On the impact of substrate electron injection on dynamic Ron in GaN-on-Si HEMTs

The impact of electron injection from the substrate on the dynamic Ron of GaN-on-Si High Electron Mobility Transistors (HEMTs) has been investigated by means of back-bias transient and vertical leakage measurements and TCAD simulations. A strong correlation between electrons injected from the substrate and on-state drain current transients is demonstrated. Moreover, the contribution of the electron-type traps in the buffer layer as opposed to the usually studied hole-like traps to the dynamic Ron is discussed. In particular, the impact of electron-like traps for different levels of substrate leakage current is studied. A TCAD model has been developed and calibrated by taking into account both off-state vertical leakage and on-state drain current transient experimental results. The proposed charge dynamic has also been assessed against state-of-the-art theories. This analysis contributes to a deeper understanding of the complex scenario of different types of traps in the buffer layer of GaN-on-Si devices and highlights the impact that trap-states can have on the on-state and off-state currents

Differential expression of ABCF2 in newly diagnosed and dasatinib-treated chronic myeloid leukemia patients

sem informação1001PB173168568520th Congress of European-Hematology-Associatio

Efficacy and safety of dasatinib vs. Imatinib in Latin american subpopulation from the dasision trial in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP)

sem informação100120th Congress of European-Hematology-Associationsem informaçã

Right ventricular-arterial uncoupling independently predicts survival in COVID-19 ARDS

Aim: To investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an Acute Respiratory Distress Syndrome (ARDS). Methods: Ninety-four consecutive patients (mean age 64 years) admitted for acute respiratory failure on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio Results: The majority of patients needed ventilatory support, which was noninvasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62 ± 13 vs. 68 ± 12 years, p = 0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO2)/fraction of inspired O2 (FIO2) ratio (270 ± 104 vs. 117 ± 57 mmHg, p < 0.001). In the non-survivors, PASP was increased (42 ± 12 vs. 30 ± 7 mmHg, p < 0.001), while TAPSE was decreased (19 ± 4 vs. 25 ± 4 mm, p < 0.001). Accordingly, the TAPSE/PASP ratio was lower than in the survivors (0.51 ± 0.22 vs. 0.89 ± 0.29 mm/mmHg, p < 0.001). At univariate/multivariable analysis, the TAPSE/PASP (HR: 0.026; 95%CI 0.01–0.579; p: 0.019) and PaO2/FIO2 (HR: 0.988; 95%CI 0.988–0.998; p: 0.018) ratios were the only independent predictors of mortality, with ROC-determined cutoff values of 159 mmHg and 0.635 mm/mmHg, respectively. Conclusions: COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO2/FIO2 in ARDS on COVID-19

A MULTICENTER, OBSERVATIONAL, AMBISPECTIVE STUDY EVALUATING EFFICACY AND SAFETY OF GENERIC IMATINIB COMPARED TO GLEEVEC IN CHRONIC MYELOGENOUS LEUKEMIA IN CHRONIC PHASE-3 MONTHS RESPONSE ANALYSIS

Univ Estadual Campinas, Hematol & Hemotherapy Ctr, Campinas, SP, BrazilUniv Fed Minas Gerais, Hosp Clin, Belo Horizonte, MG, BrazilInst Nacl Cancer, Rio De Janeiro, BrazilFac Med, Sao Paulo, BrazilUniv Sao Paulo, Sao Paulo, BrazilHemorio, Rio De Janeiro, BrazilHosp Clin Porto Alegre, Porto Alegre, RS, BrazilCtr Pesquisa Oncol Santa Catarina, Florianopolis, SC, BrazilUniv Fed Bahia, Salvador, BA, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilInst Estudos & Pesquisas Sao Lucas, Sao Paulo, BrazilUniv Estadual Campinas, Campinas, SP, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilWeb of Scienc

Produção orgânica de calêndula: um estudo de caso.

