Monitoring of miR-181a-5p and miR-155-5p Plasmatic Expression as Prognostic Biomarkers for Acute and Subclinical Rejection in de novo Adult Liver Transplant Recipients.

Background and Aims: News strategies for the accurate assessment of the state of immunosuppression (IS) in liver transplant recipients are needed to prevent rejection and minimize drug-related side effects. miRNAs can potentially be used as diagnostic or prognostic biomarkers in transplant patients. This study evaluated the capacity of a plasmatic miRNA panel (miR-155-5p, miR-122-5p, miR-181a-5p, and miR148-3p) as an early non-invasive prognostic and diagnostic biomarker for T cell-mediated acute rejection (TCMAR) and subclinical rejection (SCR) in adult liver recipients. Methods: A total of 145 liver recipients were included. All patients received a calcineurin inhibitor with or without mycophenolate mofetil and methylprednisolone. Plasmatic miRNA expression was assessed by qPCR before and at different time-points after liver transplantation. Results: Seventeen patients experienced TCMAR, and eight were diagnosed with SCR during the protocol biopsy at the 3rd month post-transplantation. Pre-transplantation, miR-155-5p expression was significantly higher in TCMAR patients and in SCR patients than in non-rejectors, and miR-181a-5p expression was also significantly higher in SCR patients than in non-rejectors. Post-transplantation, before transaminase-level modification, significantly increased miR-181a-5p, miR-155-5p, and miR-122-5p expression was observed in TCMAR and SCR patients. Binary logistic regression analyses showed, post-transplantation, that TCMAR risk was better predicted by individual expression of miR-181a-5p (LOGIT = -6.35 + 3.87*miR-181a-5p), and SCR risk was better predicted by the combination of miR-181a-5p and miR-155-5p expression (LOGIT = -5.18 + 2.27*miR-181a-5p+1.74*miR-155-5p). Conclusions: Pre-transplantation plasmatic miR-155-5p expression may be useful for stratifying low-immunologic-risk patients, and post-transplantation miR-181a-5p and miR-155-5p may be candidates for inclusion in early, non-invasive prognostic biomarker panels to prevent TCMAR or SCR and better identify patient candidates for IS minimization. Large prospective randomized multicenter trials are needed to refine the cut-off values and algorithms and validate the clinical usefulness of these biomarkers

Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease

[Background & Aims] Porto-sinusoidal vascular disease (PSVD) is a rare vascular liver disease of unknown etiology that causes portal hypertension. It usually affects young individuals and shortens live expectancy. The deregulated pathways involved in PSVD development are unknown and therefore we lack curative treatments. The purpose of this study was to integrate transcriptomic and clinical data by comprehensive network-based modeling in order to uncover altered biological processes in patients with PSVD.[Methods] We obtained liver tissue samples from 20 consecutive patients with PSVD and 21 sex- and age-matched patients with cirrhosis and 13 histologically normal livers (HNL) (initial cohort) and performed transcriptomic analysis. Microarray data were analyzed using weighted gene correlation network analysis to identify clusters of highly correlated genes differently expressed in patients with PSVD. We next evaluated the molecular pathways enriched in patients with PSVD and the core-related genes from the most significantly enriched pathways in patients with PSVD. Our main findings were validated using RNA sequencing in a different cohort of PSVD, cirrhosis and HNL (n = 8 for each group).[Results] Patients with PSVD have a distinctive genetic profile enriched mainly in canonical pathways involving hemostasis and coagulation but also lipid metabolism and oxidative phosphorylation. Serpin family (SERPINC1), the apolipoproteins (APOA, APOB, APOC), ATP synthases (ATP5G1, ATP5B), fibrinogen genes (FGB, FGA) and alpha-2-macroglobulin were identified as highly connective genes that may have an important role in PSVD pathogenesis.[Conclusion] PSVD has a unique transcriptomic profile and we have identified deregulation of pathways involved in vascular homeostasis as the main pathogenic event of disease development. [Lay summary] Porto-sinusoidal vascular disease is a rare but life-shortening disease that affects mainly young people. Knowledge of the disrupted pathways involved in its development will help to identify novel therapeutic targets and new treatments. Using a systems biology approach, we identify that pathways regulating endothelial function and tone may act as drivers of porto-sinusoidal vascular disease.This study was supported by the Instituto de Salud Carlos III FIS PI17/00398, the Ministry of Education and Science, Spain (SAF-2016-75767-R); Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR-SGR2017-517) a grant from Generalitat de Catalunya, Fondo Europeo de Desarrollo Regional (FEDER) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), funded by Instituto de Salud Carlos III. Marta Magaz is a recipient of a Río Hortega grant from Instituto de Salud Carlos III. Pol Olivas has been funded by Contractes Clínic de Recerca ”Emili Letang-Josep Font’’ 2020, granted by Hospital Clínic de Barcelona.Peer reviewe

