Cell Count Differentials by Cytomorphology and Next-Generation Flow Cytometry in Bone Marrow Aspirate: An Evidence-Based Approach

Despite a lack of evidence, a bone marrow aspirate differential of 500 cells is commonly used in the clinical setting. We aimed to test the performance of 200-cell counts for daily hematological workup. In total, 660 consecutive samples were analyzed recording differentials at 200 and 500 cells. Additionally, immunophenotype results and preanalytical issues were also evaluated. Clinical and statistical differences between both cutoffs and both methods were checked. An independent control group of 122 patients was included. All comparisons between both cutoffs and both methods for all relevant types of cells did not show statistically significant differences. No significant diagnostic discrepancies were demonstrated in the contingency table analysis. This is a real-life study, and some limitations may be pointed out, such as a different sample sizes according to the type of cell in the immunophenotype analysis, the lack of standardization of some preanalytical events, and the relatively small sample size of the control group. The comparisons of differentials by morphology on 200 and 500 cells, as well as by morphology (both cutoffs) and by immunophenotype, are equivalent from the clinical and statistical point of view. The preanalytical issues play a critical role in the assessment of bone marrow aspirate samples

Epidemiology of Multiple Myeloma

Multiple myeloma is a heterogeneous hematological malignancy in which epidemiology plays an increasingly important role. In recent years, an unprecedented intensive research, including both clinical and molecular epidemiology, has deepened the knowledge about its pathogenesis, risk factors, and prognostic factors, leading also to the approval of new drugs. Although the etiology remains largely unknown, among the confirmed risk factors, only obesity and the exposure to certain carcinogens are potentially preventable. Familial myeloma and occupational myeloma are topics of great interest. Most population-based cancer registries show a stable incidence or only a slight trend to increase. The diagnostic delay should be avoided as much as possible. Mortality rates, including early mortality, are progressively decreasing, although infection remains the leading cause of mortality. The outcome in terms of overall survival and health-related quality of life has remarkably improved, joining the group of potentially curable malignancies. Nowadays the clinical scenario is challenging. Clinical and epidemiological variables of interest should be standardized in clinical records. Patients should be included in a population-based registry network. The clinical coordination of a multidisciplinary team in a specialized unit is needed in order to maximize the outcome of every patient

Prognostic Value of Serum Paraprotein Response Kinetics in Patients With Newly Diagnosed Multiple Myeloma

Mieloma recién diagnosticado; Marcador pronósticoNewly diagnosed myeloma; Prognostic markerMieloma recent diagnosticat; Marcador pronòsticIntroduction Response kinetics is a well-established prognostic marker in acute lymphoblastic leukemia. The situation is not clear in multiple myeloma (MM) despite having a biomarker for response monitoring (monoclonal component [MC]). Materials and Methods We developed a mathematical model to assess the prognostic value of serum MC response kinetics during 6 induction cycles, in 373 NDMM transplanted patients treated in the GEM2012Menos65 clinical trial. The model calculated a “resistance” parameter that reflects the stagnation in the response after an initial descent. Results Two patient subgroups were defined based on low and high resistance, that respectively captured sensitive and refractory kinetics, with progression-free survival (PFS) at 5 years of 72% and 59% (HR 0.64, 95% CI 0.44-0.93; P = .02). Resistance significantly correlated with depth of response measured after consolidation (80.9% CR and 68.4% minimal residual disease negativity in patients with sensitive vs. 31% and 20% in those with refractory kinetics). Furthermore, it modulated the impact of reaching CR after consolidation; thus, within CR patients those with refractory kinetics had significantly shorter PFS than those with sensitive kinetics (median 54 months vs. NR; P = .02). Minimal residual disease negativity abrogated this effect. Our study also questions the benefit of rapid responders compared to late responders (5-year PFS 59.7% vs. 76.5%, respectively [P < .002]). Of note, 85% of patients considered as late responders were classified as having sensitive kinetics. Conclusion This semi-mechanistic modeling of M-component kinetics could be of great value to identify patients at risk of early treatment failure, who may benefit from early rescue intervention strategies

Efectos del ejercicio físico extracurricular vigoroso sobre la atención de escolares

