Body mass index and disease activity in chronic inflammatory rheumatic diseases: results of the Cardiovascular in Rheumatology (Carma) Project

Objective: Since obesity has been associated with a higher inflammatory burden and worse response to therapy in patients with chronic inflammatory rheumatic diseases (CIRD), we aimed to confirm the potential association between body mass index (BMI) and disease activity in a large series of patients with CIRDs included in the Spanish CARdiovascular in rheuMAtology (CARMA) registry. Methods: Baseline data analysis of patients included from the CARMA project, a 10-year prospective study of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) attending outpatient rheumatology clinics from 67 Spanish hospitals. Obesity was defined when BMI (kg/m2) was >30 according to the WHO criteria. Scores used to evaluate disease activity were Disease Activity Score of 28 joints (DAS28) in RA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS, and modified DAS for PsA. Results: Data from 2234 patients (775 RA, 738 AS, and 721 PsA) were assessed. The mean ± SD BMI at the baseline visit were: 26.9 ± 4.8 in RA, 27.4 ± 4.4 in AS, and 28.2 ± 4.7 in PsA. A positive association between BMI and disease activity in patients with RA (β = 0.029; 95%CI (0.01- 0.05); p = 0.007) and PsA (β = 0.036; 95%CI (0.015-0.058); p = 0.001) but not in those with AS (β = 0.001; 95%CI (-0.03-0.03); p = 0.926) was found. Disease activity was associated with female sex and rheumatoid factor in RA and with Psoriasis Area Severity Index and enthesitis in PsA. Conclusions: BMI is associated with disease activity in RA and PsA, but not in AS. Given that obesity is a potentially modifiable factor, adequate control of body weight can improve the outcome of patients with CIRD and, therefore, weight control should be included in the management strategy of these patients

Anti-IL-6 Receptor Tocilizumab in Refractory Graves? Orbitopathy: National Multicenter Observational Study of 48 Patients

Graves’ orbitopathy (GO) is the most common extrathyroidal manifestation of Graves’ disease (GD). Our aim was to assess the e cacy and safety of Tocilizumab (TCZ) in GO refractory to conventional therapy. This was an open-label multicenter study of glucocorticoid-resistant GO treated with TCZ. The main outcomes were the best-corrected visual acuity (BVCA), Clinical Activity Score (CAS) and intraocular pressure (IOP). These outcome variables were assessed at baseline, 1st, 3rd, 6th and 12th month after TCZ therapy onset. The severity of GO was assessed according to the European Group on Graves’ Orbitopathy (EUGOGO). We studied 48 (38 women and 10 men) patients (95 eyes); mean age standard deviation 51 11.8 years. Before TCZ and besides oral glucocorticoids, they had received IV methylprednisolone (n = 43), or selenium (n = 11). GO disease was moderate (n =29) or severe (n = 19) and dysthyroid optic neuropathy (DON) (n = 7). TCZ was used in monotherapy (n = 45) or combined (n = 3) at a dose of 8 mg/kg IV every four weeks (n = 43) or 162 mg/s.c. every week (n = 5). TCZ yielded a significant improvement in all of the main outcomes at the 1st month that was maintained at one year. Comparing the baseline with data at 1 year all of the variables improved; BCVA (0.78 0.25 vs. 0.9 0.16; p = 0.0001), CAS (4.64 1.5 vs. 1.05 1.27; p = 0.0001) and intraocular pressure (IOP) (19.05 4.1 vs. 16.73 3.4 mmHg; p = 0.007). After a mean follow-up of 16.1 2.1 months, low disease activity (CAS 3), was achieved in 88 eyes (92.6%) and TCZ was withdrawn in 29 cases due to low disease activity (n = 25) or ine cacy (n = 4). No serious adverse events were observed. In conclusion, TCZ is a useful and safe therapeutic option in refractory GO treatment.This work was also partially supported by RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain)

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

Tomar la palabra. Intertextualidad e intermedialidad como herramientas pedagógicas para la enseñanza de la literatura y otros discursos

Depto. de Lengua Española y Teoría de la LiteraturaFac. de FilologíaFALSEsubmitte

Factores psicosociales diferenciales de género en la artritis reumatoide: su influencia en el pronóstico de la enfermedad

