Incidence and prognostic impact of U2AF1 mutations and other gene alterations in myelodysplastic neoplasms with isolated 20q deletion.

BACKGROUND: In myelodysplastic neoplasms (MDS), the 20q deletion [del(20q)] is a recurrent chromosomal abnormality that it has a high co-occurrence with U2AF1 mutations. Nevertheless, the prognostic impact of U2AF1 in these MDS patients is uncertain and the possible clinical and/or prognostic differences between the mutation type and the mutational burden are also unknown. METHODS: Our study analyzes different molecular variables in 100 MDS patients with isolated del(20q). RESULTS & CONCLUSIONS: We describe the high incidence and negative prognostic impact of U2AF1 mutations and other alterations such as in ASXL1 gene to identify prognostic markers that would benefit patients to receive earlier treatment.

Preliminary Evidence on the Effectiveness of a Multidisciplinary Nutritional Support for Older People with Femur Fracture at an Orthogeriatric Unit in Spain.

To describe the nutritional and functional changes that occurred in older patients with a femur fracture following a dietary intervention and oral nutritional support implemented at an orthogeriatric unit in Aragon, Spain. Open-label, prospective study. Patients were consecutively recruited and arranged into three groups based on their CONtrolling NUTritional (CONUT®) score and nutritional needs. Nutritional status was assessed while in hospital, and at 45-, 100- and 180-days post-hospital discharge. One hundred and sixty-nine patients [mean age: 86 years (SD ± 5.48)] were recruited (July 2017 to January 2020). At admission, 53.3% were at risk of malnutrition; 26.6% were malnourished; 20.1% were well-nourished. Variable proportions of malnourished patients at admission were well-nourished 45-, 100-, and 180-days post-discharge. CONUT® and Barthel index correlations showed that as nutritional status enhanced, patients gained functionality. Dietary interventions and nutritional support may help restoring the nutritional and functional status of older patients with a femur fracture.

Response to azacitidine in patients with chronic myelomonocytic leukemia according to overlap myelodysplastic/myeloproliferative neoplasms criteria.

BACKGROUND: Azacitidine (AZA) is approved for the treatment of high-risk chronic myelomonocytic leukemia (CMML) of myelodysplastic (MD) subtype. Data of response rates using the specific response criteria for this disease are scarce. The aim of this study was to evaluate the response to AZA in patients diagnosed with CMML from the Spanish Registry of Myelodysplastic Syndromes (MDS) applying the overlap myelodysplastic/myeloproliferative neoplasms (MDS/MPN) response criteria. METHODS: We retrospectively studied 91 patients with CMML treated with at least one cycle of AZA from the Spanish Registry of MDS. As it was a real-world study, the response rate was evaluated between cycle 4 and 6, applying the MDS/MPN response criteria FINDINGS: The overall response rate at cycle 4-6 was 58%. Almost half of the patients achieved transfusion independence and one quarter showed clinical benefit, regardless of the CMML French-American-British (FAB) and World Health Organization (WHO) subtypes and CMML Specific Prognosis Scoring (CPSS) risk groups. Toxicity was higher in the MD-CMML subtype. INTERPRETATION: In our series, most CMML patients achieved an overall response rate with AZA according to the overlap-MDS/MPN response criteria regardless of the CMML FAB and WHO subtypes and CPSS risk groups. Thus, AZA may also be a treatment option for patients with the myeloproliferative CMML subtype and those with a lower-risk CPSS, but symptomatic.

Managing hematological cancer patients during the COVID-19 pandemic: an ESMO-EHA Interdisciplinary Expert Consensus.

BACKGROUND: The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group. METHODS: This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance. RESULTS AND CONCLUSION: The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.

Marie Curie: How to break the glass ceiling in science and in radiology.

Marie Curie was born in Warsaw in1867. She graduated first in her class in her undergraduate programs in physics and mathematics at Sorbonne University, and she was one of the first women to earn a PhD. She was the first woman to win a Nobel prize (in physics, together with her husband, Pierre Curie), and she was also the first person to win a second Nobel prize in another category (chemistry). Her life is an example of dedication to science based on altruism, personal growth, and tenacity. Being the first woman to break through so many barriers in a totally male-dominated science makes her an emblematic figure in the fight for equal opportunities and human rights. This article reviews her most important contributions to science in general and to diagnostic radiology in particular through her participation in the French military's radiological plan during the First World War.

Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification-an approach to classification of patients with t-MDS.

In the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p < 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.

Prostate MRI: practical guidelines for interpreting and reporting according to PI-RADS version 2.1. / Resonancia magnética de próstata: guía práctica de interpretación e informe según PI-RADS versión 2.1.

The increasing precision of multiparametric magnetic resonance imaging of the prostate, together with greater experience and standardization in its interpretation, has given this technique an important role in the management of prostate cancer, the most prevalent non-cutaneous cancer in men. This article reviews the concepts in PI-RADS version 2.1 for estimating the probability and zonal location of significant tumors of the prostate, using a practical approach that includes current considerations about the prerequisites for carrying out the test and recommendations for interpreting the findings. It emphasizes benign findings that can lead to confusion and the criteria for evaluating the probability of local spread, which must be included in the structured report.

Resonancia magnética de próstata: guía práctica de interpretación e informe según PI-RADS versión 2.1 / Prostate MRI: practical guidelines for interpreting and reporting according to PI-RADS version 2.1

La creciente precisión de la resonancia magnética multiparamétrica de próstata, en combinación con una mayor experiencia y estandarización en su interpretación, han conferido a esta técnica un papel actual sustancial en el manejo del cáncer de próstata, neoplasia no cutánea más prevalente en el varón. Revisamos los conceptos del sistema PI-RADS versión 2.1 para la estimación de la probabilidad y localización zonal de tumores significativos de próstata, con un enfoque práctico que incluye consideraciones actuales sobre los requisitos previos de la prueba y recomendaciones para su interpretación. Se hace hincapié en hallazgos benignos que pueden llevar a confusión y los criterios de valoración de la probabilidad de extensión local de la enfermedad, que deben también formar parte de un informe estructurado

The increasing precision of multiparametric magnetic resonance imaging of the prostate, together with greater experience and standardization in its interpretation, has given this technique an important role in the management of prostate cancer, the most prevalent non-cutaneous cancer in men. This article reviews the concepts in PI-RADS version 2.1 for estimating the probability and zonal location of significant tumors of the prostate, using a practical approach that includes current considerations about the prerequisites for carrying out the test and recommendations for interpreting the findings. It emphasizes benign findings that can lead to confusion and the criteria for evaluating the probability of local spread, which must be included in the structured report

Diseño de oligonucleótidos sonda para la detección de virus de interés en biodefensa / Oligonucleotide probes design for the detection of interesting in biodefense viruses

ANTECEDENTES: Los virus causan enfermedades en el hombre como la gripe, la rabia, la fiebre amarilla o la fiebre hemorrágica. Además, presentan características como alta variabilidad genética, virulencia y fácil transmisión y producción con infraestructuras mínimas, lo que les convierte en un problema de salud pública y de bioseguridad. Por todo ello, desarrollar sistemas de biodetección precisos y versátiles es un reto ante el cual, la tecnología de micromatrices de ADN, se presenta como un sistema de ideal. OBJETIVOS: Diseño de oligonucleótidos sonda para la detección de especies pertenecientes a nueve familias de virus de interés en biodefensa. Material y MÉTODOS: Se seleccionaron familias de virus de interés en biodefensa, se buscaron los genomas completos de los virus de referencia de cada una de ellas en las bases de datos (GenBank) y se identificaron fragmentos de 60 nucleótidos que cumplieran determinados condicionantes estructurales, evaluándose con BLASTN su capacidad de hibridación cruzada. RESULTADOS: Se obtuvieron los genomas de referencia de virus pertenecientes a nueve familias. Se diseñaron un total de 54 nucleótidos sonda, seis de ellos correspondientes al virus de la gripe A tipo H1N1 y se clasificaron las secuencias según su índice de identidad, permitiendo predecir la capacidad diagnóstica de las sondas diseñadas. CONCLUSIONES: Se han encontrado secuencias suficientes para identificar nueve familias de virus, de interés en la biodefensa, mediante la tecnología de hibridación de micromatrices de ADN

