Supervivencia de los pacientes con enfermedad renal crónica en tratamiento renal sustitutivo en Andalucía

Introducción: Los pacientes con enfermedad renal crónica que precisan tratamiento renal sustitutivo tienen una supervivencia menor que la población general de su misma edad. La expectativa de vida de estos enfermos depende del tipo de tratamiento renal sustitutivo empleado y de otros muchos factores relacionados con el paciente y la atención médica recibida. El objetivo principal este trabajo de investigación ha sido conocer la supervivencia de los pacientes con necesidad de tratamiento renal sustitutivo y estudiar los factores asociados a la misma con el propósito final de mejorar los resultados de mortalidad de estos enfermos. Material y método: Se ha efectuado un estudio observacional analítico de cohorte retrospectiva de todos los pacientes que iniciaron terapia renal sustitutiva en Andalucía entre el 01/01/2008 y el 31/12/2018, con datos procedentes del módulo básico del sistema de información de la coordinación autonómica de trasplantes de Andalucía. Se ha realizado el seguimiento de los pacientes hasta su fallecimiento por cualquier causa o fin de seguimiento. Se ha elaborado un modelo de supervivencia del paciente según las variables estudiadas y potencialmente implicadas en la misma. Se ha estudiado la evolución de las características de los pacientes incidentes y de su supervivencia al año y a los 3 años de iniciado el tratamiento renal sustitutivo. Resultados: Se han incluido 11551 pacientes, 62,8% [IC95% (61,9; 63,7)] hombres, de 65 años [IC95% (65,0; 66,0)] de edad mediana y laboralmente activos en el 20,9% [IC95% (19,8; 21,9)] de los casos, con una mediana de índice de comorbilidad de Charlson de 6 puntos [IC95% (6,0; 7,0)], diabéticos en un 38,5% [IC95% (37,6; 39,4)] y en un 24,5% [IC95% (23,7; 25,3)] de los casos con nefropatía diabética. El tiempo de supervivencia de los pacientes ha alcanzado una mediana de 6,8 años [IC95% (6,6; 7,0)] y un porcentaje de supervivencia del 88,7% [IC95% (88,1; 89,3)] al año, del 72,6% [IC95% (71,8; 73,4)] a los 3 años, del 59,4% [IC95% (58,4; 60,4)] a los 5 años y a los 10 años del 37,4% [IC95% (36,0; 38,8)] del inicio de tratamiento renal sustitutivo. El factor independiente más determinante de la supervivencia de los pacientes ha sido recibir un trasplante renal, con una hazard ratio de 0,16 [IC95% (0,14; 0,18)] ajustada para el resto de variables incluidas en el modelo como edad, comorbilidad, seguimiento previo en consultas específicas de nefrología, forma de inicio de terapia renal sustitutiva y acceso vascular. Las características clínicas de los pacientes han empeorado en el periodo estudio, se ha observado que tienen mayor edad, más etiología diabética y mayor comorbilidad mientras que la supervivencia de los pacientes a los 3 años de iniciada la terapia renal sustitutiva ha aumentado. Conclusiones: En la supervivencia del paciente incidente en tratamiento renal sustitutivo, recibir un trasplante renal se ha mostrado como el factor que más positivamente ha influido en la misma y su efecto beneficioso se ha mantenido, frente al tratamiento con diálisis, en pacientes con comorbilidad elevada y de características comparables. La edad, la comorbilidad, la etiología diabética de la enfermedad renal crónica y el acceso venoso tipo catéter destacan como factores independientes que han intervenido de forma negativa en la supervivencia de estos pacientes y, por el contrario, el inicio no urgente de terapia renal sustitutiva y el seguimiento previo en consultas de enfermedad renal crónica avanzada mayor a 6 meses han actuado de manera favorable a la misma. A pesar de la evolución adversa de las características de los pacientes incidentes, la supervivencia del paciente en tratamiento renal sustitutivo en Andalucía ha mejorado en el periodo analizado, si bien el número de años de vida potencialmente perdidos por estos pacientes ha sido muy elevado. El sistema de información de la coordinación autonómica de trasplantes de Andalucía ha demostrado ser una herramienta válida que ha permitido analizar de forma exhaustiva la supervivencia del paciente incidente en terapia renal sustitutiva, sus características clínicas y la evolución de ambas en el tiempo

