with RA and 500 healthy controls using TaqMan assays. The CC genotype of NLRP1 rs878329 and TT genotype of PADI4 rs2240340 were associated with RA susceptibility. The risk association of the T allele of PADI4 rs2240340 with RA was confirmed through a meta-analysis based on previous reports in Asian populations. The GG genotype of PTPN22 rs6665194 (-3508A>G) was associated with significantly reduced risk of RA. No significant association was found for NLRP1 rs6502867 T/C and PTPN22 rs2488457 G/C polymorphisms. None of the five SNPs was associated with RA's clinical features. This work supports the association of the T allele of PADI4 rs2240340 with RA in Asians. The roles of NLRP1 rs878329 G/C and PTPN22 rs6665194 A/G polymorphisms were demonstrated for the first time. We also propose rs6665194 to be a promising candidate for RA risk evaluation between ethnicities.

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., (© 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Introduction: Up to 30% of patients with rheumatoid arthritis (RA) respond inadequately to conventional non-biologic disease modifying antirheumatic drugs (nbDMARDs), and may benefit from therapy with biologic DMARDs (bDMARDs). However, the high cost of bDMARDs limits their widespread use. The Chapter of Rheumatologists, College of Physicians, Academy of Medicine, Singapore aims to define clinical eligibility for government-assisted funding of bDMARDs for local RA patients., Materials and Methods: Evidence synthesis was performed by reviewing 7 published guidelines on use of biologics for RA. Using the modified RAND/UCLA Appropriateness Method (RAM), rheumatologists rated indications for therapies for different clinical scenarios. Points reflecting the output from the formal group consensus were used to formulate the practice recommendations., Results: Ten recommendations including diagnosis of RA, choice of disease activity measure, initiation and continuation of bDMARD and option of first and second-line therapies were formulated. The panellists agreed that a bDMARD is indicated if a patient has (1) active RA with a Disease Activity Score in 28 joints (DAS28) score of ≥3.2, (2) a minimum of 6 swollen and tender joints, and (3) has failed a minimum of 2 nbDMARD combinations of adequate dose regimen for at least 3 months each. To qualify for continued biologic therapy, a patient must have (1) documentation of DAS28 every 3 months and (2) at least a European League Against Rheumatism (EULAR) moderate response by 6 months after commencement of therapy., Conclusion: The recommendations developed by a formal group consensus method may be useful for clinical practice and guiding funding decisions by relevant authorities in making bDMARDs usage accessible and equitable to eligible patients in Singapore.

To investigate the association between helplessness, disability, and disease activity with health-related quality of life (HRQoL) in a multiethnic cohort of rheumatoid arthritis (RA) patients in Singapore. This cross-sectional study was conducted at Tan Tock Seng Hospital, Department of Rheumatology, Allergy and Immunology, from October 2010 to October 2011. All patients fulfilled the American College of Rheumatology 1987 criteria for RA. Socio-demographics, clinical, and patient-reported outcome (PRO) variables were collected. HRQoL outcomes were Short Form 36 (SF-36) physical and mental component summary (PCS and MCS) scores and Short Form 6 Dimensions (SF-6D) utilities. Stepwise multiple linear regression analyses were performed using HRQoL outcomes as dependent variables in separate models and with adjustment for helplessness (Rheumatology Attitudes Index, RAI), disability (Health Assessment Questionnaire, HAQ), and disease activity (Disease Activity in 28 joints) followed by socio-demographic, clinical, and PRO variables. Complete data were provided by 473 consenting subjects [mean (SD) age: 60.02 (11.04) years, 85 % female, 77 % Chinese]. After adjustment for all measured covariates, only RAI and HAQ scores remained significantly associated with SF-36 MCS (β: -0.9, p < 0.001; β: -7.0, p < 0.001) and SF-6D utilities (β: -0.005, p < 0.001; β: -0.081, p < 0.001), respectively, while only HAQ scores were significantly associated with SF-36 PCS (β: -7.7, p < 0.001). Interventions to address the sense of helplessness and to prevent or reduce disability could improve HRQoL of RA patients.

