Predicting long-term disease control in transplant-ineligible patients with multiple myeloma: impact of an MGUS-like signature

Disease control; Multiple myeloma; BiomarkersControl de la malaltia; Mieloma múltiple; BiomarcadorsControl de la enfermedad; Mieloma múltiple; BiomarcadoresDisease control at 5 years would be a desirable endpoint for elderly multiple myeloma (MM) patients, but biomarkers predicting this are not defined. Therefore, to gain further insights in this endpoint, a population of 498 newly diagnosed transplant-ineligible patients enrolled in two Spanish trials (GEM2005MAS65 and GEM2010MAS65), has been analyzed. Among the 435 patients included in this post-hoc study, 18.6% remained alive and progression free after 5 years of treatment initiation. In these patients, overall survival (OS) rate at 10 years was 60.8% as compared with 11.8% for those progressing within the first 5 years. Hemoglobin (Hb) ≥ 12 g/dl (OR 2.74, p = 0.001) and MGUS-like profile (OR 4.18, p = 0.005) were the two baseline variables associated with long-term disease-free survival. Upon including depth of response (and MRD), Hb ≥ 12 g/dl (OR 2.27) and MGUS-like signature (OR 7.48) retained their predictive value along with MRD negativity (OR 5.18). This study shows that despite the use of novel agents, the probability of disease control at 5 years is still restricted to a small fraction (18.6%) of elderly MM patients. Since this endpoint is associated with higher rates of OS, this study provides important information about diagnostic and post-treatment biomarkers helpful in predicting the likelihood of disease control at 5 years

Groundwater intensive use and mining in south-eastern peninsular Spain: Hydrogeological, economic and social aspects

Intensive groundwater development is a common circumstance in semiarid and arid areas. Often abstraction exceeds recharge, thus continuously depleting reserves. There is groundwater mining when the recovery of aquifer reserves needs more than 50 years. The MASE project has been carried out to compile what is known about Spain and specifically about the south-eastern Iberian Peninsula and the Canary Islands. The objective was the synthetic analysis of available data on the hydrological, economic, managerial, social, and ethical aspects of groundwater mining. Since the mid-20th century, intensive use of groundwater in south-eastern Spain allowed extending and securing the areas with traditional surface water irrigation of cash crops and their extension to former dry lands, taking advantage of good soils and climate. This fostered a huge economic and social development. Intensive agriculture is a main activity, although tourism plays currently an increasing economic role in the coasts. Many aquifers are relatively high yielding small carbonate units where the total groundwater level drawdown may currently exceed 300 m. Groundwater storage depletion is estimated about 15 km3. This volume is close to the total contribution of the Tagus-Segura water transfer, but without large investments paid for with public funds. Seawater desalination complements urban supply and part of cash crop cultivation. Reclaimed urban waste water is used for irrigation. Groundwater mining produces benefits but associated to sometimes serious economic, administrative, legal and environmental problems. The use of an exhaustible vital resource raises ethical concerns. It cannot continue under the current legal conditions. A progressive change of water use paradigm is the way out, but this is not in the mind of most water managers and politicians. The positive and negative results observed in south-eastern Spain may help to analyse other areas under similar hydrogeological conditions in a less advanced stage of water use evolution

Simulador de reparación de aneurismas cerebrales para entrenamiento médico

The development of simulation systems for surgical procedures has become a topic of research in several areas such as computer engineering, robotics and medicine in recent years, mainly because these systems suppose a novel alternative for the acquisition of medical skills, planning, guidance and post-operative control; while represent significant challenges in terms of their design, implementation and validation. This paper presents the experiences and methodologies applied to the development of computerized simulators for virtual training in the Research and Technological Development Unit (UIDT) in the General Hospital of Mexico (HGM) "Dr. Eduardo Liceaga" from the National Autonomous University of Mexico (UNAM). As a case of study, we can exemplify the development of a virtual reality simulator for the repair of cerebral aneurysms, which has involved research in methods for computer simulation, visualization, tactile sensations and human-computer interactionEl desarrollo de sistemas de simulación de procedimientos quirúrgicos se ha convertido desde hace algunos años en un tema de investigación para diversas áreas que incluyen a la computación, la robótica y la medicina, pues suponen una alternativa novedosa para la adquisición de habilidades médicas, planeación, guía y control postoperatorio; al mismo tiempo que representan retos significativos en términos de su diseño, implementación y validación. En este trabajo se presentan las experiencias y metodologías aplicadas al desarrollo de simuladores computarizados para entrenamiento virtual en la Unidad de Investigación y Desarrollo Tecnológico (UIDT) en el Hospital General de México (HGM) “Dr. Eduardo Liceaga”, de la Universidad Nacional Autónoma de México (UNAM). Como caso de estudio, se ejemplifica el desarrollo de un simulador para la reparación de aneurismas cerebrales, el cual ha involucrado la investigación en métodos de simulación computacional, visualización, sensaciones táctiles e interacción humano-computadora

