68 research outputs found
High-dose steroid treatment increases free water transport in peritoneal dialysis patients
The water channel aquaporin-1 (AQP1) is the molecular counterpart of the ultrasmall pore that mediates free water transport during peritoneal dialysis (PD). Proof-of-principle studies performed in rats have shown that treatment with corticosteroids upregulates the expression of AQP1 in the peritoneal capillaries, causing a significant increase in free water transport. Whether such a beneficial effect could be observed in end-stage renal disease patients treated by PD remains unknown. Peritoneal transport parameters were evaluated in three patients on PD, shortly before and after living-donor renal transplantation and treatment with high-dose methylprednisolone (1.0-1.2 g/m2). As compared with pre-transplantation values, the post-transplantation test revealed an ∼2-fold increase in the sodium sieving and ultrasmall pore ultrafiltration volume, suggesting an effect on AQP1 water channels. In contrast, there was no change in the parameters of small solute transport. The direct involvement of AQP1 in these changes is suggested by the expression of glucocorticoid receptors in the human peritoneum and the presence of conserved glucocorticoid response elements in the promoter of the human AQP1 gen
Use of Percutaneous Ethanol Injection Therapy for Recurrent Secondary Hyperparathyroidism after Subtotal Parathyroidectomy
We evaluated the efficacy of percutaneous ethanol injection therapy (PEIT) as a therapeutic option for recurrence of secondary hyperparathyroidism after subtotal parathyroidectomy in ESRD patients. Six patients underwent PEIT. A mean of 1.3 ± 0.8 ethanol injections was performed. Nodular volume was 1.5 ± 1.7 cm3, and 2.8 ± 2.8 cm3 of ethanol was injected per patient. After ethanol injection PTH decreased significantly (1897 ± 754 to 549 ± 863 pg/mL (P < .01)). There was also a reduction in serum calcium, phosphorus and calcium-phosphorus product. A positive and significant correlation was found between nodular volume with ethanol injected and time from parathyroidectomy. Only one patient required hospitalization due to severe hypocalcaemia. In other two cases, local discomfort and temporary mild dysphonia were registered. PEIT is an effective treatment to control recurrences of secondary hyperparathyroidism postsubtotal parathyroidectomy
Renal Transplantation in a patient with Recessive Dystrophic Epidermolysis Bullosa: a case report
Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genodermatosis characterized by abnormalities in the anchoring fibrils which attach the basal cell layer of the epidermis to the underlying structures. A characteristic feature of this disorder is the presence of recurrent blistering or erosions, the result of even minor traction to these tissues. Patients with RDEB frequently develop chronic renal failure, and require renal replacement therapy being a major cause of morbidity and mortality. The role of renal transplantation in these patients is scarcely known.We present the case of an end-stage renal disease patient with RDEB treated by renal transplantation and his follow-up during a period of 83 months after the transplant. In this period, there were very low frequency of serious infections as well as the absence of skin tumors.Renal transplantation could be an alternative to renal replacement therapy in epidermolysis bullosa patients with end-stage renal disease, reducing the comorbidities associated with this treatment.</p
Two-year outcomes in de novo renal transplant recipients receiving everolimus-facilitated calcineurin inhibitor reduction regimen from TRANSFORM study
TRANSFORM was a 24-month, prospective, open-label trial in 2037 de novo renal transplant recipients (RTxRs) randomized (1:1) within 24 hours of transplantation to receive everolimus (EVR) with reduced-exposure calcineurin inhibitor (EVR+rCNI) or mycophenolate with standard-exposure CNI (MPA+sCNI). Consistent with previously reported 12-month findings, noninferiority of the EVR+rCNI regimen for the primary endpoint of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) <50 mL/min/1.73 m2 was achieved at Month 24 (47.9% vs 43.7%; difference = 4.2%; 95% confidence interval [CI] = -0.3, 8.7; P = 0.006). Mean eGFR was stable up to Month 24 (52.6 vs 54.9 mL/min/1.73m2 ) in both arms. The incidence of de novo donor-specific antibodies (dnDSA) was lower in the EVR+rCNI arm (12.3% vs 17.6%) among on-treatment patients. Although discontinuation rates due to adverse events were higher with EVR+rCNI (27.2% vs 15.0%), rates of cytomegalovirus (2.8% vs 13.5%) and BK virus (5.8% vs 10.3%) infections were lower. Cytomegalovirus infection rates were significantly lower with EVR+rCNI even in the D+/R- high-risk group (P<0.0001). In conclusion, the EVR+rCNI regimen offers comparable efficacy and graft function with low tBPAR and dnDSA rates and significantly lower incidence of viral infections relative to standard-of-care up to 24 months. This article is protected by copyright. All rights reserved
Safety and efficacy of atezolizumab in patients with autoimmune disease: subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma
Aim
Patients with pre-existing autoimmune disease (AID) are typically excluded from clinical trials of immune checkpoint inhibitors, and there are limited data on outcomes in this population. The single-arm international SAUL study of atezolizumab enrolled a broader ‘real-world’ patient population. We present outcomes in patients with a history of AID.
