Pixantrone beyond monotherapy: a review

Outcomes for patients with non-Hodgkin’s lymphoma (NHL) that proves refractory to treatment remain poor. Treatment of such patients is individualized and can include enrolment in a clinical trial of novel agents or use of one of a wide array of drug regimens. Initial treatment with anthracyclines such as doxorubicin limits options at later stages of treatment because of anthracycline-related cumulative cardiotoxicity. The aza-anthracenedione pixantrone was developed to reduce the likelihood of cardiotoxicity without compromising efficacy and is currently conditionally approved for use as monotherapy in patients with multiply-relapsed or refractory aggressive B cell NHL. The use of pixantrone in combination therapy, often to replace doxorubicin or mitoxantrone, has or is currently being investigated in numerous studies in patients with aggressive or indolent NHL and is the focus of this review. These include the R-CPOP regimen (rituximab, cyclophosphamide, pixantrone, vincristine, prednisone) for aggressive NHL in the first-line setting, including a study in elderly patients with limited cardiac function, and for patients with relapsed NHL with prior anthracycline exposure; the PSHAP regimen (pixantrone, cytarabine, prednisone, cisplatin), also in the latter setting; the PREBen/PEBen regimen (pixantrone, bendamustine and etoposide with or without rituximab) as salvage therapy; and pixantrone in combination with fludarabine, dexamethasone, and rituximab (FPD-R) for relapsed indolent NHL.Peer reviewe

Feasibility and outcomes after dose reduction of immunochemotherapy in young adults with Burkitt lymphoma and leukemia: results of the BURKIMAB14 trial

High dose -intensive or infusional intermediate -dose immunochemotherapy is highly effective treatment for Burkitt lymphoma irrespective of human immunodeficiency virus (HIV) infection. However, toxicities of these regimens are relevant, especially in older adults and elderly patients. The prospective multicenter BURKIMAB14 trial included four to six blocks of immunochemotherapy according to stage (localized: 1 and 2 non -bulky; advanced: 2 bulky, 3, 4) and age, with dose reduction in patients >55 years old. Dose -intensity of chemotherapy was reduced in patients 55 years old had a significantly higher treatment -related mortality despite dose reduction of chemotherapy. With a median follow-up of 3.61 years the 4 -year OS probability was 73% (range, 63-81%). Age (55 years) and stage (localized vs. advanced) had prognostic significance. No significant differences in OS were observed in HIV -positive versus HIV -negative patients. The results of BURKIMAB14 are similar to those of other dose -intensive immunochemotherapy trials. Age >55 years and advanced stage, but not HIV infection, were associated with poor survival. Dose reduction of chemotherapy in young adults in CMR is safe and does not impact outcomes (clinicaltrials gov. Identifier: NCT05049473)

Análisis de datos enfocado al riesgo

In the business world, exist a great concern for the control of the activities and the management of the risks that the daily operation can suppose. If this global context is added to the current situation, there is a need to have its operations controlled, risks, avoiding fraud, and adapting it to some necessary regulations. The current technological market allows us to manage a large amount of data and facilitate its subsequent analysis to improve decision making visually and faster than in the traditional way as it has been doing the last years. This project is a contribution to this clear trend, through the analysis of risk management. This project has been proposed with a double objective: On the one hand, a more theoretical analysis is proposed in the area of risk management, where we will analyze all the elements that the element that intervene in the entire management process at the executive level. On the other hand, a proof of concept is proposed starting from the concept of segregation of duties (one of the most committed controls when analyzing internal control) in order to perform an analysis of a specific case. An analysis of the complete purchasing cycle in a customer's SAP system will be performed, based on the extraction of their data and by using a business intelligence tool selected, based on a previous benchmarking where all the possibilities are valued

Análisis de la intensidad de juego durante los partidos de play-off en jugadores de baloncesto en silla de ruedas

