Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 ± 20.6% vs 93.6 ± 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 ± 5.2 mm vs 19.9 ± 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment

Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 +/- 20.6% vs 93.6 +/- 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 +/- 5.2 mm vs 19.9 +/- 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment

Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus

Objectives: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc- RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods: We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposingdirection allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results: The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 x 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 x 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions: Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

Libros de Maese Rodrigo y del Colegio de Santa María de Jesús en la Institución Colombiana

La custodia en la Institución Colombina de once libros, impresos y manuscritos, propiedad del Seminario Diocesano de Sevilla, entre los que se conservan ejemplares que pertenecieron a Rodriogo Fernández de Santaella, más conocido por Maese Rodrigo, y al Colegio de Santa María de Jesús, ha propiciado este estudio que hemos dividido en dos bloques. En el primero se hace un poco de historia de estos libros a lo largo de los siglos, así como un análisis de cada una de las obras y sus propietarios. La segunda parte del artículo recoge los once asisentos caralográficos, comprendiendo la descripción textual y notas codicológicas para los manuscritos y la aplicación de las normas ISBD(A) para los impresos

Libros de Maese Rodrigo y del Colegio de Santa María de Jesús en la Institución Colombiana

The Columbine Institution houses, among its collections, eleven printed and manuscript books which belonged to the Diocesan Serninary in Seville. Some of these books were the property of Rodrigo Fernández de Santaella, known as "Maese Rodrigo", and some originally belonged to the College of Santa María de Jesús. This article has been divided into two parts. The first section contains a short study of the history of these eleven books, along with an analysis of each of the books and their owners; the second section includes the eleven bibliographical entries, which comprise a description of the books, codicological notes for the manuscripts and the application of the ISBD(A) rules for the printed booksLa custodia en la Institución Colombina de once libros, impresos y manuscritos, propiedad del Seminario Diocesano de Sevilla, entre los que se conservan ejemplares que pertenecieron a Rodrigo Fernández de Santaella, más conocido por Maese Rodrigo, y al Colegio de Santa María de Jesús, ha propiciado este estudio que hemos dividido en dos bloques. En el primero se haceunpoco historia de estos libros a lo largo de los siglos, así como un análisis de cadaunade las obras y sus propietarios. La segunda parte del artículo recoge los once asientos catalográficos, comprendiendo la descripción textual y notas codicológicas para los manuscritos y la aplicación de las normas ISBD(A) para los impreso

Romano-republican assemblages of Cerro Macareno (La Rinconada, Sevilla): update on the 2018 campaign

Cerro Macareno es un tell protohistórico situado junto a un antiguo brazo navegable del Guadalquivir, aguas arriba de Sevilla. Se conoce principalmente por las excavaciones de salvamento llevadas a cabo en los años setenta, debido a la destrucción a la que estaba sometido por la explotación de una cantera de áridos. Estos trabajos sacaron a la luz un área industrial de inicios de la II Edad del Hierro y permitieron definir la secuencia de ocupación del antiguo asentamiento, que arranca en torno al siglo VIII a. C. y finaliza en los primeros compases de la romanización, a finales del siglo II a. C. Cuarenta años después de las últimas excavaciones, la Universidad de Sevilla ha retomado en el año 2017 el estudio de este singular yacimiento a través de un proyecto de investigación. Se ha puesto especial énfasis en las etapas de transición, entre ellas la fase romano-republicana, uno de los momentos peor conocidos en la región desde el punto de vista arqueológico. Por lo que respecta a esta última, la campaña de excavaciones realizada en 2018 permitió documentar niveles amplios y relativamente poco alterados a escasa profundidad, lo que brindaba la oportunidad de estudiar en extensión contextos domésticos en un momento en el que la cultura turdetana se encontraba en pleno proceso de transformación de las estructuras socioeconómicas y de las formas de vida, antes de los grandes cambios que se producirán durante siglo I a. C.Cerro Macareno is a protohistoric tell located next to an ancient navigable branch of the Guadalquivir, upstream from Seville. It is mainly known from the salvage excavations carried out in the 1970s, due to the destruction to which it was subjected by the exploitation of an aggregate quarry. These works brought to light an industrial area dating from the beginning of the 2nd Iron Age and made it possible to define the sequence of occupation of the ancient settlement, which began around the 8th century BC and ended in the early stages of Romanisation, at the end of the 2nd century BC. Forty years after the last excavations, in 2017 the University of Seville has resumed the study of this unique site through a research project. Special emphasis has been placed on the transitional stages, including the Roman-Republican phase, one of the worst-known periods in the region from an archaeological point of view. With regard to the latter, the excavation campaign carried out in 2018 allowed to document extensive and relatively undisturbed levels at shallow depths, which provided the opportunity to study domestic contexts at a time when the Turdetanian culture was in the midst of a process of transformation of socio-economic structures and ways of life, prior to the major changes that would take place during the 1st century BC

