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Granulocytic myeloid-derived suppressor cells (G-MDSCs) promote tumor growth and immunosuppression in multiple myeloma (MM). However, their phenotype is not well established for accurate monitoring or clinical translation. We aimed to provide the phenotypic profile of G-MDSCs based on their prognostic significance in MM, immunosuppressive potential, and molecular program. The preestablished phenotype of G-MDSCs was evaluated in bone marrow samples from controls and MM patients using multidimensional flow cytometry; surprisingly, we found that CD11b+CD14−CD15+CD33+HLADR− cells overlapped with common eosinophils and neutrophils, which were not expanded in MM patients. Therefore, we relied on automated clustering to unbiasedly identify all granulocytic subsets in the tumor microenvironment: basophils, eosinophils, and immature, intermediate, and mature neutrophils. In a series of 267 newly diagnosed MM patients (GEM2012MENOS65 trial), only the frequency of mature neutrophils at diagnosis was significantly associated with patient outcome, and a high mature neutrophil/T-cell ratio resulted in inferior progression-free survival (P < .001). Upon fluorescence-activated cell sorting of each neutrophil subset, T-cell proliferation decreased in the presence of mature neutrophils (0.5-fold; P = .016), and the cytotoxic potential of T cells engaged by a BCMA×CD3-bispecific antibody increased notably with the depletion of mature neutrophils (fourfold; P = .0007). Most interestingly, RNA sequencing of the 3 subsets revealed that G-MDSC–related genes were specifically upregulated in mature neutrophils from MM patients vs controls because of differential chromatin accessibility. Taken together, our results establish a correlation between the clinical significance, immunosuppressive potential, and transcriptional network of well-defined neutrophil subsets, providing for the first time a set of optimal markers (CD11b/CD13/CD16) for accurate monitoring of G-MDSCs in MM.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease worldwide, but a reliable non-invasive method to quantify liver steatosis in primary healthcare is not available. Circulating microRNAs have been proposed as biomarkers of severe/advanced NAFLD (steatohepatitis and fibrosis). However, the use of circulating miRNAs to quantitatively assess the % of liver fat in suspected NAFLD patients has not been investigated. We performed global miRNA sequencing in two sets of samples: human livers from organ donors (n = 20), and human sera from biopsy-proven NAFLD patients (n = 23), both with a wide range of steatosis quantified in their liver biopsies. Partial least squares (PLS) regression combined with recursive feature elimination (RFE) was used to select miRNAs associated with steatosis. Moreover, regression models with only 2 or 3 miRNAs, with high biological relevance, were built. Comprehensive microRNA sequencing of liver and serum samples resulted in two sets of abundantly expressed miRNAs (418 in liver and 351 in serum). Pearson correlation analyses indicated that 18% of miRNAs in liver and 14.5% in serum were significantly associated with the amount of liver fat. PLS-RFE models demonstrated that 50 was the number of miRNAs providing the lowest error in both liver and serum models predicting steatosis. Comparison of the two miRNA subsets showed 19 coincident miRNAs that were ranked according to biological significance (guide/passenger strand, relative abundance in liver and serum, number of predicted lipid metabolism target genes, correlation significance, etc.). Among them, miR-10a-5p, miR-98-5p, miR-19a-3p, miR-30e-5p, miR-32-5p and miR-145-5p showed the highest biological relevance. PLS regression models with serum levels of 2-3 of these miRNAs predicted the % of liver fat with errors

