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1.
Cardiovasc Revasc Med ; 21(9): 1065-1073, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31974033

RESUMO

OBJECTIVES: To determine the incidence, prognosis, and predictors of major Valve Academic Research Consortium (VARC-2) vascular complications (VCs) and percutaneous vascular closure device failure (PCDF) following contemporary percutaneous transfemoral transcatheter aortic valve replacement (TF-TAVR). BACKGROUND: Limited data exists on the incidence and predictors of VCs and PCDFs following percutaneous TF-TAVR using contemporary 14-16 French (F) sheaths. METHODS: We recorded clinical and procedural characteristics, computer tomography (CT) angiographic data, 30-day VCs, mortality, and length of stay (LOS) in all consecutive percutaneous TF-TAVRs at a single center from June 2016 to October 2018. CT measures included common femoral artery (CFA) and external iliac artery (EIA) diameters, sheath to CFA and EIA ratios (SFAR and SEIAR), depth of CFA, extent and location of CFA calcification and pelvic vessel tortuosity (2 bends ≥90°). Multivariable regression was used to predict major VCs and percutaneous closure device failure (PCDF), respectively. RESULTS: The final sample consisted of 303 percutaneous TF-TAVRs. Median age was 80 years, 51% were male, 86% Caucasian, 33% had diabetes mellitus (DM) and mean STS score was 5.8 ±â€¯3.8%. Baseline characteristics were similar in patients with vs. without VCs, other than coronary artery disease (CAD) (69% vs. 54%, respectively; p = 0.029) and DM (21% vs. 36%, respectively; p = 0.02). There were 65 (21%) vascular complications: 19 major VCs [6.3%], 29 minor [VCs 9.6%] and 17 PCDFs [5.6%]. Overall, 30-day mortality was low (2.6%). Major VCs were associated with higher mortality (42% vs. 0%, p < 0.0001) while minor VCs (3% vs. 0%, mortality p = 0.99) and PCDFs (3% vs. 0% mortality, p = 0.99) were not. PCDFs were associated with a longer median LOS (4 vs. 3 days, p = 0.02). The independent predictors of major VCs were pelvic vessel tortuosity (OR 3.1; 95% CI 1.1-9.2) and presence of CAD (OR 8.2; 95% CI 1.8-37). Female gender showed a strong trend toward increased risk (OR 3.4; CI 0.84-14; p = 0.086). There were no independent predictors of PCDF. CONCLUSION: Contemporary percutaneous TF-TAVR is associated with a low risk of mortality, major VCs and PCDFs. Major VCs confer increased mortality and PCDFs prolong LOS. Pelvic vessel tortuosity and a history of CAD predict major VCs; there were no predictors of PCDFs. These results provide a contemporary update on the incidence and implications of these important vascular complications in the current era of percutaneous TF-TAVR using 14-16F vascular sheaths.


Assuntos
Estenose da Valva Aórtica , Falha de Equipamento , Substituição da Valva Aórtica Transcateter , Idoso de 80 Anos ou mais , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Feminino , Artéria Femoral/cirurgia , Humanos , Incidência , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda
2.
Cell Cycle ; 5(5): 486-8, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16552175

RESUMO

In eukaryotes, the copy number and size of any given organelle compartment remain constant in dividing cells, underlying a tight coordination between cell division and organelle homeostasis. However, in most cases the mechanisms for this coordination remain mysterious. Here we outline a few cases where the cell cycle machinery directly impacts on organelle homeostasis, with emphasis on the control of vacuolar (lysosomal) copy number and size in budding yeast. We also discuss aspects of organelle biology that can profoundly affect certain cell cycle parameters, such as cell size.


Assuntos
Quinases Ciclina-Dependentes/metabolismo , Homeostase , Membranas Intracelulares/metabolismo , Organelas/metabolismo , Fusão de Membrana , Organelas/ultraestrutura , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/metabolismo
3.
Genes Dev ; 19(21): 2606-18, 2005 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-16230527

RESUMO

How proliferating cells maintain the copy number and overall size of their organelles is not clear. We had previously reported that in the budding yeast Saccharomyces cerevisiae the G1 cyclin Cln3p is required for vacuolar (lysosomal) homotypic fusion and loss of Cln3p leads to vacuolar fragmentation. The Cdc42p GTPase is also required for vacuole fusion. Here we show that the scaffold protein Bem1p, a critical regulator of Cdc42p activity, is a downstream effector of Cln3p and the cyclin-dependent kinase (Cdk) Cdc28p. Our results suggest that Bem1p is phosphorylated in a Cdk-dependent manner to promote vacuole fusion. Replacing Ser72 with Asp, to mimic phosphorylation at an optimal Cdk-consensus site located in the first SH3 domain of Bem1p, suppressed vacuolar fragmentation in cells lacking Cln3p. Using in vivo and in vitro assays, we found that Cln3p was unable to promote vacuole fusion in the absence of Bem1p or in the presence of a nonphosphorylatable Bem1p-Ser72Ala mutant. Furthermore, activation of Cdc42p also suppressed vacuolar fragmentation in the absence of Cln3p. Our results provide a mechanism that links cyclin-dependent kinase activity with vacuole fusion through Bem1p and the Cdc42p GTPase cycle.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Ciclinas/metabolismo , Homeostase/fisiologia , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/fisiologia , Transdução de Sinais/fisiologia , Vacúolos/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Substituição de Aminoácidos/genética , Proteína Quinase CDC28 de Saccharomyces cerevisiae , Ciclinas/genética , Proteínas de Saccharomyces cerevisiae/genética , Vacúolos/genética , Proteína cdc42 de Saccharomyces cerevisiae de Ligação ao GTP/metabolismo
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