El objetivo de este trabajo fue analizar el efecto sobre la atención de escolares de dos programas de actividad física (moderada y alta intensidad). Participaron 94 niños (n = 52) y niñas (n =42), (Edad M = 8,20; DT = 0,70) de la ciudad de Granada (España). Se empleó un diseño cuasi experimental con un grupo control y otro experimental. Se analizó amplitud de la atención y atención selectiva. Como variable de control se evaluó la aptitud cardiorrespiratoria a través de consumo de oxígeno máximo y la velocidad pico alcanzada durante actividad aeróbica máxima. Se aprecian efectos significativos a favor del programa de alta intensidad sobre dos pruebas de span atencional y ejercicios de atención selectiva, así como en valores de condición física. Se concluye que la práctica física de alta intensidad intermitente, practicada de manera regular, podría tener implicaciones positivas sobre el rendimiento cognitivo de niños y que la mejora de la condición física podría ser uno de los factores vinculados a estos cambios.The aim of this study was to analyze the effect of two programs of physical activity (moderate and high intensity physical activity), in the levels of attention of a sample of young in scholar aged. 94 children, boys=52 and girls=42 (Age M = 8.20; SD = 0.70) from Granada (Spain) participated in the investigation. A quasi-experimental design was used, with control and experimental group. Evidence of attentional span and search items on matrices with the purpose of analyzing the amplitude of the attention and selective attention were applied. As a control variable, cardiorespiratory fitness by maximum oxygen uptake and peak speed reached during maximal aerobic activity was evaluated. The results showed significant effects in favor of high-intensity program on two tests of attentional span and exercises selective attention, as well as the values of fitness. These data suggest that the physical practice of intermittent high intensity practiced regularly could have positive implications on cognitive performance of children and improving the physical condition could be one of the factors linked to these changes.O objetivo deste estudo foi analisar o efeito de dois programas de atividade física (de intensidade moderada e alta) em atenção o nível cognitivo para a escola. 94 estudantes participaram, 52 do sexo masculino, 42 do sexo feminino (Idade M = 8,20, DP = 0,70) da cidade de Granada (Espanha). Um design quase-experimental foi utilizado com um grupo controle e um grupo experimental. Amplitude de atenção e atenção seletiva foram analisados. Como variável de controle foi avaliada a aptidão cardiorrespiratória através do consumo máximo de oxigênio e velocidade de pico alcançado durante a atividade aeróbica máxima. Efeitos significativos são vistos em favor do programa de alto intensidade e dois exercícios de amplitude e exercícios de atenção selectiva, bem como valores de aptidao física. Conclui-se que a prática física de alta intensidade intermitente, praticado regularmente, pode ter implicações positivas sobre o desempenho cognitivo das crianças e condição física melhoria poderia ser um dos fatores ligados a essas mudanças

A glimpse into relapsed refractory multiple myeloma treatment in real-world practice in Spain: the GeminiS study

Relapsed-refractory multiple mieloma; Monoclonal antibodies; Observational multicenter studyMieloma múltiple recidivant-refractari; Anticossos monoclonals; Estudi observacional multicèntricMieloma múltiple recidivante-refractario; Anticuerpos monoclonales; Estudio multicéntrico observacionalObjectives: To describe the incorporation of monoclonal antibodies (mAb) in real-world (RW) practice for the treatment of patients with relapsed refractory multiple myeloma (RRMM) in a setting with other treatment alternatives. Methods: This was an observational, multicenter, ambispective study of RRMM treated with or without a mAb. Results: A total of 171 patients were included. For the group treated without mAb, the median (95% CI) progression-free survival (PFS) to relapse was 22.4 (17.8-27.0) months; partial response or better (≥PR) and complete response or better (≥CR) was observed in 74.1% and 24.1% of patients, respectively; and median time to first response in first relapse was 2.0 months and in second relapse was 2.5 months. For the group of patients treated with mAb in first or second relapse, the median PFS was 20.9 (95% CI, could not be evaluated) months; the ≥ PR and ≥ CR rates were 76,2% and 28.6%, respectively; and the median time to first response in first relapse was 1.2 month and in second relapse was 1.0 months. The safety profiles for the combinations were consistent with those expected. Conclusions: The incorporation of mAb in RW practice for the treatment of RRMM has shown good quality and speed of response with a similar safety profile shown in randomized clinical trials. Keywords: Relapsed-refractory multiple myeloma; daratumumab; monoclonal antibodies; real-world; standard of care

Cell Count Differentials by Cytomorphology and Next-Generation Flow Cytometry in Bone Marrow Aspirate: An Evidence-Based Approach

