Impacto clínico y económico en pacientes incidentes en diálisis según condición de ingreso / Clinical and economic impact on incident dialysis patients according to admission condition

INTRODUCCIÓN La enfermedad renal crónica es una patología de alta prevalencia a nivel mundial, con creciente número de pacientes con nuevo diagnóstico y acceso a instancias críticas con insuficiencia funcional en estadíos terminales. Se trata de una entidad con doble efecto; es tributaria de patologías crónicas prevalentes con gran carga de morbimortalidad cardiovascular y uso de recursos sanitarios (como diabetes o hipertensión arterial) y al mismo tiempo multiplica el impacto del riesgo (tanto clínico como económico) atribuible a las mismas. El primer año en tratamiento con diálisis de estos pacientes es donde se registran la mayor cantidad de eventos clínicos y muertes, con gran consumo de recursos sanitarios. OBJETIVO Establecer el efecto de las condiciones clínicas de pacientes incidentes a diálisis en la cantidad y severidad de eventos así como el gasto sanitario incurrido durante el primer año posterior al ingreso a tratamiento. MÉTODOS Se seleccionó una muestra retrospectiva de 20.256 pacientes incidentes en diálisis provenientes de 8 financiadores representativos de los subsectores del sistema de salud argentino, entre enero 2010 y diciembre 2015, y se los siguió durante un año posterior a la fecha de ingreso o bien su baja antes de dicho plazo por muerte, trasplante o recuperación funcional. Se consideraron variables epidemiológicas, clínicas y de cobertura relevantes para evaluar la morbimortalidad. Se aplicaron secuencialmente análisis univariantes y multivariantes para evaluar el impacto de dichos parámetros en la mortalidad (modelo de riesgos proporcionales de Cox) y aparición de eventos, consumo de prestaciones y gasto asociado (regresión logística). RESULTADOS Se encontró una alta tasa de mortalidad precoz, con un 66% de los óbitos ocurridos en el primer semestre de seguimiento; las variables asociadas con este desenlace fueron (en orden de significancia) la edad >65 años, presencia de catéter transitorio al ingreso, diagnóstico de diabetes, albuminemia <4 g/dl, diagnóstico de insuficiencia cardíaca y angina persistente. Con respecto a los eventos de internación fueron 5 veces más frecuentes en períodos cercanos al ingreso a diálisis, con duplicación en la duración de las instancias, hasta 3 veces mayor consumo de prácticas asociadas y costos 8 veces superiores (1er vs 2do semestre), encontrándose diferencias específicas entre financiadores y modelos de contratación. El gasto mensual ponderado de un paciente incidente en diálisis (tratamiento dialítico + complicaciones) resultó entre 15 a 35 veces más elevado que el valor per cápita de cobertura convencional, y este gasto llegó a ser hasta 45 veces en el período precoz (1er semestre) por aumento de complicaciones. DISCUSIÓN La población incidente en diálisis estudiada presenta alta morbimortalidad, asociada con condiciones de riesgo conocidas y de alto impacto. La carga de consumo de servicios y costos es mayor en los períodos cercanos al momento de ingreso, evidenciando una potencial falta de seguimiento previo o selección adecuada de pacientes para acceder al tratamiento

Immunolocalization of tumor necrosis factor alpha in turbot (Scophthalmus maximus, L.) tissues.

Tumor necrosis factor alpha (TNFα) is a cytokine involved in a broad spectrum of cellular and organismal responses. Its main function, as a potent pro-inflammatory mediator, has been demonstrated in numerous teleost species and there are many reports on the modulation of TNFα gene expression under pathological conditions. Nevertheless, there is still scarce knowledge about the tissue distribution and type of cells that express this cytokine in fish species, which would help to further investigate its biological activities. These studies are hampered by the lack of molecular markers for teleost that hinder the development of morphological techniques, like immunohistochemistry. The aim of this work was to develop an immunohistochemical technique for the detection of TNFα in paraffin-embedded organs from healthy turbot (Scophthalmus maximus), an economically-important marine fish species. A commercial anti-human TNFα antibody, whose specificity was confirmed by western blot analysis, was used. Immunoreactive cells were observed in higher numbers in the lymphohematopoietic organs, kidney, spleen and thymus, although TNFα-positive cells were also present in the digestive tract, liver, heart, gills and skin. Similarly to non-fish species, monocytes/macrophages appeared to be the main producers of this cytokine; nevertheless, the presence of immunoreactive rodlet cells in different tissues was also reported. The nature and distribution of the labeled cells appeared to be related with a strategic localization for defense response to antigenic challenge. The relative abundance of TNFα-positive cells in the lymphohematopoietic organs also suggests that this cytokine may have a broader role in the normal physiology of those organs. The immunohistochemical technique allowed the in-situ characterization of TNFα expression, representing a valid tool to investigate the immune response of turbot.

Differential distribution of cAMP-dependent protein kinase isoforms in various tissues of the bivalve mollusc Mytilus galloprovincialis.

The cAMP signalling pathway is involved in the regulation of basic physiological processes in bivalve molluscs. We had previously identified and characterized two isoforms of cAMP-dependent protein kinase (PKA) from the sea mussel Mytilus galloprovincialis that differ at their regulatory (R) subunit, namely, R(myt1) or R(myt2). Here we investigated the immunohistochemical expression of both PKA isoforms in various mussel tissues. R(myt1) and R(myt2) displayed a complementary subcellular localization. In general, R(myt1) was found to be uniformly distributed in the cytoplasm of most cell types, whereas R(myt2) appears to be localized only in the cell periphery and associated with certain cellular structures, such as the cilia of labial palps and gill filaments. Thus, both PKA isoforms appear to be non-redundant, but they have specific functions. R(myt1) was the main isoform present in catch muscle fibers, which suggests that PKA(myt1) may be the isoform involved in the regulation of the catch state. Conversely, R(myt2) was the only isoform detected in the cilia of gill filaments, indicating that PKA(myt2) could mediate the effects of cAMP on the ciliary beat frequency.

Differential distribution of cAMP-dependent protein kinase isoforms in the mantle of the bivalve mollusc Mytilus galloprovincialis.

Two different isoforms of the regulatory (R) subunit of cAMP-dependent protein kinase (PKA), named R(myt1) and R(myt2), had previously been identified in the sea mussel Mytilus galloprovincialis. R(myt1) and R(myt2) were differentially distributed in the various cell types comprising the mussel mantle. R(myt1) was found the only isoform to be present in the auxiliary cells of female follicles and the cubic epithelium of the middle fold of mantle edge. In contrast, only the R(myt2) isoform was detected in the subepithelial connective tissue, the endothelium of haemolymph vessels, the adipogranular and vesicular cells of reserve connective tissue, and the spermatozoa. Finally, both R(myt1) and R(myt2) coexist in some cell types but they show a different cellular localization: R(myt1) was localized in the cytoplasm whereas R(myt2) was mainly detected in the cell apical edge, cell periphery, cilia and sperm flagella. Interestingly, both R(myt1) and R(myt2) were absent in oocytes within the female gonadal follicles but, in contrast, they were highly expressed in follicle-released oocytes collected after spawning. Taken together the results show that mussel PKA isoforms are differentially distributed in the mantle cell types, which suggests that they are involved in the regulation of distinct cellular functions. On the other hand, the expression of R(myt1) and R(myt2) proteins is associated with the meiosis resumption of oocytes at the prophase I stage, which occurs in parallel to spawning.