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We compared mortality and hospitalization rates in four groups of patients with systemic sclerosis (SSc) [isolated pulmonary arterial hypertension (PAH) or interstitial lung disease (ILD), concomitant ILD-pulmonary hypertension (PH), and no/mild pulmonary involvement].In the Systemic Sclerosis Cohort Singapore (SCORE), ILD was diagnosed by HRCT and significant ILD was defined by forced vital capacity70% predicted. Patients were classified as PAH if echocardiographic systolic pulmonary artery pressure (sPAP) ≥50 mmHg or right heart catheterization (RHC) mean PAP ≥25 mmHg. Multivariable regression analyses were performed to determine factors associated with mortality and hospital admissions per year. Cox proportional hazard model was used to analyze survival.Of 490 SSc patients, 50 patients had PAH, 92 patients had ILD and 43 patients had ILD-PH. Of 93 patients with PAH or ILD-PH, 56 were based on echocardiography and 37 on RHC. Patients with ILD-PH (HR 3.77, 95% CI: 2.05-6.93) had the highest risk of death, followed by PAH (HR 3.03, 95% CI: 1.60-5.76) and ILD (HR 1.84, 95% CI: 1.04-3.28). After adjustment for confounders, PAH (HR 2.39, 95% CI: 1.13-5.07) remained independently associated with mortality, but not ILD-PH or ILD. Other factors associated with mortality were male gender, age at SSc diagnosis, malabsorption and digital ulcer/ gangrene. Increased hospitalization rate was associated with renal crisis, right heart failure and PAH medications, but not SSc groups.PAH is an independent risk factor of mortality in SSc. Increased hospitalization rate was not associated with SSc groups. Other factors associated with increased mortality and hospital admissions were identified.

Background The prevalence of symptomatic knee osteoarthritis (KOA) in Singapore is unknown. We aimed to: (i) validate questionnaires to screen for symptomatic KOA; and (ii) estimate the prevalence of symptomatic KOA in Singapore using the validated algorithms. Methods Subjects aged ≥50 years were evaluated for symptomatic KOA based on American College of Rheumatology clinical and radiographic criteria in a rheumatology clinic, and completed three sets of adapted screening questionnaires. The better performing screening questionnaire with adequate sensitivity and specificity was adminitered to a nationally representative sample of survey subjects (n = 3364) to estimate the weighted prevalence of symptomatic KOA in Singapore. Results Out of 146 subjects evaluated in the clinic, 45 had symptomatic KOA. A screening algorithm which consisted of three KOA symptoms or one symptom plus physician‐diagnosed KOA produced high specificity (0.95, 95% confidence intervals [CI]: 0.88–0.98) but low sensivity (0.44, 95% CI: 0.30–0.60). Replacing the term ‘KOA’ with ‘physician‐diagnosed ageing‐related knee problem’ improved the sensivity (0.62, 95% CI: 0.47–0.76) without significantly compromising the specificity (0.87, 95% CI: 0.79–0.93). The prevalence of symptomatic KOA weighted to the Singapore population distribution were 4.7% and 11%, using the most conservative and more liberal algorithms, respectively. There was a sharp rise in prevalence after age of 40. The weighted prevalence of KOA was higher in women and among Indian and Malay than Chinese. Conclusion Our study adapted and validated questionnaires to the local context to screen for symptomatic KOA. We estimated the prevalence of symptomatic KOA in Singapore utilizing the better‐performing algorithms.

Systemic sclerosis (SSc) is characterized by immune dysregulation, vasculopathy, and fibrosis of multiple organs. The gastrointestinal (GI) tract is the most common internal organ manifestation, which contributes to significant morbidity and mortality in patients with SSc. Emerging reports have identified unique microbial taxa alterations in the GI microbiome of patients with SSc as compared to healthy controls (HC). These taxa alterations include differences at the phyla (e.g., Bacteroidetes) and genera (e.g., Bacteroides, Clostridium, Faecalibacterium, and Lactobacillus) level. In addition, some genera have been associated with more severe GI symptoms (e.g., Prevotella and Akkermansia). This review summarizes the current evidence on factors influencing the GI microbiome, GI microbiome alterations in SSc as compared to HC, and in SSc subgroups according to disease manifestations. Current exploration in therapeutic interventions that target the GI microbiome is discussed.