Background: The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore., Methods: Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis., Results: Among the 978 patients who had received MTX, the prevalence of MTX-associated NAFLD was 4.7% (46 patients). Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g, P ≤ 0.05), weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly, P = 0.033), and fasting blood glucose (P = 0.029). Following multivariate regression analysis, only cumulative dose of MTX remained significant (P = 0.015). Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT) level (P < 0.05, standardised beta coefficient 0.512)., Conclusion: The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis.

We analyzed the epidemiological changes of rheumatoid arthritis (RA) over three decades using patients from a single center in Singapore. All patients who fulfill the 1987 American College of Rheumatology criteria for RA were invited to enroll in a prospective disease registry. We analyzed the patient demographics, disease manifestation, management and patient-reported outcomes, including quality of life (QoL), in the three categories according to the year of disease onset: before 1989 (group I), 1990-1999 (group II) and after 2000 (group III). There were 1,153 patients with 231, 532 and 390 in groups I, II and III, respectively. The mean disease durations were 25, 12 and 4.8 years, respectively. The majority was female (84.1 %) and Chinese (76.6 %) with no socio-demographic differences across the three periods. The age of onset rises and the prevalence of rheumatoid factor falls with the proximity of disease onset. Patients with most recent disease onset had the earliest access to the rheumatologist. They also had the highest tender and swollen joint counts, lowest deformed joint count and highest remission rate. Patients in group I report better mental and emotional QoL though many developed marked disability. We have documented changes of the manifestations of RA that are dependent and independent of improved treatment. Significant differences in accessibility to the rheumatologist, RA activity, functional capacity, quality of life and comorbidities were seen in subsequent cohorts due to treatment evolution and more efficient healthcare delivery.

A genome-wide association study in Japan identified the C-C chemokine receptor type 6 gene (CCR6) as associated with rheumatoid arthritis (RA). This finding has not been validated in other Asian populations. A case-control study involving 996 subjects, comprising 440 controls and 556 RA patients, was done to determine their anticyclic citrullinated peptide (anti-CCP) antibody status and CCR6 polymorphism (rs3093024) genotype. Three hundred eighty-seven patients were anti-CCP positive and 153 anti-CCP negative. Logistic regression showed that allele A was likely to increase the risk of developing RA among females via a recessive model (odds ratio [OR]=1.55, 95% confidence interval [CI]=1.01, 2.39), whereas the risk effect appeared to be reduced among males via an additive model (OR=0.60, 95% CI=0.42, 0.85). Considering only subjects who are anti-CCP positive, allele A increased RA risk among females via a recessive model (OR=1.68, 95% CI=1.07, 2.64) but decreased the risk among males via an additive model (OR=0.59, 95% CI=0.39, 0.89). We showed that CCR6 polymorphism was a risk factor among females but a protective factor among males. Functional studies are warranted to unravel the pathophysiological relevance of the gene variant and other linked variants with RA.

Patients with systemic lupus erythematosus often assess their disease activity differently from their physicians. We studied the factors associated with this discordance. The data provided by 534 systemic lupus erythematosus patients were analyzed. We compared the physician and patient assessments of lupus activity on a visual-assessment scale from the same visit. We collected clinical data and scores from MOS 36-Item Short-Form Health Survey, Systemic Lupus Erythematosus Quality-of-Life Questionnaire, Rheumatology Attitudes Index, Systemic Lupus Erythematosus Disease Activity Index, and revised Systemic Lupus Activity Measure. Patients tended to score their disease activity higher than do their physicians, when these factors were present: poorer general health assessment, presence of thrombocytopenia, hypertension and urinary sediments, and difficulty in carrying groceries. Physicians tended to score the disease activity higher than do the patients in these circumstances proteinuria, hemolysis, use of azathioprine or cyclophosphamide, tiredness, photosensitivity, higher revised Systemic Lupus Activity Measure score, casturia, and patient report of being more easily ill than are other patients. There was only moderate correlation between the discordance in the baseline and the subsequent visits. The physician assessment of disease activity at baseline correlated better with an objective measure of disease activity (revised Systemic Lupus Activity Measure) in the subsequent visit than the patient assessment. In conclusion, discordance in the perception of disease activity between patients and physicians may be amenable to intervention.