BACKGROUND: Viruses cause human diseases such as influenza, rage, yellow fever and hemorrhagic fever. In addition, they have characteristics such as high genetic variability, virulence and easy transmission and production with minimum level of infrastructure, which make them not only a public health but also a biosecurity problem. Therefore, the development of accurate and versatile biodetection systems is a challenge in which DNA microarray technology is released as an ideal system. OBJECTIVES: Probe design for virus detection by microarray technology. MATERIALS AND METHODS: Virus families with interest in biodefense were selected and the complete genomes of the reference viruses were searched in the databases (GenBank). Fragments of 60 nucleotides with some specific physical characteristics were identified. Finally, cross-hybridization capacity was also evaluated with BLASTN software. RESULTS: Viral genomes from nine families were obtained. A total of 54 probe nucleotides were designed, six of them corresponding to influenza A type H1N1 virus and the sequences were classified according to their identity index, allowing to predict the diagnostic capacity of the designed probes. CONCLUSION: It has been found enough sequences to identify nine virus families with interest in biodefense by means of the DNA microarray technology

Simulacro de Actuación de las Unidades Operativas NRBQ / Training exercise of CBN Operating Units

Antecedentes: Ante la creciente amenaza terrorista, la mayoría de los países han creado Unidades Operativas especializadas en la lucha contra armas de destrucción masiva (ADM). Uno de los puntos críticos en un incidente bioterrorista es la detección e identificación precoz de estos agentes, para lo cual es imprescindible realizar una adecuada toma de muestras, conservación, transporte y custodia de las mismas hasta el laboratorio de referencia. Objetivo: Valorar el entrenamiento de las Unidades de toma de muestras NBQ mediante la realización de simulacros. Lugar de realización: Área de Defensa Biológica del Instituto Nacional de Técnica Aeroespacial «Esteban Terradas» (INTA). Diseño: Se presenta la preparación y desarrollo de un ejercicio de entrenamiento de los Equipos de Reconocimiento (RECO) y de Muestreo e Identificación de Agentes Biológicos, Químicos y Radiológicos (SIBCRA en inglés) del Regimiento de la Defensa NBQ Valencia I (RGTO DNBQ Valencia I). Resultados: Se obtienen muestras NBQ y se evalúa la eficacia de la operativa de la toma de muestras, transmisión de los datos y coordinación general del ejercicio (AU)

Antecedents: Due to the merging terrorist threat, most of the countries have created specialized operating units to fight weapons of mass destruction. One of the critical points in a bioterrorist incident is the early detection and identification of these agents. In this sense, it is essential to perform appropriate procedures for sampling, storage, transportation and custody of them until the reference laboratory. Objective: to train the different NBC Units by means of simulacrums. Place of performance: Biological Defense Area of the National Institute of Aerospace Technique "Esteban Terradas" (INTA). Design: This paper shows the preparation and development of a training exercise of Reconnaissance teams (RECO) and Sampling and Identification of Biological, Chemical and Radiological Agents teams (SIBCRA) from NBC Defense Regiment Valencia I. Results: NBQ samples are obtained and the efficiency of the operations, sampling, data transmission and general coordination of the exercise is evaluated (AU)

Erythropoiesis-stimulating agents significantly delay the onset of a regular transfusion need in nontransfused patients with lower-risk myelodysplastic syndrome.

BACKGROUND: The EUMDS registry is an unique prospective, longitudinal observational registry enrolling newly diagnosed patients with lower-risk myelodysplastic syndrome (MDS) from 17 European countries from both university hospitals and smaller regional hospitals. OBJECTIVE: The aim of this study was to describe the usage and clinical impact of erythropoiesis-stimulating agents (ESAs) in 1696 patients enrolled between 2008 and 2014. METHODS: The effects of ESAs on outcomes were assessed using proportional hazards models weighting observations by propensity to receive ESA treatment within a subset of anaemic patients with or without a regular transfusion need. RESULTS: ESA treatment (median duration of 27.5 months, range 0-77 months) was administered to 773 patients (45.6%). Outcomes were assessed in 897 patients (484 ESA treated and 413 untreated). ESA treatment was associated with a nonsignificant survival benefit (HR 0.82, 95% CI: 0.65-1.04, P = 0.09); this benefit was larger amongst patients without prior transfusions (P = 0.07). Amongst 539 patients for whom response to ESA treatment could be defined, median time to first post-ESA treatment transfusion was 6.1 months (IQR: 4.3-15.9 months) in those transfused before ESA treatment compared to 23.3 months (IQR: 7.0-47.8 months) in patients without prior transfusions (HR 2.4, 95% CI: 1.7-3.3, P < 0.0001). Responding patients had a better prognosis in terms of a lower risk of death (HR 0.65, 95% CI: 0.45-0.893, P = 0.018), whereas there was no significant effect on the risk of progression to acute myeloid leukaemia (HR 0.71, 95% CI: 0.39-1.29, P = 0.27). CONCLUSION: Appropriate use of ESAs can significantly delay the onset of a regular transfusion need in patients with lower-risk MDS.