The complex life of DICKKOPF-1 in cancer cells

This work is licensed under a Creative Commons Attribution 4.0 International License.The role of DICKKOPF (DKK)-1 in human cancer is controversial. DKK-1 behaves as an inhibitor of the canonical Wnt/β-catenin signaling pathway acting at the plasma membrane, although several studies have proposed effects that are independent of the inhibition of β-catenin transcriptional activity, in some cases mediated by the activation of c-Jun N-terminal kinase (JNK). Recently, a proportion of DKK-1 protein has been found within the nucleus of human intestinal epithelial cells following an apical-to-basal crypt decreasing gradient, and in that of colon carcinoma cells. Moreover, we show here that in the human mammary gland DKK-1 is also present within the nucleus of many differentiated luminal epithelial cells and in that of a small proportion of myoepithelial cells. Nuclear DKK-1 binds to actively transcribed chromatin and regulates the expression of specific genes, some of which are involved in cell proliferation, survival and stemness, and in the defense against xenobiotics. This may explain the finding that while DKK-1 is downregulated more rapidly in the nucleus than in the cytosol during colon carcinoma progression, its expression remains high in a percentage of patients who do not respond to chemotherapy. Available data suggest that the accumulation of DKK-1 in the nucleus of colon carcinoma cells depends on signals from the surrounding tumor microenvironment.Work in authors' laboratories is supported by grants from Ministerio de Economía y Competitividad of Spain-Fondo Europeo de Desarrollo Regional (FEDER) (SAF2013-43468-R), Comunidad de Madrid (S2010/BMD-2344 Colomics2), and FEDER-Instituto de Salud Carlos III (RD12/0036/0021; RD12/0036/0051, PT13/0010/0012 and PI12/01552).Peer reviewe

The ERA-EDTA Registry Annual Report 2018: a summary

Background The European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) Registry collects data on kidney replacement therapy (KRT) via national and regional renal registries in Europe and countries bordering the Mediterranean Sea. This article summarizes the 2018 ERA-EDTA Registry Annual Report, and describes the epidemiology of KRT for kidney failure in 34 countries. Methods Individual patient data on patients undergoing KRT in 2018 were provided by 34 national or regional renal registries and aggregated data by 17 registries. The incidence and prevalence of KRT, the kidney transplantation activity and the survival probabilities of these patients were calculated. Results In 2018, the ERA-EDTA Registry covered a general population of 636 million people. Overall, the incidence of KRT for kidney failure was 129 per million population (p.m.p.), 62% of patients were men, 51% were ≥65 years of age and 20% had diabetes mellitus as cause of kidney failure. Treatment modality at the onset of KRT was haemodialysis (HD) for 84%, peritoneal dialysis (PD) for 11% and pre-emptive kidney transplantation for 5% of patients. On 31 December 2018, the prevalence of KRT was 897 p.m.p., with 57% of patients on HD, 5% on PD and 38% living with a kidney transplant. The transplant rate in 2018 was 35 p.m.p.: 68% received a kidney from a deceased donor, 30% from a living donor and for 2% the donor source was unknown. For patients commencing dialysis during 2009–13, the unadjusted 5-year survival probability was 42.6%. For patients receiving a kidney transplant within this period, the unadjusted 5-year survival probability was 86.6% for recipients of deceased donor grafts and 93.9% for recipients of living donor grafts

Epigenetic repression of ROR2 has a Wnt-mediated, pro-tumourigenic role in colon cancer

9 páginas, 4 figuras.-- et al.[Background]: Wnt factors control cell differentiation through semi-independent molecular cascades known as the β-catenin-dependent (canonical) and -independent (non-canonical) Wnt signalling pathways. Genetic and epigenetic alteration of components of the canonical Wnt signalling pathway is one of the primary mechanisms underlying colon cancer. Despite increasing evidence of the role of the non-canonical pathways in tumourigenesis, however, the underlying molecular mechanisms are poorly understood. [Results]: Here we report that the receptor tyrosine kinase-like orphan receptor 2 (ROR2), a transmembrane receptor for Wnt factors that activates non-canonical pathways, is frequently repressed by aberrant promoter hypermethylation in human colon cancer cell lines and primary tumours. By restoring ROR2 activity in colon cancer cells harbouring ROR2 promoter hypermethylation, we show that the role of ROR2 in colon cancer cells is mediated, at least in part, by canonical Wnt and that its epigenetic-dependent loss can be pro-tumourigenic. [Conclusions]: Our data show the importance of epigenetic alterations of ROR2 in colon cancer, highlighting the close interconnection between canonical and non-canonical Wnt signalling pathways in this type of tumour.AM is funded by the Spanish Ministerio de Ciencia e Innovación (MICINN; SAF2007-60341, ISCIII-RETIC RD06/0020/0009), VC receives a fellowship from the Spanish FPU Research Programme, EL and CH are recipients of fellowships from the Spanish FIS Research Programme. The Instituto Universitario de Oncología is supported by Obra Social Cajastur, Spain. This work was supported by the MICINN (PI061267; PS09/02454; Ref. 200820I172).Peer reviewe

