Lupus nephritis management guidelines compared

In the past years, many (randomized) trials have been performed comparing the treatment strategies for lupus nephritis. In 2012, these data were incorporated in six different guidelines for treating lupus nephritis. These guidelines are European, American and internationally based, with one separate guideline for children. They offer information on different aspects of the management of lupus nephritis including induction and maintenance treatment of the different histological classes, adjunctive treatment, monitoring of the patient, definitions of response and relapse, indications for (repeat) renal biopsy, and additional challenges such as the presence of vascular complications, the pregnant SLE patient, treatment in children and adolescents and considerations about end-stage renal disease and transplantation. In this review, we summarize the guidelines, determine the common ground between them, highlight the differences and discuss recent literature

Palmoplantar Pustulosis-like Eruption Induced by Baricitinib for Treatment of Rheumatoid Arthritis

Objectives: Baricitinib is an orally active Janus kinase (JAK) inhibitor used in the treatment of moderate to severe rheumatoid arthritis (RA). Materials and methods: Here, we report the case of a 56-year-old Caucasian male diagnosed with RA who developed palmoplantar pustulosis (PPP) while being treated with baricitinib. Results: The patient’s PPP resolved after discontinuation of baricitinib and recurred when this was restarted. Based on causality assessment, it was considered a drug-induced PPP. Conclusion: To the authors’ knowledge, this is the first case of baricitinib-induced PPP

Management of lupus nephritis: a systematic literature review informing the 2019 update of the joint EULAR and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations.

OBJECTIVES: To analyse the current evidence for the management of lupus nephritis (LN) informing the 2019 update of the EULAR/European Renal Association-European Dialysis and Transplant Association recommendations. METHODS: According to the EULAR standardised operating procedures, a PubMed systematic literature review was performed, from January 1, 2012 to December 31, 2018. Since this was an update of the 2012 recommendations, the final level of evidence (LoE) and grading of recommendations considered the total body of evidence, including literature prior to 2012. RESULTS: We identified 387 relevant articles. High-quality randomised evidence supports the use of immunosuppressive treatment for class III and class IV LN (LoE 1a), and moderate-level evidence supports the use of immunosuppressive treatment for pure class V LN with nephrotic-range proteinuria (LoE 2b). Treatment should aim for at least 25% reduction in proteinuria at 3 months, 50% at 6 months and complete renal response (<500-700 mg/day) at 12 months (LoE 2a-2b). High-quality evidence supports the use of mycophenolate mofetil/mycophenolic acid (MMF/MPA) or low-dose intravenous cyclophosphamide (CY) as initial treatment of active class III/IV LN (LoE 1a). Combination of tacrolimus with MMF/MPA and high-dose CY are alternatives in specific circumstances (LoE 1a). There is low-quality level evidence to guide optimal duration of immunosuppression in LN (LoE 3). In end-stage kidney disease, all methods of kidney replacement treatment can be used, with transplantation having the most favourable outcomes (LoE 2b). CONCLUSIONS: There is high-quality evidence to guide the initial and subsequent phases of class III/IV LN treatment, but low-to-moderate quality evidence to guide treatment of class V LN, monitoring and optimal duration of immunosuppression

Editorial: Lupus and the Brain: Advances in Neuropsychiatric Systemic Lupus Erythematosus

Editorial on the Research Topic Lupus and the Brain: Advances in Neuropsychiatric Systemic Lupus Erythematosu

Quantitative identification of functional connectivity disturbances in neuropsychiatric lupus based on resting-state fMRI: a robust machine learning approach