ABO incompatibility does not influence transfusion requirements in patients undergoing single-unit umbilical cord blood transplantation.

Hematopoietic stem cell transplantation is usually performed without considering the ABO compatibility between donor and recipient. There are few studies analyzing ABO matching impact on transfusion outcome of umbilical cord blood transplantation (UCBT) recipients. The aim of this study was to analyze factors influencing transfusion outcome, highlighting the ABO matching between donor and recipient. This study has reviewed data from 318 patients who underwent single unit UCBT at la Fe University Hospital from January 2000 to December 2014. There were no differences between RBC and platelet (PLT) requirements or RBC and PLT transfusion independence according to ABO matching between donor and recipient. RBC and PLT requirements were statistically correlated (ρ=0,841, P<0.001). A total of 170 and 188 patients achieved RBC and PLT independence, respectively, within 180 days after UCBT. Persistence of recipient isoagglutinins was detected in 6.8% of patients with major ABO incompatibility at median of 176 days (103-269) after UCBT. Autoimmune haemolytic anemia was diagnosed in 15 patients, 12 of them due to cold antibodies. In conclusion, ABO matching has not influenced transfusion requirements of patients undergoing UCBT.

4Kscore Test, Prostate Cancer Prevention Trial-Risk Calculator y European Research Screening Prostate-Risk Calculator en la predicción del cáncer de próstata de alto grado; estudio preliminar / A Preliminary Study of the Ability of the 4Kscore test, the Prostate Cancer Prevention Trial-Risk Calculator and the European Research Screening Prostate-Risk Calculator for Predicting High-Grade Prostate Canc

Introducción: Frente al sobrediagnóstico y al sobretratamiento en cáncer de próstata (CaP) se establecen estrategias terapéuticas como la vigilancia activa o la terapia focal, o métodos para precisar el diagnóstico del CaP de alto grado (CaP-AG), Gleason ≥ 7, como la resonancia magnética multiparamétrica o nuevos marcadores como el 4Kscore Test (4KsT). Es nuestro propósito testar mediante un estudio piloto la capacidad del 4KsT como identificador de CaP-AG (suma de Gleason ≥ 7) en biopsia de próstata (Bx) y compararlo con otros modelos pronósticos multivariantes disponibles, como el Prostate Cancer Prevention Trial-Risk Calculator 2.0 (PCPTRC 2.0) y elEuropean Research Screening Prostate Cancer-Risk Calculator 4 (ERSPC-RC 4). Material y métodos: Cincuenta y un pacientes sometidos a BxP según práctica clínica habitual, con un mínimo de 10 cilindros. Diagnóstico de CaP-AG consensuado por 4 uropatólogos. Comparación de las predicciones ofrecidas por los diferentes modelos mediante prueba U Mann-Whitney, áreas bajo la curva ROC (AUC) (test de DeLong), funciones de densidad de probabilidad, diagramas de caja y curvas de utilidad clínica (CUC). Resultados: Un 43% presentaron CaP y un 23,5% CaP-AG. Las medianas de probabilidad de 4KsT, PCPTRC 2.0 y ERSPC-RC 4 fueron significativamente diferentes entre los pacientes con CaP-AG y no CaP-AG (p ≤ 0,022), siendo más diferenciadas en el caso de 4KsT (mediana en CaP-AG: 51,5% [percentil 25-75: 25-80,5%], frente a 16% [P 25-75: 8-26,5%] en no CaP-AG [p = 0,002]). Todos los modelos mostraron AUC por encima de 0,7 sin diferencias significativas entre ninguno de ellos y 4KsT (p ≥ 0,20). Las funciones de densidad de probabilidad y diagramas de caja muestran una buena capacidad discriminativa, especialmente en los modelos de ERSPC-RC 4 y 4KsT. Las CUC muestran como un punto de corte del 9% de 4KsT identifica a todos los CaP-AG y permite un ahorro del 22% de biopsias, similar a lo que ocurre con los modelos de ERSPC-RC 4 y un punto de corte del 3%. Conclusiones: Los modelos predictivos evaluados ofrecen una buena capacidad de discriminación del CaP-AG en Bx. 4KsT es un buen modelo clasificatorio en su conjunto, seguido de ERSPC-RC 4 y PCPTRC 2.0. Las CUC permiten sugerir puntos de corte de decisión clínica: 9% para 4KsT y 3% en ERSPC-RC 4. Este estudio preliminar debe ser interpretado con cautela por su limitado tamaño muestral