Monitoring of miR-181a-5p and miR-155-5p Plasmatic Expression as Prognostic Biomarkers for Acute and Subclinical Rejection in de novo Adult Liver Transplant Recipients

Background and Aims: News strategies for the accurate assessment of the state of immunosuppression (IS) in liver transplant recipients are needed to prevent rejection and minimize drug-related side effects. miRNAs can potentially be used as diagnostic or prognostic biomarkers in transplant patients. This study evaluated the capacity of a plasmatic miRNA panel (miR-155-5p, miR-122-5p, miR-181a-5p, and miR148-3p) as an early non-invasive prognostic and diagnostic biomarker for T cell-mediated acute rejection (TCMAR) and subclinical rejection (SCR) in adult liver recipients.Methods: A total of 145 liver recipients were included. All patients received a calcineurin inhibitor with or without mycophenolate mofetil and methylprednisolone. Plasmatic miRNA expression was assessed by qPCR before and at different time-points after liver transplantation.Results: Seventeen patients experienced TCMAR, and eight were diagnosed with SCR during the protocol biopsy at the 3rd month post-transplantation. Pre-transplantation, miR-155-5p expression was significantly higher in TCMAR patients and in SCR patients than in non-rejectors, and miR-181a-5p expression was also significantly higher in SCR patients than in non-rejectors. Post-transplantation, before transaminase-level modification, significantly increased miR-181a-5p, miR-155-5p, and miR-122-5p expression was observed in TCMAR and SCR patients. Binary logistic regression analyses showed, post-transplantation, that TCMAR risk was better predicted by individual expression of miR-181a-5p (LOGIT = −6.35 + 3.87*miR-181a-5p), and SCR risk was better predicted by the combination of miR-181a-5p and miR-155-5p expression (LOGIT = −5.18 + 2.27*miR-181a-5p+1.74*miR-155-5p).Conclusions: Pre-transplantation plasmatic miR-155-5p expression may be useful for stratifying low-immunologic-risk patients, and post-transplantation miR-181a-5p and miR-155-5p may be candidates for inclusion in early, non-invasive prognostic biomarker panels to prevent TCMAR or SCR and better identify patient candidates for IS minimization. Large prospective randomized multicenter trials are needed to refine the cut-off values and algorithms and validate the clinical usefulness of these biomarkers

TFG 2014/2015

Amb aquesta publicació, EINA, Centre universitari de Disseny i Art adscrit a la Universitat Autònoma de Barcelona, dóna a conèixer el recull dels Treballs de Fi de Grau presentats durant el curs 2014-2015. Voldríem que un recull com aquest donés una idea més precisa de la tasca que es realitza a EINA per tal de formar nous dissenyadors amb capacitat de respondre professionalment i intel·lectualment a les necessitats i exigències de la nostra societat. El treball formatiu s’orienta a oferir resultats que responguin tant a paràmetres de rigor acadèmic i capacitat d’anàlisi del context com a l’experimentació i la creació de nous llenguatges, tot fomentant el potencial innovador del disseny.Con esta publicación, EINA, Centro universitario de diseño y arte adscrito a la Universidad Autónoma de Barcelona, da a conocer la recopilación de los Trabajos de Fin de Grado presentados durante el curso 2014-2015. Querríamos que una recopilación como ésta diera una idea más precisa del trabajo que se realiza en EINA para formar nuevos diseñadores con capacidad de responder profesional e intelectualmente a las necesidades y exigencias de nuestra sociedad. El trabajo formativo se orienta a ofrecer resultados que respondan tanto a parámetros de rigor académico y capacidad de análisis, como a la experimentación y la creación de nuevos lenguajes, al tiempo que se fomenta el potencial innovador del diseño.With this publication, EINA, University School of Design and Art, affiliated to the Autonomous University of Barcelona, brings to the public eye the Final Degree Projects presented during the 2014-2015 academic year. Our hope is that this volume might offer a more precise idea of the task performed by EINA in training new designers, able to speak both professionally and intellectually to the needs and demands of our society. The educational task is oriented towards results that might respond to the parameters of academic rigour and the capacity for contextual analysis, as well as to considerations of experimentation and the creation of new languages, all the while reinforcing design’s innovative potential