El presente trabajo tiene por objeto simplificar los procesos de reconversión de la materia orgánica sometida al lombricompostaje , sin dejar de lado el abanico de posibilidades de aplicación de diversas estrategias de manejo de las poblaciones de lombrices “rojas” (mal llamadas Californianas) y principalmente atendiendo a las necesidades/posibilidades de aplicación para cada modalidad de conducción de las lombrices y centrado en la economía de mano de obra para atender al lombricultivo de Eisenia fetida y Eisenia andrei. Con esta contribución se pretende delinear un ayudante práctico apuntando a la autosuficiencia del lombricultor que se inicia y deseé agregar valor al desperdicio que poseé para reconvertirlo en un abono de excelencia. Esta guía responde a necesidades detectadas en alumnos de nuestros cursos y capacitaciones, tanto presenciales como a distancia. La guía resulta, en buena medida, de actividades en curso en Colonia Cushamen y Fofo Cahuel (Chubut), que se integran con la apicultura regional y el manejo en torno a diversos cultivos (forrajes) y producciones (caprinos en particular) con miras a la autosuficiencia productiva, incluso con proyecciones en lo comercial (v.gr. lacto-quesero). Estación Experimental Agropecuaria Bariloche Fil: Schuldt, Miguel. Instituto Nacional de Tecnologia Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Agencia de Extension Rural El Bolson; Argentina Fil: Schuldt, Miguel. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Argentina Fil: Pareja, E. Asociación de Productores El Bolsón; Argentina Fil: Castrillo, Nelson. Asociación de Productores El Bolsón; Argentina Fil: Butto, A. Asociación de Productores El Bolsón; Argentina Fil: Cardozo, Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Agencia de Extensión Rural El Bolsón; Argentina

Esta guía es para Ud. que desea saber cómo abordar la cría de lombrices rojas, una actividad amigable con él entorno que posibilita transformar desechos de origen vegetal y animal en abono, una manera de reinsertar un simple desperdicio (¿basura?) como fertilizante a nuestro ya castigado entorno. Un fertilizante con propiedades que lo distinguen por su excelencia y sentar bases para abordar corrientes de residuos diversas con nuestras “vedetes rojas”, desde los desperdicios que surgen en su hogar hasta corrientes de residuos originados ya sea en la producción vegetal, desde la huerta hasta cultivos extensivos y en la cría de distintos animales (aves, cerdos, conejos, cabras, vacas, caballos, etc.) a partir de sus estiércoles. Parece adecuado centrar la práctica en el lombricultivo a escala familiar. Una modalidad simple de procesar los residuos y que, además de familiarizarnos con su manejo, permite la obtención de una población de lombrices para luego utilizarlas como semillero para abordar la reconversión de corrientes de residuos vinculados con la producción animal a cualquier escala (véase estratégias de conducción). Estación Experimental Agropecuaria Bariloche Fil: Schuldt, Miguel. Instituto Nacional de Tecnologia Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Agencia de Extension Rural El Bolson; Argentina Fil: Schuldt, Miguel. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Argentina Fil: Pareja, E. Asociación de Productores El Bolsón; Argentina Fil: Castrillo, Nelson. Asociación de Productores El Bolsón; Argentina Fil: Butto, A. Asociación de Productores El Bolsón; Argentina Fil: Cardozo, Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Agencia de Extensión Rural El Bolsón; Argentina

Clinical hepatocyte transplantation short-term efficacy has been demonstrated; however, some major limitations, mainly due to the shortage of organs, the lack of quality of isolated cells and the low cell engraftment after transplantation, should be solved for increasing its efficacy in clinical applications. Cellular stress during isolation causes an unpredictable loss of attachment ability of the cells, which can be aggravated by cryopreservation and thawing. In this work, we focused on the use of a Good Manufacturing Practice (GMP) solution compared with the standard cryopreservation medium, the University of Wisconsin medium, for the purpose of improving the functional quality of cells and their ability to engraft in vivo, with the idea of establishing a biobank of cryopreserved human hepatocytes available for their clinical use. We evaluated not only cell viability but also specific hepatic function indicators of the functional performance of the cells such as attachment efficiency, ureogenic capability, phase I and II enzymes activities and the expression of specific adhesion molecules in vitro. Additionally, we also assessed and compared the in vivo efficacy of human hepatocytes cryopreserved in different media in an animal model of acute liver failure. Human hepatocytes cryopreserved in the new GMP solution offered better in vitro and in vivo functionality compared with those cryopreserved in the standard medium. Overall, the results indicate that the new tested GMP solution maintains better hepatic functions and, most importantly, shows better results in vivo, which could imply an increase in long-term efficacy when used in patients.

