Tumor-specific T cell responses are strongly impaired in CNI-treated patients but recover after mTOR-i conversion, reducing SCC relapses.

BackgroundVariability in the management of glomerulonephritis may negatively impact efficacy and safety. However, there are little/no data on actual variability in the treatment of minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) in adults. We assessed Spanish practice patterns for the management of adult nephrotic syndrome due to MCD or FSGS. The absence of reasonably good evidence on treatment for a disease often increases the variability substantially. Identification of evidence–practice gaps is the first necessary step in the knowledge-to-action cyclical process. We aim to analyse the real clinical practice in adults in hospitals in Spain and compare this with the recently released Kidney Disease: Improving Global Outcomes clinical practice guideline for glomerulonephritis.MethodsParticipating centres were required to include all adult patients (age >18 years) with a biopsy-proven diagnosis of MCD or FSGS from 2007 to 2011. Exclusion criteria included the diagnosis of secondary nephropathy.ResultsWe studied 119 Caucasian patients with biopsy-proven MCD (n = 71) or FSGS (n = 48) from 13 Spanish hospitals. Of these patients, 102 received immunosuppressive treatment and 17 conservative treatment. The initial treatment was steroids, except in one patient in which mycophenolate mofetil was used. In all patients, the steroids were given as a single daily dose. The mean duration of steroid treatment at initial high doses was 8.7 ± 13.2 weeks and the mean global duration was 38 ± 32 weeks. The duration of initial high-dose steroids was <4 weeks in 41% of patients and >16 weeks in 10.5% of patients. We did find a weak and negative correlation between the duration of whole steroid treatment in the first episode and the number of the later relapses (r = −0.24, P = 0.023). There were 98 relapses and they were more frequent in MCD than in FSGs patients (2.10 ± 1.6 versus 1.56 ± 1.2; P = 0.09). The chosen treatment was mainly steroids (95%). Only seven relapses were treated with another drug as a first-line treatment: two relapses were treated with mycophenolate and five relapses were treated with anticalcineurinics. A second-line treatment was needed in 29 patients (24.4%), and the most frequent drugs were the calcineurin inhibitors (55%), followed by mycophenolate mofetil (31%). Although cyclophosphamide is the recommended treatment, it was used in only 14% of the patients.ConclusionsWe found variation from the guidelines in the duration of initial and tapered steroid therapy, in the medical criteria for classifying a steroid-resistant condition and in the chosen treatment for the second-line treatment. All nephrologists started with a daily dose of steroids as the first-line treatment. The most frequently used steroid-sparing drug was calcineurin inhibitors. Cyclophosphamide use was much lower than expected.

ResumenLos bosques subantárticos de las montañas fueguinas son consideradas una de las pocas áreas silvestres que quedan en el planeta; sin embargo, las perturbaciones humanas como incendios forestales, especies exóticas, etc. agravan su degradación. En 2012, se inició un incendio de origen humano en una remota zona de bosque y montaña, y dos años después comenzó un proyecto de reforestación para restaurar el dosel natural. Los renovales de la especie nativa de árbol Nothofagus se obtuvieron de zonas no perturbadas utilizando el método de raíz desnuda. En este estudio se evaluó la influencia de (1) los macroambientes (considerando la topografía natural y la fisonomía de la vegetación) y microambientes (topografía, cobertura del dosel, sustrato y cobertura del sotobosque) afectados por el fuego; y (2) el tamaño de extracción de los renovales (tamaño inicial), sobre la supervivencia y el crecimiento de los renovales plantados, a lo largo de 5 años. La supervivencia total de los renovales fue del 41,4%, con una tasa media de crecimiento de 8,46 cm año−1. La supervivencia y el crecimiento fueron influenciados por las variables estudiadas. A nivel de macroambiente, los renovales mostraron mayor éxito en zonas bien drenadas, mientras que a nivel de microambiente los renovales mostraron mejor desempeño en los que contribuyen a retener la humedad del suelo y evitar la evapotranspiración. Concluimos que las características ambientales influyen diferencialmente dependiendo de la escala de análisis. Para restaurar bosques templados quemados aplicando el método de repique directo a raíz desnuda, recomendamos utilizar renovales de Nothofagus de <40 cm de altura para obtener mejores resultados. En este sentido, demostramos la eficacia del método ya que se obtuvieron resultados comparables en otras experiencias de restauración. Este método también puede ser aplicado en áreas sin material de vivero y cuando la biología de las plantas sea apropiada, por ejemplo, el crecimiento superficial de los sistemas radiculares, la formación de bancos naturales de plántulas de árboles, etc. Este trabajo representa una de las pocas experiencias de restauración a medio plazo reportadas para los bosques más australes del planeta: nuestros hallazgos podrían ser aplicados en otras experiencias de reforestación, logrando mejoras notables en el proceso de recuperación.