Our objective was to investigate the serum levels of interferon-inducible protein-10 (IP-10) in systemic lupus erythematosus (SLE) and their correlation with disease activity and organ manifestations. Serum IP-10 levels were assessed in 464 SLE patients and 50 healthy donors. Disease activity was assessed by the revised SLE Activity Measure, and the concomitant active organ manifestations, anti-ds DNA antibody titres, complement levels and erythrocyte sedimentation rates recorded. Peripheral blood mononuclear cell (PBMC) synthesis of IP-10 in SLE patients and controls was determined by in vitro cultures stimulated with mitogen or lipopolysaccharide. Elevated serum IP-10 levels were observed in SLE patients, which were significantly higher in the presence of active haematological and mucocutaneous manifestations. SLE PBMCs exhibited enhanced spontaneous IP-10 production in vitro. Serial IP-10 levels correlated with longitudinal change in SLE activity, even at low levels where anti-dsDNA antibody and complement levels remain unchanged. These data demonstrate that IP-10 levels are increased in SLE and serum IP-10 may represent a more sensitive marker for monitoring disease activity than standard serological tests.

Introduction: The aim of this study was to ascertain the outcomes of chronic hepatitis B (CHB) infection following immunosuppressive therapy in 38 consecutive oriental patients with systemic rheumatic diseases., Materials and Methods: This is a retrospective consecutive, non-comparative study., Results: The majority of patients were female (26, 68.4%), predominantly Chinese (92.1%), with a mean age 54 +/- 14 years (range, 16 to 87). The mean duration of rheumatic disease was 9 +/- 11 years (range, 0.1 to 48), with rheumatoid arthritis (52.6%) and systemic lupus erythematosus (23.7%) being the most common. The mean duration of CHB infection was 6 +/- 5 years (range, 0.1 to 17), with the majority diagnosed during pre-methotrexate screening (50.0%) and asymptomatic transaminitis following initiation of immunosuppressive therapy (23.7%). Upon diagnosis of rheumatic disease, all patients had normal alanine aminotransferase (ALT). Of these, 18.2% were positive for hepatitis B e antigen (HBeAg) and 78.1% were positive for anti- HBe antibody. Twenty (52.6%) developed ALT elevation, which was more than twice the upper limit of normal in 12 patients. ALT normalised spontaneously in 12 patients without hepatic decompensation or change in therapy. Seven (18.4%) patients received lamivudine for 18 +/- 22 months (range, 2 to 61). Two patients developed YMDD mutation subsequently treated with adefovir (1) and adefovir/lamivudine (1). There were 3 (7.9%) hepatitis B virus (HBV)-unrelated deaths [infection (2), genitourinary malignancy (1)], and 1 from HBV-reactivation complicated by septicaemia. None have developed hepatocellular carcinoma., Conclusion: Elevated ALT occurred in 52.6% of patients, with only 18.4% requiring anti-viral therapy for HBV reactivation. HBV-related mortality was low. With the appropriate precautionary measures, prednisolone and immunosuppressants (except methotrexate and leflunomide) may be used safely in patients where clinically indicated.