The main objective of the study was to analyze the game intensity in wheelchair basketball players (WB) during play-off matches. This study involved nine WB players of Spanish first division league (34.8 ± 7.8 years). Six play-off matches were analyzed and participants were divided into three groups according to the minutes they had played: players who had played between 30-40 minutes (WB30-40), players who had played between 20-30 minutes (WB20-30) and players who had played between 1 second and 20 minutes (WB1-19). For every game the heart rate (HR) was monitored by telemetry, and in addition, the tympanic temperature and blood lactate concentration samples were obtained before and immediately after each match. Significant differences (P<0.05) were observed in all intensity zones between WB30-40 and WB1-19 groups. The WB30-40 players spent 36.4% of the total time over 85% of maximum HR, while WB20-30 and WB1-19 players only spent 16.1 and 9.2% of the total time. Moreover, in all groups both tympanic temperature (from 1.5 to 2.0%, P<0.05) and lactate concentration (81.1 to 125.0%, P <0.05) increased significantly. The game intensity monitored by HR is different for WB players according to the minutes they had played (WB30-40, WB20-30 and WB1-19). The results of our study showed that the WB30- 40 group obtained higher percentage of time spent at high intensity (> 85% of maximum HR) than other groups, with a significant increase in body temperature and blood lactate concentration. Coaches and physical trainers should be aware of these physiological differences when planning the season and post-match sessions.El principal objetivo del estudio fue analizar la intensidad de juego en jugadores de baloncesto en silla de ruedas (BSR) durante los partidos de play-off. En este estudio participaron nueve jugadores masculinos de BSR de primera división (34,8 ± 7,8 años). En total se analizaron seis partidos y los participantes fueron divididos en tres grupos según los minutos jugados: jugadores que jugaron 30-40 minutos (BSR30-40), jugadores que jugaron 20- 29 minutos (BSR20-30) y los que jugaron entre 1 segundo y 19 minutos (BSR1-19). Durante todos los partidos se monitorizó la frecuencia cardíaca (FC), y además, se obtuvo la temperatura timpánica y la concentración de lactato sanguíneo antes e inmediatamente después de cada partido. Se encontraron diferencias significativas (P<0,05) en todas las zonas de intensidad entre el grupo BSR30-40 y BSR1-19. Los jugadores BSR30-40 pasaron un 36,4% del tiempo total por encima del 85% de la FCmáx, mientras que los jugadores BSR20-30 y BSR1-19 solo pasaron un 16,1 y un 9,2% del tiempo total. En todos los grupos tanto la temperatura timpánica (1,5-2,0%, P<0,05) como la concentración de lactato (81,1-125,0%, P<0,05) aumentó significativamente. Los resultados obtenidos en nuestro estudio exponen que los jugadores del grupo BSR30-40 pasaron mayor porcentaje de tiempo a alta intensidad (>85% de la FCmáx), con un aumento significativo de la temperatura y la concentración de lactato sanguíneo. Los entrenadores y preparadores físicos deberían tener en cuenta estas diferencias fisiológicas en función de los minutos jugados a la hora de planificar la temporada y los descansos post partido

La "résolution de problèmes comme recherche": Une contribution au paradigme constructiviste de l'apprentissage des sciences

La proposition que nous présentons dans cet article est une contribution pour orienter l'enseignement vers des modèles de résolution de problèmes qui soient en cohérence avec la créativité du travail scientifique. Il s'agit de faire résoudre des problèmes ouverts intéressants pour l’élève et favorisant la pensée productive, non seulement dans les processus de résolution des problèmes mais en les insérant dans des processus d’apprentissage constructiviste des sciences. Ce travail s’appuie sur les études et les résultats obtenus dans l’application du “Modèle de Résolution de Problèmes comme Recherche" et dans la conception et la réalisation de travaux pratiques, principalement en physique et chimie. Nous faisons une proposition didactique qui consiste à considérer ces activités de l’enseignement des sciences, initialement isolées, comme des composantes d’un même processus d’enseignement s’appuyant sur le traitement de situations problématiques ouvertes avec une orientation similaire à celle qui constitue réellement un travail de recherche.Contribución de la resolución de problemas como investigación al paradigma constructivista de aprendizaje de las ciencias C. J. Furió, J. Iturbe, M. Reyes, V. José La propuesta que se hace en este artículo trata de contribuir a orientar la enseñanza hacia modelos de resolución de problemas coherentes con la creatividad del trabajo científica, tratando de solucionar situaciones problemáticas abiertas interesantes para el alumno y favoreciendo el pensamiento productivo, no sólo en el proceso de resolución de dichos problemas, sino insertándolo en los procesos de aprendizaje constructivista de la ciencias. Apoyándose en los trabajos y en los resultados que están obteniédose en la aplicación del Modelo de resolución de Problemas como Investigación y en el diseño y realización de trabajos prácticos, en Física y Química fundamentalmente inconexas, como variantes de un mismo proceso de enseñanza de la Ciencias, inicialmente inconexas, como variantes de un mismo proceso de enseñanza en forma de tratamiento de situaciones problemáticas abiertas con una orientación similar a lo que realmente constituye el trabajo de investigación.Furio Mas Carlos José, Iturbe Barrenetxea Jacinto, Vicente Reyes Martin José, Carballo Cristina, Larcher Claudine. La "résolution de problèmes comme recherche": Une contribution au paradigme constructiviste de l'apprentissage des sciences. In: Aster, recherches en didactique des sciences expérimentales, n°19, 1994. La didactique des sciences en Europe. pp. 87-102

Targeted UPLC-MS Metabolic Analysis of Human Faeces Reveals Novel Low-Invasive Candidate Markers for Colorectal Cancer