Methods
Patients with locally advanced/metastatic urinary tract carcinoma received atezolizumab 1200 mg every 3 weeks until loss of clinical benefit or unacceptable toxicity. The primary end-point was safety. Overall survival (OS) was a secondary end-point. Subgroup analyses of AID patients were prespecified.
Results
Thirty-five of 997 treated patients had AID at baseline, most commonly psoriasis ( n = 15). Compared with non-AID patients, AID patients experienced numerically more adverse events (AEs) of special interest (46% versus 30%; grade ≥3 14% versus 6%) and treatment-related grade 3/4 AEs (26% versus 12%), but without relevant increases in treatment-related deaths (0% versus 1%) or AEs necessitating treatment discontinuation (9% versus 6%). Pre-existing AID worsened in four patients (11%; two flares in two patients); three of the six flares resolved, one was resolving, and two were unresolved. Efficacy was similar in AID and non-AID patients (median OS, 8.2 versus 8.8 months, respectively; median progression-free survival, 4.4 versus 2.2 months; disease control rate, 51% versus 39%).
Conclusions
In 35 atezolizumab-treated patients with pre-existing AID, incidences of special- interest and treatment-related AEs appeared acceptable. AEs were manageable, rarely requiring atezolizumab discontinuation. Treating these patients requires caution, but pre-existing AID does not preclude atezolizumab therapy
Inhibitor of DNA Binding 3 Limits Development of Murine Slam-Associated Adaptor Protein-Dependent “Innate” γδ T cells
Id3 is a dominant antagonist of E protein transcription factor activity that is induced by signals emanating from the alphabeta and gammadelta T cell receptor (TCR). Mice lacking Id3 were previously shown to have subtle defects in positive and negative selection of TCRalphabeta+ T lymphocytes. More recently, Id3(-/-) mice on a C57BL/6 background were shown to have a dramatic expansion of gammadelta T cells.Here we report that mice lacking Id3 have reduced thymocyte numbers but increased production of gammadelta T cells that express a Vgamma1.1+Vdelta6.3+ receptor with restricted junctional diversity. These Vgamma1.1+Vdelta6.3+ T cells have multiple characteristics associated with "innate" lymphocytes such as natural killer T (NKT) cells including an activated phenotype, expression of the transcription factor PLZF, and rapid production of IFNg and interleukin-4. Moreover, like other "innate" lymphocyte populations, development of Id3(-/-) Vgamma1.1+Vdelta6.3+ T cells requires the signaling adapter protein SAP.Our data provide novel insight into the requirements for development of Vgamma1.1+Vdelta6.3+ T cells and indicate a role for Id3 in repressing the response of "innate" gammadelta T cells to SAP-mediated expansion or survival
Aplicación de multi-metodologías para la gestión y evaluación de sistemas sociales y tecnológicos. Tomo II
Introducción; PARTE I: 1. Performance of justice in Argentina. AHP Ratings model. Curchod M. y Alberto C.; 2. Temporary study efficiency of the academic units at Universidad Nacional de Córdoba. Alberto C. y Carignano C.; 3. Estudio de la permanencia en el mercado de las entidades bancarias argentinas utilizando el índice de Malmquist. Peretto C y Alberto C.; 4. Una aplicación del análisis de la envolvente de datos para evaluar la eficiencia de la justicia en Argentina. Alberto C., Curchod M. y Azcona N. ; 5. Variantes de la programación multiobjetivo. Ercole R. y Carignano C.; 6. Comparación de métodos de agregación y ponderación de la construcción de un indicador del desarrollo humano de paises latinoamericanos. Funes M., Racagni J. y Guevel H.; Comparación de procedimientos de normalización y métrica en la construcción de indicadores compuestos de bien estar social utilizando el método Topsis. Funes M, Racagni J, Guevel H y Minolli S.; 8. Modelos mixtos para analizar la relación entre crecimiento y deuda externa pública en países en desarrollo en el período 2000-2007. Stímolo M. I. y Funes M.; 9.Proyección del débito fiscal IVA utilizando técnicas de simulación. Lamberghini Nicklison J.P. y Reano V.; 10. Recursos y tecnología didáctica. Estrategias para mejorar la comunicación. Funes Alvarez M.P. y Amateis S.; 11. Relevamiento y análisis de aportes recientes al método Topsis. Santa Cruz C. y Assef Z.; PARTE II: 12. Análisis de un problema de selección de grupos de trabajo mediante investigación operativa Soft. Cabrera G., Zanazzi L., Castellini A. y Salamon A.; 13. Métodos multivariantes para segmentar preferencias.Referentes y aplicación. Boaglio L., Pedrotti B., Salamon A. y Gonzalez A.; 14. Técnica SODA para la elaboración de mapa colectivo. Aplicación en la retención del talento en el área informática. Salamon A., Boaglio L., Cuozzo J., Pedrotti B. y Cabrera G.; 15. La gestión de los residuos patógenos en la UNC. Un problema abordado desde la multimetodologías. Pontelli D., Conforte D., Zanazzi J.L., Castellini M.A. y
Dimitroff M.; 16. Enfoque multimetodológico aplicado para ordenar la puesta en marcha de una planta. Badaró C., Bolatti J., Moya C., Royón J., Vitali, S. y Zanazzi J.F.Un grupo de docentes investigadores vinculados a la disciplina denominada Investigación Operativa (IO), inició hace tiempo atrás su aproximación al enfoque multi-metodológico. La mayoría de estos profesores trabaja en la Universidad Nacional de Córdoba, en las Facultades de Ciencias Económicas y de Ciencias Exactas, Físicas y Naturales.
