70 research outputs found

    Diseño y elaboración de una dieta específica para pacientes con esofagitis eosinofílica

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    La esofagitis eosinofílica es una condición inflamatoria crónica definida por síntomas de disfunción esofágica, infiltración por eosinófilos del epitelio esofágico y ausencia de otras causas potenciales de eosinofilia esofágica. Aunque la administración de corticoesteroides tópicos puede proporcionar alivio sintomático y regresión de las lesiones histológicas, la recidiva suele ser la norma tras su retirada. Este hecho, unido a los efectos secundarios de los corticoides ha conducido a la implantación de estrategias basadas en la supresión de ciertos alimentos capaces de inducir una respuesta inmunoalérgica tras su contacto con la mucosa del esófago. La dieta de exclusión de 4 alimentos (leche, trigo, huevos y legumbres) es una buena opción ya que más del 80% de los casos de Eo tienen su origen en el consumo de uno o más de éstos. El propósito de este trabajo es la elaboración de una dieta específica de exclusión de 4 alimentos para Eo capaz de evitar cualquier deterioro nutricional

    Machine Learning Improves Risk Stratification in Myelodysplastic Neoplasms: An Analysis of the Spanish Group of Myelodysplastic Syndromes

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    Machine learning; Risk stratification; Myelodysplastic neoplasmsAprendizaje automático; Estratificación del riesgo; Neoplasias mielodisplásicasAprenentatge automàtic; Estratificació del risc; Neoplàsies mielodisplàstiquesMyelodysplastic neoplasms (MDS) are a heterogeneous group of hematological stem cell disorders characterized by dysplasia, cytopenias, and increased risk of acute leukemia. As prognosis differs widely between patients, and treatment options vary from observation to allogeneic stem cell transplantation, accurate and precise disease risk prognostication is critical for decision making. With this aim, we retrieved registry data from MDS patients from 90 Spanish institutions. A total of 7202 patients were included, which were divided into a training (80%) and a test (20%) set. A machine learning technique (random survival forests) was used to model overall survival (OS) and leukemia-free survival (LFS). The optimal model was based on 8 variables (age, gender, hemoglobin, leukocyte count, platelet count, neutrophil percentage, bone marrow blast, and cytogenetic risk group). This model achieved high accuracy in predicting OS (c-indexes; 0.759 and 0.776) and LFS (c-indexes; 0.812 and 0.845). Importantly, the model was superior to the revised International Prognostic Scoring System (IPSS-R) and the age-adjusted IPSS-R. This difference persisted in different age ranges and in all evaluated disease subgroups. Finally, we validated our results in an external cohort, confirming the superiority of the Artificial Intelligence Prognostic Scoring System for MDS (AIPSS-MDS) over the IPSS-R, and achieving a similar performance as the molecular IPSS. In conclusion, the AIPSS-MDS score is a new prognostic model based exclusively on traditional clinical, hematological, and cytogenetic variables. AIPSS-MDS has a high prognostic accuracy in predicting survival in MDS patients, outperforming other well-established risk-scoring systems

    Evaluation of the outcomes of newly diagnosed patients with high-risk myelodysplastic syndrome according to the initial therapeutical strategies chosen in usual clinical practice

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    Clinical practice; Myelodysplastic syndrome; TreatmentPràctica clínica; Síndrome mielodisplàstica; TractamentPráctica clínica; Síndrome mielodisplásico; TratamientoMyelodysplastic syndromes (MDS) are a heterogeneous group of diseases without a care standard and show variability in treatment outcomes. This Spanish, observational, prospective study ERASME (CEL-SMD-2012-01) assessed the evolution of newly diagnosed and treatment-naïve high-risk MDS patients (according to IPPS-R). 204 patients were included: median age 73.0 years, 54.4% males, 69.6% 0-1 ECOG, and 94.6% with comorbidities. Active treatment was the most common strategy (52.0%) vs. stem cell transplantation (25.5%) and supportive care/watchful-waiting (22.5%). Overall (median) event-free survival was 7.9 months (9.1, 8.3, and 5.3); progression-free survival: 10.1 months (12.9, 12.8, and 4.3); and overall survival: 13.8 months (15.4, 14.9; 8.4), respectively, with significant differences among groups. Adverse events (AEs) of ≥3 grade were reported in 72.6% of patients; serious AEs reported in 60.6%. 33.1% of patients died due to AEs. Three patients developed second primary malignant neoplasms (median: 8.2 months). Our study showed better outcomes in patients receiving active therapy early after diagnosis

    Análisis de las causas de muerte en pacientes con síndrome mielodiplásico : experiencia de un centro

