Advances of Genomic Medicine in Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a common type of inflammatory arthritis found in up to 40% of patients with psoriasis. Although early diagnosis is important for reducing the risk of irreversible structural damage, there are no adequate screening tools for this purpose, and there are no clear markers of predisposition to the disease. Much evidence indicates that PsA disorder is complex and heterogeneous, where genetic and environmental factors converge to trigger inflammatory events and the development of the disease. Nevertheless, the etiologic events that underlie PsA are complex and not completely understood. In this review, we describe the existing data in PsA in order to highlight the need for further research in this disease to progress in the knowledge of its pathobiology and to obtain early diagnosis tools for these patients.post-print536 K

Therapeutic goals and treatment response evaluation in moderate to severe psoriasis: an experts opinion document

Objective: To critically analyse and define therapeutic objectives, response to treatment evaluation and related decisions in psoriasis. Methods: Expert consensus meetings, a systematic and narrative reviews and a collaborative Delphi procedure were carried out. A steering committee from the Spanish Group of Psoriasis was established who based on the reviews generated a set of related statements. Subsequently, a group of 40 experts tested their agreement with the statements, through 3 Delphi rounds. Results: We found a great variability in clinical guidelines regarding to the definition of treatment goal and the response. In general, treatment failure was considered if a PASI50 is not achieved. The panel of experts agreed on (1) clearly differentiate between ideal and a realistic goals when establishing the therapeutic goal in moderate to severe psoriasis; (2) treatment goals should be in general established regardless of the type of drug for psoriasis; (3) treatment failure if PASI75 response is not reached; (4) an absolute PASI is in general preferred to the rate of PASI improvement from baseline; (5) disease characteristics, patients and physicians opinions/needs and treatment adherence influence treatment goals. Conclusions: A clear treatment decision making framework is vital to improve management of psoriasis.KEY MESSAGES Psoriasis characteristics, patients and physicians opinions/needs and treatment adherence influence treatment goals. Different disease indexes could be used to assess treatment response but absolute PASI is preferred In general psoriasis treatment failure should be considered if PASI75 response is not reachedThis project was promoted and funded by the Spanish Academy of Dermatology and Venereology (AEDV) with unrestricted grant from Leo Pharma

Assessment of the Association of Health with the Liberalisation of Trade in Services under the World Trade Organisation

Background: The liberalisation of trade in services which began in 1995 under the General Agreement on Trade in Services (GATS) of the World Trade Organisation (WTO) has generated arguments for and against its potential health effects. Our goal was to explore the relationship between the liberalisation of services under the GATS and three health indicators – life expectancy (LE), under-5 mortality (U5M) and maternal mortality (MM) - since the WTO was established. Methods and Findings: This was a cross-sectional ecological study that explored the association in 2010 and 1995 between liberalisation and health (LE, U5M and MM), and between liberalisation and progress in health in the period 1995–2010, considering variables related to economic and social policies such as per capita income (GDP pc), public expenditure on health (PEH), and income inequality (Gini index). The units of observation and analysis were WTO member countries with data available for 2010 (n = 116), 1995 (n = 114) and 1995–2010 (n = 114). We conducted bivariate and multivariate linear regression analyses adjusted for GDP pc, Gini and PEH. Increased global liberalisation in services under the WTO was associated with better health in 2010 (U5M: 20.358 p,0.001; MM: 20.338 p = 0.001; LE: 0.247 p = 0.008) and in 1995, after adjusting for economic and social policy variables. For the period 1995–2010, progress in health was associated with income equality, PEH and per capita income. No association was found with global liberalisation in services. Conclusions: The favourable association in 2010 between health and liberalisation in services under the WTO seems to reflect a pre-WTO association observed in the 1995 data. However, this liberalisation did not appear as a factor associated with progress in health during 1995–2010. Income equality, health expenditure and per capita income were more powerful determinants of the health of populations.This study was funded by the Carlos III Health Institute and the Programme for Promotion of Biomedical and Health Sciences (http://www.isciii.es/) of the Spanish Ministry of Health and Consumer Affairs (Ref. PI060295)

Cálculo de la huella de carbono de la producción de cereal de invierno en condiciones de secano