The most promising alternatives to heart transplantation are left ventricular assist devices and artificial hearts; however, their use has been limited by thrombotic complications. To reduce these, sintered titanium (Ti) surfaces were developed, but thrombosis still occurs in approximately 7.5% of patients. We have invented a rapid-seeding technology to minimize the risk of thrombosis by rapid endothelialization of sintered Ti with human cord blood-derived endothelial cells (hCB-ECs). Human cord blood-derived endothelial cells were seeded within minutes onto sintered Ti and exposed to thrombosis-prone low fluid flow shear stresses. The hCB-ECs adhered and formed a confluent endothelial monolayer on sintered Ti. The exposure of sintered Ti to 4.4 dynes/cm2 for 20 hr immediately after rapid seeding resulted in approximately 70% cell adherence. The cell adherence was not significantly increased by additional ex vivo static culture of rapid-seeded sintered Ti before flow exposure. In addition, adherent hCB-ECs remained functional on sintered Ti, as indicated by flow-induced increase in nitric oxide secretion and reduction in platelet adhesion. After 15 day ex vivo static culture, the adherent hCB-ECs remained metabolically active, expressed endothelial cell functional marker thrombomodulin, and reduced platelet adhesion. In conclusion, our results demonstrate the feasibility of rapid-seeding sintered Ti with blood-derived hCB-ECs to generate a living antithrombotic surface.

Introduction Breastfeeding is known to improve the well-being of a mother and her infant, and about half of all new mothers breastfeed, but it is unknown how breastfeeding is pursued in systemic lupus erythematosus (SLE; lupus) patients. We sought to determine the rate of breastfeeding and the factors influencing this among women with lupus. In addition, we reassessed the current safety data in lactation of lupus medications. Methods Data were collected from lupus patients enrolled in a prospective registry who fulfilled the 2012 SLICC criteria, had a live birth, and for whom postpartum breastfeeding status was known. Data included physician assessments of lupus activity and medications, breastfeeding intentions during pregnancy and practice following pregnancy. The safety of medications in breastfed infants was assessed through a comprehensive review of LactMed, a national database about medications in lactation. Results A total of 51 pregnancies in 84 women with lupus were included in the study. Half of the lupus patients ( n = 25, 49%) chose to breastfeed. The rate of breastfeeding was not significantly affected by socioeconomic factors. In contrast, low postpartum lupus activity, term delivery, and a plan to breastfeed early in pregnancy were significantly associated with breastfeeding in lupus patients. In reviewing the most up-to-date data, the majority of lupus medications appear to have very minimal transfer into breast milk and are likely compatible with breastfeeding. Conclusion Half of women with lupus breastfed and most desire to breastfeed. Hydroxychloroquine, azathioprine, methotrexate, and prednisone have very limited transfer into breast milk and may be continued while breastfeeding.

Background Concomitant pulmonary hypertension and interstitial lung disease in systemic sclerosis (SSc-PH-ILD) represents a distinct subpopulation of SSc with poorer prognosis in Western studies. In Asian patients, characterisation of SSc-PH-ILD is still lacking. Objectives To analyse hospital admissions, survival and prognostic markers among SSc patients with PH, ILD or concomitant PH-ILD in the Scleroderma Cohort Singapore. Methods In this study involving 3 tertiary Rheumatology institutions Jan 2008 to , Oct 2016 SSc patients with significant pulmonary involvement were included. ILD was based on high resolution computed tomography and predicted FVC Results Among 490 patients, 92 had ILD, 50 PH and 43 PH-ILD (table 1). Of 93 patients with PH or PH-ILD, 56 were based on echocardiography and 37 on RHC. The 5 year survival was 79%, 87% and 90% in PH, PH-ILD and ILD subgroup, respectively (figure 1). In multivariable analysis, PH was significantly associated with 2.8-fold increased risk of death. Male gender, malabsorption, digital ulcerations and renal crisis were also significantly associated with mortality (table 2). No significant difference in hospital admissions/year among different subgroups. Increased hospital admissions were associated with renal crisis, right heart failure and use of PH medications. Conclusions Compared to those with ILD or PH-ILD, SSc-PH patients had increased mortality, but not hospitalisation rates. This could be due to small sample size or short follow up duration. We identified risk factors associated with worse outcomes in SSc patients with significant pulmonary involvement. Disclosure of Interest None declared

