Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Front Cardiovasc Med ; 10: 1129943, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37363095

RESUMO

Background: Use of the proteasome inhibitor carfilzomib has become a standard of care in patients with relapsed/refractory multiple myeloma. An association between carfilzomib and cardiovascular adverse events has been well documented, but this had not been investigated in a racially diverse population. Black patients in particular are underrepresented in the reported outcomes of treatment with carfilzomib. Objective: The purpose of this study was to identify risk factors for carfilzomib-associated cardiovascular events in a diverse, single-center population. Methods: We conducted a retrospective review of 161 patients with multiple myeloma treated with carfilzomib between 2011 and 2020 at the University of Maryland Medical Center. Over half (86) were Black patients, with the remainder (75) being White patients. We did a multivariate analysis to determine risk factors for developing cardiovascular events during treatment with carfilzomib. Results: There was no statistically significant association with cardiotoxicity and race, gender, or age at first dose of carfilzomib. In multivariable analysis, patients with history of hypertension had a higher risk of cardiotoxicity [adjusted odds ratio (OR): 2.5; 95% CI: 1.1-5.9; P = 0.03] as did those with a history of smoking [OR: 2.8; 95% CI: 1.3-6.4; P = 0.01]. Conclusions: Here we report the largest cohort of Black patients treated with carfilzomib as yet reported. The results of this single center retrospective study show history of hypertension and smoking are associated with carfilzomib associated cardiotoxicity in a diverse patient population. There is a need for well-designed prospective studies enrolling a diverse population to investigate potential interventions to prevent carfilzomib-associated cardiotoxicity.

2.
Heart Lung Circ ; 28(5): 752-760, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29748060

RESUMO

BACKGROUND: Pulmonary artery (PA) pulsitility index (PAPi) is a novel haemodynamic index shown to predict right ventricular failure in acute inferior myocardial infarction and post left ventricular assist device surgery. We hypothesised that PAPi calculated as [PA systolic pressure - PA diastolic pressure]/right atrial pressure (RAP) would be associated with mortality in the National Institutes of Health Registry for Primary Pulmonary Hypertension (NIH-RPPH). METHODS: The impact of PAPi, the Pulmonary Hypertension Connection (PHC) risk score, right ventricular stroke work, pulmonary artery capacitance (PAC), other haemodynamic indices, and demographic characteristics was evaluated in 272 NIH-RPPH patients using multivariable Cox proportional hazards (CPH) regression and receiver operating characteristic (ROC) analysis. RESULTS: In the 272 patients (median age 37.7+/-15.9years, 63% female), the median PAPi was 5.8 (IQR 3.7-9.2). During 5years of follow-up, 51.8% of the patients died. Survival was markedly lower (32.8% during the first 3years) in PAPi quartile 1 compared with the remaining patients (58.5% over 3years in quartiles 2-4; p<0.0001). The best multivariable CPH survival model included PAPi, the PHC-Risk score, PAC, and body mass index (BMI). In this model, the adjusted hazard ratio for death with increasing PAPi was 0.946 (95% CI 0.905-0.989). The independent ROC areas for 5-year survival based on bivariable logistic regression for PAPi, BMI, PHC Risk, and PAC were 0.63, 0.62, 0.64, and 0.65, respectively (p<0.01). The ROC area for 5-year survival for the multivariable logistic model with all four covariates was 0.77 (p<0.0001). CONCLUSIONS: Pulmonary artery pulsatility index was independently associated with survival in PAH, highlighting the utility of PAPi in combination with other key measures for risk stratification in this population.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Artéria Pulmonar/fisiopatologia , Pressão Propulsora Pulmonar/fisiologia , Fluxo Pulsátil/fisiologia , Sistema de Registros , Adulto , Ecocardiografia , Feminino , Hemodinâmica , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Artéria Pulmonar/diagnóstico por imagem , Curva ROC , Fatores de Risco , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia , Adulto Jovem
3.
Dalton Trans ; 47(20): 6954-6964, 2018 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-29721567