Apresenta-se caracterização do processo de produção agrícola orgânica de Calendula officinalis L. no Estado de Santa Catarina, evidenciando particularidades e discrepâncias frente aos modelos já descritos na literatura especializada, a partir de visitas a campo, observação participante e entrevistas com um produtor de plantas medicinais. Identificaram-se como principais particularidades a saúde na agricultura familiar, demonstrada pela prática da cultura orgânica, além do controle de pragas e manuseio da produção. Os principais problemas ou divergências evidenciados foram: características do solo; época de plantio da calêndula e suas etapas posteriores, como transplante e floração. Aspectos da colheita foram discrepantes quanto ao período do dia indicado para o procedimento, bem como a ausência de informações do produtor quanto à existência de outros incentivos governamentais ao setor agrícola. Recomenda-se aos extensionistas rurais e/ou instituições competentes que busquem orientar os produtores orgânicos de calêndula para promover a adequação das práticas de cultivo dessa espécie medicinal

Clinical features and outcomes of 134 Brazilians with acute promyelocytic leukemia who received ATRA and anthracyclines

We report an increased incidence of high relapse risk features in 157 APL Brazilian patients. Out of 134 patients treated with ATRA and anthracyclines, only 91 (67.9%) achieved remission because 43 (32%) died during induction. the death rate during consolidation was 10.5%. Bleeding complications were the most frequent cause of failure (21.6%).Med Sch Riberao Preto, Dept Internal Med, Ribeirao Preto, BrazilHosp Amaral Carvalho, Bone Marrow Transplantat Unit, Jau, BrazilUniv Fed Minas Gerais, Hematol Serv, Belo Horizonte, MG, BrazilSanta Casa São Paulo, Hematol Serv, São Paulo, BrazilFundacao Pio XII Barretos, Barretos, BrazilClin Hematol Riberao Preto, Ribeirao Preto, BrazilUniversidade Federal de São Paulo, Dept Hematol & Hemotherapy, São Paulo, BrazilUniv Estadual Campinas, Hemoctr, Campinas, BrazilSt Jude Childrens Hosp, Internal Outreach Program, Memphis, TN USAUniversidade Federal de São Paulo, Dept Hematol & Hemotherapy, São Paulo, BrazilWeb of Scienc

Reduced SLIT2 is Associated with Increased Cell Proliferation and Arsenic Trioxide Resistance in Acute Promyelocytic Leukemia

Simple Summary In solid tumors, the altered expression of embryonic genes such as the SLIT-ROBO family has been associated with poor prognosis, while little is known about their role in acute myeloid leukemia (AML). Previous studies reported frequent hypermethylation of SLIT2 mediated by the methyltransferase enzyme EZH2 and more recently the PML protein, which are commonly found to be aberrantly expressed in AML. Here, we aim to assess retrospectively the clinical relevance of the SLIT2 gene in acute promyelocytic leukemia, a homogenous subtype of AML. We demonstrated that reduced SLIT2 expression was associated with high leukocyte counts and reduced overall survival in different APL cohorts. STLI2 treatment decreased APL growth, while SLIT2 knockdown accelerated cell cycle progression and proliferation. Finally, reduced expression of SLIT2 in murine APL blasts resulted in fatal leukemia associated with increased leukocyte counts in vivo. These findings demonstrate that SLIT2 can be considered as a prognostic marker in APL, and a potential candidate for clinical studies of a more heterogeneous disease, such as AML. The SLIT-ROBO axis plays an important role in normal stem-cell biology, with possible repercussions on cancer stem cell emergence. Although the Promyelocytic Leukemia (PML) protein can regulate SLIT2 expression in the central nervous system, little is known about SLIT2 in acute promyelocytic leukemia. Hence, we aimed to investigate the levels of SLIT2 in acute promyelocytic leukemia (APL) and assess its biological activity in vitro and in vivo. Our analysis indicated that blasts with SLIT2(high) transcript levels were associated with cell cycle arrest, while SLIT2(low) APL blasts displayed a more stem-cell like phenotype. In a retrospective analysis using a cohort of patients treated with all-trans retinoic acid (ATRA) and anthracyclines, high SLIT2 expression was correlated with reduced leukocyte count (p = 0.024), and independently associated with improved overall survival (hazard ratio: 0.94; 95% confidence interval: 0.92-0.97; p <0.001). Functionally, SLIT2-knockdown in primary APL blasts and cell lines led to increased cell proliferation and resistance to arsenic trioxide induced apoptosis. Finally, in vivo transplant of Slit2-silenced primary APL blasts promoted increased leukocyte count (p = 0.001) and decreased overall survival (p = 0.002) compared with the control. In summary, our data highlight the tumor suppressive function of SLIT2 in APL and its deteriorating effects on disease progression when downregulated