Nitinol-based vascular devices, for example, peripheral and intracranial stents, are limited by thrombosis and restenosis. To ameliorate these complications, we developed a technology to promote vessel healing by rapidly seeding (QuickSeeding) autologous blood-derived endothelial cells (ECs) onto modified self-expanding nitinol stent delivery systems immediately before implantation. Several thousand micropores were laser-drilled into a delivery system sheath surrounding a commercial nitinol stent to allow for exit of an infused cell suspension. As suspension medium flowed outward through the micropores, ECs flowed through the delivery system attaching to the stent surface. The QuickSeeded ECs adhered to and spread on the stent surface following 24-h in vitro culture under static or flow conditions. Further, QuickSeeded ECs on stents that were deployed into porcine carotid arteries spread to endothelialize stent struts within 48 h (n = 4). The QuickSeeded stent struts produced significantly more nitric oxide in ex vivo flow circuits after 24 h, as compared to static conditions (n = 5). In conclusion, ECs QuickSeeded onto commercial nitinol stents within minutes of implantation spread to form a functional layer in vitro and in vivo, providing proof of concept that the novel QuickSeeding method with modified delivery systems can be used to seed functional autologous endothelium at the point of care. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1658-1665, 2016.

Aim: Peripheral blood-derived endothelial cells (pBD-ECs) are an attractive tool for cell therapies and tissue engineering, but have been limited by their low isolation yield. We increase pBD-EC yield via administration of the chemokine receptor type 4 antagonist AMD3100, as well as via a diluted whole blood incubation (DWBI). Materials & Methods: Porcine pBD-ECs were isolated using AMD3100 and DWBI and tested for EC markers, acetylated LDL uptake, growth kinetics, metabolic activity, flow-mediated nitric oxide production and seeded onto titanium tubes implanted into vessels of pigs. Results: DWBI increased the yield of porcine pBD-ECs 6.6-fold, and AMD3100 increased the yield 4.5-fold. AMD3100-mobilized ECs were phenotypically indistinguishable from nonmobilized ECs. In porcine implants, the cells expressed endothelial nitric oxide synthase, reduced thrombin-antithrombin complex systemically and prevented thrombosis. Conclusion: Administration of AMD3100 and the DWBI method both increase pBD-EC yield.

Nitinol-based vascular devices, for example, peripheral and intracranial stents, are limited by thrombosis and restenosis. To ameliorate these complications, we developed a technology to promote vessel healing by rapidly seeding (QuickSeeding) autologous blood-derived endothelial cells (ECs) onto modified self-expanding nitinol stent delivery systems immediately before implantation. Several thousand micropores were laser-drilled into a delivery system sheath surrounding a commercial nitinol stent to allow for exit of an infused cell suspension. As suspension medium flowed outward through the micropores, ECs flowed through the delivery system attaching to the stent surface. The QuickSeeded ECs adhered to and spread on the stent surface following 24-h in vitro culture under static or flow conditions. Further, QuickSeeded ECs on stents that were deployed into porcine carotid arteries spread to endothelialize stent struts within 48 h (n = 4). The QuickSeeded stent struts produced significantly more nitric oxide in ex vivo flow circuits after 24 h, as compared to static conditions (n = 5). In conclusion, ECs QuickSeeded onto commercial nitinol stents within minutes of implantation spread to form a functional layer in vitro and in vivo, providing proof of concept that the novel QuickSeeding method with modified delivery systems can be used to seed functional autologous endothelium at the point of care. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1658-1665, 2016.