Neuropsychiatric systemic lupus erythematosus (NPSLE) is an autoimmune entity comprised of heterogenous syndromes affecting both the peripheral and central nervous system. Research on the pathophysiological substrate of NPSLE manifestations, including functional neuroimaging studies, is extremely limited. The present study examined person-specific patterns of whole-brain functional connectivity in NPSLE patients (n = 44) and age-matched healthy control participants (n = 39). Static functional connectivity graphs were calculated comprised of connection strengths between 90 brain regions. These connections were subsequently filtered through rigorous surrogate analysis, a technique borrowed from physics, novel to neuroimaging. Next, global as well as nodal network metrics were estimated for each individual functional brain network and were input to a robust machine learning algorithm consisting of a random forest feature selection and nested cross-validation strategy. The proposed pipeline is data-driven in its entirety, and several tests were performed in order to ensure model robustness. The best-fitting model utilizing nodal graph metrics for 11 brain regions was associated with 73.5% accuracy (74.5% sensitivity and 73% specificity) in discriminating NPSLE from healthy individuals with adequate statistical power. Closer inspection of graph metric values suggested an increased role within the functional brain network in NSPLE (indicated by higher nodal degree, local efficiency, betweenness centrality, or eigenvalue efficiency) as compared to healthy controls for seven brain regions and a reduced role for four areas. These findings corroborate earlier work regarding hemodynamic disturbances in these brain regions in NPSLE. The validity of the results is further supported by significant associations of certain selected graph metrics with accumulated organ damage incurred by lupus, with visuomotor performance and mental flexibility scores obtained independently from NPSLE patients. View Full-Text Keywords: neuropsychiatric systemic lupus erythematosus; rs-fMRI; graph theory; functional connectivity; surrogate data; machine learning; visuomotor ability; mental flexibilit

Use of rituximab in systemic lupus erythematosus: a single center experience over 14 years

OBJECTIVES: To describe the clinical outcome and safety of rituximab (RTX) treatment in systemic lupus erythematosus (SLE) patients with severe manifestations or refractory to standard immunosuppressive therapy, treated at a single center. METHODS: This was a retrospective analysis of all patients with SLE treated with RTX at one center between June 2000 and December 2013. The clinical outcome was assessed by determining BILAG scores, anti dsDNA and C3 levels before and six months after RTX treatment. For safety analysis, adverse events and deaths were recorded. RESULTS: Of a total of 115 patients, 93.9% were female; mean age at diagnosis was 26.39±11.90 years: mean disease duration at first RTX treatment was 91.96±84.80 months. A BILAG score variation of -11.26±11.38 (p<0.001) was recorded six months after first RTX treatment; 40% of patients had a complete response and 27% had a partial response; in 36.5% of patients, C3 levels increased over 25%, and in 33.5% dsDNA levels decreased over 50%. Depletion of CD19+ cells was achieved in 94.0% of patients. Hypogammaglobulinemia was detected in 14.9% of patients, with significant reduction for IgM (p<0.001) and IgG (p=0.001) levels. Severe infections, infusion-related and hypersensitivity reactions occurred in 7%, 3.5% and 2.6% of patients. Of the 115 patients, 62 patients had repeated RTX treatments, with an average number of 1.95±1.17 cycles per patient and a mean interval between infusions of 21.44±20.11 months. At the end of follow-up, 11 patients were deceased; 6 had cardiovascular events. CONCLUSION: RTX treatment was effective in decreasing disease activity, with low incidence of adverse effects. This article is protected by copyright. All rights reserved

Current–Mode Fractional–Order Electronically Controllable Integrator Design

This contribution presents a design of a current–mode fractional–order electronically controllable integrator which can be used as a building block for a design of fractional–order (FO) circuits. The design is based on a 2nd–order Follow–the–Leader–Feedback topology which is suitably approximated to operate as an integrator of a fractional order. The topology is based on Operational Transconductance Amplifiers (OTAs), Adjustable Current Amplifiers (ACAs) and Current Follower (CF). The proposed structure offers the ability of the electronic control of its fractional order and also the electronic control of the frequency band. Simulations in Cadence IC6 (spectre) and more importantly experimental measurements were carried out to support the proposal. If wider bandwidth where the approximation is valid is required, a higher order structure must be used as also shown in this paper by utilization of a 4th–order FLF topology