¿Existe un intervalo de tiempo de isquemia fría seguro para el injerto renal?

Objective: It is aimed to characterize the true relationship of the cold ischemia time (CIT) with graft survival and with the principal post-transplantation events.aterial and methods: We analyzed 378 kidney transplants, studying the relationship of the CIT with graft survival using a univariate analysis according to the COX model and seeking the optimum cutoff according to the Kaplan-Meier method and log-rank test. The relationship between CIT and the principal events of the post-transplant was studied using the binary logistic regression. Results: The mean follow-up of all the group was 77.8 months (± 51 SD) and the mean CIT was 14.8 hours (± 5.1 SD). The univariate analysis revealed that the CIT was not related with the graft survival as a continuous variable (OR = 1.04; 95% CI: 0.9-1.08; p > 0.05). On establishing the cutoff at 18 hours, we found differences in the actuarial survival. Survival at 5 years was 91% with CIT 18 h. Each hour of cold ischemia increased risk of delay in the graft function by 10% (OR = 1.1; 95% CI: 1.05-1.15; p < 0.001) and also conditioned a greater incidence of acute rejection (41.5% vs. 55.3%; p = 0.02) and less time to the first rejection episode (72.6 days ± 137 vs. 272.2 days ± 614.8; p = 0.023) after 18 hours. The CIT did not seem to be related (p < 0.05) with the rest of the post-transplantation events, such as surgical complications or hospital admissions. Conclusions: In our experience, cold ischemia under 18 hours does not seem to negatively affect graft survival

Functional Enrichment Analysis of Regulatory Elements

This work has been partially supported by FEDER/Junta de Andalucia-Consejeria de Economia y Conocimiento/(grant CV20-36723), grant PID2020-119032RB-I00, MCIN/AEI/10.13039/501100011033 and FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades (Grant P20_00335).Statistical methods for enrichment analysis are important tools to extract biological information from omics experiments. Although these methods have been widely used for the analysis of gene and protein lists, the development of high-throughput technologies for regulatory elements demands dedicated statistical and bioinformatics tools. Here, we present a set of enrichment analysis methods for regulatory elements, including CpG sites, miRNAs, and transcription factors. Statistical significance is determined via a power weighting function for target genes and tested by theWallenius noncentral hypergeometric distribution model to avoid selection bias. These new methodologies have been applied to the analysis of a set of miRNAs associated with arrhythmia, showing the potential of this tool to extract biological information from a list of regulatory elements. These new methods are available in GeneCodis 4, a web tool able to perform singular and modular enrichment analysis that allows the integration of heterogeneous information.FEDER/Junta de Andalucia-Consejeria de Economia y Conocimiento CV20-36723MCIN/AEI PID2020-119032RB-I00FEDER/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades P20_0033

Case of emphysematous pyelonephritis in kidney allograft: Conservative treatment

Emphysematous pyelonephritis is an acute necrotizing infection with gas in the kidney and perinephric space that carries a bad prognosis. Apart from its predisposing clinical entities, diabetes mellitus and immune-incompetence are quite common in patients with this infection. We report a case of a 53-year-old kidney transplant recipient diabetic male, suffering from recurrent fever, abdominal pain and nausea episodes. Immediate broad-spectrum antibiotics were administered and percutaneous drainage was performed after the diagnosis. The bacteria involved were Stahpylococcus epidermidis and Escherichia coli. After 4 weeks of antibiotic treatment and abscesses drainage, the case was resolved. Consecutives urine cultures and ultrasonographies confirm the complete resolution of the disease. We discuss the predisposing factors, clinical presentation and management

Safety, activity, and molecular heterogeneity following neoadjuvant non-pegylated liposomal doxorubicin, paclitaxel, trastuzumab, and pertuzumab in HER2-positive breast cancer (Opti-HER HEART): an open-label, single-group, multicenter, phase 2 trial