RESUMEN: Estudio trasversal comparativo entre dos grupos de pacientes homogéneos de mujeres y hombres con Artritis Reumatoide, intentando abarcar todos los aspectos relacionados con dicha enfermedad, los puramente biológicos, demográficos, manejo de la enfermedad, comorbilidades y diversos factores psicosociales para evaluar si existen diferencias pronósticas medidas en calidad de vida y discapacidad entre ambos géneros y cuáles de esos factores si los hubiere se asocian a dichas diferencias. En nuestro estudio, no hemos encontrado diferencias a nivel biológico, pero si en ciertos factores demográficos como diferencias significativas en la jubilación precoz de los hombres y mayor realización de tareas domésticas en las mujeres, también en el perfil de comorbilidades entre ambos grupos, así como una menor calidad de vida en las mujeres y mayor discapacidad posiblemente asociada a la depresión y osteoporosis mayor en este grupo y quizá un afrontamiento peor de la enfermedad de las mismas respecto a los hombres.ABSTRACT: This is a cross sectional study between two homogeneous groups of male and female Rheumatoid Arthritis patients, trying to comprise all the different aspects related to this disease, pure biological factors, demographical ones, treatments, comorbidities, and other psychological issues to evaluate if there are gender differences in the quality of life or disability between both groups and which factors are the cause of these differences. In our study, we have not found any differences in the biological aspects of the disease but we have found differences in various demographical data and a different comorbid profile between them and a worse quality of life and more disability in the female group maybe associated to the depression or osteoporosis more prevalent in this group and maybe a worse illness behaviour in this group with respect to the male patient group

TNF inhibitors exert a "hidden" beneficial effect in the cardiovascular lipoprotein profile of RA patients

Purpose: A high cardiovascular risk has been described in patients with rheumatoid arthritis (RA); the effects of different biological agents have also been described in these patients. The aim of the present study is to examine the effects of tumor necrosis factor inhibitors (TNFi) in the lipoprotein profile of RA patients using a broad laboratory assessment including a large number of non-routine tests. Patients and Methods: RA patients treated with and without TNFi (70 patients in each group) were cross-sectionally compared regarding a broad spectrum of lipoprotein parameters including serum levels of total and HDL, LDL and VLDL cholesterol triglycerides, lipoprotein A (LpA), apolipoprotein A1 (Apo A), B100 (Apo B) and paroxonase. For each lipoprotein subfraction (HDL, LDL and VLDL), we assess specific concentrations of cholesterol, triglycerides, phospholipids and proteins and total mass of each one. Additionally, HDL Apo A, LDL and VLDL Apo B concentrations and number of particles of LDL and VLDL were also determined. Exploratory univariate and multivariate analyses of the different variables were performed. Results: Seventy patients in each subset were enrolled. Patients on treatment with TNFi showed a trend to be younger and to have a longer disease duration. Regarding the lipoprotein analyses, borderline significant higher levels of serum Apo A were detected and an independent association with lower HDL mass, LDL triglyceride, VLDL cholesterol, VLDL Apo B, VLDL mass, number of VLDL cholesterol molecules and number of particles of VLDL was clearly observed. Conclusion: TNFi treatment was associated with beneficial atherogenic effects at the lipoprotein level especially centered in the VLDL-related parameters consistent with a reduction of the atherogenic risk.Funding: This study was carried out with the support of Instituto de Salud Carlos III (ISCIII) (grant number PI0810119)

The Combination of an mRNA Immunogen, a TLR7 Agonist and a PD1 Blocking Agent Enhances In-Vitro HIV T-Cell Immune Responses

The development of new strategies to achieve a functional cure for HIV remains a priority. We tested a novel HIV therapeutic vaccine using unmodified mRNA (TMEP-B) and mRNA modified by 1-methyl-3′-pseudouridylyl (TMEP-Bmod) expressing both a multiepitopic sequences from Gag, Pol, and Nef proteins, including different CD4 and CD8 T-cell epitopes functionally associated with HIV control in transfected monocyte-derived dendritic cells (MDDCs) obtained from HIV infected patients. In vitro assays were used to test the mRNAs alone and in combination with immunomodulator agents, such as the TLR-7 agonist Vesatolimod and the PD-1 antagonist Nivolumab to try to improve HIV-specific cellular immune responses. Combining the mRNAs with the immunomodulators enhanced HIV-specific T-cell responses, together with the secretion of IFNγ, IP10, MIP-1α, and MIP-1β, which are fundamental mediators of viral control. Our data suggest that the mRNA vaccine prototypes TMEP-B and TMEP-Bmod, when combined with Vesatolimod and/or Nivolumab, could achieve functional cure for patients with HIV

Lactancia materna en España y factores relacionados con su instauración y mantenimiento: estudio LAyDI (PAPenRed)