Propiedades fisicoquímicas del aceite de semillas de Jatropha curcas de poblaciones silvestres en México

The need for studying sources of renewable energy is important starting from potential oleaginous plants. Jatropha curcas seed is characterized by its high oil content. In Mexico studies are focused on evaluating the physicochemical properties of J. curcas oil in wild plants cultivated in the southern region. The objective of this study was to evaluate these properties in three ecotypes of wild J. curcas of Sinaloa and their oil application in biodiesel production. The oil content of the germ was found to be 52 to 56%. Viscosity, density, acidity index, peroxide, iodine, and refraction showed no significant differences in the seeds collected from the three ecotypes in our study. The most abundant saturated fatty acids were palmitic (4 to 6%) and stearic (3 to 4%). The most abundant unsaturated fatty acids were oleic (44 to 46%) and linoleic (42 to 44%). Physicochemical characteristics of J. curcas oil of Sinaloa specimens are similar to those of southern Mexico and other countries, which suggest that the germplasm of the northwestern part of the country could be considered for conservation, rational utilization, and biodiesel production.Existe la necesidad de estudiar fuentes renovables de energía a partir de plantas oleaginosas con este potencial. La semilla de Jatropha curca se caracteriza por su alto contenido de aceite. En México solo existen estudios enfocados en evaluar las propiedades fisicoquímicas del aceite de J. curcas silvestre y cultivada en la región sur. El objetivo de este trabajo, fue evaluar las propiedades fisicoquímicas del aceite de J. curcas silvestre en tres ecotipos del estado de Sinaloa (noroeste de México) y su aplicación en la elaboración de biodiesel. Los resultados obtenidos fueron que el contenido de aceite del germen fue de 52 a 56%. La viscosidad, densidad específica, índice de acidez, peróxido, yodo y refracción no mostraron diferencias significativas en las semillas colectadas en los tres ecotipos en estudio. Los ácidos grasos saturados más abundantes fueron el palmítico (4 a 6%) y esteárico (3 a 4%). Los ácidos grasos insaturados más abundantes fueron el oleico (44 a 46%) y linoleico (42 a 44%). Las características fisicoquímicas del aceite de J. curcas de Sinaloa son similares a las del sur de México y otros países, esto sugiere que el germoplasma del noroeste del país podría ser considerado para su conservación, aprovechamiento racional y producción de biodiesel

Integrated analysis of randomized controlled trials evaluating bortezomib + lenalidomide + dexamethasone or bortezomib + thalidomide + dexamethasone induction in transplant-eligible newly diagnosed multiple myeloma

ObjectiveProviding the most efficacious frontline treatment for newly diagnosed multiple myeloma (NDMM) is critical for patient outcomes. No direct comparisons have been made between bortezomib + lenalidomide + dexamethasone (VRD) and bortezomib + thalidomide + dexamethasone (VTD) induction regimens in transplant-eligible NDMM.MethodsAn integrated analysis was performed using patient data from four trials meeting prespecified eligibility criteria: two using VRD (PETHEMA GEM2012 and IFM 2009) and two using VTD (PETHEMA GEM2005 and IFM 2013-04).ResultsThe primary endpoint was met, with VRD demonstrating a noninferior rate of at least very good partial response (>= VGPR) after induction vs VTD. GEM comparison demonstrated improvement in the >= VGPR rate after induction for VRD vs VTD (66.3% vs 51.2%; P = .00281) that increased after transplant (74.4% vs 53.5%). Undetectable minimal residual disease rates post induction (46.7% vs 34.9%) and post transplant (62.4% vs 47.3%) support the benefit of VRD vs VTD. Treatment-emergent adverse events leading to study and/or treatment discontinuation were less frequent with VRD (3%, GEM2012; 6%, IFM 2009) vs VTD (11%, IFM 2013-04).ConclusionThese results supported the benefit of VRD over VTD for induction in transplant-eligible patients with NDMM. The trials included are registered with ClinicalTrials.gov (NCT01916252, NCT01191060, NCT00461747, and NCT01971658)

Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma

[EN]For patients with smoldering multiple myeloma, the standard of care is observation until symptoms develop. However, this approach does not identify high-risk patients who may benefit from early intervention. In this randomized, open-label, phase 3 trial, we randomly assigned 119 patients with high-risk smoldering myeloma to treatment or observation. Patients in the treatment group received an induction regimen (lenalidomide at a dose of 25 mg per day on days 1 to 21, plus dexamethasone at a dose of 20 mg per day on days 1 to 4 and days 12 to 15, at 4-week intervals for nine cycles), followed by a maintenance regimen (lenalidomide at a dose of 10 mg per day on days 1 to 21 of each 28-day cycle for 2 years). The primary end point was time to progression to symptomatic disease. Secondary end points were response rate, overall survival, and safety. After a median follow-up of 40 months, the median time to progression was significantly longer in the treatment group than in the observation group (median not reached vs. 21 months; hazard ratio for progression, 0.18; 95% confidence interval [CI], 0.09 to 0.32; P<0.001). The 3-year survival rate was also higher in the treatment group (94% vs. 80%; hazard ratio for death, 0.31; 95% CI, 0.10 to 0.91; P=0.03). A partial response or better was achieved in 79% of patients in the treatment group after the induction phase and in 90% during the maintenance phase. Toxic effects were mainly grade 2 or lower. Early treatment for patients with high-risk smoldering myeloma delays progression to active disease and increases overall survival. (Funded by Celgene; ClinicalTrials.gov number, NCT00480363.)