RESUMO

Many microbes acquire environmental Fe by secreting organic chelators, siderophores, which possess the characteristics of a high and specific binding affinity for iron(iii) that results in the formation of thermodynamically stable, and kinetically inert iron(iii) complexes. Mechanisms to overcome the kinetic inertness include the labilization of iron(iii) by means of ternary complex formation with small chelators. This study describes a kinetic investigation of the labilization of iron(iii) between two stable binding sites, the prototypical siderophore ferrioxamine B and EDTA, by the bidentate siderophore mimic, 1,2-dimethyl-3-hydroxy-4-pyridinone (L1, H(DMHP)). The proposed mechanism is substantiated by investigating the iron(iii) exchange reaction between ferrioxamine B and H(DMHP) to form Fe(DMHP)3, as well as the iron(iii) exchange from Fe(DMHP)3 to EDTA. It is also shown that H(DMHP) is a more effective catalyst for the iron(iii) exchange reaction than bidentate hydroxamate chelators reported previously, supporting the hypothesis that chelator structure and iron(iii) affinity influence low denticity ligand facilitated catalysis of iron(iii) exchange reactions. The results are also discussed in the context of the design and use of combination chelator therapies in the treatment of Fe overload in humans.


Assuntos
Terapia por Quelação/métodos , Compostos Férricos/química , Quelantes de Ferro/química , Ferro/metabolismo , Piridonas/química , Bactérias/metabolismo , Catálise , Deferiprona , Desferroxamina/química , Ácido Edético/química , Compostos Férricos/uso terapêutico , Humanos , Ácidos Hidroxâmicos/química , Transporte de Íons , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/terapia , Cinética , Ligantes
4.
Lab Invest ; 96(6): 602-9, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26999660

RESUMO

We previously observed that high-dose angiotensin receptor blocker (ARB) can induce regression of existing glomerulosclerosis. We also found that proliferator-activated recepto-γ (PPARγ) agonist can attenuate glomerulosclerosis in a nondiabetic model of kidney disease, with specific protection of podocytes. We now assessed effects of combination therapy with ARB and pioglitazone on established glomerulosclerosis. Sprague-Dawley male rats underwent 5/6 nephrectomy (5/6 Nx) at week 0 and renal biopsy at week 8. Rats were randomized to groups with equal starting moderate glomerulosclerosis, and treated with ARB, PPARγ agonist (pioglitazone), combination or vehicle from weeks 8 to 12. Body weight, systolic blood pressure (SBP), and urinary protein (UP) were measured at intervals. In rats with established sclerosis, SBP, UP, and GS were equal in all groups at week 8 before treatment by study design. Untreated control rats had hypertension, decreased GFR, and progressive proteinuria and glomerulosclerosis at week 12. Only combination therapy significantly ameliorated hypertension and proteinuria. ARB alone or pioglitazone alone had only numerically lower SBP and UP than vehicle at week 12. Both pioglitazone alone and combination had significantly less decline in GFR than vehicle. Combination-induced regression of glomerulosclerosis in more rats from weeks 8 to 12 than ARB or pioglitazone alone. In parallel, combination treatment reduced plasminogen activator inhibitor-1 expression and macrophage infiltration, and preserved podocytes compared with vehicle. These results were linked to increased AT2 receptor and Mas1 mRNA in the combination group. PPARγ agonists in combination with ARB augment regression of glomerulosclerosis, with downregulation of injurious RAAS components vs PPARγ alone, with increased anti-fibrotic/healing RAAS components, enhanced podocyte preservation, and decreased inflammation and profibrotic mechanisms.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , PPAR gama/agonistas , Tiazolidinedionas/administração & dosagem , Animais , Benzimidazóis/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Creatinina/sangue , Progressão da Doença , Quimioterapia Combinada , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/fisiopatologia , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Oxidiazóis/administração & dosagem , Pioglitazona , Podócitos/efeitos dos fármacos , Podócitos/patologia , Proteinúria/tratamento farmacológico , Proto-Oncogene Mas , Ratos , Ratos Sprague-Dawley , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA