Intravenous Busulfan and Melphalan as a Conditioning Regimen for Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma: A Matched Comparison to a Melphalan-Only Approach

AbstractMelphalan 200 mg/m2 (MEL200) is the standard conditioning regimen administered to newly diagnosed patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). Few alternatives have been explored in order to improve the antimyeloma activity of this conditioning. We compare i.v. busulfan (BU) 9.6 mg/kg and MEL 140 mg/m2 (MEL140) versus MEL200 mg/m2 as a conditioning regimen before ASCT for newly diagnosed patients with MM. For this purpose, 51 patients receiving i.v. BU plus MEL were compared to 102 patients receiving MEL200 mg/m2 in a 1:2 matched control analysis. Matching criteria included age, clinical stage at diagnosis, and response to induction therapy. No differences in the overall and complete response (CR) rates were observed after ASCT between both groups. After a median follow-up of 63 and 50 months in control and BU plus MEL groups, progression-free survival (PFS) was 24 and 33 months, respectively (P = .10). Most frequent toxicities included mucositis and febrile neutropenia in both groups. No case of sinusoidal obstruction syndrome was observed. Transplant-related mortality was 4% and 2% in BU plus MEL and control groups, respectively. ASCT conditioned with i.v. BU plus MEL may be considered an effective and well-tolerated alternative to a MEL-only approach as a conditioning regimen for patients with MM who are candidates for ASCT. (Clinicaltrials.gov identifier: NCT00560053 and NCT00804947.

QUALIFICAÇÃO DE PRODUTORES RURAIS VISANDO FUTURA ADESÃO A SISTEMAS DE CERTIFICAÇÕES SOCIOAMBIENTAIS

A implantação de um Sistema de Gestão Socioambiental em uma empresa traz consigo, implicitamente, melhorias em várias frentes, tais como, estrutura organizacional, atividades de planejamento, definição de responsabilidade, práticas e procedimentos, bem como processos e recursos para desenvolver, implantar, alcançar, rever e manter a política ambiental estabelecida pela empresa. Prepara, consequentemente, a empresa para a obtenção inclusive de uma Certificação Socioambiental. Este trabalho foi desenvolvido, a partir de um estudo de caso em 10 (dez) propriedades rurais independentes que fornecem cana-de-açúcar a uma usina localizada na região Noroeste do Estado de São Paulo/Brasil. Utilizou-se, portanto, uma metodologia que considerasse as questões sociais, econômicas e ambientais específicas da região e que tivesse uma natureza descritiva e orientação epistemológica qualitativa. A opção por este estudo deve acontecer “a partir do desejo do pesquisador de explicar algumas situações a partir da prática” (GODOY, 2006, p.127). Eisenhardt (1989) ainda discute, em favor deste método, como uma fonte de exploração de situações organizacionais típicas, cujos casos podem ser especialmente reveladores. Foi proposta, impulsionada pela Agenda 21 local, como pré-requisito, uma qualificação direcionada aos Produtores Rurais. Tal processo de qualificação foi estruturado e sistematizado com base no Sistema Comunitário de Ecogestão e Auditoria (Eco-Management and Audit Scheme - EMAS II), Regulamento CE, Conselho Europa nº 761/2001 – e nas Normas da família NBR ISO 14.000, ISO 16.001:2004 OHSAS 18.001 e SA 8000. A Agenda 21, segundo Ribeiro (1998), é um “método prático para “ecologizar” uma administração municipal, estadual ou nacional, em cada um de seus setores”. O estudo sugere a implantação do Sistema de Gestão Socioambiental a partir do (Proprietário ou seu Representante: Pecuarista, Agricultor e/ou Silvicultor). Concluiu-se finalmente, posteriormente, a um processo de capacitação do Produtor Rural sobre noções sobre o funcionamento das peculiaridades de um sistema de “Certificação Socioambiental”, pela possibilidade de se formular um manual de “Boas Práticas Agrícolas

Identification of a Novel Modulator of Thyroid Hormone Receptor-Mediated Action

Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle. Methodology/Principal Findings. We have identified a gene, named DOR, abundantly expressed in insulin-sensitive tissues such as skeletal muscle and heart, whose expression is highly repressed in muscle from obese diabetic rats. DOR expression is up-regulated during muscle differentiation and its loss-of-function has a negative impact on gene expression programmes linked to myogenesis or driven by thyroid hormones. In agreement with this, DOR enhances the transcriptional activity of the thyroid hormone receptor TRa1. This function is driven by the N-terminal part of the protein. Moreover, DOR physically interacts with TR a1 and to T3-responsive promoters, as shown by ChIP assays. T3 stimulation also promotes the mobilization of DOR from its localization in nuclear PML bodies, thereby indicating that its nuclear localization and cellular function may be related. Conclusions/Significance. Our data indicate that DOR modulates thyroid hormone function and controls myogenesis. DOR expression is down-regulated in skeletal muscle in diabetes. This finding may be of relevance for the alterations in muscle function associated with this disease

Otimização de um programa Kaizen em uma empresa do setor metal mecânico

Manter um programa de melhoria contínua ativo dentro das organizações é um desafio permanente para os gestores. Após a implantação, muitos programas perdem força e caem em descrédito. Este artigo apresenta o programa Kaizen em uma empresa do setor metal mecânico, tendo como objetivo avaliar as etapas de implantação, as facilidades e dificuldades enfrentadas após a implantação e contribuir com sugestões de melhorias. O escopo do trabalho fundamenta-se na base Kaizen e suas práticas de implantação, focando na mudança cultural e comportamental dos funcionários de chão de fábrica. O resultado mostrou que são grandes as chances de abandonar a ferramenta após o surgimento das primeiras melhorias. Para evitar isso, o comprometimento das lideranças e os resultados obtidos em curto período de tempo são elementos vitais

The effect of excess fluid balance on the mortality rate of surgical patients: a multicenter prospective study

INTRODUCTION: In some studies including small populations of patients undergoing specific surgery, an intraoperative liberal infusion of fluids was associated with increasing morbidity when compared to restrictive strategies. Therefore, to evaluate the role of excessive fluid infusion in a general population with high-risk surgery is very important. The aim of this study was to evaluate the impact of intraoperative fluid balance on the postoperative organ dysfunction, infection and mortality rate. METHODS: We conducted a prospective cohort study during one year in four ICUs from three tertiary hospitals, which included patients aged 18 years or more who required postoperative ICU after undergoing major surgery. Patients who underwent palliative surgery and whose fluid balance could change in outcome were excluded. The calculation of fluid balance was based on preoperative fasting, insensible losses from surgeries and urine output minus fluid replacement intraoperatively. RESULTS: The study included 479 patients. Mean age was 61.2 ± 17.0 years and 8.8% of patients died at the hospital during the study. The median duration of surgery was 4.0 (3.2 to 5.5) h and the value of the Simplified Acute Physiology Score (SAPS) 3 score was 41.8 ± 14.5. Comparing survivors and non-survivors, the intraoperative fluid balance from non-survivors was higher (1,950 (1,400 to 3,400) mL vs. 1,400 (1,000 to 1,600) mL, P <0.001). Patients with fluid balance above 2,000 mL intraoperatively had a longer ICU stay (4.0 (3.0 to 8.0) vs. 3.0 (2.0 to 6.0), P <0.001) and higher incidence of infectious (41.9% vs. 25.9%, P = 0.001), neurological (46.2% vs. 13.2%, P <0.001), cardiovascular (63.2% vs. 39.6%, P <0.001) and respiratory complications (34.3% vs. 11.6%, P <0.001). In multivariate analysis, the fluid balance was an independent factor for death (OR per 100 mL = 1.024; P = 0.006; 95% CI 1.007 to 1.041). CONCLUSIONS: Patients with excessive intraoperative fluid balance have more ICU complications and higher hospital mortality

