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1.
Thromb Res ; 208: 148-155, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34798446

RESUMO

INTRODUCTION: Patients with central nervous system malignancies have limited representation in studies evaluating DOACs for VTE treatment. This study evaluated the safety and efficacy of DOACs in comparison with LMWH for cancer-associated VTE in patients with primary brain tumors or secondary brain metastases. MATERIALS & METHODS: In this multicenter, retrospective cohort study, adult patients with a diagnosis of primary brain tumor or secondary brain metastases who received either a DOAC or LMWH for treatment of cancer-associated VTE were evaluated. The primary outcome was the cumulative incidence of any intracranial hemorrhage within a 6-month period following the initiation of anticoagulation. Secondary outcomes included the cumulative incidence of any bleeding event, and recurrent VTE events. RESULTS: Between January 1, 2012 and October 9, 2019, one-hundred eleven patients met inclusion criteria. The 6-month cumulative incidence of intracranial hemorrhage was 4.3% (95% CI, 0.74-13.2%) in the DOAC group, compared to 5.9% (95% CI, 1.5-14.9%) in the LMWH group (p = 0.61). The 6-month cumulative incidence of bleeding events was 14.3% (95% CI, 6.2-25.8%) in the DOAC group, compared to 27.8% (95% CI, 15.5-41.6%) in the LMWH group (p = 0.10). The 6-month cumulative incidence of recurrent VTE events was 5.6% in the DOAC group (95% CI, 1.5-14.2%), compared to 6.6% in the LMWH group (95% CI, 1.7-16.5%) (p = 0.96). No differences were found with respect to other secondary outcomes. CONCLUSION: There were no significant differences in bleeding or recurrent VTE events between DOACs and LMWH. These findings suggest DOACs may be safe and effective for VTE treatment in this patient population.


Assuntos
Neoplasias Encefálicas , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Neoplasias Encefálicas/complicações , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Estudos Retrospectivos , Tromboembolia Venosa/tratamento farmacológico
2.
Clin Lymphoma Myeloma Leuk ; 20(12): e961-e985, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32839138

RESUMO

BACKGROUND: Although novel agents have changed the treatment landscape of multiple myeloma (MM), cytotoxic chemotherapy regimens continue to have a role in aggressive or rapidly progressive disease. In such cases, our institution has utilized a hyperfractionated cyclophosphamide regimen (termed mCAD), similar to hyper-CVAD, in which vincristine is omitted or replaced with a proteasome inhibitor (PI), either bortezomib or carfilzomib. On occasion, doxorubicin is also omitted because of patient history and provider preference. PATIENTS AND METHODS: We retrospectively reviewed the charts of adult patients with MM receiving mCAD regimens at our institution between 2012 and 2016 and analyzed utilization patterns, toxicity profiles, and clinical outcomes. RESULTS: A total of 131 patients received mCAD, including 9% for newly diagnosed MM (NDMM), 18% attempting to optimize response to frontline therapy (OPT-MM), and 73% for treatment of relapsed/refractory MM (RRMM). Renal dysfunction was common; 31% had estimated glomerular filtration rate < 50 mL/min and 14% were dialysis dependent. The overall response rate was 83%, 63%, and 67% with a median progression-free survival of 17.4, 23.7, and 4.2 months, respectively, for NDMM, OPT-MM, and RRMM. Median overall survival was not reached for NDMM or OPT-MM, and was 15.2 months for RRMM. Most patients (90%) bridged to subsequent therapy, including 32% who proceeded to autologous transplantation. Hematologic, infectious, and cardiac toxicities were common and were similar to those expected for cytotoxic chemotherapy. CONCLUSION: mCAD regimens were safe and active across patient groups, including patients with renal dysfunction. Most patients were able to bridge to subsequent therapy.


Assuntos
Mieloma Múltiplo/tratamento farmacológico , Inibidores de Proteassoma/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteassoma/farmacologia , Estudos Retrospectivos
3.
Hematol Oncol ; 35(1): 130-134, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26228379

RESUMO

Lenalidomide is often used in the maintenance setting for multiple myeloma and has been linked to the development of secondary primary malignancies. The mechanism of lenalidomide causing secondary malignancies has not been fully elucidated, but case reports and phase 3 trials have captured this uncommon occurrence. A case series describing development of secondary acute lymphoblastic leukemia in patients receiving lenalidomide maintenance therapy is presented. Based on data published in the literature thus far and commonalities among patients in this case series, secondary acute lymphoblastic leukemia is likely duration related rather than dose related. Increased cognizance of this secondary malignancy will allow for a more accurate characterization of its true incidence. Regimens for acute lymphoblastic leukemia can be used for management of secondary acute lymphoblastic leukemia with plan for stem cell transplantation. Further studies are needed to identify risk factors for development of secondary malignancy and the best management approach for these patients. Copyright © 2015 John Wiley & Sons, Ltd.


