Next-generation sequencing in bone marrow failure syndromes and isolated cytopenias: experience of the spanish network on bone marrow failure sundromes

© 2021 the Author(s).Inherited bone marrow failure syndromes (IBMFSs) are a group of congenital rare diseases characterized by bone marrow failure, congenital anomalies, high genetic heterogeneity, and predisposition to cancer. Appropriate treatment and cancer surveillance ideally depend on the identification of the mutated gene. A next-generation sequencing (NGS) panel of genes could be 1 initial genetic screening test to be carried out in a comprehensive study of IBMFSs, allowing molecular detection in affected patients. We designed 2 NGS panels of IBMFS genes: version 1 included 129 genes and version 2 involved 145 genes. The cohort included a total of 204 patients with suspected IBMFSs without molecular diagnosis. Capture-based targeted sequencing covered > 99% of the target regions of 145 genes, with more than 20 independent reads. No differences were seen between the 2 versions of the panel. The NGS tool allowed a total of 91 patients to be diagnosed, with an overall molecular diagnostic rate of 44%. Among the 167 patients with classified IBMFSs, 81 patients (48%) were diagnosed. Unclassified IBMFSs involved a total of 37 patients, of whom 9 patients (24%) were diagnosed. The preexisting diagnosis of 6 clinically classified patients (6%) was amended, implying a change of therapy for some of them. Our NGS IBMFS gene panel assay is a useful tool in the molecular diagnosis of IBMFSs and a reasonable option as the first tier genetic test in these disorders

Next-generation Sequencing in Bone Marrow Failure Syndromes and Isolated Cytopenias : Experience of the Spanish Network on Bone Marrow Failure Syndromes

Inherited bone marrow failure syndromes (IBMFSs) are a group of congenital rare diseases characterized by bone marrow failure, congenital anomalies, high genetic heterogeneity, and predisposition to cancer. Appropriate treatment and cancer surveillance ideally depend on the identification of the mutated gene. A next-generation sequencing (NGS) panel of genes could be 1 initial genetic screening test to be carried out in a comprehensive study of IBMFSs, allowing molecular detection in affected patients. We designed 2 NGS panels of IBMFS genes: version 1 included 129 genes and version 2 involved 145 genes. The cohort included a total of 204 patients with suspected IBMFSs without molecular diagnosis. Capture-based targeted sequencing covered > 99% of the target regions of 145 genes, with more than 20 independent reads. No differences were seen between the 2 versions of the panel. The NGS tool allowed a total of 91 patients to be diagnosed, with an overall molecular diagnostic rate of 44%. Among the 167 patients with classified IBMFSs, 81 patients (48%) were diagnosed. Unclassified IBMFSs involved a total of 37 patients, of whom 9 patients (24%) were diagnosed. The preexisting diagnosis of 6 clinically classified patients (6%) was amended, implying a change of therapy for some of them. Our NGS IBMFS gene panel assay is a useful tool in the molecular diagnosis of IBMFSs and a reasonable option as the first tier genetic test in these disorders

Red de coordinación de la implantación del primer curso del grado en Tecnologías de la Información para la Salud

En este trabajo se ha intentado recoger las acciones que se han llevado a cabo en la coordinación de la implantación del primer curso del nuevo grado de Tecnologías de la Información para la Salud, grado con un marcado carácter multidisciplinar que condiciona la enseñanza de los contenidos. Entre estas acciones se han revisado las guías de cada asignatura participante en la red y se han realizado reuniones de seguimiento de la implantación de las asignaturas para detectar fortalezas y debilidades en el proceso docente. También se ha contado con la opinión de alumnos bien a través de encuestas bien directamente en conversaciones con los representantes del alumnado. Pretendemos que las conclusiones obtenidas tras el análisis de resultados se puedan aplicar el curso que viene y, de esta forma, avanzar en la implantación de la titulación con calidad y, especialmente, con el objetivo de formar egresados que satisfagan las necesidades de la sociedad

La construcción social del problema conflicto trabajo-familia: análisis político, mediático y de la realidad

El presente documento comprende el Proyecto de Investigación que responde a la propuesta financiada por la convocatoria pública de proyectos de I+D del Ministerio de Trabajo y Asuntos Sociales (Instituto de la Mujer) de 2007- 2008 con 19.084,55 euros, “La construcción social del problema conflicto trabajo-familia. Análisis político, mediático y de la realidad”. Este proyecto, sin embargo, se enmarca en una línea de investigación más amplia que abarca una serie de trabajos realizados y a realizar en los próximos años, en los que se plantean preguntas muy concretas e hipótesis más abstractas en torno a un tema nuclear en la sociedad de la información, el conflicto familia-trabajo/trabajo-familia, que está minando la calidad de vida de algunos ciudadanos y que es causa de algunas desigualdades importantes en función de género.Instituto de la Muje

Do handwritten words magnify lexical effects in visual word recognition?