Optimal start in dialysis shows increased survival in patients with chronic kidney disease

Objective To compare the survival among patients with chronic kidney disease who had optimal starts of renal replacement therapy, dialysis or hemodialysis, with patients who had suboptimal starts. Methods A retrospective cohort consisting of >18 year-old patients who started renal replacement therapy, using peritoneal dialysis or hemodialysis, in any public hospital or associated center of the Andalusian Public Health System, between the 1st of January of 2006 and the 15th of March of 2017. The optimal start was defined when all the following criteria were met: a planned dialysis start, a minimum of six-month follow-up by a nephrologist, and a first dialysis method coinciding with the one registered at 90 days. The information was obtained from the registry of the Information System of the Transplant Autonomic Coordination of Andalusia. Results A total of 10,692 patients were studied. 4,377 (40.9%) of these patients died. A total of 4,937 patients (46.17%) achieved optimal starts of renal replacement therapy and showed higher survival rates (HR 0.669; 95% CI 0.628–0.712) in the multivariate analysis of Cox regression model

NADPH oxidase 1 as a new regulator of the WNT pathway and the protective effect of vitamin D in colorectal cancer

Trabajo presentado en el 43rd Annual Meeting of the SEBBM, celebrado en Barcelona (España) del 19 al 22 de julio de 2021.Worldwide, colorectal cancer (CRC) is the third most common malignant neoplasm and the second leading cause of cancer-associated mortality, with an estimated increase in global prevalence of 60% by 2030 (1,2). Mutational inactivation of adenomatous polyposis coli (APC) is the hallmark of CRC and leads to an overactivation of WNT signaling that favors the development and progression of CRC (3). Large epidemiological studies suggest that the diabetic population is at increased risk for site-specific cancers, including CRC (4). Our laboratory has shown that hyperglycemia induces the accumulation of ROS in CRC but not healthy cells, driving the activation of a newly described ROS/AMPK/EP300 axis that enhances Wnt/b-catenin signaling. Increased EP300 leads to increased acetylation of β-catenin at K354, a requirement for nuclear accumulation and transcriptional activation of WNT target genes (5,6). The critical role driven by ROS suggest a possible involvement of the NADPH oxidases (NOX family, as a source of ROS. Specifically, NOX 1 and NOX 4 are expressed in colon epithelial cells, and their overexpression in CRC cells promotes cell proliferation and invasiveness (7,8,9,10). Our results indicate that hyperglycemia significantly increases NOX1 levels, in correlation with increased ROS production in CRC cells, suggesting a possible regulation of the ROS/ AMPK/EP300 axis by NOX1. Antioxidant mechanisms dealing with NOX1-induced ROS should be effective against CRC. Vitamin D (1α, 25-dihydroxyvitamin D3) is a powerful antioxidant that inhibits proliferation and promotes differentiation of CRC cells at least partially through inhibition of Wnt/β-catenin signalling. Consequently, vitamin D deficiency is associated with poor survival to CRC (11,12). Our results indicate that vitamin D causes a reduction in the levels and / or activity of some members of the NOX family by turning off the ROS/AMPK/EP300/β-catenin axis and its proliferative and tumorigenic effects. The data suggest a new antitumor mechanism of vitamin D linked to its anti-oxidant action. Our results integrate independent epidemiological links between vitamin D deficiency, diabetes and cancer in one overarching and unifying mechanism

Nuclear DICKKOPF-1 as a biomarker of chemoresistance and poor clinical outcome in colorectal cancer

Sporadic colorectal cancer (CRC) insurgence and progression depend on the activation of Wnt/β-catenin signaling. Dickkopf (DKK)-1 is an extracellular inhibitor of Wnt/β-catenin signaling that also has undefined β-catenin-independent actions. Here we report for the first time that a proportion of DKK-1 locates within the nucleus of healthy small intestine and colon mucosa, and of CRC cells at specific chromatin sites of active transcription. Moreover, we show that DKK-1 regulates several cancer-related genes including the cancer stem cell marker aldehyde dehydrogenase 1A1 (ALDH1A1) and Ral-binding protein 1-associated Eps domain-containing 2 (REPS2), which are involved in detoxification of chemotherapeutic agents. Nuclear DKK-1 expression is lost along CRC progression; however, it remains high in a subset (15%) of CRC patients (n = 699) and associates with decreased progression-free survival (PFS) after chemotherapy administration and overall survival (OS) [adjusted HR, 1.65; 95% confidence interval (CI), 1.23-2.21; P = 0.002)]. Overexpression of ALDH1A1 and REPS2 associates with nuclear DKK-1 expression in tumors and correlates with decreased OS (P = 0.001 and 0.014) and PFS. In summary, our findings demonstrate a novel location of DKK-1 within the cell nucleus and support a role of nuclear DKK-1 as a predictive biomarker of chemoresistance in colorectal cancer

