Cancer complicating systemic lupus erythematosus--a dichotomy emerging from a nested case-control study

We determined whether any individual cancers are increased or decreased in a cohort of 595 patients with systemic lupus erythematosus (SLE) followed for up to 32 years at the University College London Hospitals Lupus Clinic, looking for any associated clinical or serological factors and the prognosis after cancer diagnosis

A model problem for conformal parameterizations of the Einstein constraint equations

We investigate the possibility that the conformal and conformal thin sandwich (CTS) methods can be used to parameterize the set of solutions of the vacuum Einstein constraint equations. To this end we develop a model problem obtained by taking the quotient of certain symmetric data on conformally flat tori. Specializing the model problem to a three-parameter family of conformal data we observe a number of new phenomena for the conformal and CTS methods. Within this family, we obtain a general existence theorem so long as the mean curvature does not change sign. When the mean curvature changes sign, we find that for certain data solutions exist if and only if the transverse-traceless tensor is sufficiently small. When such solutions exist, there are generically more than one. Moreover, the theory for mean curvatures changing sign is shown to be extremely sensitive with respect to the value of a coupling constant in the Einstein constraint equations.Comment: 40 pages, 4 figure

Why do patients with myositis die? A retrospective analysis of a single-centre cohort

OBJECTIVES: Causes of death in inflammatory myopathies have rarely been studied. We have assessed a cohort of myositis patients followed in a single centre over a 37-year period, reviewing the mortality rate, causes of death and predictors of poor prognosis. METHODS: We performed a single-centre, retrospective study on patients aged ≥16 years fulfilling 3 or 4 of the Bohan and Peter criteria, noting their demographic data, clinical features, serology, treatment and outcome. RESULTS: Of 97 patients identified, 74.2% were female. The mean age at diagnosis was 40.5 years (SD 13.2). 38.1% had adult-onset dermatomyositis, 36.1% adult-onset polymyositis and 25.8% overlap myositis. 96.9% had upper and lower limb involvement (UL+/LL+) and 62.9% had a highest CK≥10 times the upper limit of normal. 33% had significant infection(s). The disease course was chronic persistent in 29.9%, relapsing and remitting in 34% and monophasic in 36.1%. All received steroids and 92.8% other immunosuppressant(s). The median follow-up was 9 years (IQR 11.5). The estimated cumulative proportion survival at 5, 10, 15 and 20 years were 94.6%, 82.2%, 72,1% and 66.1%, respectively. 24.7% of patients died, mostly due to infection (29.2%). In univariate analysis, lung involvement (HR 1.78, p=0.013), infection (HR 4.18, p=0.003) and UL+/LL+ (HR 0.13, p=0.010) were statistically significantly associated with the risk of death. In the multivariate analysis infection (HR 3.68, p=0.009) and UL+/LL+ (HR 0.16, p=0.027) were statistically significantly associated with survival. CONCLUSIONS: A good long-term survival is reported. Nevertheless, careful follow-up of myositis patients is important

Spontaneous curvature cancellation in forced thin sheets

In this paper we report numerically observed spontaneous vanishing of mean curvature on a developable cone made by pushing a thin elastic sheet into a circular container. We show that this feature is independent of thickness of the sheet, the supporting radius and the amount of deflection. Several variants of developable cone are studied to examine the necessary conditions that lead to the vanishing of mean curvature. It is found that the presence of appropriate amount of radial stress is necessary. The developable cone geometry somehow produces the right amount of radial stress to induce just enough radial curvature to cancel the conical azimuthal curvature. In addition, the circular symmetry of supporting container edge plays an important role. With an elliptical supporting edge, the radial curvature overcompensates the azimuthal curvature near the minor axis and undercompensates near the major axis. Our numerical finding is verified by a crude experiment using a reflective plastic sheet. We expect this finding to have broad importance in describing the general geometrical properties of forced crumpling of thin sheets.Comment: 13 pages, 12 figures, revtex

Differential peripheral B cell phenotype in patients with primary Sjögren’s syndrome (pSS) compared to secondary Sjögren’s syndrome associated with systemic lupus erythematosus (SS/SLE)

Introduction: Peripheral B-cell abnormalities, a feature of both systemic lupus erythematosus (SLE) and primary Sjogren’s syndrome (pSS), are implicated in the pathogenesis of both diseases and correlate with disease activity. This study aims to investigate how the defective B-cell phenotype in pSS patients compares to patients with SS and SLE (SS/SLE), and whether abnormalities in B-cell phenotype could be related to differential B-cell lipid-raft expression and B-cell activating factor (BAFF) receptor function in patients with pSS and SLE and secondary SS (SS/SLE). Methods: Blood samples and clinical and laboratory parameters from 32 patients with pSS and SS/SLE and 13 age/sex matched HC were obtained. We used flow-cytometry to perform B-cell immunophenotyping and analysed lipid-raft expression (marker of B-cell activation). In vitro cultures were also used to assess lipid-raft expression in response to BAFF. Results: Patients with SS/SLE had a significantly decreased Bm1 and Bm5 and increased Bm2 populations compared to HC (p=0.031, p=0.035 and p=0.01, respectively), and increased Bm2 compared to pSS (p=0.027). Bm1-cells were decreased in both pSS and SS/SLE patients compared to HC (p=0.028 and p= 0.031, respectively). Both age and disease duration correlated strongly with Bm2’ cells in SS/SLE patients (r=0.9572, p= 0.0428), and the immunosuppressive treatment correlated negatively with the number of circulating Bm2 and Bm2’ cell in pSS (r = -0.54, p=0.01 and r = -0.56, p=0.008, respectively). B-cells from patients with pSS had a significant increase in lipid-raft expression compared to HC (p=0.01) and patients with SS/SLE (p<0.05). Lipid-raft levels correlated with BAFF-receptor expression in HC and SS/SLE B-cells (p=0.17, r=0.694) but not in pSS patients. Both disease activity score (ESSDAI) and IgG level correlated positively with lipid rafts expression in B cells from patients with pSS (r = 0.79, p=0.004 and r =0.53, p=0.04, respectively). Conclusion: Patients with SS/SLE had more significant B-cell abnormalities compared to HC and pSS, detectable even in a small number of patients. Also the relationship between lipid-raft and BAFF-receptor expression was altered between pSS and SS/SLE patients, and correlated with the disease activity and IgG levels in pSS group, suggesting that therapies targeting BAFF might be particularly successful in the SS/SLE sub-group of patients

Rituximab in the treatment of inflammatory myopathies: a review

Several uncontrolled studies have encouraged the use of rituximab (RTX) in patients with myositis. Unfortunately, the first placebo-phase trial to assess the efficacy of RTX in refractory myositis did not show a significant difference between the two treatment groups, and doubts have been expressed about its study design. In this review we present an up-to-date overview of the reported experiences of RTX therapy in myositis. A PubMed search was performed to find all the available cases of refractory myositis patients treated with RTX up to July 2015. The following terms were assessed: inflammatory myopathies OR anti-synthetase syndrome OR polymyositis OR dermatomyositis AND RTX. A total of 48 studies were included. We identified 458 patients with myositis treated with RTX. We found a rate of response to RTX of 78.3%. RTX can play a role in the management of patients with myositis, at least in those with positive myositis-specific autoantibodies