Published online: 27 Oct 2015An examination of how the word recognition system is able to process handwritten words is fundamental to formulate a comprehensive model of visual word recognition. Previous research has revealed that the magnitude of lexical effects (e.g., the word-frequency effect) is greater with handwritten words than with printed words. In the present lexical decision experiments, we examined whether the quality of handwritten words moderates the recruitment of top-down feedback, as reflected in word-frequency effects. Results showed a reading cost for difficult-to-read and easy-to-read handwritten words relative to printed words. But the critical finding was that difficult-to-read handwritten words, but not easy-to-read handwritten words, showed a greater word-frequency effect than printed words. Therefore, the inherent physical variability of handwritten words does not necessarily boost the magnitude of lexical effects.This research has been partially supported by the Spanish Government [grant number PSI2014–53444-P], [grant number PSI2012-31448] and by the European Research Council [grant number ERC-2011-ADG-295362]

Evaluating the Validity and Reliability of the Beliefs About Medicines Questionnaire in Low-Income, Spanish-Speaking Patients With Diabetes in the United States

Purpose The purpose of this study was to examine the reliability and validity of a Spanish version of the Beliefs about Medicines Questionnaire (BMQ) as a measure to evaluate beliefs about medications and to differentiate adherent from nonadherent patients among low-income Latino patients with diabetes in the United States. Methods Seventy-three patients were administered the BMQ and surveyed for evidence of medication nonadherence. Internal consistency of the BMQ was assessed by Cronbach's alpha along with performing a confirmatory factor analysis. Criterion validity was assessed by comparing mean scores on 3 subscales of the BMQ (General Overuse, General Harm, and Specific Necessity-Concerns difference score) between adherent patients and patients reporting nonadherence for 3 different reasons (unintentional nonadherence, cost-related nonadherence, and nonadherence due to reasons other than cost) using independent samples t tests. Results The BMQ is a reliable instrument to examine beliefs about medications in this Spanish-speaking population. Construct validity testing shows nearly identical factor loading as the original construct map. General Overuse scores were significantly more negative for patients reporting each reason for nonadherence compared with their adherent counterparts. Necessity-Concerns difference scores were significantly more negative for patients reporting nonadherence for reasons other than cost compared with those who did not report this reason for nonadherence. Conclusion The Spanish version of the BMQ is appropriate to assess beliefs about medications in Latino patients with type 2 diabetes in the United States and may help identify patients who become nonadherent to medications for reasons other than out-of-pocket costs

Changes in the epidemiology of invasive fungal disease in a Pediatric Hematology and Oncology Unit: the relevance of breakthrough infections

Abstract Background Invasive fungal disease (IFD) is a significant cause of morbimortality in children under chemotherapy or hematopoietic stem cell transplant (HSCT). The purpose of this study is to describe the changes in the IFD epidemiology that occurred in a Pediatric Hematology-Oncology Unit (PHOU) with an increasing activity over time. Methods Retrospective revision of the medical records of children (from 6 months to 18 years old) diagnosed with IFD in the PHOU of a tertiary hospital in Madrid (Spain), between 2006 and 2019. IFD definitions were performed according to the EORTC revised criteria. Prevalence, epidemiological, diagnostic and therapeutic parameters were described. Comparative analyses were conducted using Chi-square, Mann-Whitney and Kruskal-Wallis tests, according to three time periods, the type of infection (yeast vs mold infections) and the outcome. Results Twenty-eight episodes of IFD occurred in 27 out of 471 children at risk (50% males; median age of 9.8 years old, [IQR 4.9-15.1]), resulting in an overall global prevalence of 5.9%. Five episodes of candidemia and 23 bronchopulmonary mold diseases were registered. Six (21.4%), eight (28.6%) and 14 (50%) episodes met criteria for proven, probable and possible IFD, respectively. 71.4% of patients had a breakthrough infection, 28.6% required intensive care and 21.4% died during treatment. Over time, bronchopulmonary mold infections and breakthrough IFD increased (p=0.002 and p=0.012, respectively), occurring in children with more IFD host factors (p=0.028) and high-risk underlying disorders (p=0.012). A 64% increase in the number of admissions in the PHOU (p<0.001) and a 277% increase in the number of HSCT (p=0.008) were not followed by rising rates of mortality or IFD/1000 admissions (p=0.674). Conclusions In this study, we found that yeast infections decreased, while mold infections increased over time, being most of them breakthrough infections. These changes are probably related to the rising activity in our PHOU and an increase in the complexity of the baseline pathologies of patients. Fortunately, these facts were not followed by an increase in IFD prevalence or mortality rates