The estimation of steatosis in a liver graft is mandatory prior to liver transplantation, as the risk of graft failure increases with the level of infiltrated fat. However, the assessment of liver steatosis before transplantation is typically based on a qualitative or semiquantitative characterization by visual inspection and palpation and histological analysis. Thus, there is an unmet need for transplantation surgeons to have access to a diagnostic tool enabling an in situ fast classification of grafts prior to extraction. In this study, we have assessed an attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic method compatible with the requirements of an operation room for the evaluation of the lipid contents in human livers. A set of 20 human liver biopsies obtained from organs intended for transplantation were analyzed by expert pathologists, ATR-FTIR spectroscopy, lipid biochemical analysis, and UPLC-ESI(+/-)TOFMS for lipidomic profiling. Comparative analysis of multisource data showed strong correlations between ATR-FTIR, clinical, and lipidomic information. Results show that ATR-FTIR captures a global picture of the lipid composition of the liver, along with information for the quantification of the triradylglycerol content in liver biopsies. Although the methodology performance needs to be further validated, results support the applicability of ATR-FTIR for the in situ determination of the grade of liver steatosis at the operation room as a fast, quantitative method, as an alternative to the qualitative and subjective pathological examination.

The subject of research was the characteristics of the slopes and the processes acting as factors of the formation of landslides. The aim of the work was to analyze the potential danger of the development of landslide processes in the Zabala sector, in the equatorial Andes. The morphometric method was used.It is established that the slopes with angles of inclination up to 15 ° constitute 27,8 % of the investigated area. Angles of inclination from 15 ° to 25 ° make 28,7 % of the area. From 25 ° to 45 ° - 40,8 %; and over 45 ° - 2,7 %. The factors that increase the risk of landslide development in the studied area are: steep angles of inclination of the surface, earthquakes, gully erosion, trimming of the lower part of the slope. The results of the work can be applied for assessment of geomorphological risks.Key words: slope, morphometric characteristics, geomorphological risks, equatorial Andes, steeply inclined кандидат географических наук, Кравченко Р. А., Пареха Э. С., Флорес Й. Г. О потенциальной опасности развития оползневых процессов в зоне завала, Эквадор / Universidad UTE, Эквадор, г. Кито; Российский государственный гидрометеорологический университет, Российская федерация, Санкт-Петербург; Национальный исследовательский Томский политехнический университет, Российская федерация, ТомскПредметом исследования являлись характеристики склонов и процессов, выступающих как факторы формирования оползней. Цель работы состояла в анализе потенциальной опасности развития оползневых процессов в секторе Завала, в экваториальных Андах. Использовался морфометрический метод. Установлено, что склоны с углами наклона до 15° составляют 27,8 % исследованной территории. Углы наклона от 15° до 25° имеет 28,7 % площади. От 25° до 45° - 40,8 %; и свыше 45° - 2,7 %.Факторами увеличивающими опасность развития оползней на изученной территории являются: крутые углы наклона поверхности, землетрясения, овражная эрозия, подрезка нижней части склона. Результаты работы могут быть применены для оценки геоморфологических рисков.Ключевые слова: cклон, морфометрические характеристики, геоморфологические риски, экваториальные Анды, круто наклонные склоны

The investigation of linear erosion forms was carried out at the city of Quito (Equatorial Andes). The study was aimed to define the correlation between rill forms with different length parameters in the key-site area located nearby Zabala. It is stated that the rill forms with the length up to 50 m (58%) prevail. The gullies with the length of more than 200 m make 9% of all rill forms. Nevertheless, these gullies, as a rule, create main channels that provoke the formation of multiple side forms in the process of regressive erosion. The further development of the linear erosion causes the dissection of the investigated area that increases the risk for landslide developments., {"references":["de Paez, P. A., Tamayo, M. L., & de la Torre, J. G. (2004). Geography of Ecuador. Madrid, Cultural, 360. (in Spanish).","De Noni, G., & Trujillo, G. (1990). Degradación del suelo en el Ecuador. Principal es causas y al gunas reflexiones sobre la conservación de este recurso. In: Informe ORSTOM. Quito, 383-394. (in Spanish).","Kravchenko, R. (2013). Influence of sediment from the Gullies in the development of erosion forms. Enfoque UTE, 4(2), 35-44. (In Spanish).","Kravchenko, R., Flores, Y. G., & Pareja, E. S. (2017). The colluvial deposits in the gullies of the northern part of the Quito region, Ecuador. Bulletin of Science and Practice, (4), 191-195."]}