1 copia .pdf (A-3) del original presentado por los autores.La agricultura es una importante fuente de emisión de gases de efecto invernadero (GEI) a la atmósfera. • Varios estudios han determinado el impacto de diversas técnicas de manejo agrícola en las emisiones de GEI del suelo a la atmósfera. Sin embargo, existe la necesidad de obtener una mayor información de todo el sistema agrícola y de considerar, así, las emisiones de GEI asociadas a los diferentes procesos y actividades que se dan durante una determinada campaña agrícola (análisis de la huella de carbono). • Este trabajo tiene como finalidad calcular la huella de carbono de la producción de cereal en agroecosistemas mediterráneos de secano del NE español bajo diferentes sistemas de manejo agrícola.Este estudio se ha financiado por la Comisión Interministerial de Ciencia y Tecnología de España (AGL2007‐66320‐C02‐01 y AGL 2010‐22050‐C03‐01/02) y por el Gobierno de Aragón y La Caixa (GALC‐ 050/2011).Peer reviewe

Cardiovascular Screening Practices and Statin Prescription Habits in Patients with Psoriasis among Dermatologists, Rheumatologists and Primary Care Physicians.

Patients with psoriasis have a higher prevalence of cardiovascular risk factors. This study evaluated cardiovascular screening practices and statin prescribing habits among dermatologists, rheumatologists and primary care physicians (PCPs) through an online questionnaire, which was distributed through the Spanish scientific societies of the above-mentioned specialties. A total of 299 physicians (103 dermatologists, 94 rheumatologists and 102 PCPs) responded to the questionnaire. Of these, 74.6% reported screening for smoking, 37.8% for hypertension, 80.3% for dyslipidaemia, and 79.6% for diabetes mellitus. Notably, only 28.4% performed global screening, defined as screening for smoking, hypertension, dyslipidaemia, and diabetes mellitus by the same physician, and 24.4% reported calculating 10-year cardiovascular disease (CVD) risk, probably reflecting a lack of comprehensive cardiovascular risk assessment in these patients. This study also identified unmet needs for awareness of cardiovascular comorbidities in psoriasis and corresponding screening and treatment recommendations among PCPs. Of PCPs, 61.2% reported not being aware of the association between psoriasis and CVD and/or not being aware of its screening recommendations, and 67.6% did not consider psoriasis as a risk-enhancing factor when deciding on statin prescription. Thirteen dermatologists (12.6%) and 35 rheumatologists (37.2%) reported prescribing statins. Among those who do not prescribe, 49.7% would be willing to start their prescription.post-print492 K

From Messengers to Receptors in Psoriasis: The Role of IL-17RA in Disease and Treatment.

The paradigm of psoriasis as a Th17-driven disease has evolved in the last years towards a much deeper knowledge of the complex pathways, mechanisms, cells, and messengers involved, highlighting the crucial role played by the IL-17 family of cytokines. All IL-17 isoforms signal through IL-17R. Five subunits of IL-17R have been described to date, which couple to form a homo- or heteroreceptor complex. Characteristically, IL-17RA is a common subunit in all hetero-receptors. IL-17RA has unique structural—containing a SEFIR/TILL domain—and functional—requiring ACT-1 for signaling—properties, enabling Th17 cells to act as a bridge between innate and adaptive immune cells. In psoriasis, IL-17RA plays a key role in pathogenesis based on: (a) IL-17A, IL-17F, and other IL-17 isoforms are involved in disease development; and (b) IL-17RA is essential for signaling of all IL-17 cytokines but IL-17D, whose receptor has not been identified to date. This article reviews current evidence on the biology and role of the IL-17 family of cytokines and receptors, with focus on IL-17RA, in psoriasis and some related comorbidities, and puts them in context with current and upcoming treatments.post-print1.096 K

Correction: Vidal et al. From Messengers to Receptors in Psoriasis: The Role of IL-17RA in Disease and Treatment. Int. J. Mol. Sci. 2021, 22, 6740.

