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K Binymin1,3, AL Herrick1, GL Carlson2, SJ Hopkins21University of Manchester, Rheumatic Diseases Centre, 2Infection Injury and Inflammation Group, and Brain Injury Research Group, Manchester Academic Health Science Centre and University of Manchester Faculty of Medical and Human Sciences, Salford Royal Hospitals NHS Trust, Salford, UK; 3Southport District General Hospital, Southport, UKIntroduction: Cachexia is associated with rheumatoid arthritis (RA), but whether it is attributable primarily to reduced dietary intake or increased metabolism is unclear, as is the association with inflammation. To examine whether rheumatoid cachexia is related to increased energy expenditure, reduced food intake, or an inflammatory cytokine response we undertook a prospective, longitudinal study of patients with RA, during periods of relative relapse and remission of inflammation.Methods: Sixteen patients admitted to hospital with a flare of RA were assessed clinically to determine disease activity and were re-examined 6 weeks later. Their fat-free mass (FFM), dietary intake, resting energy expenditure (REE), and plasma concentrations of interleukin-6 (IL-6) were also measured. Data were compared with those from 16 healthy, age- and sex-matched controls.Results: At baseline the body weight, body mass index, and FFM of patients with RA were significantly lower than those of controls. Disease activity scores of patients (6.39 ± 0.8) were reduced when the patients were re-examined 6 weeks later (5.23 ± 1.26) and FFM was no longer statistically different from that of controls (visit 1 = 25.8 ± 10.1 and visit 2 = 26.8 ± 9.5 versus controls = 32.3 ± 10.9). There were no differences in food intake between patients and controls or between patients studied at the 2 time points, but REE was greater in patients after correcting for FMM (visit 1 = 62.2 ± 24.7, visit 2 = 59.7 ± 26.3 versus controls = 46.0 ± 13.7). Plasma IL-6 concentrations were significantly higher in patients than controls. Although IL-6 was not significantly correlated with REE, lower REE measurements were not observed when the plasma IL-6 concentration increased.Conclusion: Reduced FFM in patients with RA is not attributable to reduced food intake. Energy expenditure is greater in patients when corrected for FFM, particularly in patients with acute flares of disease activity. Although clearly not the only factor involved, increased production of IL-6 may contribute to increasing REE.Keywords: rheumatoid arthritis, cachexia, free-fat mass, fat mass, resting energy expenditure, interleukin-6

Bisexual men experience significant health disparities likely related to biphobia. Biphobia presents via several preconceptions, including that bisexuality is transitory, and that bisexual men act as viral bridges between men who have sex with men and heterosexual populations. We analyzed data from a prospective cohort of gay and bisexual men, the Multicenter AIDS Cohort Study, to test these preconceptions. Men reporting both male and female sexual partners (MSMW) between 2002 and 2009 (n = 111) were classified as behaviorally bisexual. We assessed five hypotheses over two domains (transience of bisexual behavior and viral bridging). No evidence was found supporting the transitory nature of bisexuality. Trajectories of bisexual behavior were not transient over time. We found little evidence to support substantial viral bridging behavior. Notably, HIV-positive MSMW reported lower proportions of female partners than HIV-negative MSMW. Our results provide no empirical support for bisexual transience and scant support for viral bridging hypotheses. Our results provide key data showing that male bisexual behavior may be stable over long time periods and that behaviorally bisexual men's risk to female sexual partners may be lower than expected.

Objectives: Low body weight is an easily assessable cause of Raynaud's phenomenon (RP), and is frequently overlooked by clinicians. We aim to investigate the association of low body weight (body mass index < 18.5 kg/m2), involuntary weight loss, and nutritional restrictions with the presence of RP. Method: Participants from the Lifelines Cohort completed a validated self-administered connective tissue disease questionnaire. Subjects who reported cold-sensitive fingers and biphasic or triphasic colour changes were considered to suffer from RP. Patient characteristics, anthropometric measurements, and nutritional habits were collected. Statistical analyses was stratified for gender. Results: Altogether, 93 935 participants completed the questionnaire. The prevalence of RP was 4.2% [95% confidence interval (CI) 4.1–4.4%], and was three-fold higher in women than in men (5.7% vs 2.1%, p < 0.001). Subjects with RP had a significantly lower daily caloric intake than those without RP. Multivariate analysis, correcting for creatinine level, daily caloric intake, and other known aetiological factors associated with RP, revealed that low body weight [men: odds ratio (OR) 5.55 (95% CI 2.82–10.93); women: 3.14 (2.40–4.10)] and involuntary weight loss [men: OR 1.32 (1.17–1.48); women: 1.31 (1.20–1.44)] were significantly associated with the presence of RP. Low-fat diet was also associated with RP in women [OR 1.27 (1.15–1.44)]. Conclusion: Low body weight and prior involuntary weight loss are associated with an increased risk of RP in both men and women. This study emphasizes that low body weight and weight loss are easily overlooked risk factors for RP, and should be assessed and monitored in subjects with RP. [ABSTRACT FROM AUTHOR]