Effect of an Interdisciplinary Weight Loss and Lifestyle Intervention on Obstructive Sleep Apnea Severity: The INTERAPNEA Randomized Clinical Trial

This study was supported by grants FPU16/01093 (Dr Carneiro-Barrera), FPU14/04172 (Dr Amaro-Gahete), and FPU19/01609 (Mr Jurado-Fasoli) from the Spanish Ministry of Education and Vocational Training; grant SOMM17/6107/UGR (via European Regional Development Funds) from the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (Dr Ruiz); and funding from the University of GranadaLoMonaco S.L. Sleep Research Cathedra and the University of Granada Plan Propio de Investigacion 2016Excellence Actions: Unit of Excellence on Exercise and Health.IMPORTANCE Obesity is the leading cause of obstructive sleep apnea (OSA); however, the effects of weight loss and lifestyle interventions on OSA and comorbidities remain uncertain. OBJECTIVE To evaluate the effect of an interdisciplinary weight loss and lifestyle intervention on OSA and comorbidities among adults with moderate to severe OSA and overweight or obesity. DESIGN, SETTING, AND PARTICIPANTS The InterdisciplinaryWeight Loss and Lifestyle Intervention for OSA (INTERAPNEA) study was a parallel-group open-label randomized clinical trial conducted at a hospital-based referral center in Granada, Spain, from April 1, 2019, to October 23, 2020. The study enrolled 89 Spanish men aged 18 to 65 years with moderate to severe OSA and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 25 or greater who were receiving continuous positive airway pressure (CPAP) therapy. The sole inclusion of men was based on the higher incidence and prevalence of OSA in this population, the differences in OSA phenotypes between men and women, and the known effectiveness of weight loss interventions among men vs women. INTERVENTIONS Participants were randomized to receive usual care (CPAP therapy) or an 8-week weight loss and lifestyle intervention involving nutritional behavior change, aerobic exercise, sleep hygiene, and alcohol and tobacco cessation combined with usual care. MAIN OUTCOMES AND MEASURES The primary end point was the change in the apnea-hypopnea index (AHI) from baseline to the intervention end point (8 weeks) and 6 months after intervention. Secondary end points comprised changes in other OSA sleep-related outcomes, body weight and composition, cardiometabolic risk, and health-related quality of life. RESULTS Among 89 men (mean [SD] age, 54.1 [8.0] years; all of Spanish ethnicity; mean [SD] AHI, 41.3 [22.2] events/h), 49 were randomized to the control group and 40 were randomized to the intervention group. The intervention group had a greater decrease in AHI (51% reduction; change, –21.2 events/h; 95%CI, –25.4 to –16.9 events/h) than the control group (change, 2.5 events/h; 95% CI, –2.0 to 6.9 events/h) at the intervention end point, with a mean between-group difference of –23.6 events/h (95%CI, –28.7 to –18.5 events/h). At 6 months after intervention, the reduction in AHI was 57%in the intervention group, with a mean between-group difference of –23.8 events/h (95% CI, –28.3 to –19.3 events/h). In the intervention group, 18 of 40 participants (45.0%) no longer required CPAP therapy at the intervention end point, and 6 of 40 participants (15.0%) attained complete OSA remission. At 6 months after intervention, 21 of 34 participants (61.8%) no longer required CPAP therapy, and complete remission of OSA was attained by 10 of 34 participants (29.4%). In the intervention vs control group, greater improvements in body weight (change, –7.1 kg [95%CI, −8.6 to −5.5 kg] vs −0.3 kg [95%CI, −1.9 to 1.4 kg]) and composition (eg, change in fat mass, −2.9 kg [95%CI, −4.5 to −1.3 kg] vs 1.4 kg [95%CI, −0.3 to 3.1 kg]), cardiometabolic risk (eg, change in blood pressure, −6.5mmHg [95%CI, −10.3 to −2.6mmHg] vs 2.2mmHg [95%CI, −2.1 to 6.6mm Hg]), and health-related quality of life (eg, change in Sleep Apnea Quality of Life Index, 0.8 points [95%CI, 0.5-1.1 points] vs 0.1 points [95%CI, −0.3 to 0.4 points]) were also found at the intervention end point. CONCLUSIONS AND RELEVANCE In this study, an interdisciplinary weight loss and lifestyle intervention involving Spanish men with moderate to severe OSA and had overweight or obesity and were receiving CPAP therapy resulted in clinically meaningful and sustainable improvements in OSA severity and comorbidities as well as health-related quality of life. This approach may therefore be considered as a central strategy to address the substantial impact of this increasingly common sleepdisordered breathing condition.Spanish Government FPU16/01093 FPU14/04172 FPU19/01609Junta de Andalucia SOMM17/6107/UGRUniversity of GranadaLoMonaco S.L. Sleep Research CathedraUniversity of Granada Plan Propio de Investigacion 2016Excellence Actions: Unit of Excellence on Exercise and Healt