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    Los síndrome mielodisplásicos (SMD) son un conjunto de neoplasias hematológicas muy heterogéneas en cuanto a evolución clínica y pronóstico, que van desde enfermedades indolentes hasta enfermedades agresivas, con una rápida progresión a LMA y una supervivencia inferior a un año. Las causas de muerte (CDM) de los SMD no están bien estudiadas, particularmente la CDM no leucémica. La importancia de conocer las CDM, radica en la implicación terapeútica. En este estudio se demuestra que la mayoría de los SMD, independientemente del grupo de riesgo, fallecen de causas relacionadas con el SMD, lo que justificaría una intevención terapeútica precoz.Els síndromes mielodisplàsiques (SMD) són un conjunt de neoplàsies hematològiques molt heterogènies en quant a evolució clínica i pronòstic, que van des de malalties indolents fins a malalties agressivesñ amb una ràpida progressió a LMA i supervivència inferior a un any. Les causes de mort (CDM) dels SMD no estan ben estudiades, particularment la CDM no leucèmica. La importància de conèixer les CDM, rau en la implicació terapèutica. En aquest estudi es demostra que la majoria dels SMD, independentment del grup de risc, moren de causes relacionades amb el SMD, el que justificaria una intevenció terapèutica precoç

    Predicting Productive Performance in Grow-Finisher Pigs Using Birth and Weaning Body Weight

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    peer-reviewedThis study aimed to (1) investigate the effect of birth and weaning body weight (BW) on performance indicators of grow-finisher pigs and (2) estimate birth and weaning BW cut-off values in order to identify slow growing pigs (SGP). Pigs (n = 144) were classified as SMALL (0.9 ± 0.13 kg) or BIG (1.4 ± 0.20 kg) at birth and re-classified as SMALL (5.4 ± 1.6 kg) or BIG (6.3 ± 1.91 kg) at weaning. Individual BW was recorded bi-weekly, and feed intake was recorded on a daily basis. Average daily gain (ADG) and feed intake, feed conversion ratio (FCR) and days to target slaughter weight (TSW) were calculated. SMALL–SMALL pigs had lower ADG (p 0.05). Pigs weaned at <3.7 kg BW would likely be SGP. Pigs born at ≥1.1 kg BW or weaned at ≥6.4 kg BW are more likely to reach TSW at 22 weeks of age. The results suggest that birth BW might not be the best predictor for subsequent performance, as some small-born pigs were able to catch up with their bigger counterparts. The cut-off values identified could be used to design specific management and nutritional strategies for SGP

    Single-cell transcriptional profile of CD34+ hematopoietic progenitor cells from del(5q) myelodysplastic syndromes and impact of lenalidomide

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    Hematopoietic progenitor cells; Myelodysplastic syndromes; LenalidomideCélulas progenitoras hematopoyéticas; Síndromes mielodisplásicos; LenalidomidaCèl·lules progenitores hematopoietiques; Síndromes mielodisplàstiques; LenalidomidaWhile myelodysplastic syndromes with del(5q) (del(5q) MDS) comprises a well-defined hematological subgroup, the molecular basis underlying its origin remains unknown. Using single cell RNA-seq (scRNA-seq) on CD34+ progenitors from del(5q) MDS patients, we have identified cells harboring the deletion, characterizing the transcriptional impact of this genetic insult on disease pathogenesis and treatment response. Interestingly, both del(5q) and non-del(5q) cells present similar transcriptional lesions, indicating that all cells, and not only those harboring the deletion, may contribute to aberrant hematopoietic differentiation. However, gene regulatory network (GRN) analyses reveal a group of regulons showing aberrant activity that could trigger altered hematopoiesis exclusively in del(5q) cells, pointing to a more prominent role of these cells in disease phenotype. In del(5q) MDS patients achieving hematological response upon lenalidomide treatment, the drug reverts several transcriptional alterations in both del(5q) and non-del(5q) cells, but other lesions remain, which may be responsible for potential future relapses. Moreover, lack of hematological response is associated with the inability of lenalidomide to reverse transcriptional alterations. Collectively, this study reveals transcriptional alterations that could contribute to the pathogenesis and treatment response of del(5q) MDS

    The transcription factor DDIT3 is a potential driver of dyserythropoiesis in myelodysplastic syndromes