Antecedents: L'assaig Opti-HER HEART tenia com a objectiu optimitzar l'activitat i minimitzar el risc cardíac combinant trastuzumab, pertuzumab i paclitaxel amb doxorubicina liposomal no pegilada en el tractament del càncer de mama precoç HER2-positiu. Mètodes: Els pacients amb càncer de mama HER2 positiu en fase II-IIIB van rebre trastuzumab neoadjuvant, pertuzumab, paclitaxel i una doxorubicina liposomal no pegilada cada tres setmanes durant sis cicles. El principal criteri final va ser la seguretat cardíaca durant la teràpia neoadjuvant. Es van avaluar els esdeveniments cardíacs tipus A (insuficiència cardíaca congestiva simptomàtica) i B (reducció asimptomàtica de la fracció d'ejecció del ventricle esquerre). Els criteris finals secundaris van incloure l'avaluació de la taxa de resposta patològica completa (pCR) i la taxa de resposta global, entre d'altres. Com a anàlisi exploratòria ad-hoc , es va mesurar l'expressió de 55 gens relacionats amb el càncer de mama, inclosos els gens PAM50 , en 58 mostres de tumors basals i 60 mostres quirúrgiques. Resultats: Es van reclutar vuitanta-tres pacients. La incidència d'esdeveniments cardíacs durant el tractament neoadjuvant va ser del 2,4%. No es va observar cap esdeveniment cardíac de tipus A. La taxa global de pCR va ser del 56,6% (interval de confiança (IC) del 95%: 45,3-67,5%). El subtipus enriquit amb HER2, que representava el 52,0% de totes les mostres basals, es va associar amb una taxa de pCR més alta en comparació amb els tumors no enriquits amb HER2 (83,3% vs. 46,3%; odds ratio 5,76; 95% CI 1,71-19,42). L'associació de subtipus amb pCR va ser independent de les variables clínicopatològiques conegudes, inclòs l'estat del receptor hormonal. En comparació amb les mostres basals, els exemplars quirúrgics van mostrar una significativa regulació descendent dels nivells relacionats amb la proliferació ( MKI67 i CCNB1 ) i ERBB2 , i una regulació ascendent significativa dels relacionats amb la llum (ESR1 i PGR ) i gens immunes ( CD8A ). Conclusions: La combinació de doble bloqueig HER2 amb trastuzumab i pertuzumab amb paclitaxel i doxorubicina liposomal no pegilada s'associa amb una baixa taxa d'esdeveniments cardíacs. El subtipus enriquit amb HER2 s'associa a una alta taxa de pCR

Meta-Analysis of the Effects of Foods and Derived Products Containing Ellagitannins and Anthocyanins on Cardiometabolic Biomarkers: Analysis of Factors Influencing Variability of the Individual Responses

peer-reviewedUnderstanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers. The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored. Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes. Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts. Additionally, we found an indication of a small increase in HDL-cholesterol most significant with nuts and, in flow-mediated dilation by nuts and berries. Most of these effects were detected in obese/overweight people but we found limited or non-evidence in normoweight individuals or of the influence of sex or smoking status. The effects of other factors, i.e., habitual diet, health status or country where the study was conducted, were inconsistent and require further investigation.This article is based upon work from COST Action FA1403—POSITIVe “Interindividual variation in response to consumption of plant food bioactives and determinants involved” supported by COST (European Cooperation in Science and Technology, http://www.cost.eu/). The authors thank the financial support of the COST Action FA1403 “POSITIVe” to conduct a short-term scientific mission to K.C. at CEBAS-CSIC (A.G.-S. and M.T.G.-C.) during which the data analysis was performed

Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inhibitors. A potential SNP association with response to etanercept

Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all nonredundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the metaanalysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNPsThis work was supported by the Instituto de Salud Carlos III (ISCIII, Spain) through grants PI14/01651, PI17/01606 and RD16/0012/0014 to AG and PI12/01909 to JJG-R. These grants are partially financed by the European Regional Development Fund of the EU (FEDER

Validation Study Of Genetic Biomarkers Of Response To Tnf Inhibitors In Rheumatoid Arthritis

Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA), given their variable response to TNF inhibitors (TNFi). However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi. The validation was attempted in 581 patients with RA that had not been treated with biologic antirheumatic drugs previously. Their response to TNFi was evaluated at 3, 6 and 12 months in two ways: change in the DAS28 measure of disease activity, and according to the EULAR criteria for response to antirheumatic drugs. Association of these parameters with the genotypes, obtained by PCR amplification followed by single-base extension, was tested with regression analysis. These analyses were adjusted for baseline DAS28, sex, and the specific TNFi. However, none of the proposed biomarkers was validated, as none showed association with response to TNFi in our study, even at the time of assessment and with the outcome that showed the most significant result in previous studies. These negative results are notable because this was the first independent validation study for 12 of the biomarkers, and because they indicate that prudence is needed in the interpretation of the proposed biomarkers of response to TNFi even when they are supported by very low p values. The results also emphasize the requirement of independent replication for validation, and the need to search protocols that could increase reproducibility of the biomarkers of response to TNFi

Incidence of co-infections and superinfections in hospitalised patients with COVID-19: a retrospective cohort study