Objective: To assess the reliability, validity and sensitivity to change of a Chinese version of the 36-item Short-Form Health Survey (SF-36) in Chinese-speaking patients with rheumatoid arthritis (RA) in Singapore., Methods: The psychometric properties of the Chinese Hong Kong standard version of the SF-36 were assessed in 401 RA patients. The construct validity of the Chinese SF-36 was assessed by comparison with the American College of Rheumatology (ACR) functional status, a validated Chinese Health Assessment Questionnaire (C-HAQ) and markers of RA activity and severity., Results: The overall Cronbach's coefficient alpha was 0.921, reflecting excellent internal consistency. The instrument showed reasonable test-retest reliability except in the social functioning (SF) subscale. There was a significant ceiling effect in the role physical (RP), SF and role emotional (RE) subscales and a floor effect in the RP and RE subscales. Physical function (PF) and SF were strongly correlated with C-HAQ and patient's assessment of RA activity [Pearson's correlation coefficient (r) ranging from -0.41 to -0.53] and moderately correlated with ACR functional status (r = -0.35 and -0.3, respectively). Weak correlations were also found between the Chinese SF-36 and markers of RA activity, deformed joint count and radiographic damage. PF and SF were the subscales most responsive to change in quality of life (QOL)., Conclusion: The Chinese SF-36 showed reasonable reliability, criterion validity and responsiveness with limitations in certain subscales. Overall, the physical domains and PF in particular may be the most ideal psychometric measures of QOL in RA.

Objectives: Systemic lupus erythematosus (SLE), a chronic illness with an unpredictable and variable course, profoundly affects the quality of life (QOL). General health questionnaires are used to assess QOL in SLE, but a disease-specific instrument could offer enhanced responsiveness and content validity. We detail the steps we took to develop and validate a new SLE-specific QOL instrument, SLEQOL., Methods: Rheumatology professionals nominated items that they felt were important determinants of QOL of SLE patients. One hundred SLE patients were asked to assess the importance and frequency of occurrence of these items and to suggest those that had not been listed. Item reduction was performed using Rasch model and factor analyses to create a new questionnaire in English. This final questionnaire was administered to a cohort of 275 patients to study its psychometric properties., Results: Fifty-one items covering a wide range of QOL concerns were identified. The patients' responses led to the elimination of 11. The new questionnaire of 40 items was found to have Cronbach's alpha of 0.95 and to consist of eight domains covering physical, mental and social QOL issues. It has good test-retest reliability, poor to fair cross-sectional correlation with the SF-36, with poor correlation with lupus activity or damage indices. The SLEQOL was more responsive to change than the SF-36., Conclusions: We have developed a new 40-item SLEQOL in English and showed that it is valid for use in SLE patients in Singapore. It offers better content validity and responsiveness to change than the SF-36.

The purposes of this investigation were 2-fold: to study the physical properties and sealing ability of Viscosity Enhanced Root Repair Material (VERRM); and, to compare them with Mineral Trioxide Aggregate (MTA). VERRM has a composition similar to mineral trioxide aggregate, with handling characteristics and consistency similar to commercially available materials such as IRM and Super EBA. The pH, setting times, solubility, radiopacity, dimensional change upon setting, and apical sealing ability of VERRM were evaluated and compared to that of ProRoot MTA (GMTA) and ProRoot MTA (Tooth Colored Formula) (WMTA). The results showed that VERRM had physical properties similar to WMTA. VERRM and WMTA showed significantly greater dye penetration than GMTA (p < 0.05) when used as a root-end filling material. There was no significant difference in depth of dye penetration between VERRM and WMTA. Further development of VERRM is indicated to produce a biocompatible root-end filling material with superior handling characteristics.