The studies were conducted on the territory of the equatorial Andes. The aim of the work was to determine the ratio of gully forms of various lengths on the key section. The authors used field research and the program ArcGIS 10.3 basing on the study of orthophotos. It is established that gully forms with a length of up to 50 m, constituting 37%, prevail. The gullies over 400 m long make only 8% of all erosion forms. Lateral short gullies retain the potential for peak growth as a result of regressive erosion. The work can be used in such scientific areas as fluvial geomorphology and soil protection from erosion.Key words: erosion forms, equatorial Andes, slop, regressive erosion, morphometric parametersкандидат географических наук, Кравченко Р. А., Пареха Э .С., Флорес Й. Г., О длине оврагов в секторе «COLINAS DE BELLAVISTA», ЭКВАДОР / Университет УТЕ, Эквадор, г. Кито; Российский государственный гидрометеорологический университет, Российская федерация, Санкт-Петербург; Национальный исследовательский Томский политехнический университет, Российская федерация, ТомскИсследования проводились на территории экваториальных Анд. Целью работы было определение соотношения овражных форм различной длины на ключевом участке. Использовались программа ArcGIS 10.3 на основе изучения ортофотоснимков, и проводились полевые исследования. Установлено, что преобладают овражные формы длиной до 50 м, составляющие 37 %. Овраги длиной свыше 400 м составляют лишь 8 % от всех эрозионных форм. Боковые короткие овраги сохраняют потенциальную возможность для вершинного прироста в результате регрессивной эрозии. Работа может быть использована в таких научных направлениях, как флювиальная геоморфология и защита почв от эрозии.Ключевые слова: эрозионные формы, экваториальные Анды, склон, регрессивная эрозия, морфометрические параметры