Psychosocial and behavioural factors in the regulation of weight: Self-regulation, self-efficacy and locus control

Objetivo: Identificar la relación y el comportamiento de la autorregulación, autoeficacia y locus control en la regulación del peso, en población adulta con obesidad, sobrepeso y normopeso. Método: Se realizó un estudio transversal en el Centro de Salud del Coto (Gijón) entre el 1 de abril al 30 de julio de 2015. La muestra estuvo formada por personas entre 18-65 años que contaran con un registro del índice de masa corporal en los dos últimos años. Los criterios de exclusión fueron: enfermedad médica grave, trastornos de la alimentación o mujeres embarazadas. Se midieron variables conductuales: autorregulación del peso corporal (Inventario de autorregulación del peso corporal), autoeficacia percibida en la regulación del peso (Inventario autoeficacia percibida en la regulación del peso) y locus control en la regulación del peso (Inventario Locus control en la regulación del peso). Variables antropométricas: peso (kg) y talla (m), índice de masa corporal. Resultados: Se incluyeron 106 participantes: 32 con obesidad, 28 con sobrepeso y 46 con normopeso. Se encontraron diferencias estadísticamente significativas entre los 3 grupos de estudio para las variables escala total de autoeficacia (F = 61,77; p < 0,01), escala total de autorregulación (F = 45,97; p < 0,01), locus control interno (F = 13,92; p = 0,019), locus control otros poderosos (F = 9,21; p < 0,01) y locus control azar (F = 3,50; p = 0,011). Conclusiones: La existencia de una relación entre el índice de masa corporal y las variables conductuales de autoeficacia, autorregulación y locus control, plantea a los profesionales sanitarios la necesidad de incluir los factores psicológicos o conductuales en cualquier actividad preventiva y de intervención dirigida al control del peso.Objective: To identify the relationship and behaviour of the variables of self-control, self-efficacy and locus control in weight regulation of obese, overweight and normal weight adults. Method: Transversal study undertaken in the Health Centre of El Coto (Gijón) from 1 st April to 30th July 2015. Participants: Subjects between 18-65 years of age with a body mass index recording within the last two years. Exclusions: serious medical illness, eating disorders or pregnant women. Main measurements: Behavioural variables: self-regulation of body weight (Inventory of self-control of body weight), perceived self-efficacy in weight regulation (Inventory of perceived self-efficacy in weight regulation) and locus control in weight regulation (Inventory of locus control in weight regulation). Anthropometric variables: weight (kg) and height (m), body mass index. Results: One hundred and six participants were included: 32 were obese, 28 overweight and 46 normal weight. Significant differences were found between the 3 study groups for total scale of self-efficacy (F=61.77; p<.01), total scale of self-regulation (F=45.97; p<.01), internal locus control (F=13.92; p=.019), other weighty influences of locus control (F=9.21; p<.01) and random locus control (F=3.50; p=.011). Conclusions: The relationship between body mass index and behavioural variables of self-efficacy, self-regulation and locus control, suggests the need for healthcare professionals to include psychological factors of behaviour in any preventive action and intervention directed at weight control

The Pathophysiology of Portal Vein Thrombosis in Cirrhosis: Getting Deeper into Virchows Triad

Portal vein thrombosis (PVT) is a common complication among patients with cirrhosis. However, its pathophysiology is not well established and there are currently very few predictive factors, none of which are actually useful, from a clinical perspective. The contribution of each of the vertices of Virchow's triad, e.g., blood hypercoagulability, blood flow, and portal vein endothelial damage in the development of PVT is not clear. In this review, we aim to recapitulate the latest studies on the field of PVT development in order to understand its mechanisms and discuss some of the future directions in the study of this important complication of cirrhosis

Prevalence and associated factors of frailty in adults over 70 years in the community