Background The clinical manifestations of autosomal dominant polycystic kidney disease (ADPKD) usually appear in adulthood, however pediatric series report a high morbidity. The objective of the study was to analyze the clinical characteristics of young ADPKD adults. Methods Family history, hypertension, albuminuria, eGFR and imaging tests were examined in 346 young adults (18-30 years) out of 2580 patients in the Spanish ADPKD registry (REPQRAD). A literature review searched for reports on hypertension in series with more than 50 young (age &lt;30 years) ADPKD patients. Results The mean age of this young adult cohort was 25.24 (SD 3.72) years. The mean age at diagnosis of hypertension was 21.15 (SD 4.62) years, while in the overall REPQRAD population was 37.6 years. The prevalence of hypertension was 28.03% and increased with age (18 to 24 years: 16.8%, 25 to 30 years: 36.8%). Although prevalence was lower in women than in men, the age at onset of hypertension (21 years) was similar in both sexes. Mean eGFR was 108 (SD 21) ml/min/1.73m2, 38.0% had liver cysts and 3.45% of those studied had intracranial aneurysms. In multivariate analyses, hematuria episodes and kidney length were independent predictors of hypertension (AUC 0.75). The prevalence of hypertension in 22 pediatric cohorts was 20-40%, but no literature reports on hypertension in young ADPKD adults were found. Conclusions Young adults present non-negligible ADPKD-related morbidity. This supports the need for a thorough assessment of young adults at risk of ADPKD that allows early diagnosis and treatment of hypertension.

The sub‐Antarctic forests in Tierra del Fuego mountains are considered one of the few remaining wilderness areas on the planet; however, human disturbances like wildfires, exotic species, and so forth exacerbate their degradation. In 2012, a human‐caused wildfire started in a remote forest‐mountain area, and 2 years after that, a reforestation project began to restore the natural canopy layer. Saplings of the native Nothofagus trees were obtained through the bare root method from undisturbed areas. In this study, we evaluated the influence of (1) macro‐ (considering natural topography and vegetation physiognomy) and micro‐environments (topography, canopy cover, substrate, and understory cover) affected by fire; and (2) the extraction size of the saplings (initial size), on survival and growth of planted saplings, over 5 years. Total sapling survival was 41.4% with a mean growth rate of 8.46 cm year−1. Survival and growth were influenced by the studied variables. At a macro‐environment level, tree saplings showed higher success in well‐drained zones, meanwhile at the micro‐environment level saplings performed better in those that contribute to retain soil moisture and avoiding evapotranspiration. We conclude that environmental features influence differentially depending on the scale of analysis. To restore burnt temperate forests applying the bare root method, we recommended using Nothofagus saplings <40 cm tall for better results. In this sense, we demonstrated the effectiveness of the method since comparable results were obtained in other restoration experiences. This method can also be applied in areas without nursery material, when the biology of tagged plants was appropriated, for example shallow growth of root systems, formation of natural tree seedling banks. This work represents one of the few medium‐term restoration experiences reported for the southernmost forests of the planet: our findings could be applied in other reforestation experiences, making noticeable improvements in the recovery process.