[Proposal for the use of anakinra in acute respiratory distress secondary to COVID-19]. / Propuesta de uso de anakinra en el distrés respiratorio agudo secundario a COVID-19.

The outcome of the SARS-CoV-2 (COVID-19) infection fundamentally affects the lung field, causing acute respiratory distress syndrome (ARDS). This process is an inflammatory picture, involving an NLRP3 inflamosome-triggered cytokine storm, the main player in alveolar destruction. IL-1 beta stands out among the cytokines that are triggered in this picture. Anakinra is a potent biological drug, capable of blocking this IL-1ß. We propose its use in controlling ARDS secondary to COVID-19 infection.

Tuning the Morphology in the Nanoscale of NH4CN Polymers Synthesized by Microwave Radiation: A Comparative Study.

A systematic study is presented to explore the NH4CN polymerization induced by microwave (MW) radiation, keeping in mind the recent growing interest in these polymers in material science. Thus, a first approach through two series, varying the reaction times and the temperatures between 130 and 205 °C, was conducted. As a relevant outcome, using particular reaction conditions, polymer conversions similar to those obtained by means of conventional thermal methods were achieved, with the advantage of a very significant reduction of the reaction times. The structural properties of the end products were evaluated using compositional data, spectroscopic measurements, simultaneous thermal analysis (STA), X-ray diffraction (XRD), and scanning electron microscopy (SEM). As a result, based on the principal component analysis (PCA) from the main experimental results collected, practically only the crystallographic features and the morphologies in the nanoscale were affected by the MW-driven polymerization conditions with respect to those obtained by classical syntheses. Therefore, MW radiation allows us to tune the morphology, size and shape of the particles from the bidimensional C=N networks which are characteristic of the NH4CN polymers by an easy, fast, low-cost and green-solvent production. These new insights make these macromolecular systems attractive for exploration in current soft-matter science.

[Proposal for the use of anakinra in acute respiratory distress secondary to COVID-19]. / Propuesta de uso de anakinra en el distrés respiratorio agudo secundario a COVID-19.

The outcome of the SARS-CoV-2 (COVID-19) infection fundamentally affects the lung field, causing acute respiratory distress syndrome (ARDS). This process is an inflammatory picture, involving an NLRP3 inflamosome-triggered cytokine storm, the main player in alveolar destruction. IL-1 beta stands out among the cytokines that are triggered in this picture. Anakinra is a potent biological drug, capable of blocking this IL-1ß. We propose its use in controlling ARDS secondary to COVID-19 infection.

Hydroxychloroquine is associated with a lower risk of polyautoimmunity: data from the RELESSER Registry.

OBJECTIVES: This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. METHODS: RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. RESULTS: Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. CONCLUSION: Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies.

Nefrocalcinosis en una paciente con artritis reumatoide y síndrome de Sjögren secundario / Nephrocalcinosis in a patient with rheumatoid arthritis and secondary Sjögren's syndrome

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Genome-wide association study meta-analysis identifies five new loci for systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with a complex genetic inheritance. Genome-wide association studies (GWAS) have significantly increased the number of significant loci associated with SLE risk. To date, however, established loci account for less than 30% of the disease heritability and additional risk variants have yet to be identified. Here we performed a GWAS followed by a meta-analysis to identify new genome-wide significant loci for SLE. METHODS: We genotyped a cohort of 907 patients with SLE (cases) and 1524 healthy controls from Spain and performed imputation using the 1000 Genomes reference data. We tested for association using logistic regression with correction for the principal components of variation. Meta-analysis of the association results was subsequently performed on 7,110,321 variants using genetic data from a large cohort of 4036 patients with SLE and 6959 controls of Northern European ancestry. Genetic association was also tested at the pathway level after removing the effect of known risk loci using PASCAL software. RESULTS: We identified five new loci associated with SLE at the genome-wide level of significance (p < 5 × 10- 8): GRB2, SMYD3, ST8SIA4, LAT2 and ARHGAP27. Pathway analysis revealed several biological processes significantly associated with SLE risk: B cell receptor signaling (p = 5.28 × 10- 6), CTLA4 co-stimulation during T cell activation (p = 3.06 × 10- 5), interleukin-4 signaling (p = 3.97 × 10- 5) and cell surface interactions at the vascular wall (p = 4.63 × 10- 5). CONCLUSIONS: Our results identify five novel loci for SLE susceptibility, and biologic pathways associated via multiple low-effect-size loci.