Objetivo: Estimar la prevalencia y analizar los factores asociados al síndrome de fragilidad en adultos ≥ 70 años, pertenecientes a un centro de salud de Asturias. Diseño: Estudio observacional transversal. Emplazamiento: Centro de Salud El Llano, Asturias. Participantes: Adultos ≥ 70 años. Mediciones principales: La fragilidad se definió por la presencia de ≥ 3 criterios del fenotipo de fragilidad de Fried. Variables secundarias: características sociodemográficas, estado de salud, estado funcional, estado cognitivo-afectivo y riesgo social. Se realizó un análisis bivariante y regresión logística. Resultados: Se incluyeron 408 participantes con una edad media de 79,8 (DE 6,6) años, el 59,1% eran mujeres. La prevalencia de fragilidad fue del 27,7% y del 44,9% para la prefragilidad. El perfil sociodemográfico es de una mujer (77%), de elevada edad (> 84 años) (50,4%), sin estudios (65,5%), viuda (48,7%), con bajo nivel económico (47,8%) y en riesgo social (OR: 3,3; IC 95%: 2,5-4). Los factores que se asociaron estadísticamente con el síndrome de fragilidad fueron: comorbilidad alta (OR: 2,7; IC 95%: 1,5-5), polimedicación (OR: 1,9; IC 95%: 1,3-3), percepción de la calidad de vida con la salud (OR: 0,95; IC 95%: 0,93-0,97); deambulación alterada (OR: 17,9; IC 95%: 7,1-45,3), apoyo para la marcha (OR: 10,5; IC 95%: 4,7-23,4), alto riesgo de caídas (OR: 6,4; IC 95%: 3,8-10,8), dependencia para las ABVD (OR: 4; IC 95%: 2,4-6,6), AIVD (OR: 9,7; IC 95%: 4,7-20), discapacidad (OR: 37,7; IC 95%: 52,2-274,5), deterioro cognitivo (OR: 4,1; IC 95%: 1,8-9,3) y depresión (OR: 4,8; IC 95%: 2,7-8,7). Conclusiones: La fragilidad es un síndrome multifactorial de elevada prevalencia en los mayores de 70 años, en el que además de los criterios de fragilidad de Fried deben de ser analizados aspectos del estado de salud, funcionales, cognitivos-afectivos y sociales.Objective: To estimate the prevalence and analyze the factors associated with frailty syndrome, in adults ≥70 years old, belonging to a health center in Asturias. Design: Observational cross-sectional study. Participants: Adults ≥70 years of age. Site: Health Centre of Llano (Asturias). Main measurements: Frailty was defined by the presence of ≥3 criteria of Fried's frailty phenotype. Secondary variables: sociodemographic characteristics, health status, functional status, cognitive-affective status and social risk. A bivariate analysis and logistic regression were performed. Results: Four hundred eight participants were included, with a mean age of 79.8 (SD 6.6), 59.1% female. The prevalence of frailty was 27.7% and 44.9% for pre-frailty. The sociodemographic profile is that of a woman (77%), of high age (>84 years) (50.4%), without studies (65.5%), widow (48.7%) with low economic status (47.8%) and at social risk (OR: 3.3; 95% CI: 2.5-4). Factors that were statistically associated with frailty syndrome were: high comorbidity (OR: 2.7; 95% CI: 1.5-5), polypharmacy (OR: 1.9; 95% CI: 1.3-3), perception of quality of life with health (OR: 0.95; 95% CI: 0.93-0.97), impaired ambulation (OR: 17.9; 95% CI: 7.1-45.3), support for walking (OR: 10.5; 95% CI: 4.7-23.4), high risk of falls (OR: 6.4; 95% CI: 3.8-10.8), ABVD (OR: 4; 95% CI: 2.4-6.6), AIVD (OR: 9.7; 95% CI: 4.7-20), disability (OR: 37.7; 95% CI: 52.2-274.5), cognitive impairment (OR: 4.1; 95% CI: 1.8-9.3) and depression (OR: 4.8; 95% CI: 2.7-8.7). Conclusions: Frailty is a multifactorial syndrome, with a high prevalence in those over 70 years of age, in which, in addition to Fried's criteria of frailty, aspects of health, functional, cognitive-affective and social status must be analyzed.Esta investigación ha sido financiada por la Fundación para la Investigación e Innovación Biosanitaria del Principado de Asturias. Beca Fomento de Proyectos de Investigación entre Investigadores de Atención Primaria y Cuidados de Salud, por el Instituto de Investigación Sanitaria del Principado de Asturias

Porto-sinusoidal vascular disorder in chronic HBV: A significant coexistence not to be overlooked