where public housing is meant only for lower income families, vast majority of Singapore residents reside in the public housing flats that they own. During the time of recruitment, about 85% of the population in Singapore lived in public housing flats. We have attempted to adjust for socioeconomic status by including educational level as a covariate in the multivariable models. We do not perceive that income or housing type may have biological interaction with smoking or BMI that will modify the effects of these two exposures on the risk of TKR in our study population. Hence, although the study has excluded a small minority of the population by not recruiting those living in private housing, we do not think this exclusion will invalidate the extrapolation of our results and conclusions to those who are living in private housing in the population.

Summary Purpose Data on the association between body mass index (BMI) and risk of knee osteoarthritis (KOA) are sparse for Asian populations who are leaner than Western populations. We evaluated the association between BMI and risk of total knee replacement (TKR) due to severe KOA among Chinese in Singapore. Methods We used data from the Singapore Chinese Health Study (SCHS), a population-based prospective cohort of 63,257 Chinese men and women, aged 45–74 years at enrollment from 1993 to 1998. Information on height, weight, diet and lifestyle factors were obtained via in-person interviews. TKR cases for severe KOA were identified via linkage with the nationwide hospital discharge database through 2011. Cox regression and weighted least squares regression were used in the analysis. Results The mean BMI among cohort participants was 23.1 kg/m 2 , and more than two-thirds had BMI below 25 kg/m 2 . A total of 1649 had TKR attributable to severe KOA. Risk of TKR increased in a strong dose-dependent manner with increasing BMI throughout the 15–32 kg/m 2 range and became less clear at BMI >32 kg/m 2 . In the BMI range 16–27 kg/m 2 , there was a 27% increase in TKR risk for each unit increase in BMI ( P for trend 2 , the risk estimates of TKR were all statistically significant with increasing unit of BMI ≥21 kg/m 2 . Results were similar for men and women. Conclusion Our results provided evidence for a constant mechanical mechanism underlying BMI and KOA initiation and/or progression.

Background Knee osteoarthritis (OA) is one of the leading causes of disability worldwide. The prevalence of knee OA is higher in Chinese than Caucasian subjects, despite the lower body mass index in Chinese populations.1,2 Among other Asian ethnicities, the prevalence of knee OA may also be high, and the prevalence of knee OA in the multi-ethnic Singapore population is still unknown. Objectives Our study aimed to estimate the prevalence of knee OA in the general population of Singapore, using a validated questionnaire consisting of 3 knee OA symptoms or 1 symptom and a physician diagnosis (sensitivity of 54%, specificity of 87%).3 Methods We recruited a subset of subjects from the National Health Surveillance Survey (NHSS) 2013 who provided telephone numbers. Consenting subjects were invited to complete a validated screening questionnaire by mail.3 If no response was received after 4 weeks, the subjects were interviewed by telephone to complete the screening questionnaire. The national prevalence of knee OA was estimated by accounting for the proportion of subjects who provided telephone numbers; it was weighted to the gender, age, and ethnic distribution profiles of the final respondents. Results From the NHSS cohort of respondents (n=9,631 subjects), 4,633 (48.1%) subjects provided telephone numbers. A total of 3,364 sets of screening questionnaires were completed, out of 4,557 sent (response rate=73.8%). The demographic profile of the responders were not significantly different from the original NHSS cohort profile. The estimated national prevalence of knee OA was 11%. Women (13.1%) had a higher prevalence of knee OA than men (8.8%). The prevalence of knee OA increased with age and was 19.7% for age ≥60 years old, compared to 8.6% for age 18–59 years old. Across the different ethnic groups, knee OA was more prevalent among Indian (20.5%), followed by Malay (17.7%), and Chinese (9.3%). Conclusions Using a validated screening questionnaire, we estimated the national prevalence of knee OA in the multi-ethnic Singapore population. Indian and Malay had higher prevalence of knee OA, which could be attributed to the higher prevalence of obesity among these ethnic groups as compared to Chinese.4 References Zhang, Y., et al., Comparison of the prevalence of knee osteoarthritis between the elderly Chinese population in Beijing and whites in the United States: The Beijing Osteoarthritis Study. Arthritis Rheum, 2001. 44(9): p. 2065–2071. Felson, D., et al., High prevalence of lateral knee osteoarthritis in Beijing Chinese compared with Framingham Caucasian subjects. Arthritis Rheum, 2002. 46(5): p. 1217–22. Leung, Y., et al., Evaluation of three screening questionnaires for use in identifying symptomatic knee osteoarthritis in the general population. Ann Rheum Dis, 2013. 72: p. A975. MOH, National Health Survey. 2010: Singapore. Disclosure of Interest None declared