Efficacy and Safety of de Novo and Early Use of Extended-release Tacrolimus in Heart Transplantation.

INTRODUCTION AND OBJECTIVES: The extended-release formulation of tacrolimus (ERT) allows once-daily dosage, thus simplifying the immunosuppressive regimen. This study aimed to describe the safety and efficacy of the de novo and early use of ERT in heart transplantation. METHODS: This was an observational, retrospective, multicenter study comparing the safety and efficacy of the de novo use of ERT (ERT group [n=94]), standard-release tacrolimus (SRT group [n=42]) and early conversion (EC) from SRT to ERT (EC group [n=44]). Extended-release tacrolimus was used between 2007 and 2012. One-year incidence rates of acute rejection, infection, and cytomegalovirus infection were analyzed. Safety parameters were also evaluated. RESULTS: There were no significant between-group differences in the daily dose or trough levels of tacrolimus during the first year after transplantation. The rejection incidence rates were 1.05 (95%CI, 0.51-1.54), 1.39 (95%CI, 1.00-1.78), and 1.11 (95%CI, 0.58-1.65) episodes per patient-years in the SRT group, ERT group, and EC group, respectively (P=.48). The infection incidence rates were 0.75 (95%CI, 0.60-0.86), 0.62 (95%CI, 0.52-0.71), and 0.55 (95%CI, 0.40-0.68) in the SRT group, ERT group, and EC group, respectively (P=.46). Cytomegalovirus infection occurred in 23.8%, 20.2%, and 18.2% of the patients, respectively (P=.86). No significant between-group differences were found in laboratory tests or in allograft function. There was 1 death in the SRT group and 2 in the ERT group. CONCLUSIONS: Both de novo and early use of ERT seem to have similar safety and efficacy profiles to conventional SRT-based immunosuppression.

Characteristics of patients with fibromyalgia.

BACKGROUND: Fibromyalgia is characterised by generalized pain. A search of the available literature found no previous reports describing the specific characteristics of patients with fibromyalgia. OBJECTIVES: To describe characteristics of patients with fibromyalgia. MATERIAL AND METHODS: Case-control study including 50 patients with fibromyalgia and 50 gender and age-matched controls. After obtaining written informed consent for the study, demographic data were collected and pain in the leg, ankle and foot area was measured using a visual analogue scale (VAS). A general physical examination to test mobility and rigidity of the foot joints was also performed. Patients were also asked about their shoe utilisation habits. RESULTS: The results confirm that patients with fibromyalgia experience significantly more pain in the whole leg, ankle and foot areas than the control subjects. For this reason they use significantly more pain-killing drugs than the control subjects. However, this increase in pain is not associated with stiffness or mobility abnormalities in this series. In addition, patients with fibromyalgia show no increase in the rate of hyperkeratosis or other foot lesions. CONCLUSIONS: Patients with fibromyalgia do not seem to show a higher rate of foot lesions or a peculiar pattern of foot involvement compared to age and gender-matched controls.

Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a genetically complex rheumatic disease characterized by heterogeneous clinical manifestations of unknown etiology. Recent studies have suggested the existence of a genetic basis for SLE heterogeneity. The objective of the present study was to identify new genetic variation associated with the clinically relevant phenotypes in SLE. METHODS: A two-stage pathway-based approach was used to identify the genetic variation associated with the main clinical phenotypes in SLE. In the discovery stage, 482 SLE patients were genotyped using Illumina Human Quad610 microarrays. Association between 798 reference genetic pathways from the Molecular Signatures Database and 11 SLE phenotypes was tested using the set-based method implemented in PLINK software. Pathways significantly associated after multiple test correction were subsequently tested for replication in an independent cohort of 425 SLE patients. Using an in silico approach, we analyzed the functional effects of common SLE therapies on the replicated genetic pathways. The association of known SLE risk variants with the development of the clinical phenotypes was also analyzed. RESULTS: In the discovery stage, we found a significant association between the vascular endothelial growth factor (VEGF) pathway and oral ulceration (P value for false discovery rate (P FDR) < 0.05), and between the negative regulation signaling pathway of retinoic acid inducible gene-I/melanoma differentiation associated gene 5 and the production of antinuclear antibodies (P FDR < 0.05). In the replication stage, we validated the association between the VEGF pathway and oral ulceration. Therapies commonly used to treat mucocutaneous phenotypes in SLE were found to strongly influence VEGF pathway gene expression (P = 4.60e-4 to 5.38e-14). Analysis of known SLE risk loci identified a strong association between PTPN22 and the risk of hematologic disorder and with the development of antinuclear antibodies. CONCLUSIONS: The present study has identified VEGF genetic pathway association with the risk of oral ulceration in SLE. New therapies targeting the VEGF pathway could be more effective in reducing the severity of this phenotype. These findings represent a first step towards the understanding of the genetic basis of phenotype heterogeneity in SLE.

Relationship between damage clustering and mortality in systemic lupus erythematosus in early and late stages of the disease: cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry.

OBJECTIVES: To identify patterns (clusters) of damage manifestations within a large cohort of SLE patients and evaluate the potential association of these clusters with a higher risk of mortality. METHODS: This is a multicentre, descriptive, cross-sectional study of a cohort of 3656 SLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestations were identified. Then, overall clusters were compared as well as the subgroup of patients within every cluster with disease duration shorter than 5 years. RESULTS: Three damage clusters were identified. Cluster 1 (80.6% of patients) presented a lower amount of individuals with damage (23.2 vs 100% in clusters 2 and 3, P < 0.001). Cluster 2 (11.4% of patients) was characterized by musculoskeletal damage in all patients. Cluster 3 (8.0% of patients) was the only group with cardiovascular damage, and this was present in all patients. The overall mortality rate of patients in clusters 2 and 3 was higher than that in cluster 1 (P < 0.001 for both comparisons) and in patients with disease duration shorter than 5 years as well. CONCLUSION: In a large cohort of SLE patients, cardiovascular and musculoskeletal damage manifestations were the two dominant forms of damage to sort patients into clinically meaningful clusters. Both in early and late stages of the disease, there was a significant association of these clusters with an increased risk of mortality. Physicians should pay special attention to the early prevention of damage in these two systems.

Towards a highly-efficient fuel-cell catalyst: optimization of Pt particle size, supports and surface-oxygen group concentration.

In the present work, methanol oxidation reaction was investigated on Pt particles of various diameters on carbon-nanofibers and carbon-black supports with different surface-oxygen concentrations, aiming for a better understanding of the relationship between the catalyst properties and the electrochemical performance. The pre-synthesized Pt nanoparticles in ethylene glycol, prepared by the polyol method without using any capping agents, were deposited on different carbon supports. Removal of oxygen-groups from the carbon supports had profound positive effects on not only the Pt dispersion but also the specific activity. The edge structures on the stacked graphene sheets in the platelet carbon-nanofibers provided a strong interaction with the Pt particles, significantly reconstructing them in the process. Such reconstruction resulted in the formation of more plated Pt particles on the CNF than on the carbon-black and exposure of more Pt atoms with relatively high co-ordination numbers, and thereby higher specific activity. Owing to the combined advantages of optimum Pt particle diameter, an oxygen-free surface and the unique properties of CNFs, Pt supported on heat-treated CNFs exhibited a higher mass activity twice of that of its commercial counterpart.