Objectives: To describe the burden, epidemiology and outcomes of co-infections and superinfections occurring in hospitalized patients with coronavirus disease 2019 (COVID-19). Methods: We performed an observational cohort study of all consecutive patients admitted for ≥48 hours to the Hospital Clinic of Barcelona for COVID-19 (28 February to 22 April 2020) who were discharged or dead. We describe demographic, epidemiologic, laboratory and microbiologic results, as well as outcome data retrieved from electronic health records. Results: Of a total of 989 consecutive patients with COVID-19, 72 (7.2%) had 88 other microbiologically confirmed infections: 74 were bacterial, seven fungal and seven viral. Community-acquired co-infection at COVID-19 diagnosis was uncommon (31/989, 3.1%) and mainly caused by Streptococcus pneumoniae and Staphylococcus aureus. A total of 51 hospital-acquired bacterial superinfections, mostly caused by Pseudomonas aeruginosa and Escherichia coli, were diagnosed in 43 patients (4.7%), with a mean (SD) time from hospital admission to superinfection diagnosis of 10.6 (6.6) days. Overall mortality was 9.8% (97/989). Patients with community-acquired co-infections and hospital-acquired superinfections had worse outcomes. Conclusions: Co-infection at COVID-19 diagnosis is uncommon. Few patients developed superinfections during hospitalization. These findings are different compared to those of other viral pandemics. As it relates to hospitalized patients with COVID-19, such findings could prove essential in defining the role of empiric antimicrobial therapy or stewardship strategies

Análisis de resultados del segundo curso del Máster de Ingeniería de Caminos, Canales y Puertos en la EPS de la UA

La completa implantación del Máster de Ingeniería de Caminos, Canales y Puertos en su primera promoción (dos cursos), ha supuesto un hito respecto a la modificación, adecuación y puesta en funcionamiento de la nueva normativa de la Universidad de Alicante para aquellas titulaciones basadas en el EEES, desde el inicio del Plan de Estudios de Ingeniería de Caminos, Canales y Puertos en el año 2005. Para este análisis de los resultados obtenidos, se tomará como base la documentación aprobada por la Agencia Nacional de Acreditación (ANECA), estudiando la aplicación e implementación de todos los contenidos que se habían desarrollado en la preparación del Plan de Estudios, de forma que se pueda comprobar si el alumno ha adquirido (o podido adquirir), en cada uno de los casos, los objetivos y las competencias inherentes al Máster de Ingeniería de Caminos, Canales y Puertos (MICCP) de la Universidad de Alicante; asimismo, se compararán los datos obtenidos en el presente trabajo de investigación con los correspondientes al Primer Curso del Máster desarrollado en los cursos 2013-14 [1] y 2014-15 [2], al objeto de analizar el comportamiento de los alumnos en ambos primeros cursos académicos. En cualquier caso, no debe dejarse de lado en el análisis de los resultados que se hayan obtenido, que la entrada en vigor de este máster mantiene reservas profesionales (según Orden CIN 309/2009) [3] para los egresados de la titulación, de forma que esta circunstancia ha significado una total implicación de los departamentos y docentes, obligando a la modificación de los sistemas de evaluación, enseñanza y planificación de cada una de las asignaturas, con resultados muy esperanzadores en varios de los casos

Análisis de resultados de las asignaturas de primer curso en la implantación del máster de Ingeniería de Caminos, Canales y Puertos en la EPS de la UA

La puesta en funcionamiento del Primer Curso del Máster de Ingeniería de Caminos, Canales y Puertos en la Universidad de Alicante ha supuesto un reto de adaptación y modificación de los criterios que se venían empleando desde la entrada en vigor del Plan de Estudios de Ingeniería de Caminos, Canales y Puertos en el año 2005. Para ello, se ha partido de la información que se remitió en su momento para su aprobación a la Agencia Nacional de Acreditación (ANECA), implementando y aplicando todos aquellos parámetros que se definieron ex profeso en su momento, de forma que el alumnado pudiera adquirir los conocimientos y competencias asociadas a cada una de las asignaturas en las que ha recibido docencia en este primer curso de implantación del Máster de Ingeniería de Caminos, Canales y Puertos (MICCP) en la Universidad de Alicante. En ningún caso debe olvidarse que la entrada en vigor de este máster mantiene reservas profesionales (según Orden CIN 309/2009) [1] para los egresados de la titulación, obligando a que la totalidad de departamentos y docentes implicados en su desarrollo, implementaran criterios específicos relacionados con los sistemas de evaluación, enseñanza y planificación de la materia a impartir, si bien debe indicarse que, a tenor de los resultados obtenidos en las distintas asignaturas de este primer curso, no han sido todo los eficaces que en un primer momento pudieran esperarse