Genetic and phenotypic characterisation of HIV-associated aggressive B-cell non-Hodgkin lymphomas, which do not occur specifically in this population: diagnostic and prognostic implications

The frequency of aggressive subtypes of B-cell non-Hodgkin lymphoma (B-NHL), such as high-grade B-cell lymphomas (HGBL) with MYC and BCL2 and/or BCL6 rearrangement (HGBL-DH/TH) or Burkitt-like lymphoma (BL) with 11q aberration, is not well known in the HIV setting. We aimed to characterise HIV-associated aggressive B-NHL according to the 2017 WHO criteria, and to identify genotypic and phenotypic features with prognostic impact. Seventy-five HIV-associated aggressive B-NHL were studied by immunohistochemistry (CD10, BCL2, BCL6, MUM1, MYC, and CD30), EBV-encoded RNAs (EBERs), and fluorescence in situ hybridisation (FISH) to evaluate the status of the MYC, BCL2, and BCL6 genes and chromosome 11q. The 2017 WHO classification criteria and the Hans algorithm, for the cell-of-origin classification of diffuse large B-cell lymphomas (DLBCL), were applied. In DLBCL cases, the frequencies of MYC and BCL6 rearrangements (14.9 and 27.7%, respectively) were similar to those described in HIV-negative patients, but BCL2 rearrangements were infrequent (4.3%). MYC expression was identified in 23.4% of DLBCL cases, and coexpression of MYC and BCL2 in 13.0%, which was associated with a worse prognosis. As for BL cases, the expression of MUM1 (30.4%) conferred a worse prognosis. Finally, the prevalence of HGBL-DH/TH and BL-like with 11q aberration are reported in the HIV setting. The phenotypic and genotypic characteristics of HIV-associated aggressive B-NHL are similar to those of the general population, except for the low frequency of BCL2 rearrangements in DLBCL. MYC and BCL2 coexpression in DLBCL, and MUM-1 expression in BL, have a negative prognostic impact on HIV-infected individuals.Peer reviewe

Coordinación y seguimiento de la docencia semipresencial en el Máster Universitario en Ingeniería Informática

El Máster Universitario en Ingeniería Informática de la Universidad de Alicante está regulado según las recomendaciones establecidas para la ordenación de las enseñanzas de Máster en el ámbito de la Ingeniería Informática, ofreciendo una formación avanzada en las tecnologías de la informática que capacita para la elaboración, planificación, dirección y coordinación de proyectos, así como su gestión técnica y económica en todos los ámbitos de la ingeniería informática, siguiendo criterios de calidad y medioambientales. El propósito principal de este trabajo de investigación docente es el seguimiento y coordinación de la docencia semipresencial en las asignaturas del Máster Universitario en Ingeniería Informática, tanto en la metodología docente como en los materiales y la carga de trabajo para el alumnado. Puesto que la implantación de la semipresencialidad es novedosa en este curso, es especialmente importante la coordinación entre todas las asignaturas y el seguimiento del desarrollo académico para detectar y solventar los posibles problemas que puedan aparecer y establecer un plan de mejoras que permita la mejora continua de la titulación. Para ello, se han realizado reuniones de coordinación de todos los responsables de asignaturas del Máster y reuniones con el alumnado para comprobar el progreso académico a lo largo del curso

Docencia semipresencial en el Máster en Ingeniería Informática

En este artículo se describe el trabajo realizado por la red de investigación en docencia universitaria denominada “Docencia semipresencial en el Máster en Ingeniería Informática” y que ha pretendido trabajar en las diferentes asignaturas del Máster en Ingeniería Informática de la Universidad de Alicante con el fin de dotarlas de un carácter semipresencial de una forma coordinada e integrada. Se ha creado un grupo de trabajo dentro de la comisión académica del máster y se ha impulsado una colaboración estrecha entre los responsables de todas las asignaturas del Máster en Ingeniería Informática a la hora de usar todos los mecanismos necesarios para dotar a las respectivas asignaturas del carácter semipresencial. Ha sido muy importante el apoyo que se ha tenido del ICE en este sentido, por ejemplo mediante la solicitud y realización de un curso específico sobre bLearning