Mass spectrometry vs immunofixation for treatment monitoring in multiple myeloma

Monitoring of the monoclonal protein (M-protein) by electrophoresis and/or immunofixation (IFE) has long been used to assess treatment response in multiple myeloma (MM). However, with the use of highly effective therapies, the M-protein becomes frequently undetectable, and more sensitive methods had to be explored. We applied IFE and mass spectrometry (EXENT&FLC-MS) in serum samples from newly diagnosed MM patients enrolled in the PETHEMA/GEM2012MENOS65 obtained at baseline (n = 223), and after induction (n = 183), autologous stem cell transplantation (n = 173), and consolidation (n = 173). At baseline, the isotypes identified with both methods fully matched in 82.1% of samples; in the rest but 2 cases, EXENT&FLC-MS provided additional information to IFE with regards to the M-protein(s). Overall, the results of EXENT&FLC-MS and IFE were concordant in >80% of cases, being most discordances due to EXENT&FLC-MS+ but IFE cases. After consolidation, IFE was not able to discriminate 2 cohorts with different median progression-free survival (PFS), but EXENT&FLC-MS did so; furthermore, among IFE patients, EXENT&FLC-MS identified 2 groups with significantly different median PFS (P = .0008). In conclusion, compared with IFE, EXENT&FLC-MS is more sensitive to detect the M-protein of patients with MM, both at baseline and during treatment, and provides a more accurate prediction of patients' outcome

Motivación y estimación del tiempo en el uso de herramientas internet informacionales y dialógicas

Se analiza la relación existente entre el grado de interés o motivación y estimación del tiempo (aspectos psicológicos) en la realización de tareas informacionales y dialógicas (aspectos comunicacionales) mediadas por internet en adolescentes chilenos. Se empleó una muestra estratificada de 120 estudiantes de 7 liceos de Chile con una media de edad de 15 años. Todos los participantes debían realizar de forma sucesiva dos tareas por internet: una primera tarea de comunicación vertical (búsqueda de información con el empleo del Google) y una segunda tarea de comunicación horizontal (diálogo por mensajería). Para cada una de las tareas se medía el tiempo percibido y el grado de interés. Los resultados muestran un interés significativamente mayor y un tiempo estimado significativamente menor en la tarea de comunicación horizontal. Desde aquí se pueden proyectar usos informacionales y educativos de interne

NGS-Based Molecular Karyotyping of Multiple Myeloma: Results from the GEM12 Clinical Trial

Simple Summary Multiple Myeloma (MM) is considered an incurable chronic disease, which prognosis depends on the presence of different genomic alterations. To accomplish a complete molecular diagnosis in a single essay, we have designed and validated a capture-based NGS approach to reliably identify pathogenic mutations (SNVs and indels), genomic alterations (CNVs and chromosomic translocations), and IGH rearrangements. We have observed a good correlation of the results obtained using our capture panel with data obtained by both FISH and WES techniques. In this study, the molecular classification performed using our approach was significantly associated with the stratification and outcome of MM patients. Additionally, this panel has been proven to detect specific IGH rearrangements that could be used as biomarkers in patient follow-ups through minimal residual disease (MRD) assays. In conclusion, we think that MM patients could benefit from the use of this capture-based NGS approach with a more accurate, single-essay molecular diagnosis. Next-generation sequencing (NGS) has greatly improved our ability to detect the genomic aberrations occurring in multiple myeloma (MM); however, its transfer to routine clinical labs and its validation in clinical trials remains to be established. We designed a capture-based NGS targeted panel to identify, in a single assay, known genetic alterations for the prognostic stratification of MM. The NGS panel was designed for the simultaneous study of single nucleotide and copy number variations, insertions and deletions, chromosomal translocations and V(D)J rearrangements. The panel was validated using a cohort of 149 MM patients enrolled in the GEM2012MENOS65 clinical trial. The results showed great global accuracy, with positive and negative predictive values close to 90% when compared with available data from fluorescence in situ hybridization and whole-exome sequencing. While the treatments used in the clinical trial showed high efficacy, patients defined as high-risk by the panel had shorter progression-free survival (p = 0.0015). As expected, the mutational status of TP53 was significant in predicting patient outcomes (p = 0.021). The NGS panel also efficiently detected clonal IGH rearrangements in 81% of patients. In conclusion, molecular karyotyping using a targeted NGS panel can identify relevant prognostic chromosomal abnormalities and translocations for the clinical management of MM patients