Low invasive tests with high sensitivity for colorectal cancer and advanced precancerous lesions will increase adherence rates, and improve clinical outcomes. We have performed an ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC-(TOF) MS)-based metabolomics study to identify faecal biomarkers for the detection of patients with advanced neoplasia. A cohort of 80 patients with advanced neoplasia (40 advanced adenomas and 40 colorectal cancers) and 49 healthy subjects were analysed in the study. We evaluated the faecal levels of 105 metabolites including glycerolipids, glycerophospholipids, sterol lipids and sphingolipids. We found 18 metabolites that were significantly altered in patients with advanced neoplasia compared to controls. The combinations of seven metabolites including ChoE(18:1), ChoE(18:2), ChoE(20:4), PE(16:0/18:1), SM(d18:1/23:0), SM(42:3) and TG(54:1), discriminated advanced neoplasia patients from healthy controls. These seven metabolites were employed to construct a predictive model that provides an area under the curve (AUC) median value of 0.821. The inclusion of faecal haemoglobin concentration in the metabolomics signature improved the predictive model to an AUC of 0.885. In silico gene expression analysis of tumour tissue supports our results and puts the differentially expressed metabolites into biological context, showing that glycerolipids and sphingolipids metabolism and GPI-anchor biosynthesis pathways may play a role in tumour progression

Cuestionario de autoevaluación de áreas de conocimiento : adaptación del modelo europeo de la EFQM

Desarrollado en la Universidad de Burgos por un grupo de catorce profesores de diversas áreas de conocimiento de la Escuela Politécnica Superior. El trabajo ha consistido en la elaboración de un documento que pretende ser una herramienta de ayuda, para mejorar el funcionamiento de las áreas de conocimiento -unidades básicas de organización de la docencia y la investigación en la universidad actual-. El documento contiene un cuestionario de autoevaluación adaptado para áreas de conocimiento y profesores, siguiendo el Modelo Europeo de Gestión de la Calidad Total de la European Foundation for Quality Management. El documento es autosuficiente conteniendo: una breve introducción del modelo de autoevaluación, las instrucciones de cumplimentación y el cuestionario propiamente dicho. El método para su elaboración ha consistido en la aplicación de las técnicas de calidad: liderazgo del director del trabajo, tormenta de ideas, trabajo en equipo para la puesta en común, prueba piloto, medida de resultados, y retroalimentación para mejorar el resultado final. La principal utilidad del trabajo puede ser la reflexión y la acción de mejora que puede realizar un área de conocimiento tras someterse a la autoevaluación de manera voluntaria, honesta y comprometida. El trabajo no está publicado.Castilla y LeónES

Feasibility and outcomes after dose reduction of immunochemotherapy in young adults with Burkitt lymphoma and leukemia : results of the BURKIMAB14 trial

High dose-intensive or infusional intermediate-dose immunochemotherapy is highly effective treatment for Burkitt lymphoma irrespective of human immunodeficiency virus (HIV) infection. However, toxicities of these regimens are relevant, especially in older adults and elderly patients. The prospective multicenter BURKIMAB14 trial included four to six blocks of immunochemotherapy according to stage (localized: 1 and 2 non-bulky; advanced: 2 bulky, 3, 4) and age, with dose reduction in patients >55 years old. Dose-intensity of chemotherapy was reduced in patients ≤55 years old after achieving complete metabolic response (CMR). Their outcomes were compared with those of similar patients included in the former BURKIMAB08 trial, in which there was no dose reduction. CMR was attained in 86 of 107 (80%) patients (17/19 in localized stages and 69/88 in advanced stages). Patients from the BURKIMAB14 trial ≤55 years old showed similar overall survival (OS), fewer infections and cytopenias than patients from the BURKIMAB08 trial. Patients >55 years old had a significantly higher treatment- related mortality despite dose reduction of chemotherapy. With a median follow-up of 3.61 years the 4-year OS probability was 73% (range, 63-81%). Age (≤55 vs. >55 years) and stage (localized vs. advanced) had prognostic significance. No significant differences in OS were observed in HIV-positive versus HIV-negative patients. The results of BURKIMAB14 are similar to those of other dose-intensive immunochemotherapy trials. Age >55 years and advanced stage, but not HIV infection, were associated with poor survival. Dose reduction of chemotherapy in young adults in CMR is safe and does not impact outcomes (clinicaltrials gov. Identifier: NCT05049473)

Allogeneic hematopoietic stem cell transplantation in Fanconi anemia:the European Group for Blood and Marrow Transplantation experience

Key Points The best survival benefit of HSCT is observed in patients with FA who are transplanted before 10 years with bone marrow after a fludarabine-based regimen. Long-term outcome of patients with FA after transplantation is mainly affected by secondary malignancies and chronic graft-versus-host disease.</jats:p