Otimização de um programa Kaizen em uma empresa do setor metal mecânico

Manter um programa de melhoria contínua ativo dentro das organizações é um desafio permanente para os gestores. Após a implantação, muitos programas perdem força e caem em descrédito. Este artigo apresenta o programa Kaizen em uma empresa do setor metal mecânico, tendo como objetivo avaliar as etapas de implantação, as facilidades e dificuldades enfrentadas após a implantação e contribuir com sugestões de melhorias. O escopo do trabalho fundamenta-se na base Kaizen e suas práticas de implantação, focando na mudança cultural e comportamental dos funcionários de chão de fábrica. O resultado mostrou que são grandes as chances de abandonar a ferramenta após o surgimento das primeiras melhorias. Para evitar isso, o comprometimento das lideranças e os resultados obtidos em curto período de tempo são elementos vitais

El comportamiento de la lactatemia y frecuencia cardiaca durante esfuerzos con intensidades de competencias en la carrera a pie de los triatletas de la Selección Nacional de Cuba / The behavior of lactatemia and heart rate during efforts with intensities

Las exigencias competitivas en el deporte de alto rendimiento se incrementan como resultado de la imposición constante de nuevos récords, el aprovechamiento de la ciencia y la tecnología será unos de los factores protagonistas de este proceso. Al respecto se impone utilizar medios, métodos y procedimientos más efectivos para superar los niveles de rendimiento. La investigación contó con un diseño preexperimento de control mínimo para un solo grupo con pretest - postest de naturaleza cuantitativa y cualitativa. Se trabajó con una muestra de 6 triatletas con un promedio de edad de 23 años, con más de 7 años de experiencia que representan el 100 % de la población de la Pre Selección Nacional de Cuba. Se aplicó un sistema de test con cargas incrementales que permite conocer el comportamiento de los niveles de lactato y frecuencia cardiaca en la carrera de los triatletas de la selección nacional de Cuba para su mejor desempeño en la preparación competitiva. Se utilizaron métodos del nivel teórico, empírico y estadístico los cuales posibilitaron constatar su veracidad durante todo el proceso de investigación. Existió una mejora significativa en la tolerancia al lactato en los triatletas, por lo que existió un incremento en el rendimiento de la carrera corroborado por los resultados en los Juegos Centroamericanos y del Caribe Veracruz 2014. Abstract &nbsp;The competitive demands in high performance sport are increased as a result of the constant imposition of new records, the use of science and technology will be one of the main factors of this process. In this regard, it is necessary to use more effective means, methods and procedures to overcome performance levels. The research had a minimum control preexperiment design for a single group with pretest - posttest of quantitative and qualitative nature. We worked with a sample of 6 triathletes with an average age of 23 years, with more than 7 years of experience that represented 100% of the population of the Pre National Selection of Cuba. We applied a test system with incremental loads that allows us to know the behavior of lactate levels and heart rate in the triathletes of the national team of Cuba for their best performance in competitive preparation. Methods of the theoretical, empirical and statistical level were used, which made it possible to verify their veracity throughout the research process. There was a significant improvement in lactation tolerance in the triathletes, so there was an increase in the performance of the race corroborated by the results in the Central American and Caribbean Games Veracruz 2014

Blood test dynamics in hospitalized COVID-19 patients: Potential utility of D-dimer for pulmonary embolism diagnosis

Background: A higher incidence of thrombotic events, mainly pulmonary embolism (PE), has been reported in hospitalized patients with COVID-19. The main objective was to assess clinical and laboratory differences in hospitalized COVID-19 patients according to occurrence of PE. Methods: This retrospective study included all consecutive patients hospitalized with COVID-19 who underwent a computed tomography (CT) angiography for PE clinical suspicion. Clinical data and median blood test results distributed into weekly periods from COVID-19 symptoms onset, were compared between PE and non-PE patients. Results: Ninety-two patients were included, 29 (32%) had PE. PE patients were younger (63.9 (SD 13.7) vs 69.9 (SD 12.5) years). Clinical symptoms and COVID-19 CT features were similar in both groups. PE was diagnosed after a mean of 20.0 (SD 8.6) days from the onset of COVID-19 symptoms. Corticosteroid boluses were more frequently used in PE patients (62% vs. 43%). No patients met ISTH DIC criteria. Any parameter was statistically significant or clinically relevant except for D-Dimer when comparing both groups. Median values [IQR] of D-dimer in PE vs non-PE patients were: week 2 (2010.7 [770.1-11208.9] vs 626.0 [374.0-2382.2]; p = 0.004); week 3 (3893.1 [1388.2-6694.0] vs 1184.4 [461.8-2447.8]; p = 0.003); and week 4 (2736.3 [1202.1-8514.1] vs 1129.1 [542.5-2834.6]; p = 0.01). Median fold-increase of D-dimer between week 1 and 2 differed between groups (6.64 [3.02-23.05] vs 1.57 [0.64-2.71], p = 0.003); ROC curve AUC was 0.879 (p = 0.003) with a sensitivity and specificity for PE of 86% and 80%, respectively. Conclusions: Among hospitalized COVID-19 patients, D-dimer levels are higher at weeks 2, 3 and 4 after COVID-19 symptom onset in patients who develop PE. This difference is more pronounced when the fold increase between weeks 1 and 2 is compared