Este Libro, presenta algunas de las investigaciones realizadas en esa dirección. El texto contiene una Introducción y dos grandes secciones, una primera que supone que el proceso de toma dedecisiones es desarrollado por un decisor único. La segunda se orienta a los procesos donde es necesario considerar las posturas de diferentes actores. Los contenidos de cada capítulo se fundamentan en trabajos presentados por los autores en distintos Congresos, tanto a nivel nacional como internacional. Cabe destacar que son aportes que han pasado por evaluaciones controladas por los comités científicos de cada uno de los eventos, lo que permite suponer que cumplen con los estándares de calidad para este tipo de documentos.
El libro recoge diversos aportes positivos. En primer lugar se propone una estructura general para la realización de estudios con enfoque multi-metodológico. Esta propuesta se plantea desde la propia introducción y luego es sostenida y ampliada en los distintos capítulos. Además, se presentan y emplean diferentes métodos de apoyo a la toma de decisiones, que ofrecen un sustento adecuado cuando la responsabilidad por la decisión recae en un decisor único o una entidad que funciona como tal.
Por otra parte, el libro analiza y enumera métodos que contribuyen a estructurar los problemas de decisión. Estas aproximaciones son muy útiles en situaciones que presentan un elevado nivel de complejidad, en las que no resultan evidentes los objetivos a cumplir, ni las acciones posibles. Donde inclusive, el entorno es difícilmente valorable. Otro aporte que se considera valioso es la presentación del paradigma de la decisión grupal, como una problemática diferente a la tradicionalmente adoptada cuando el tomador de decisiones es único. Para fortalecer este aspecto, se analizan algunas metodologías que pueden utilizarse cuando la responsabilidad por la decisión recae en un grupo.Fil: Zanazzi, José Luis. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Alberto, Catalina Lucía. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Carignano, Claudia Etna. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Amateis, Sabrina. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Assef, Zaida Melina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Azcona, Noelia. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Badaró, Carmen. Universidad Nacional de Córdoba. Laboratorio de Hemoderivados; Argentina.Fil: Boaglio, Laura Leonor. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Bollati, Gilberto Juan. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Cabrera, Gabriela Pilar. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Castellini, María Alejandra. Universidad Nacional de Salta. Facultad de Ingeniería; Argentina.Fil: Conforte, José María. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Cuozzo, José Domingo. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Curchod, Miguel Angel. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Dimitroff, Magdalena. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Ercole, Raúl Alberto. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Funes, Mariana. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Funes Álvarez, María Paula. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: González, Analía. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Guevel, Hernán. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Lamberghini Nicklison, Juan Pablo. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Massari, Paulina Sofía. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Minolli, Santiago. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Moya, Cristian. Universidad Nacional de Córdoba. Laboratorio de Hemoderivados; Argentina.Fil: Pedrotti, Beatriz Isabel. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Peretto, Claudia. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Pontelli, Daniel Alberto. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Racagni, Josefina. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Reano, Verónica. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Royon, Jesica Analía. Universidad Nacional de Córdoba. Laboratorio de Hemoderivados; Argentina.Fil: Salomon, Alicia Guillermina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Santa Cruz, Carolina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Stímolo, María Inés. Universidad Nacional de Córdoba. Facultad de Ciencias Económicas; Argentina.Fil: Vitali, María Susana. Universidad Nacional de Córdoba. Laboratorio de Hemoderivados; Argentina.Fil: Zanazzi, José Francisco. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina
Altimetry for the future: Building on 25 years of progress
In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion
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