Biomarcadores y complicaciones relacionadas con el trasplante haploidéntico de progenitores hematopoyéticos con ciclofosfamida postrasplante

El trasplante alogénico de progenitores hematopoyéticos (alo-TPH) supone el tratamiento curativo para diferentes patologías hematológicas. No todos los pacientes disponen de un donante HLA idéntico, por lo que el uso del alo-TPH haploidéntico con ciclofosfamida postrasplante (Cy-post) ha supuesto una opción alternativa óptima que permite que casi todos los pacientes dispongan de donante. En este contexto, el conocimiento de las peculiaridades de esta plataforma de trasplante, así como la detección de diferentes biomarcadores que permitan predecir la aparición de complicaciones postrasplante son esenciales para optimizar y personalizar el tratamiento de estos pacientes. El síndrome de liberación de citocinas (SLC) es una complicación casi exclusiva del alo-TPH haploidéntico secundario a la interaccionan los linfocitos T alorreactivos del donante con los tejidos del receptor. Además, en los últimos años se han descrito diferentes biomarcadores que se han relacionado con la aparición de enfermedad injerto contra receptor (EICR), resistencia al tratamiento esteroideo y mortalidad tóxica relacionada con el trasplante (MRT). Tres de los biomarcadores más estudiados en otras plataformas de trasplante son la elafina, el ST2 y el REG3α. En esta Tesis Doctoral hemos analizado el SLC y los biomarcadores descritos previamentes en la cohorte más larga de trasplantes haploidénticos con Cy-post descritas hasta el momento. Se ha realizado la misma mediante la modalidad de compendio de artículos, que incluye los siguientes trabajos: Artículo 1: Solán L, Landete E, Bailén R, Dorado N, Oarbeascoa G, Anguita J, Díez-Martín JL, Kwon M. Cytokine release syndrome after allogeneic stem cell transplantation with posttransplant cyclophosphamide. Hematol Oncol. 2020 Oct;38(4):597-603. doi: 10.1002/hon.2772. Artículo 2: Solán L, Kwon M, Carbonell D, Dorado N, Balsalobre P, Serrano D, Chicano-Lavilla M, Anguita J, Gayoso J, Díez-Martín JL, Martínez-Laperche C, Buño I. ST2 and REG3α as Predictive Biomarkers After Haploidentical Stem Cell Transplantation Using Posttransplantation High-Dose Cyclophosphamide. Front Immunol. 2019 Oct 9;10:2338. doi: 10.3389/fimmu.2019.02338. Artículo 3: Solán L, Carbonell D, Muñiz P, Dorado N, Landete E, Chicano-Lavilla M, Anguita J, Gayoso J, Kwon M, Díez-Martín JL, Martínez-Laperche C, Buño I. Elafin as a Predictive Biomarker of Acute Skin Graft-Versus-Host Disease After Haploidentical Stem Cell Transplantation Using Post-Transplant High-Dose Cyclophosphamide. Front Immunol. 2021 Feb 19;12:516078. doi: 10.3389/fimmu.2021.516078

Propuesta didáctica para el análisis de las emociones a partir de danza-creación y la audición musical en la asignatura de Educación Física en Educación Primaria.

En este trabajo se realiza una propuesta en el ámbito de la Educación Física, en Educación Primaria, a partir de actividades originales creadas en función de la improvisación y la creación en la danza, con apoyo de la audición musical, para los alumnos de 3º ciclo.Para el diseño de las actividades me he basado en la metodología propia de la danza creación, partiendo del libro de Inmaculada, Tena Expresión corporal desde la danza creación, además de otros estudios que nombro a lo largo del trabajo.Las actividades diseñadas responden al siguiente esquema: definición-inductor; descripción de la actividad; aspectos curriculares; audición musical vinculada a la actividad; y lo que se espera que los alumnos realicen en ellas. Estas se centran en desarrollar las diferentes emociones seleccionadas con los estudiantes con los que se realiza esta propuesta didáctica. Las emociones seleccionadas son algunas de las denominadas, emociones básicas: miedo; enfado; tristeza; alegría; sorpresa; y paz.Las conclusiones a las que he llegado es que la danza-creación ofrece múltiples posibilidades didácticas y creativas a través de actividades interdisciplinares, y que trabajo puede resultar de utilidad para mi desarrollo docente en el ámbito de la educación física, realizando pequeñas modificaciones en el mismo, para poder utilizarlo en otros ciclos educativos.<br /