Introduction: To prevent the overdiagnosis and overtreatment of prostate cancer (PC), therapeutic strategies have been established such as active surveillance and focal therapy, as well as methods for clarifying the diagnosis of high-grade prostate cancer (HGPC) (defined as a Gleason score ≥7), such as multiparametric magnetic resonance imaging and new markers such as the 4Kscore test (4 KsT). By means of a pilot study, we aim to test the ability of the 4 KsT to identify HGPC in prostate biopsies (Bx) and compare the test with other multivariate prognostic models such as the Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPTRC 2.0) and the European Research Screening Prostate Cancer Risk Calculator 4 (ERSPC-RC 4). Material and methods: Fifty-one patients underwent a prostate Bx according to standard clinical practice, with a minimum of 10 cores. The diagnosis of HGPC was agreed upon by 4 uropathologists. We compared the predictions from the various models by using the Mann-Whitney U test, area under the ROC curve (AUC) (DeLong test), probability density function (PDF), box plots and clinical utility curves. Results: Forty-three percent of the patients had PC, and 23.5% had HGPC. The medians of probability for the 4 KsT, PCPTRC 2.0 and ERSPC-RC 4 were significantly different between the patients with HGPC and those without HGPC (p≤.022) and were more differentiated in the case of 4 KsT (51.5% for HGPC [25-5 percentile: 25-80.5%] vs. 16% [P 25-75: 8-26.5%] for non-HGPC; p=.002). All models presented AUCs above 0.7, with no significant differences between any of them and 4 KsT (p≥.20). The PDF and box plots showed good discriminative ability, especially in the ERSPC-RC 4 and 4 KsT models. The utility curves showed how a cutoff of 9% for 4 KsT identified all cases of HGPC and provided a 22% savings in biopsies, which is similar to what occurs with the ERSPC-RC 4 models and a cutoff of 3%. Conclusions: The assessed predictive models offer good discriminative ability for HGPCs in Bx. The 4 KsT is a good classification model as a whole, followed by ERSPC-RC 4 and PCPTRC 2.0. The clinical utility curves help suggest cutoff points for clinical decisions: 9% for 4 KsT and 3% for ERSPC-RC 4. This preliminary study should be interpreted with caution due to its limited sample size

Unidad de Neurología Pediátrica del Hospital Universitario Ramón y Cajal / Pediatric Neurology Unit of the Hospital Universitario Ramón y Cajal

La Unidad de Neurología Pediátrica, integrada en el Servicio de Pediatría del Hospital Universitario Ramón y Cajal, con acreditación docente por la Sociedad Española de Neurología Pediátrica, ha desarrollado su actividad trabajando en diferentes patologías neurológicas y adaptándose a las necesidades demandadas actualmente por la sociedad, como son los problemas del neurodesarrollo, la epilepsia o las enfermedades nenromusculares. En este trabajo se resume la labor desarrollada a nivel asistencial, docente e investigador, en los últimos 25 años (AU)

The Pediatric Neurology Unit, integrated in the Pediatric Department of the University Hospital Ramón y Cajal, certified in teaching by the Spanish Society of Pediatric Neurology, has been working in several neurological pathologies taking into account the most demanding needs of the society, such us neurodevelopmental problems, epilepsy or neuromuscular diseases. This Work summarizcs the actuation carried out in medical activity, teaching and research performance over de last 25 years (AU)