RESUMO
Percutaneous occlusion of the left atrial appendage is increasingly being used as an alternative for stroke prevention in patients with non-valvular atrial fibrillation at high risk of complications from long term anticoagulation. We describe a case of left atrial appendage perforation during Watchman device implantation requiring emergency repair of the left atrium using sternotomy and cardiopulmonary bypass. Technical considerations for surgical decision making are discussed; in hemodynamically unstable patients as well as those at high risk for embolization.
Assuntos
Apêndice Atrial , Fibrilação Atrial , Embolização Terapêutica , Acidente Vascular Cerebral , Anticoagulantes , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Humanos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do TratamentoRESUMO
Natural killer (NK) cells contribute to host immunity, including tumor surveillance, through the production of interferon gamma (IFN-gamma). Although there is some knowledge about molecular mechanisms that induce IFN-gamma in NK cells, considerably less is known about the mechanisms that reduce its expression. Here, we investigate the role of the Hlx transcription factor in IFN-gamma production by NK cells. Hlx expression is induced in monokine-activated NK cells, but with delayed kinetics compared to IFN-gamma. Ectopic Hlx expression decreases IFN-gamma synthesis in primary human NK cells and IFN-gamma promoter activity in an NK-like cell line. Hlx protein levels inversely correlate with those of STAT4, a requisite factor for optimal IFN-gamma transcription. Mechanistically, we provide evidence indicating that Hlx overexpression accelerates dephosphorylation and proteasome-dependent degradation of the active Y693-phosphorylated form of STAT4. Thus, Hlx expression in activated NK cells temporally controls and limits the monokine-induced production of IFN-gamma, in part through the targeted depletion of STAT4.