Background &amp; Aims: Porto-sinusoidal vascular disorder (PSVD) encompasses a group of liver diseases with vascular abnormalities that can cause portal hypertension in the absence of cirrhosis. The new diagnostic criteria allow for coexistence with other liver diseases, however its relationship with chronic hepatitis B (CHB) remains unclear. This study aimed to assess HBV prevalence in a PSVD cohort and evaluate its clinical impact. Methods: This retrospective study was conducted on patients with PSVD at Hospital Clínic Barcelona. HBV serology was evaluated, and patients were categorized into HBV chronic infection, past infection, or no HBV exposure. Clinical characteristics and outcomes were compared. Results: We included 155 patients with PSVD. Prevalence of CHB and past HBV infection in patients with PSVD was higher than in the general population (5.8% vs. 0.5%, p <0.0001 and 20% vs. 9.1%, p <0.0001, respectively). Patients with CHB had a significant delay in PSVD diagnosis compared to those without CHB (11 [5–25] vs. 1 [0–3] years, p = 0.002) and had a more advanced disease (MELD score 12 [9–17] vs. 9 [7–11], p = 0.012) at the time of PSVD diagnosis. The clinical evolution of PSVD in patients with CHB was marked by a significantly higher transplantation rate at the last follow-up (33% vs. 4.1%, p = 0.001). Conclusions: Recognizing the coexistence of PSVD and CHB is important for timely diagnosis and optimal management, highlighting the potential benefits of specialized care for potentially improved outcomes. Impact and implications: The new diagnostic criteria for porto-sinusoidal vascular disorder (PSVD) allow for coexistence with other liver diseases. The results of the present study highlight, for the first time, a non-negligible prevalence of chronic hepatitis B in the PSVD population that was previously unknown. Coexistence may challenge and delay the PSVD diagnosis and is associated with a more unfavorable clinical course. Our findings will increase awareness of this coexistence and improve PSVD diagnosis and management. Furthermore, the data will encourage new studies to determine the prevalence and clinical behavior of other chronic liver diseases that coexist with PSVD

Increased sinusoidal pressure impairs liver endothelial mechanosensing, uncovering novel biomarkers of portal hypertension

Background &amp; Aims: Portal hypertension (PH) is a frequent and severe clinical syndrome associated with chronic liver disease. Considering the mechanobiological effects of hydrostatic pressure and shear stress on endothelial cells, we hypothesised that PH might influence the phenotype of liver sinusoidal endothelial cells (LSECs) during disease progression. The aim of this study was to investigate the effects of increased hydrodynamic pressure on LSECs and to identify endothelial-derived biomarkers of PH. Methods: Primary LSECs were cultured under normal or increased hydrodynamic pressure within a pathophysiological range (1 vs. 12 mmHg) using a microfluidic liver-on-a-chip device. RNA sequencing was used to identify pressure-sensitive genes, which were validated in liver biopsies from two independent cohorts of patients with chronic liver disease with PH (n = 73) and participants without PH (n = 23). Biomarker discovery was performed in two additional independent cohorts of 104 patients with PH and 18 patients without PH. Results: Transcriptomic analysis revealed marked deleterious effect of pathological pressure in LSECs and identified chromobox 7 (CBX7) as a key transcription factor diminished by pressure. Hepatic CBX7 downregulation was validated in patients with PH and significantly correlated with hepatic venous pressure gradient. MicroRNA 181a-5p was identified as pressure-induced upstream regulator of CBX7. Two downstream targets inhibited by CBX7, namely, E-cadherin (ECAD) and serine protease inhibitor Kazal-type 1 (SPINK1), were found increased in the bloodstream of patients with PH and were highly predictive of PH and clinically significant PH. Conclusions: We characterise the detrimental effects of increased hydrodynamic pressure on the sinusoidal endothelium, identify CBX7 as a pressure-sensitive transcription factor, and propose the combination of two of its reported products as biomarkers of PH. Impact and Implications: Increased pressure in the portal venous system that typically occurs during chronic liver disease (called portal hypertension) is one of the main drivers of related clinical complications, which are linked to a higher risk of death. In this study, we found that pathological pressure has a harmful effect on liver sinusoidal endothelial cells and identified CBX7 as a key protein involved in this process. CBX7 regulates the expression of E-cadherin and SPINK1, and consequently, measuring these proteins in the blood of patients with chronic liver disease allows the prediction of portal hypertension and clinically significant portal hypertension