Assuntos
Fatores Imunológicos/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Talidomida/análogos & derivados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/etiologia , Estudos Retrospectivos , Fatores de Risco , Transplante de Células-Tronco , Talidomida/efeitos adversos , Resultado do Tratamento , Adulto Jovem
4.
Genome Biol Evol ; 6(5): 1166-73, 2014 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-24787621

RESUMO

We report the chloroplast genomes of a tree fern (Dicksonia squarrosa) and a "fern ally" (Tmesipteris elongata), and show that the phylogeny of early land plants is basically as expected, and the estimates of divergence time are largely unaffected after removing the fastest evolving sites. The tree fern shows the major reduction in the rate of evolution, and there has been a major slowdown in the rate of mutation in both families of tree ferns. We suggest that this is related to a generation time effect; if there is a long time period between generations, then this is probably incompatible with a high mutation rate because otherwise nearly every propagule would probably have several lethal mutations. This effect will be especially strong in organisms that have large numbers of cell divisions between generations. This shows the necessity of going beyond phylogeny and integrating its study with other properties of organisms.


Assuntos
Evolução Biológica , Gleiquênias/genética , Filogenia , Genética Populacional , Genoma de Cloroplastos , Dados de Sequência Molecular , Taxa de Mutação , Nova Zelândia
5.
Mol Biol Evol ; 31(1): 177-83, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24136916

RESUMO

The phylogenetic branching order of the green algal groups that gave rise to land plants remains uncertain despite its fundamental importance to understanding plant evolution. Previous studies have demonstrated that land plants evolved from streptophyte algae, but different lineages of streptophytes have been suggested to be the sister group of land plants. To better understand the evolutionary history of land plants and to determine the potential effects of "long-branch attraction" in phylogenetic reconstruction, we analyzed a chloroplast genome data set including three new chloroplast genomes from streptophyte algae: Coleochaetae orbicularis (Coleochaetales), Nitella hookeri (Charales), and Spirogyra communis (Zygnematales). We further applied a site pattern sorting method together with site- and time-heterogeneous models to investigate the branching order among streptophytes and land plants. Our chloroplast phylogenomic analyses support previous hypotheses based on nuclear data in placing Zygnematales alone, or a clade consisting of Coleochaetales plus Zygnematales, as the closest living relatives of land plants.


Assuntos
Clorófitas/genética , Embriófitas/genética , Genoma de Cloroplastos , Evolução Biológica , Clorófitas/classificação , DNA de Algas/genética , DNA de Cloroplastos/genética , Embriófitas/classificação , Filogenia , Análise de Sequência de DNA
6.
PLoS Pathog ; 7(12): e1002408, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22144898

RESUMO

Effectors of the bacterial type III secretion system provide invaluable molecular probes to elucidate the molecular mechanisms of plant immunity and pathogen virulence. In this report, we focus on the AvrBs2 effector protein from the bacterial pathogen Xanthomonas euvesicatoria (Xe), the causal agent of bacterial spot disease of tomato and pepper. Employing homology-based structural analysis, we generate a three-dimensional structural model for the AvrBs2 protein and identify catalytic sites in its putative glycerolphosphodiesterase domain (GDE). We demonstrate that the identified catalytic region of AvrBs2 was able to functionally replace the GDE catalytic site of the bacterial glycerophosphodiesterase BhGlpQ cloned from Borrelia hermsii and is required for AvrBs2 virulence. Mutations in the GDE catalytic domain did not disrupt the recognition of AvrBs2 by the cognate plant resistance gene Bs2. In addition, AvrBs2 activation of Bs2 suppressed subsequent delivery of other Xanthomonas type III effectors into the host plant cells. Investigation of the mechanism underlying this modulation of the type III secretion system may offer new strategies to generate broad-spectrum resistance to bacterial pathogens.


Assuntos
Proteínas de Bactérias/química , Modelos Moleculares , Fatores de Virulência/química , Xanthomonas/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sistemas de Secreção Bacterianos/fisiologia , Capsicum/microbiologia , Solanum lycopersicum/microbiologia , Mutação , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Estrutura Terciária de Proteína , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Xanthomonas/genética , Xanthomonas/metabolismo , Xanthomonas/patogenicidade
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