EDUCORE project: a clinical trial, randomised by clusters, to assess the effect of a visual learning method on blood pressure control in the primary healthcare setting

<p>Abstract</p> <p>Background</p> <p>High blood pressure (HBP) is a major risk factor for cardiovascular disease (CVD). European hypertension and cardiology societies as well as expert committees on CVD prevention recommend stratifying cardiovascular risk using the SCORE method, the modification of lifestyles to prevent CVD, and achieving good control over risk factors. The EDUCORE (Education and Coronary Risk Evaluation) project aims to determine whether the use of a cardiovascular risk visual learning method - the EDUCORE method - is more effective than normal clinical practice in improving the control of blood pressure within one year in patients with poorly controlled hypertension but no background of CVD;</p> <p>Methods/Design</p> <p>This work describes a protocol for a clinical trial, randomised by clusters and involving 22 primary healthcare clinics, to test the effectiveness of the EDUCORE method. The number of patients required was 736, all between 40 and 65 years of age (n = 368 in the EDUCORE and control groups), all of whom had been diagnosed with HBP at least one year ago, and all of whom had poorly controlled hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic ≥ 90 mmHg). All personnel taking part were explained the trial and trained in its methodology. The EDUCORE method contemplates the visualisation of low risk SCORE scores using images embodying different stages of a high risk action, plus the receipt of a pamphlet explaining how to better maintain cardiac health. The main outcome variable was the control of blood pressure; secondary outcome variables included the SCORE score, therapeutic compliance, quality of life, and total cholesterol level. All outcome variables were measured at the beginning of the experimental period and again at 6 and 12 months. Information on sex, age, educational level, physical activity, body mass index, consumption of medications, change of treatment and blood analysis results was also recorded;</p> <p>Discussion</p> <p>The EDUCORE method could provide a simple, inexpensive means of improving blood pressure control, and perhaps other health problems, in the primary healthcare setting;</p> <p>Trial registration</p> <p>The trial was registered with ClinicalTrials.gov, number NCT01155973 [<url>http://ClinicalTrials.gov</url>].</p

Current situation of shared decision making in osteoporosis: A comprehensive literature review of patient decision aids and decision drivers

Abstract Background and Aims Osteoporosis is a systemic skeletal disease characterized by low bone mass and microstructural deterioration of bone tissues, resulting in bone fragility and increased fracture risk. It is the most common bone‐related disease in the population. However, the proportion of patients who start treatment but discontinue it during the first year is very high (around 50%). Endeavors are made to promote patient participation in treatment by implementing patient decision aids (PDA), whose function is to help the patient make disease‐related decisions. We aim to summarize the characteristics of the currently available PDA for osteoporosis, as well as deciding factors. Methods Comprehensive review of the literature. Results Currently, eleven PDAs can be found for osteoporosis. These PDA have different characteristics or options such as information about treatments tailored to patient needs, graphic information of the results (to facilitate understanding), personal histories (learning), tests to check the knowledge acquired, provision of evidence, clinical practice guidelines or a final summary to share with their doctor. Only five of these PDAs can be considered complete since they provide relevant disease information and therapeutic options to the patient, promote patient's reflection and foment patient‐physician discussion. Conclusions This study provides an update on the current state of decision making on osteoporosis and available PDA, which can help engage the patient through shared decision‐making by considering, among other things, patient preferences. Physicians should consider PDA, as it may promote adherence and effectiveness of treatment