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Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Aterosclerosis subclínica en pacientes con psoriasis. Utilidad diagnostica de la ecografía arterial femoral y análisis de relación con la resistencia a la insulina

La psoriasis es una enfermedad compleja, crónica e inflamatoria, de etiología desconocida, y relacionada patogénicamente con mecanismos inmunológicos, que afecta de forma principal a la piel y articulaciones, si bien también se ha asociado a múltiples comorbilidades, como son obesidad, hipertensión, dislipemia, diabetes tipo 2, enfermedad renal crónica, depresión y otras, entre las que destaca el desarrollo precoz de aterosclerosis y en consecuencia enfermedad cardiovascular (ECV)1. Un estudio reciente estima una prevalencia de psoriasis en España de 2,3% de la población sin diferencias significativas entre sexos. Según la edad la prevalecía sigue una curva ascendente desde los 16 años hasta los 60-69 años. Se conoce que los pacientes con psoriasis, presenta un riesgo aumentado de infarto de miocardio, que desarrollan a edades más jóvenes que la población general y ante igualdad en factores de riesgo cardiovasculares. Además, la esperanza de vida en pacientes con psoriasis grave se reduce en 4 a 5 años como consecuencia de ECV. En este sentido, ha quedado bien establecido que el análisis de los factores de riesgo cardiovasculares tradicionales, incluidos en diferentes escalas de riesgo cardiovascular en la población general como el Framinghan o el SCORE (Systematic COronary Risk Evaluation) no son adecuados para la evaluación del riesgo de enfermedad coronaria en pacientes con psoriasis. Estos datos ponen de manifiesto la dificultad de la detección precoz de arteriosclerosis en fase subclínica, así como la imposibilidad de adoptar medidas preventivas que puedan reducir el riesgo de enfermedad coronaria en estos pacientes antes de que presenten manifestaciones clínicas de ECV. Por estas razones, se ha propuesto que los pacientes con psoriasis deberían ser sometidos a adecuadas pruebas de cribado que permitan identificar a aquellos que tienen un elevado riesgo de presentar ECV, resaltando la necesidad de disponer de una prueba que sea, simple, fácil de realizar, no invasiva y de bajo coste económico. La ecografía arterial de alta resolución reúne estos criterios, sin embargo, en la psoriasis, hasta la fecha actual, utilizando ecografía solo se han estudiado las arterias carótidas, inicialmente midiendo el engrosamiento intima-media, que en la actualidad se acepta es un método inadecuado y débil predictor de aterosclerosis, que no mejora la capacidad diagnóstica de los factores de riesgo tradicionales, y su uso ha dejado de ser recomendado en las guías del American College of Cardiology/American Heart Association guidelines. En algunos estudios, también se ha utilizado la ecografía arterial de carótidas para valorar la presencia de placas de ateroma, pero los resultados han sido contradictorios en cuanto a su prevalencia en pacientes con psoriasis. Estudios de autopsia en individuos de la población general han revelado que la presencia de placas de ateroma en arterias femorales, pero no en las arterias carótidas, constituyen un predictor significativo de aterosclerosis coronaria y de mortalidad por cardiopatía isquémica. Y en concordancia con estos datos, estudios en sujetos sanos han puesto de manifiesto, mediante estudio ecográfico, que las placas de ateroma femorales son más prevalentes que las de carótida, y se asocian con mayor frecuencia a la existencia de aterosclerosis coronaria. Por otro lado, el mayor riesgo de infarto de miocardio que presentan a edades más jóvenes los pacientes con psoriasis, y que no son justificables por los factores de riesgo cardiovascular clásicos, ha permitido sugerir que otros factores podrían estar implicados en el desarrollo precoz y acelerado de aterosclerosis en estos pacientes. En este sentido, estudios previos han mostrado una relación entre la psoriasis y la diabetes mellitus tipo 2, además, la resistencia a la insulina, íntimamente asociada a la psoriasis, y a enfermedades inflamatorias crónicas, constituye un conocido factor de riesgo cardiovascular. Basándonos en lo anterior, planteamos la posibilidad de que el puente de unión patogénico entre psoriasis y aterosclerosis sea, al menos en parte, la presencia de resistencia a la insulina, incluso en pacientes sin diabetes. Nuestra hipótesis en el presente estudio es que la detección ecográfica de placas de ateroma para el cribado de aterosclerosis subclínica en la psoriasis podría ser más útil en las arterias femorales que en carótidas, y que la resistencia a la insulina podría estar implicada en el desarrollo de aterosclerosis acelerada en estos pacientes. En la presente tesis doctoral se da cuenta de los conocimientos actuales sobre la relación entre psoriasis y aterosclerosis, para posteriormente dar paso a exponer los objetivos del estudio, material y métodos, resultados, discusión, y conclusiones