Haploidentical transplantation in high-risk pediatric leukemia: A retrospective comparative analysis on behalf of the Spanish working Group for bone marrow transplantation in children (GETMON) and the Spanish Grupo for hematopoietic transplantation (GETH).

A total of 192 pediatric patients, median age 8.6 years, with high-risk hematological malignancies, underwent haploidentical stem cell transplantation (haplo-HSCT) using post-transplantation cyclophosphamide (PT-Cy), or ex vivo T cell-depleted (TCD) graft platforms, from January 1999 to December 2016 in 10 centers in Spain. Some 41 patients received an unmanipulated graft followed by PT-Cy for graft-vs-host disease (GvHD) prophylaxis. A total of 151 patients were transplanted with CD3-depleted peripheral blood stem cells (PBSCs) by either CD34+ selection, CD3+ CD19+ depletion, TCRαβ+ CD19+ depletion or CD45RA+ depletion, added to CD34+ selection for GvHD prophylaxis. The PBSCs were the only source in patients following ex vivo TCD haplo-HSCT; bone marrow was the source in 9 of 41 patients following PT-CY haplo-HSCT. Engraftment was achieved in 91.3% of cases. A donor younger than 30 years, and the development of chronic GvHD were positive factors influencing survival, whereas positive minimal residual disease (MRD) before transplant and lymphoid disease were negative factors. The probability of relapse increased with lymphoid malignancies, a donor killer-cell immunoglobulin-like receptor (KIR) haplotype A and positive MRD pretransplant. No difference was found in overall survival, disease-free survival or relapse incidence between the two platforms. Relapse is still of concern in both platforms, and it should be the focus of future efforts. In conclusion, both platforms for haplo-HSCT were effective and could be utilized depending on the comfort level of the center

Haploidentical transplantation in high‐risk pediatric leukemia: A retrospective comparative analysis on behalf of the Spanish working Group for bone marrow transplantation in children (GETMON) and the Spanish Grupo for hematopoietic transplantation (GETH)

A total of 192 pediatric patients, median age 8.6 years, with high‐risk hematological malignancies, underwent haploidentical stem cell transplantation (haplo‐HSCT) using post‐transplantation cyclophosphamide (PT‐Cy), or ex vivo T cell‐depleted (TCD) graft platforms, from January 1999 to December 2016 in 10 centers in Spain. Some 41 patients received an unmanipulated graft followed by PT‐Cy for graft‐vs‐host disease (GvHD) prophylaxis. A total of 151 patients were transplanted with CD3‐depleted peripheral blood stem cells (PBSCs) by either CD34+ selection, CD3+CD19+ depletion, TCRαβ+CD19+ depletion or CD45RA+ depletion, added to CD34+ selection for GvHD prophylaxis. The PBSCs were the only source in patients following ex vivo TCD haplo‐HSCT; bone marrow was the source in 9 of 41 patients following PT‐CY haplo‐HSCT. Engraftment was achieved in 91.3% of cases. A donor younger than 30 years, and the development of chronic GvHD were positive factors influencing survival, whereas positive minimal residual disease (MRD) before transplant and lymphoid disease were negative factors. The probability of relapse increased with lymphoid malignancies, a donor killer‐cell immunoglobulin‐like receptor (KIR) haplotype A and positive MRD pretransplant. No difference was found in overall survival, disease‐free survival or relapse incidence between the two platforms. Relapse is still of concern in both platforms, and it should be the focus of future efforts. In conclusion, both platforms for haplo‐HSCT were effective and could be utilized depending on the comfort level of the center.Research funding: National Health Service of Spain, Instituto de Salud Carlos III (ISCIII), FONDOS FEDER grant (FIS). Grant Number: PI18/01301, the CRIS Cancer Foundation, the Association Pablo Ugarte