Experiência brasileira utilizando terapia sequencial de alta dose seguido de transplante autólogo de célula-tronco hematopoética para linfomas malignos

Using the overall survival (OS), disease free survival (DFS) and progression free survival (PFS), as well as associated toxicity, the purpose of this work was to evaluate the effectiveness of HDS followed by ASCT as salvage therapy. A retrospective analysis was performed of 106 patients with high grade non-Hodgkin lymphoma receiving HDS followed by ASCT, between 1998 and 2006. Median age was 45 years (Range: 8-65), with 66 (62%) men. Histopathological classification was: 78% DLBCL patients, 12% T and anaplastic and 9% Mantle cell lymphomas; 87% had B cell and 12% T cell lymphomas; 83% were stage III-IV (Ann Arbor Staging), 63% had B symptoms, 32% had bone marrow involvement, 62% bulky disease and 42% high-intermediate or high risk IPI. After HDCY, 9 patients died, 7 from toxicity and 2 from sepsis. Eighty patients underwent ASCT, 47% were in complete remission (CR) and 15% died, all from toxicity. Their OS was 45% over 8 years. During the follow-up, another 35 patients died [4 CR, 1 partial response (PR), 2 relapsed disease (RD) and 28 disease progression (DP)], 11 (31%) had not performed ASCT. OS was 37%; DFS was 49% and PFS 28%. OS by diagnosis was 42% for DLBCL, 40% for T-cell (8 y) and 20% for Mantle Cell (6 y) (P=NS). OS by B symptom patients was 22% vs. 58% (P=0.002) and PFS was 23% vs. 37% (P=0.03). Patients who achieved CR after HDCY (38) had significantly better OS and PFS (38% and 17%) than patients who remained in DP (P<0.0001). Cox Regression demonstrated therapeutic lines before HDCY (Relative risk - RR = 1.41; CI 95%: 1.04-1.90; P= 0.02) and PD both before (RR = 2.70; CI 95%: 1.49-4.91, P<0.001) and after HDCY (RR = 5.38; 95% CI: 2.93-9.87; P<0.0001). Conclusions: Our study suggests HDS is an efficient treatment to improve status and to reduce tumoral burden. Regardless of toxicity-related mortality it is feasible, especially considering the poor prognosis of patients.A proposta deste trabalho foi avaliar a eficácia da HDS seguida do transplante autólogo como terapia de salvamento através da sobrevida global, livre de doença e livre de progressão bem como sua toxicidade. Realizou-se estudo retrospectivo com 106 pacientes com LNH de alto grau de malignidade entre 1998 e 2006. A mediana de idade foi 45 anos (8-65); 62% homens; DLBCL, 78%; 12%, T e anaplásico e 9%, linfoma da zona do manto; 87%, células B; 83% estádios III-IV; 63% com sintomas B; 32% com infiltração da medula óssea ao diagnóstico; 62% com grande massa e 42% com IPI de alto risco ou intermediário. Após alta dose de ciclofosfamida (HDCY), nove pacientes faleceram. Oitenta pacientes realizaram o transplante, sendo que 47% estavam em RC e 15% faleceram devido à toxicidade. A sobrevida global foi de 45% em oito anos para estes pacientes. Trinta e cinco pacientes não realizaram o transplante por causas diversas. Sobrevida global para todos os pacientes foi de 42%, DLBCL, 40%; T-cell, 40% e zona do manto, 20% (P=NS). Pacientes que obtiveram RC após HDCY tiveram melhor sobrevida global e livre de progressão (38% e 17%, respectivamente) do que os que permaneceram em PD (P<0.0001). O modelo de Cox resultou que o número de linhas terapêuticas antes da HDCY (RR 1.41 IC 95%: 1.04-1.90, P=0.02) e PD antes da HDCY (RR 2.70, IC 95%: 1.49-4.91, P<0.001) e após HDCY (RR 5.38, IC 95%: 2.93-9.87, P<0.0001). Nosso estudo sugere que HDS é um método eficiente de tratamento para melhorar o status e reduzir a massa tumoral. Em relação à toxicidade, é factível, especialmente em pacientes de prognóstico ruim91