Estudio del patrón de expresión de microRNAs en el hueso osteoporótico

Objetivos: Identificar microRNAs (miRNAs) diferencialmente expresados en muestras óseas con fractura osteoporótica respecto a huesos sanos. Material y métodos: Se extrajo RNA total a partir de hueso trabecular fresco del cuello femoral de mujeres sometidas a reemplazo de cadera, ya sea debido a fractura osteoporótica (n=6) o por artrosis en ausencia de osteoporosis (según la DMO) (n=6). Las muestras se hibridaron en un array de miRNAs y se realizaron diagramas de PCA y de mapa de calor. Para la comparación de los niveles de expresión, se fijó como significativo un umbral de cambio de >1,5 veces y un valor p<0,05 en la t de Student (corregido para múltiples pruebas). Resultados: Tanto los análisis de PCA como el mapa de calor mostraron una agrupación de las muestras según si eran de fractura o no. Se detectaron 790 miRNAs en las muestras de hueso, 82 de los cuales estaban alterados en las muestras osteoporóticas. Tras la validación en otro panel de 6 muestras osteoporóticas y 6 no osteoporóticas mediante PCR a tiempo real de los miRNAs más significativos, y para los que existía un ensayo disponible, se confirmaron los miRNAs miR-320a y miR-22-3p. Estos dos miRNAs se detectaron en cultivos de osteoblastos primarios, aunque no mantenían el mismo patrón de expresión que en las muestras de hueso total. Conclusiones: Hemos demostrado que existen diferencias en la expresión de miRNAs en muestras con fractura osteoporótica, lo que abre nuevas perspectivas para la investigación y diseño de nuevas terapias.Objectives: To identify microRNAs (miRNAs) differentially expressed in bone samples with osteoporotic fracture compared with healthy bones. Methods: Total RNA was extracted from fresh trabecular bone of the femoral neck of women undergoing hip replacement surgery, either because to osteoporotic fracture (n=6) or in the absence of osteoarthritis osteoporosis (based on BMD) (n=6). The samples were hybridized on an array of miRNAs and PCA diagrams and heat map were made. To compare expression levels, >1.5 times and a value p<0.05 Student's T test (corrected for multiple testing) was set as a threshold of significant change. Results: Both PCA analysis and the heat map showed a samples grouping whether there was fracture or not. 790 were detected miRNAs in bone samples, 82 of which were altered in the osteoporotic samples. After validation in another panel of 6 samples 6 osteoporotic and non-osteoporotic by PCR real time of the most significant miRNAs, and for which there was a test available, the miRNAs, miR-320a and miR22-3p were confirmed. These two miRNAs were detected in cultures of primary osteoblasts, although they did not maintain the same pattern of expression in total bone samples. Conclusions: We have shown that there are differences in the expression of miRNAs in samples with osteoporotic fracture. This opens prospects for research and design of new therapies.Este trabajo ha sido financiado por la Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF; RD12/0043/0022), y la ayuda FIS PI13/00116 (Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación) y los fondos FEDE

ZBTB16-RARα-Positive Atypical Promyelocytic Leukemia: A Case Report

Background: The majority of patients with acute promyelocytic leukemia (APL) manifest a specific chromosomal translocation t(15;17)(q22;q21), characterized by the fusion of RARA and PML genes. However, a proportion of APL cases are due to variant translocations, being t(11;17) (q23;q21) the most common amongst them. With the major exception of ZBTB16-RARA t(11;17) APL, these variant APL cases present similar morphological features as classic APL and are characterized by a lack of differentiation response to retinoids. Case summary: We describe the case of variant APL with the ZBTB16-RARA fusion gene, showing a distinct morphology of classical APL, characterized by crystalline intracytoplasmic inclusions in both peripheral blood (PB) and bone marrow (BM) patients’ blasts. Our patient was treated with two courses of intensive chemotherapy, initiating maintenance treatment with all-trans retinoic acid (ATRA) on day twenty-eight of the second course. Our patient achieved complete remission (CR) once the intensive chemotherapy was combined with ATRA.Conclusions: This is the second case described of APL with t(11;17) that showed crystalline intracytoplasmic inclusions. The finding of these morphological features may suggest the presence of a variant translocation with RARA, being that both cases described are related to the presence of t(11;17). Despite induction treatment with intensive chemotherapy that included a seven-day continuous treatment with cytarabine (200 mg/m2), plus daily idarubicin (12 mg/m2) during the first three days, our patient did not achieve complete remission (CR) until scheduled 3 + 7 regimen combined with ATRA treatment was established. This observation suggests that ATRA may be partially effective in some ZBTB16-RARA APLs

Flow Cytometry and Molecular Techniques Could Complement Morphological Detection of Leukemic Infiltration in Ascitic Fluids: A Case Report

Extramedullary involvement of acute myeloid leukemia (AML) is infrequent, and ascitic infiltration is even more unusual. We present a case of a 48-year-old woman diagnosed with NPM1-mutated AML that debuted with ascites, for which morphological studies of the ascitic fluid did not detect leukemic infiltration, maybe due to technical problems in the sample preparation. Multiparameter flow cytometry (MFC) detected a blast population compatible with AML, and allele-specific PCR detected NPM1-mutated transcripts. Body fluid infiltrations are an infrequent initial manifestation or sign of progression in AML. As far as we know, this is the first reported case of an NPM1-mutated AML that debuted with ascites, and also the first description of the utilization of molecular techniques to detect the leukemic origin of the ascites. This case highlights that, given that allele-specific PCR and MFC increase the sensitivity of morphological studies, these techniques should be routinely applied in the study of any kind of effusion detected in an AML patient