Objetivo: Demostrar que el efecto protector contra la Hepatitis B en estudiantes menores de 30 años del área de Ciencias de la Salud susceptibles es similar luego de completar los dos esquemas de vacunación (acortado y convencional) en menor tiempo y con menos dosis. Hipotesis: Los 3 esquemas de dosificación en la vacuna contra la hepatitis B generan anticuerpos por encima de 10 ug/100 ml generando igual efecto de protección. Diseño: Analítico, experimental, longitudinal, prospectivo y de cohortes concurrentes. Material y Métodos: Un total de 100 alumnos de ambos sexos de Tecnología Médica de la Facultad de Medicina de la UNMSM susceptibles fueron enrolados, quedaron para el análisis final, 89 alumnos tomando en cuenta los criterios de inclusión y exclusión de acuerdo al objetivo de estudio. Se administró la vacuna a la dosis de 20 ug del antigeno de superficie en 1 mL, en tres esquemas de dosificación; 0, 1, 6 meses, 0,1,2 meses y 0,1 meses y se tomaron muestras de sangre antes y a 1,2, 6 y 7 meses de la primera dosis de vacuna para determinación de anti.HBs. Se definió como seroprotección un valor o = a 10 mUI/mL de anti-HBs. Resultados: en base a los 89 alumnos menores de 30 años, cuya edad promedio fue 23.5 años, siendo el 51.7% (46) del sexo masculino y 48.3% (43) sexo femenino. A los 30 días de la primera dosis el 12.4% alcanzó protección, a los 30 días posterior a la segunda dosis el 98.8% y a los 180 días el 100% de protección. Después de la segunda dosis los tres grupos alcanzaron títulos protectores, y al final del estudio los niveles promedios de anticuerpos estuvieron entre 532.7 mUI/mL y 1237.2 mUI/mL Conclusiones: En el presente estudio se logró alcanzar hasta los 7 meses después de la primera dosis, igual efecto protector contra la Hepatitis B mediante la administración de la vacuna con tres esquemas de vacunación diferentes: esquema convencional de tres dosis (0,1,6 meses), esquema acortado de dos dosis( 0,1 mes) y esquema acortado de tres dosis( 0,1,2 meses). Se plantea la posibilidad de un esquema con dos dosis en personas menores de 30 años, el cual tendría un mayor índice de cumplimiento y un menor costo e igual beneficio protector. Objetive: To prove the protector effect of vaccine against hepatitis B in susceptible health sciences students, younger than 30 years old with three schedule of vaccination, two of them are three conventional doses and another one with two doses. Hypothesis: Three schedules of vaccination against hepatitis B produce antibody response over 10 IU/ml Design: This is a analytical, expetimental, longitudinal., prospective and concurrents cohort study. Subjects and Methods: Overall of 100 susceptible medical technology students both sexs from Medicine Faculty of San Marcos University were enlisted; final analysis were done with 89 students.Vaccine doses administred was a HBsAg 20 ug/mL in three schedules: : 0,1 and 6 months, 0,1 and 2 months and 0,1 month and were taken blood samples before and 1,2,6, and 7 months after first doses of vaccine in order to determine anti HBs levels. Results: Final analysis was done in 89 students with 23.5 years old on average; 51.6% were males and 48.3% females. Thirty days after first doses 12.4% of vaccinated were protected, 98.8% after second doses and 100% at 180 days after first doses: Serum antibody levels at the end of study were betwem 532.7 mIU/mL and 1237.2 mIU/ml Conclusions: The results of our study indicate that seven months after first doses of hepatitis B vaccine has a similar seroprotection levels of anti HBs with any of three schedule used. This results seggest that we could be to recomend a two doses schedule for persons younger than 30 years old.

This study reveals the analysis of the colluvial deposits in the gullies in the Equatorial Andes. The key site is located in the norther Quito suburb. A diversity of widespread colluvial deposits is a specific characteristic of the territory. The analysis showed the coincidence of the soil texture of the gullies and colluvial deposits. The authors came to the conclusion that the studied deposits are lately formed. For being a result of gully sloughing that occurred within the dry season, the deposits are insignificantly converted. The impact of additional factors is considered to be minimal.

Adult hepatocyte transplantation is limited by scarce availability of suitable donor liver tissue for hepatocyte isolation. New cell-based therapies are being developed to supplement whole-organ liver transplantation, to reduce the waiting-list mortality rate, and to obtain more sustained and significant metabolic correction. Fetal livers and unsuitable neonatal livers for organ transplantation have been proposed as potential useful sources of hepatic cells for cell therapy. However, the major challenge is to use alternative cell sources for transplantation that can be derived from reproducible methods. Different types of stem cells with hepatic differentiation potential are eligible for generating large numbers of functional hepatocytes for liver cell therapy to treat degenerative disorders, inborn hepatic metabolic diseases, and organ failure. Clinical trials are designed to fully establish the safety profile of such therapies and to define target patient groups and standardized protocols.

The worldwide shortage of donor livers for organ and hepatocyte transplantation has prompted the search for alternative therapies for intractable liver diseases. Cell-based therapy is envisaged as a useful therapeutic option to recover and stabilize the lost metabolic function for acute liver failure, end-stage and congenital liver diseases, or for those patients who are not considered eligible for organ transplantation. In recent years, research to identify alternative and reliable cell sources for transplantation that can be derived by reproducible methods has been encouraged. Human pluripotent stem cells (PSCs), which comprise both embryonic and induced PSCs, may offer many advantages as an alternative to hepatocytes for liver cell therapy. Their capacity for expansion, hepatic differentiation and self-renewal make them a promising source of unlimited numbers of hepatocyte-like cells for treating and repairing damaged livers. Immunogenicity and tumorigenicity of human PSCs remain the bottleneck for successful clinical application. However, recent advances made to develop disease-corrected hepatocyte-like cells from patients' human-induced PSCs by gene editing have opened up many potential gateways for the autologous treatment of hereditary liver diseases, which may likely reduce the risk of rejection and the need for lifelong immunosuppression. Well-defined methods to reduce the expression of oncogenic genes in induced PSCs, including protocols for their complete and safe hepatic differentiation, should be established to minimize the tumorigenicity of transplanted cells. On top of this, such new strategies are currently being rigorously tested and validated in preclinical studies before they can be safely transferred to clinical practice with patients.