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S217 2010 to 2075. Albeit the expected costs are mainly driven by female patients, the relative increase in TKA associated costs are greater in men than inwomen due to population shifts. In those aged 80þ, the costs for TKR will increase by 106% and in those aged 90þ by 624%, indicating that perioperative costs in these decades will additionally increase the TKR-associated costs due to co-morbidity, perioperative complications and prolonged postoperative rehabilitation. As the assumptions in this analysis are conservatively taken, the future socio-economic burden to Austrian society might be greater as projected in this study. Fig. 1. Projected numbers of TKR implants in Austria for individuals in their 5th, 6th, 7th, 8th and 9thþ decade with stratification for gender between 2010–2075. Low (ageing), main (most likely) and upper (growth) scenarios are based on population projections of STATISTICS Austria and Austrian prosthesis register. 381 RELATIONSHIP BETWEEN LOW RANGE BODY MASS INDEX AND TOTAL KNEE REPLACEMENT, THE SINGAPORE CHINESE HEALTH STUDY Y.Y. Leung yz, M. Noviani z, J.C. Allen z, L-W. Ang x, R-W. Wang k{, J-M. Yuan k{, W-P. Koh#yy. yDept. of Rheumatology & Immunology, Singapore Gen. Hosp., Singapore, Singapore; zDuke NUS Graduate Med. Sch., Singapore, Singapore, Singapore; x Epidemiology & Disease Control Div., Ministry of Hlth., Singapore, Singapore; kDiv. of Cancer Control and Population Sci., Univ. of Pittsburgh Cancer Inst., Pittsburgh, PA, USA; {Dept. of Epidemiology, Graduate Sch. of Publ. Hlth., Univ. of Pittsburgh, Pittsburgh, PA, USA; Duke NUS Graduate Med. Sch. Singapore, Singapore, Singapore, USA; yy Saw Swee Hock Sch. of Publ. Hlth., Natl. Univ. of Singapore, Singapore, Singapore Purpose: Data on the association between low body mass index (BMI) ranges and risk of knee OA are sparse. We evaluated the association of BMI and total knee replacement (TKR) due to severe knee OA amongst elderly Chinese in Singapore who had low BMI. Methods: We used data from the Singapore Chinese Health Study, a population based prospective cohort of 63,257 Chinese men and women, aged 45 to 74 years old during enrollment in 1993–1998. Detailed information on height, weight, demographic characters, smoking, current diet and lifestyle factors were obtained through inperson interviews. TKR cases indicated for severe knee OA were identified via linkage with nationwide hospital discharge database up to 31 December 2011. We used Cox regression methods to analyze BMI in relation to TKR risk with adjustment for age, gender, education, smoking status, comorbidities and physical activity level. Results: From 52,780 subjects with known BMI data, 1,649 subjects with incident TKR due to severe knee OAwere identified. Themean BMI was 23.1 ( 3.6) kg/m2 and 75% of subjects had BMI