Objectives: To study serum levels of transforming growth factor beta-1 (TGFbeta1) and the expression of TGFbeta1 in in vitro peripheral blood mononuclear cell (PBMC) cultures in oriental ankylosing spondylitis (AS) patients, and to determine their association with codon 10 and 25 TGFB1 gene polymorphisms., Methods: Serum levels of TGFbeta1 were measured by enzyme-linked immunosorbent assay (ELISA). The ability of PBMCs to synthesize TGFbeta1 and other cytokines was assessed by in vitro cultures stimulated with mitogen. Genomic DNA was extracted from PBMCs of AS patients (n=72) or unrelated healthy controls (n=96). The codon 10 and 25 polymorphisms in the TGFB1 gene were analysed using standard polymerase chain reaction-based methods., Results: AS patients had significantly higher serum TGFbeta1 levels than controls (P<0.001). There was no difference in the distribution of codon 10 and 25 TGFB1 genotypes between AS patients and controls. Incubation of AS and control PBMC with phytohaemagglutinin (PHA) led to upregulation of TGFbeta1, interleukin-10, tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) assessed by ELISA. Importantly, PHA-induced TGFbeta1 production was significantly enhanced in AS patients compared with normal controls whereas the production of the pro-inflammatory cytokines TNFalpha and IFNgamma was reduced., Conclusions: Our results show that AS patients express significantly higher levels of serum TGFbeta1 independent of the codon 10 and 25 genotype. Activation of AS PBMCs led to enhanced TGFbeta1 production accompanied by reduction of TNFalpha and IFNgamma while the converse was observed in normal controls.

Introduction: Arthritis and endophthalmitis are both recognised complications of meningococcal infection. They may occur in the presence or absence of meningitis or meningococcaemia. Primary meningococcal arthritis (PMA) and endophthalmitis are important diagnoses to recognise as delayed treatment would result in permanent joint and eye damage. We report the first patient with both PMA and meningococcal endophthalmitis and present a review of the literature., Clinical Picture: An afebrile, non-toxic, 54-year-old female presented with arthritis and a painful red left eye following an episode of diarrhoea. An initial diagnosis of reactive arthritis with uveitis was made. However, subsequent microbiological investigations isolated Neisseria meningitides thus confirming the final diagnosis., Treatment: Antibiotics were instituted., Outcome: There was complete resolution of the arthritis but her left eye vision had deteriorated to just perception of light., Conclusion: The presentations of PMA and meningococcal endophthalmitis are often confusing. This should be considered in the differential diagnosis of reactive arthritis and acute dermatitis-arthritis syndrome.

Medium-sized artery aneurysms are rare in patients with systemic lupus erythematosus (SLE). We report on a 21-year-old Chinese man with SLE and secondary antiphospholipid syndrome (APS) who presented with acute abdominal pain due to a ruptured right hepatic artery aneurysm. He was also found to have aneurysms of the left hepatic artery and splenic artery on autopsy. There have been only eight cases of hepatic artery aneurysm and one case of splenic artery aneurysm associated with SLE in the English literature. Abdominal aneurysm must be suspected in SLE patients presenting with acute abdominal pain, haemoperitoneum or occult bleeding.

Objective: To examine the relationship between ethnicity and major organ involvement at and after diagnosis in community-based cohorts of Caucasian and Chinese systemic lupus erythematosus (SLE) patients resident in Rochester, Minnesota, and Singapore, respectively., Methods: Clinical manifestations at and after diagnosis were compared in Caucasian and Chinese SLE patients. The association between ethnicity and disease manifestations at and after diagnosis was determined using logistic regression and Cox proportional hazards models, respectively, adjusting for the influence of demographic, socioeconomic, disease-related, and therapy-related factors., Results: At diagnosis, Caucasian SLE patients were 3 times more likely than Chinese SLE patients to have serositis (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.01-9.71), nearly 7 times more likely to have a hematologic disorder (OR 6.95, 95% CI 2.20-21.97), and far less likely to have a malar rash (OR 0.19, 95% CI 0.07-0.54) or positive antinuclear antibodies (OR 0.11, 95% CI 0.03-0.52). Ethnicity was not associated with the prevalence of proteinuria or central nervous system (CSN) and other major organ involvement at diagnosis. After diagnosis, there was a trend toward less development of proteinuria and other major organ involvement in Caucasians (relative risk [RR] 0.47, 95% CI 0.19-1.15, and RR 0.22, 95% CI 0.05-1.04, respectively)., Conclusion: Chinese SLE patients are far less likely to have serositis or a hematologic disorder at diagnosis and may be more likely to develop proteinuria or CNS or other major organ involvement over the course of the disease, compared with Caucasian SLE patients. This may contribute to the increased mortality seen in Chinese SLE patients.