Crigler-Najjar type 1 disease is a rare inherited metabolic disease characterized by high levels of unconjugated bilirubin due to the complete absence of hepatic uridine diphosphoglucuronate-glucuronosyltransferase activity. Hepatocyte transplantation (HT) has been proposed as an alternative treatment for Crigler-Najjar syndrome, but it is still limited by the quality and the low engraftment and repopulation ability of the cells used. Because of their attachment capability and expression of adhesion molecules as well as the higher proportion of hepatic progenitor cells, neonatal hepatocytes may have an advantage over adult cells. Adult or neonatal hepatocytes were transplanted into Gunn rats, a model for Crigler-Najjar disease. Engraftment and repopulation were studied and compared by immunofluorescence (IF). Additionally, the serum bilirubin levels, the presence of bilirubin conjugates in rat serum, and the expression of uridine diphosphate glucuronosyltransferase 1 family polypeptide A1 (UGT1A1) in rat liver samples were also analyzed. Here we show that neonatal HT results in long-term correction in Gunn rats. In comparison with adult cells, neonatal cells showed better engraftment and repopulation capability 3 days and 6 months after transplantation, respectively. Bilirubinemia decreased in the transplanted animals during the whole experimental follow-up (6 months). Bilirubin conjugates were also present in the serum of the transplanted animals. Western blots and IF confirmed the presence and expression of UGT1A1 in the liver. This work is the first to demonstrate the advantage of using neonatal hepatocytes for the treatment of Crigler-Najjar in vivo. Liver Transpl 21:801-811, 2015. (c) 2015 AASLD.

Early allograft dysfunction (EAD) dramatically influences graft and patient outcomes. A lack of consensus on an EAD definition hinders comparisons of liver transplant outcomes and management of recipients among and within centers. We sought to develop a model for the quantitative assessment of early allograft function [Model for Early Allograft Function Scoring (MEAF)] after transplantation. A retrospective study including 1026 consecutive liver transplants was performed for MEAF score development. Multivariate data analysis was used to select a small number of postoperative variables that adequately describe EAD. Then, the distribution of these variables was mathematically modeled to assign a score for each actual variable value. A model, based on easily obtainable clinical parameters (ie, alanine aminotransferase, international normalized ratio, and bilirubin) and scoring liver function from 0 to 10, was built. The MEAF score showed a significant association with patient and graft survival at 3-, 6- and 12-month follow-ups. Hepatic steatosis and age for donors; cold/warm ischemia times and postreperfusion syndrome for surgery; and intensive care unit and hospital stays, Model for End-Stage Liver Disease and Child-Pugh scores, body mass index, and fresh frozen plasma transfusions for recipients were factors associated significantly with EAD. The model was satisfactorily validated by its application to an independent set of 200 patients who underwent liver transplantation at a different center. In conclusion, a model for the quantitative assessment of EAD severity has been developed and validated for the first time. The MEAF provides a more accurate graft function assessment than current categorical classifications and may help clinicians to make early enough decisions on retransplantation benefits. Furthermore, the MEAF score is a predictor of recipient and graft survival. The standardization of the criteria used to define EAD may allow reliable comparisons of recipients' treatments and transplant outcomes among and within centers. Liver Transpl 21:38-46, 2015. (c) 2014 AASLD.