Despite a lack of evidence, a bone marrow aspirate differential of 500 cells is commonly used in the clinical setting. We aimed to test the performance of 200-cell counts for daily hematological workup. In total, 660 consecutive samples were analyzed recording differentials at 200 and 500 cells. Additionally, immunophenotype results and preanalytical issues were also evaluated. Clinical and statistical differences between both cutoffs and both methods were checked. An independent control group of 122 patients was included. All comparisons between both cutoffs and both methods for all relevant types of cells did not show statistically significant differences. No significant diagnostic discrepancies were demonstrated in the contingency table analysis. This is a real-life study, and some limitations may be pointed out, such as a different sample sizes according to the type of cell in the immunophenotype analysis, the lack of standardization of some preanalytical events, and the relatively small sample size of the control group. The comparisons of differentials by morphology on 200 and 500 cells, as well as by morphology (both cutoffs) and by immunophenotype, are equivalent from the clinical and statistical point of view. The preanalytical issues play a critical role in the assessment of bone marrow aspirate samples

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)

A common variant within the HNF1B gene is associated with overall survival of multiple myeloma patients: results from the IMMEnSE consortium and meta-analysis

Diabetogenic single nucleotide polymorphisms (SNPs) have recently been associated with multiple myeloma (MM) risk but their impact on overall survival (OS) of MM patients has not been analysed yet. In order to investigate the impact of 58 GWAS-identified variants for type 2 diabetes (T2D) on OS of patients with MM, we analysed genotyping data of 936 MM patients collected by the International Multiple Myeloma rESEarch (IMMENSE) consortium and an independent set of 700 MM patients recruited by the University Clinic of Heidelberg. A meta-analysis of the cox regression results of the two sets showed that rs7501939 located in the HNF1B gene negatively impacted OS (HRRec = 1.44, 95% CI = 1.18-1.76, P = 0.0001). The meta-analysis also showed a noteworthy gender-specific association of the SLC30A8(rs13266634) SNP with OS. The presence of each additional copy of the minor allele at rs13266634 was associated with poor OS in men whereas no association was seen in women (HRMen-Add = 1.32, 95% CI 1.13-1.54, P = 0.0003). In conclusion, these data suggest that the HNF1B(rs7501939) SNP confers poor OS in patients with MM and that a SNP in SLC30A8 affect OS in men.This work was supported by grants from the FIBAO foundation (Granada, Spain), from the CRIS foundation against cancer, from the Cancer Network of Excellence (RD12/10 Red de Cáncer), from the Instituto de Salud Carlos III (Madrid, Spain; PI12/02688) and from the Dietmar Hopp Foundation and the German Ministry of Education and Science (BMBF: CLIOMMICS [01ZX1309]).FIBAO foundation (Granada, Spain), from the CRIS foundation against cancer, from the Cancer Network of Excellence (RD12/10 Red de Cáncer), from the Instituto de Salud Carlos III (Madrid, Spain; PI12/02688) and from the Dietmar Hopp Foundation and the German Ministry of Education and Science (BMBF: CLIOMMICS [01ZX1309]info:eu-repo/semantics/publishedVersio

La prueba: teoría y práctica

Especialistas de talla mundial discurren en torno al núcleo básico de la administración de la justicia: la prueba, un tema fundamental que —precisamente por su carácter basilar— tiende a ser pasado por alto o a revisarse de manera superficial. En esta obra colectiva, se estudian —desde una perspectiva tanto conceptual como práctica— problemas fundamentales en torno a la prueba, desde diferentes puntos de vista que se soportan en diversas áreas del conocimiento como la filosofía, la epistemología, la psicología, entre otras. Modestia aparte, no es fortuito que en el prólogo del libro Bujosa Vadell declare que “está llamado a ser obra de cabecera para los juristas que, desde la academia y desde el foro, se preocupan por una conducción adecuada de la actividad probatoria”. Así pues, académicos, juristas, abogados litigantes y jueces tienen a su disposición la décima segunda entrega del Grupo de Investigaciones en Derecho Procesal, de la Universidad de Medellín, reconocido mundialmente por su compromiso y dedicación a la hora de coordinar esta ya tradicional serie de libros de investigación en derecho procesal.https://catalogo.udem.edu.co/la-prueba-teoria-y-practica--derecho-procesal-civil.html#.XbdVx-gzbc