Objective: The burden of disability associated with systemic sclerosis (SSc) is being increasingly recognized. Our aim was to test the hypothesis that changes in functional ability over time differ between patients with limited (lcSSc) and diffuse cutaneous (dcSSc) subtypes, and that in dcSSc (but not lcSSc) these changes correlate with skin thickening.Method: This was a retrospective analysis of data collected prospectively between 2005 and 2016 at a single centre. Data recorded at annual review visits included modified Rodnan skin score (mRSS) and Health Assessment Questionnaire Disability Index (HAQ-DI). Yearly rates of mRSS and HAQ-DI change were assessed by individual linear regressions, and those gradients were compared between disease groups (lcSSc/dcSSc) for each of early/late disease (less/greater than 5 years' duration).Results: The study included 402 patients (110 dcSSc, 292 lcSSc), with mean length of follow-up of 5.5 years (sd 3.5). Mean baseline HAQ-DI was 1.4 in dcSSc and 1.2 in lcSSc. In dcSSc, increased mRSS was associated with worsening disability (ρ = 0.36, p = 0.004) during early but not late disease (ρ = 0.12, p = 0.331). In lcSSc, changes in mRSS were not associated with changes in disability for early (ρ = -0.15, p = 0.173) or late disease (ρ = 0.10, p = 0.137).Conclusion: These findings confirm high disability in patients with SSc. A relationship between HAQ-DI and mRSS (worsening mRSS associated with increasing disability) was found only in patients with early dcSSc, suggesting that in other patient subgroups other factors play the major role. [ABSTRACT FROM AUTHOR]

History of surgical debridement, anticentromere antibody, and disease duration are associated with calcinosis in patients with systemic sclerosis. The confirmation of an association with calcinosis is also of interest ([4]): calcinosis is thought to be associated with severity of digital vasculopathy/ischaemia and with disease duration ([6], [7]). Male patients were more likely to have digital pitting (p = 0.025), and all patients with digital pitting were more likely to have calcinosis (p < 0.001). [Extracted from the article]

Objectives: Systemic sclerosis (SSc)-related calcinosis is often painful and disabling. Our aim was to examine its clinical and serological associates, and whether it is possible to build a model to predict the presence of calcinosis.Method: This was a retrospective cross-sectional study. Clinical and demographic variables examined were: age, gender, disease subtype, SSc duration, previous intravenous prostanoid infusions, surgical debridement and/or amputation, autoantibody status (anticentromere and antitopoisomerase), pulmonary fibrosis, and pulmonary hypertension. Univariable logistic regression was used to investigate associations between demographic and clinical factors and the odds of clinical calcinosis, then multivariable regression to obtain adjusted odds ratios (ORs) and confidence intervals (CIs).Results: A total of 317 patients (86% female, median age 60 years) were included: 94 (30%) had clinically apparent calcinosis. Age and gender were similar in those with and without calcinosis. Only surgical debridement (OR 3.55, 95% CI 1.71-7.53), anticentromere status (OR 2.32, 95% CI 1.27-4.32), and disease duration (OR 1.08, 95% CI 1.04-1.11) remained significant predictors after adjusting for other variables. In combination, the selected variables explained approximately 18% of the variation in the outcome but did not grant sufficient predictive power to discriminate between those with and without calcinosis [Nagelkerke's R(2) = 0.18, area under the receiver operating characteristic curve (AuROC) = 0.51, both adjusted for optimism].Conclusions: History of surgical debridement, positive anticentromere antibody, and disease duration were independently associated with calcinosis. However, the low explanatory and discriminatory power of a multiple logistic regression model suggests there are other important predictors of calcinosis unaccounted for in this analysis. [ABSTRACT FROM AUTHOR]

If GAVE is recognized early, local therapy in the form of endoscopic haemostatic procedures such as argon plasma has been highly effective in patients with bleeding gastric vascular ectasia ([4]). Our two patients demonstrate how GAVE should always be suspected in a patient with SSc who presents with either an acute gastrointestinal bleed or iron-deficiency anaemia. Gastric antral vascular ectasia (GAVE, or "watermelon stomach") is an insufficiently recognized gastrointestinal feature of systemic sclerosis (SSc). [Extracted from the article]