The imbalance between the number of potential beneficiaries and available organs, originates the search for new therapeutic alternatives, such as Hepatocyte transplantation (HT). Even though this is a treatment option for these patients, the lack of unanimity of criteria regarding indications and technique, different cryopreservation protocols, as well as the different methodology to assess the response to this therapy, highlights the need of a Consensus Conference to standardize criteria and consider future strategies to improve the technique and optimize the results. Our aim is to review and update the current state of hepatocyte transplantation, emphasizing the future research attempting to solve the problems and improve the results of this treatment. (C) 2013 AEC. Published by Elsevier Espana, S.L. All rights reserved.

Background & Aims: Early allograft dysfunction (EAD) dramatically influences graft and patient outcome after orthotopic liver transplantation and its incidence is strongly determined by donor liver quality. Nevertheless, objective biomarkers, which can assess graft quality and anticipate organ function, are still lacking. This study aims to investigate whether there is a preoperative donor liver metabolomic biosignature associated with EAD. Methods: A comprehensive metabolomic profiling of 124 donor liver biopsies collected before transplantation was performed by mass spectrometry coupled to liquid chromatography. Donor liver grafts were classified into two groups: showing EAD and immediate graft function (IGF). Multivariate data analysis was used to search for the relationship between the metabolomic profiles present in donor livers before transplantation and their function in recipients. Results: A set of liver graft dysfunction-associated biomarkers was identified. Key changes include significantly increased levels of bile acids, lysophospholipids, phospholipids, sphingomyelins and histidine metabolism products, all suggestive of disrupted lipid homeostasis and altered histidine pathway. Based on these biomarkers, a predictive EAD model was built and further evaluated by assessing 24 independent donor livers, yielding 91% sensitivity and 82% specificity. The model was also successfully challenged by evaluating donor livers showing primary nonfunction (n = 4). Conclusions: A metabolomic biosignature that accurately differentiates donor livers, which later showed EAD or IGF, has been deciphered. The remarkable metabolomic differences between donor livers before transplant can relate to their different quality. The proposed metabolomic approach may become a clinical tool for donor liver quality assessment and for anticipating graft function before transplant. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.

This work has been partially supported by CDTI (ref. IDI-20101153) and by MICINN (ref. TIN2010-20999-C04-01) and by GVA (ref. ACOMP/2012/181). The work of Francisco Martı´nez-Martı´nez has been supported by the Spanish Government under the FPI Grant BES2011-046495. We would also like to express our deep gratitude to the Hospital Clı´nica Benidorm for its participation in this project.

There are few studies focusing on long-term complications in liver transplant (LT) recipients. The aim of this study was to define the outcome of LT recipients having survived at least 10 years from LT. Of 323 adult LT done between 1991 and 1997, the 167(52%) alive >10 years post-LT (baseline time) formed the study population. Long-term outcome measures included the following: immunosuppression, metabolic complications [obesity, arterial hypertension (AH), diabetes, dislypidemia], cardiovascular events (CVE), chronic renal dysfunction-CRD, and de novo tumors. Median age at LT was 50 years. Most common indication was postnecrotic cirrhosis (89%), mostly because of HCV (46%). At study-baseline (10 years post-LT), 29% were obese and AH, diabetes, dislypidemia, and CRD were present in 75%, 30%, 42%, and 36%, respectively. In most cases, these complications were already present 1 year post-LT; less than one quarter developed them onward. The 6 year cumulative survival since baseline reached 84% (n = 24 deaths), with most deaths related to recurrent graft diseases (mostly HCV) followed by de novo tumors or CVE. 1, 3, 5 and 10 years cumulative rates of CVE and de novo tumors since baseline were 2%, 5%, 10% and 17%, and 1%, 3%, 6% and 13%, respectively. Chronic renal impairment was independently associated with survival and development of CVE since baseline. The medium-term survival of 'long-term survivors', i.e. patients alive 10 years after LT is good, but metabolic complications and CRD are common and continue to increase afterwards. Cardiovascular events and de novo tumors increase gradually over time and represent a major cause of late mortality.