Identification of a novel modulator of thyroid hormone receptor-mediated action

Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle. Methodology/Principal Findings. We have identified a gene, named DOR, abundantly expressed in insulin-sensitive tissues such as skeletal muscle and heart, whose expression is highly repressed in muscle from obese diabetic rats. DOR expression is up-regulated during muscle differentiation and its loss-of-function has a negative impact on gene expression programmes linked to myogenesis or driven by thyroid hormones. In agreement with this, DOR enhances the transcriptional activity of the thyroid hormone receptor TRa1. This function is driven by the N-terminal part of the protein. Moreover, DOR physically interacts with TR a1 and to T3-responsive promoters, as shown by ChIP assays. T3 stimulation also promotes the mobilization of DOR from its localization in nuclear PML bodies, thereby indicating that its nuclear localization and cellular function may be related. Conclusions/Significance. Our data indicate that DOR modulates thyroid hormone function and controls myogenesis. DOR expression is down-regulated in skeletal muscle in diabetes. This finding may be of relevance for the alterations in muscle function associated with this disease

Isatuximab in combination with lenalidomide and dexamethasone in patients with high-risk smoldering multiple myeloma: Updated safety run-in results from the randomized phase 3 ithaca study

Background: Results from a randomized, Phase 3 study by the Spanish Myeloma Group (PETHEMA/GEM) previously showed that treatment with lenalidomide plus dexamethasone (Rd) may delay progression to active disease in patients (pts) with high-risk smoldering multiple myeloma (SMM), compared with observation. To further improve outcomes, addition of the anti-CD38 antibody isatuximab (Isa) to lenalidomide and dexamethasone (Isa-Rd) for the treatment of pts with high-risk SMM is being evaluated in the ongoing, randomized, multi-center, Phase 3 ITHACA study (NCT04270409). Initial findings from the safety run-in analysis of this trial have shown a manageable safety profile and encouraging, preliminary anti-myeloma activity. We now report updated safety and efficacy results from the safety run-in part of ITHACA at a median follow-up of 19.4 months. Methods: Pts were included in the study if they had been diagnosed within 5 years with SMM (per the International Myeloma Working Group [IMWG] criteria) and had high-risk SMM according to the Mayo '20-2-20' and/or updated PETHEMA model criteria. Pts who had received prior anti-myeloma treatment were not eligible. Enrolled pts received Isa 10 mg/kg IV on day (D) 1, 8, 15, and 22 in cycle (C) 1, D1 and D15 C2-12, D1 C13-36; plus R D1-21 (25 mg C1-9; 10 mg C10-24) and d weekly (40 mg, 20 mg for ≥75 yr-old pts C1-9; 20 mg C10-24). Cycle duration was 28 days. Safety evaluations included treatment-emergent AEs (TEAEs)/serious AEs and laboratory parameters, graded by NCI-CTCAE v5.0. Response was determined by IMWG criteria (2016). Mandatory imaging by MRI and/or low-dose whole-body CT/PET-CT, and assessments of minimal residual disease (MRD, by next-generation sequencing in pts with very good partial response [VGPR] or better), were performed at protocol-defined time points. The primary study objective for the safety run-in was to confirm the recommended dose of Isa in combination with Rd. Overall response rate (ORR) and MRD negativity rate at 10-5 sensitivity were included as secondary endpoints.Sanof