Resumen: Objetivo: Conocer estadísticas reales sobre lactancia materna en España, así como factores socioculturales y perinatales que afectan a su inicio y mantenimiento. Diseño: Estudio prospectivo, multicéntrico, longitudinal, de ámbito nacional (estudio LAyDI). Sitio: Consulta de pediatras de atención primaria. Participantes: Cohorte de recién nacidos entre abril de 2017 y marzo de 2018 en España que se siguieron hasta los dos años en ocho visitas. Medidas principales: Se analizaron las tasas de los diferentes tipos de lactancia en cada visita y también se analizaron variables relacionadas con la gestación, el parto, el período neonatal, sociales, económicas y biológicas. Resultados: Muestra inicial de 1.946 (50,1% varones). El 90,7% decidieron iniciar lactancia materna al nacimiento. La cifra de lactancia materna exclusiva (LME) fue del 66,4% a los 15 días y del 35,2% a los 6 meses. Cualquier tipo de lactancia materna (lactancia materna total [LMT]) a los 6 meses fue del 61,7%. La supervivencia de LMT presentó una mediana de 6,0 meses (IC 95%: 6,0-6,1). Variables relacionadas con LME a los 15 días: hijos previos, nivel de educación de madre, ausencia de enfermedad durante el embarazo, no separación madre e hijo al nacer, no utilización de chupete, no existencia de problemas en pezones, y momento de decisión tipo lactancia. Variables relacionadas con mayor duración LMT son: la relación mayor de 5 años de los padres, no usar de chupete, colecho al mes de vida, decidir lactancia materna antes del embarazo, recibir información sobre lactancia durante el embarazo y utilizar apoyo de asociaciones. Conclusiones: El abandono temprano de la lactancia materna es un problema importante en las sociedades occidentales. Existen factores sobre los que se puede actuar para mejorar resultados. Abstract: Objective: To find out actual statistics on breastfeeding in Spain, as well as sociocultural and perinatal factors that affect its initiation and maintenance. Design: Prospective, multicentre, longitudinal, nationwide study (XXX study). Site: Primary care paediatricians’ office. Participants: Cohort of newborns born between April 2017 and March 2018 in Spain who were followed up to two years of age in 8 visits. Main measures: Rates of different types of breastfeeding were analysed at each visit and variables related to gestation, delivery, neonatal period, social, economic and biological variables were also analysed. Results: Initial sample of 1946 (50.1% male). 90.7% decided to initiate breastfeeding at birth. Exclusive breastfeeding (EBF) was 66.4% at 15 days and 35.2% at 6 months. Any type of breastfeeding (total breastfeeding [TBF]) at 6 months was 61.7%. Median survival from TBF was 6.0 months (95% CI: 6.0-6.1). Variables related to EBF at 15 days: previous children, mother's level of education, absence of illness during pregnancy, no separation of mother and child at birth, no dummy use, no nipple problems, and time of decision to breastfeed. Variables related to longer duration of TBF: relationship of parents older than 5 years, no dummy use, co-sleeping at one month of life, deciding to breastfeed before pregnancy, receiving information on breastfeeding during pregnancy and using support from associations. Conclusions: Early abandonment of breastfeeding is a major problem in Western societies. There are factors that can be worked on to improve outcomes

Assessment of human SARS CoV-2-Specific T-Cell responses elicited In Vitro by new computationally designed mRNA immunogens (COVARNA)

The COVID-19 pandemic has brought significant changes and advances in the field of vaccination, including the implementation and widespread use of encapsidated mRNA vaccines in general healthcare practice. Here, we present two new mRNAs expressing antigenic parts of the SARS-CoV-2 spike protein and provide data supporting their functionality. The first mRNA, called RBD-mRNA, encodes a trimeric form of the virus spike protein receptor binding domain (RBD). The other mRNA, termed T-mRNA, codes for the relevant HLA I and II spike epitopes. The two mRNAs (COVARNA mRNAs) were designed to be used for delivery to cells in combination, with the RBD-mRNA being the primary source of antigen and the T-mRNA working as an enhancer of immunogenicity by supporting CD4 and CD8 T-cell activation. This innovative approach substantially differs from other available mRNA vaccines, which are largely directed to antibody production by the entire spike protein. In this study, we first show that both mRNAs are functionally transfected into human antigen-presenting cells (APCs). We obtained peripheral blood mononuclear cell (PBMC) samples from three groups of voluntary donors differing in their immunity against SARS-CoV-2: non-infected (naïve), infected-recovered (convalescent), and vaccinated. Using an established method of co-culturing autologous human dendritic cells (hDCs) with T-cells, we detected proliferation and cytokine secretion, thus demonstrating the ability of the COVARNA mRNAs to activate T-cells in an antigen-specific way. Interestingly, important differences in the intensity of the response between the infected-recovered (convalescent) and vaccinated donors were observed, with the levels of T-cell proliferation and cytokine secretion (IFNγ, IL-2R, and IL-13) being higher in the vaccinated group. In summary, our data support the further study of these mRNAs as a combined approach for future use as a vaccine.This study was partially supported by grants from the Spanish Ministry of Economy (MINECO) (grants: SAF-2017-88089-R and RTI2018-096309-B-I00); the Fondo Europeo para el Desarrollo Regional (FEDER); the SPANISH AIDS Research Network RD16/0025/0002 and RD16/0025/0014-ISCIII-FEDER (RIS); projects FIS PI18/00699, COV20/00214, FIS PI22/00814, and ICI20/00067 financed by the Instituto de Salud Carlos III (ISCIII) and co-financed by the European Union; the HIVACAT program; the CERCA Programme/Generalitat de Catalunya SGR 615 and SGR 653; and by the European Commission [grant numbers: FP7-HEALTH-2013-INNOVATION-1 602570-2 and H2020-SC1-2016-2017 (H2020-SC1-2016-RTD) Proposal: 731626-HIVACAR]