Síndrome de Maroteaux-Lamy en un niño de 10 años / Maroteaux-Lamy’ Syndrom in a 10 years old child

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Lumbalgia crónica como primer síntoma en la rotura de aneurisma aórtico abdominal: a propósito de 2 casos clínicos / No disponible

No disponble

Pseudotumor orbitario refractario tratado con rituximab en paciente con lupus eritematoso sistémico. A propósito de un caso / Resistant orbital pseudotumor treated with rituximab in ap atient with systemic lupus erythematosus. A case presentation

Las manifestaciones oculares en el lupus eritematoso sistémico (LES) son relativamente frecuentes, con mayor prevalencia de la queratoconjuntivitis seca. Sin embargo, la aparición de exoftalmos unilateral secundario a pseudotumor orbitario en pacientes con LES es extremadamente rara 1–7, y en ocasiones puede presentarse refractaria al tratamiento farmacológico convencional (glucocorticoides e inmunosupresores). A continuación presentamos el caso de una paciente con LES y pseudotumor orbitario refractario a tratamiento con ciclofosfamida y excelente respuesta clínica con desaparición de la clínica oftalmológica tras el inicio de la terapia con rituximab(1gx2), eficacia mantenida tras la infusión de dos ciclos completos sin incidencias (AU)

Ocular manifestations in Systemic Lupus Erythematosus(SLE)are relatively frequent, with a major prevalence of the Keratoconjunctivitis sicca. Nevertheless, the appearance of unilateral exophthalmos secondary to orbital pseudotumor in patients with SLE is extremely rare 1–7, and on occasion it can be refractory to conventional pharmacological treatment(glucocorticoids and immunosuppressants). We present the case of a patient with SLE and orbital pseudotumor refractory to treatment with Cyclophosphamide(CF) and an excellent clinical response, with disappearance of the ophthalmological condition after the beginning of the rapy with Rituximab (1gx2), continuing after the infusion of two complete cycles without incidents (AU)

Actualización del Documento de Consenso de la Sociedad Española de Reumatología sobre el uso de terapias biológicas en la artritis reumatoide / Update of the Consensus Statement of the Spanish Society of Rheumatology on the management of biologic therapies in rheumatoid arthritis

Objetivo Servir de referencia para reumatólogos e implicados en el tratamiento de la artritis reumatoide que vayan a utilizar o consideren la utilización de terapias biológicas en su manejo. Métodos Las recomendaciones se emitieron siguiendo la metodología de grupos nominales y basadas en revisiones sistemáticas. El nivel de evidencia y el grado de recomendación se clasificaron según el modelo del Center for Evidence Based Medicine de Oxford y el grado de acuerdo se extrajo por técnica Delphi. Resultados Se realizan recomendaciones sobre el uso de los siete agentes biológicos disponibles para la artritis reumatoide en la actualidad en nuestro país. El objetivo del tratamiento es lograr la remisión de la enfermedad lo más precozmente posible. Se revisan las indicaciones y matizaciones del uso de terapias biológicas y cuál debe ser la evaluación previa y la vigilancia del paciente con estos fármacos. Conclusiones Se presentan las actualizaciones a las recomendaciones SER para el uso de terapias biológicas en pacientes con artritis reumatoide(AU)

Objective To provide a reference to rheumatologists and to those involved in the treatment of RA who are using, or about to use biologic therapy. Methods Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. Results We have produced recommendations on the use of the seven biologic agents available for RA in our country. The objective of treatment is to achieve the remission of the disease as quickly as possible. Indications and nuances regarding the use of biologic therapy were reviewed as well as the evaluation that should be performed prior to administration and the follow up of patients undergoing this therapy. Conclusions We present an update on the SER recommendations for the use of biologic therapy in patients with RA(AU)

[Update of the Consensus Statement of the Spanish Society of Rheumatology on the management of biologic therapies in rheumatoid arthritis]. / Actualización del Documento de Consenso de la Sociedad Española de Reumatología sobre el uso de terapias biológicas en la artritis reumatoide.

OBJECTIVE: To provide a reference to rheumatologists and to those involved in the treatment of RA who are using, or about to use biologic therapy. METHODS: Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and grade of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. RESULTS: We have produced recommendations on the use of the seven biologic agents available for RA in our country. The objective of treatment is to achieve the remission of the disease as quickly as possible. Indications and nuances regarding the use of biologic therapy were reviewed as well as the evaluation that should be performed prior to administration and the follow up of patients undergoing this therapy. CONCLUSIONS: We present an update on the SER recommendations for the use of biologic therapy in patients with RA.