Two case reports with dens evaginatus are presented. Each patient had one tooth affected. There was a prominent tubercle on the occlusal surface of the mandibular second premolar. Under local anesthesia and rubber dam isolation a partial pulpotomy was conducted and mineral trioxide aggregate was placed. After 6 months the teeth were removed as part of planned orthodontic treatment. Histological examination of these teeth showed an apparent continuous dentin bridge formation in both teeth, and the pulps were free of inflammation. These cases show that mineral trioxide aggregate can be used as an alternative to existing materials in the proplylactic treatment of dens evaginatus.

In recent years, new disease modifying agents including leflunomide and tumour necrosis factor (TNF) antagonists have been used to treat patients with rheumatoid arthritis (RA). Leflunomide prevents proliferation of activated lymphocytes by inhibiting dihydroorotate dehydrogenase, a critical step in de novo pyrimidine synthesis. Leflunomide has been shown to be as effective as sulfasalazine and methotrexate (MTX) in placebo-controlled trials. It also improves physical function, quality of life measures and retards radiographic progression. TNF antagonists include infliximab and etanercept. Infliximab is a chimeric TNF monoclonal antibody. Repeated infusions of low dose infliximab (1 mg/kg) are ineffective if given alone. Addition of MTX to infliximab has been shown to prolong the duration of clinical response. Etanercept is a human TNF receptor p75 Fc fusion protein. In active RA patients with suboptimal response to MTX, additional clinical benefit was obtained by the addition of infliximab or etanercept to MTX. The main side effect of etanercept is injection site reaction. However, the long-term effect of TNF antagonists in the development of infection, malignancy and autoimmune disease remains unknown.

Many root end filling materials for apical surgeries have been identified either for scientific evaluation or clinical usage but none meets the requirements of an ideal root end filling material. Recently a new cement, Mineral Trioxide Aggregate (MTA) was researched as a potential root end filling material and showed promising results. This paper reports the significant findings of research done on MTA as a root end filling material and presents a clinical case where apical surgery was performed using MTA as retrograde filling.

The aim of this retrospective study was to investigate the epidemiology, yield of investigations and proportion of patients who develop systemic lupus erythematosus (SLE) among the subsets of cutaneous lupus erythematosus (LE) in the Singapore Asian population. One hundred and twenty-five patients were diagnosed with cutaneous LE on clinico-pathological correlation, of which 73 had discoid lupus erythematosus (DLE), eight had subacute cutaneous LE (SCLE), 22 had acute LE lesions and the remainder had other less common forms of cutaneous LE. Histology was consistent with LE in 94.4% and suggestive in 4.8%. Direct immunofluorescence was positive in 61% of DLE, 86% of SCLE and 80% of acute LE cases. Antinuclear antibody (ANA) was present in the majority of acute LE (85%) and SCLE (88%) but only in 25% of DLE. Eight patients (11%) presenting with DLE had definite SLE at first presentation and two (2.7%) subsequently several months later. Of these patients, six had only mucocutaneous and serological criteria but two had major organ involvement. Five SCLE patients (63%) fulfilled the criteria for SLE, including two with major organ involvement.

Nocardia, a gram positive variably acid-fast aerobic bacterium is an opportunistic pathogen in immunocompromised hosts. We present 5 cases of nocardiosis in patients with systemic lupus erythematosus. We emphasize the clinical features, radiologic findings, and antibiotic sensitivity. Lung involvement was the predominant manifestation; others include brain abscess, retinitis, thyroiditis, and diaphragmatic infiltration. We describe the first cases of pulmonary nocardiosis presenting as pneumothorax and the use of fine needle aspiration cytology in diagnosing nocardial thyroiditis.