Systemic sclerosis-related calcinosis can affect the breast - but malignancy should always be excluded One of the clinical key manifestations of systemic sclerosis (SSc) is calcinosis (deposits of calcium-containing salts in the skin and subcutaneous tissues), which is present in at least 25% of patients with SSc ([[1]]). Despite the background of widespread calcinosis in this patient and the probability that the breast lump was due to SSc-related calcinosis, she received a comprehensive assessment to ensure that the lesion was non-malignant. [Extracted from the article]

The past 10 years have seen the publication of results from several multicentre clinical trials in primary and systemic sclerosis (SSc)-related Raynaud phenomenon. The publication of these studies has occurred as a result of new insights into the pathogenesis of Raynaud phenomenon, which are directing new treatment approaches, and increased international collaboration between clinicians and scientists. Although the pathogenesis of Raynaud phenomenon is complex, abnormalities of the blood vessel wall, of neural control mechanisms and of intravascular (circulating) factors are known to interact and contribute. Key players relevant in drug development include nitric oxide, endothelin-1, alpha adrenergic receptor activation, abnormal signal transduction in vascular smooth muscle, oxidative stress and platelet activation. The main advances in diagnosis have been a clearer understanding of autoantibodies and of abnormal nailfold capillary patterns as independent predictors of SSc, and widespread use and increased availability of capillaroscopy. The ultimate aim is to translate the advances made in the pathophysiology and early diagnosis into development of treatments to prevent and reverse digital vascular dysfunction and injury. This Review provides an update of the pathogenesis, diagnosis and treatment of Raynaud phenomenon. Current and future treatment approaches are discussed, and some key unanswered questions are highlighted. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To test the intra- and interobserver variability, among clinicians with an interest in systemic sclerosis (SSc), in defining digital ulcers. METHODS: Thirty-five images of finger lesions, incorporating a wide range of abnormalities at different sites, were duplicated, yielding a data set of 70 images. Physicians with an interest in SSc were invited to take part in the Web-based study, which involved looking through the images in a random sequence. The sequence differed for individual participants and prevented cross-checking with previous images. Participants were asked to grade each image as depicting 'ulcer' or 'no ulcer,' and if 'ulcer,' then either 'inactive' or 'active.' Images of a range of exemplar lesions were available for reference purposes while participants viewed the test images. Intrarater reliability was assessed using a weighted kappa coefficient with quadratic weights. Interrater reliability was estimated using a multirater weighted kappa coefficient. RESULTS: Fifty individuals (most of them rheumatologists) from 15 countries participated in the study. There was a high level of intrarater reliability, with a mean weighted kappa value of 0.81 (95% confidence interval [95% CI] 0.77, 0.84). Interrater reliability was poorer (weighted kappa = 0.46 [95% CI 0.35, 0.57]). CONCLUSION: The poor interrater reliability suggests that if digital ulceration is to be used as an end point in multicenter clinical trials of SSc, then strict definitions must be developed. The present investigation also demonstrates the feasibility of Web-based studies, for which large numbers of participants can be recruited over a short time frame. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The lack of randomized controlled trials (RCTs) in pulmonary fibrosis in systemic sclerosis (SSc) has hampered an evidence-based approach to treatment. This RCT was undertaken to investigate the effects of intravenous (IV) cyclophosphamide (CYC) followed by azathioprine (AZA) treatment in pulmonary fibrosis in SSc. METHODS: Forty-five patients were randomized to receive low-dose prednisolone and 6 infusions (monthly) of CYC followed by oral AZA, or placebo. Primary outcome measures were change in percent predicted forced vital capacity (FVC) and change in single-breath diffusing capacity for carbon monoxide (DLCO). Secondary outcome measures included changes in appearance on high-resolution computed tomography and dyspnea scores. An intent-to-treat statistical analysis was performed. RESULTS: At baseline, there were no significant group differences in factors linked to outcome, including severity of pulmonary fibrosis and autoantibody status. Sixty-two percent of the patients completed the first year of treatment. Withdrawals included 9 patients (6 from the placebo group) with significant decline in lung function, 2 with treatment side effects (both from the active treatment group), and 6 with non-trial-related comorbidity. No hemorrhagic cystitis or bone marrow suppression was observed. Estimation of the relative treatment effect (active treatment versus placebo) adjusted for baseline FVC and treatment center revealed a favorable outcome for FVC of 4.19%; this between-group difference showed a trend toward statistical significance (P = 0.08). No improvements in DLCO or secondary outcome measures were identified. CONCLUSION: This trial did not demonstrate significant improvement in the primary or secondary end points in the active treatment group versus the group receiving placebo. However, for FVC there was a trend toward statistical significance between the 2 groups. This suggests that treatment of pulmonary fibrosis in SSc with low-dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease. Therapy was well tolerated with no increase in serious adverse events. [ABSTRACT FROM AUTHOR]