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    Haematopoietic stem cells; Myelodysplastic syndrome; TranscriptomicsCèl·lules mare hematopoètiques; Síndrome mielodisplàstic; TranscriptòmicaCélulas madre hematopoyéticas; Síndrome mielodisplásico; TranscriptómicaMyelodysplastic syndromes (MDS) are hematopoietic stem cell (HSC) malignancies characterized by ineffective hematopoiesis, with increased incidence in older individuals. Here we analyze the transcriptome of human HSCs purified from young and older healthy adults, as well as MDS patients, identifying transcriptional alterations following different patterns of expression. While aging-associated lesions seem to predispose HSCs to myeloid transformation, disease-specific alterations may trigger MDS development. Among MDS-specific lesions, we detect the upregulation of the transcription factor DNA Damage Inducible Transcript 3 (DDIT3). Overexpression of DDIT3 in human healthy HSCs induces an MDS-like transcriptional state, and dyserythropoiesis, an effect associated with a failure in the activation of transcriptional programs required for normal erythroid differentiation. Moreover, DDIT3 knockdown in CD34+ cells from MDS patients with anemia is able to restore erythropoiesis. These results identify DDIT3 as a driver of dyserythropoiesis, and a potential therapeutic target to restore the inefficient erythroid differentiation characterizing MDS patients.This work was supported by the Instituto de Salud Carlos III and co-financed by ERDF A way of making Europe (PI17/00701, and PI20/01308) (F.P.) and (PI19/00726) (T.E.), CIBERONC (CB16/12/00489) (F.P.); Gobierno de Navarra (AGATA 0011-1411-2020-000010/0011-1411-2020-000011 and DIANA 0011-1411-2017-000028/0011-1411-2017-000029/0011-1411-2017-000030) (F.P.); Fundación La Caixa (GR-NET NORMAL-HIT HR20-00871) (F.P.); and Cancer Research UK [C355/A26819], FC AECC and AIRC under the Accelerator Award Program, and MCIN/AEI/10.13039/501100011033 and by ERDF A way of making Europe [RTI2018-101708-A-I00] (M.H.). Moreover, this work was supported by PhD fellowships from Gobierno de Navarra (0011-0537-2019-000001) (N.B.), and (0011-0537-2020-000022) (A.D.-M.); a PhD fellowship from Ministerio de Ciencia, Innovación y Universidades (FPU18/05488) (M.A.); an Investigador AECC award from the Fundación AECC (INVES19059EZPO) (T.E.), H2020 Marie S. Curie IF Action, European Commission, Grant Agreement No. 898356 (M.H.); and by grants RYC2018-025502-I (A.A.) and PRE2018-084542 (R.R.) funded by MCIN/AEI/10.13039/501100011033 and by ESF Investing in your future. We particularly acknowledge the patients and healthy donors for their participation in this study, and the Biobank of the University of Navarra for its collaboration

    Cell free circulating tumor DNA in cerebrospinal fluid detects and monitors central nervous system involvement of B-cell lymphomas

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    The levels of cell free circulating tumor DNA (ctDNA) in plasma correlate with treatment response and outcome in systemic lymphomas. Notably, in brain tumors, the levels of ctDNA in the cerebrospinal fluid (CSF) are higher than in plasma. Nevertheless, their role in central nervous system (CNS) lymphomas remains elusive. We evaluated the CSF and plasma from 19 patients: 6 restricted CNS lymphomas, 1 systemic and CNS lymphoma, and 12 systemic lymphomas. We performed whole exome sequencing or targeted sequencing to identify somatic mutations of the primary tumor, then variant-specific droplet digital polymerase chain reaction was designed for each mutation. At time of enrollment, we found ctDNA in the CSF of all patients with restricted CNS lymphoma but not in patients with systemic lymphoma without CNS involvement. Conversely, plasma ctDNA was detected in only 2 out of 6 patients with restricted CNS lymphoma with lower variant allele frequencies than CSF ctDNA. Moreover, we detected CSF ctDNA in one patient with CNS lymphoma in complete remission and in one patient with systemic lymphoma, 3 and 8 months before CNS relapse was confirmed, indicating that CSF ctDNA might detect CNS relapse earlier than conventional methods. Finally, in two cases with CNS lymphoma, CSF ctDNA was still detected after treatment even though no tumoral cells were observed by flow cytometry (FC), indicating that CSF ctDNA detected residual disease better than FC. In conclusion, CSF ctDNA can detect CNS lesions better than plasma ctDNA and FC. In addition, CSF ctDNA predicted CNS relapse in CNS and systemic lymphomas

    Service-learning in the Spanish university system : A study based on deans? perception

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    La tercera misión de la universidad implica devolver a la sociedad parte de lo que de ella recibe. Este modo de entender la relación entre sociedad y universidad supone la implementación de nuevas metodologías de enseñanza-aprendizaje, en las cuales el profesorado deja de ser un mero transmisor de conocimiento, y los estudiantes adquieren un papel activo y crítico en respuesta a las necesidades sociales. El aprendizaje-servicio es una estrategia metodológica que combina la formación teórica en un ámbito de conocimiento con su aplicación a través de la prestación de un servicio a la comunidad. Esta metodología es apropiada para hacer posible la tercera misión de la institución universitaria. El objetivo de este trabajo es comprender la disposición de las facultades y escuelas universitarias de España para promover y crear oportunidades que den lugar a la implementación de proyectos de ApS en sus centros. Entre las conclusiones del estudio cabe destacar la percepción institucional, ya que el uso de esta metodología convierte a la universidad en una institución más abierta, que interactúa con la comunidad y el entorno, ampliando su campo de formación más allá del conocimiento técnico y científico, para brindar un servicio de transformación social
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