Blocking the PD-1/PD-L1 pathway has emerged as a potential therapy to restore impaired immune responses in human immunodeficiency virus (HIV)-infected individuals. Most reports have studied the impact of the PD-L1 blockade on effector cells and neglected possible effects on regulatory T cells (Treg cells), which play an essential role in balancing immunopathology and antiviral effector responses. The aim of this study was to define the consequences of ex vivo PD-L1 blockade on Treg cells from HIV-infected individuals. We observed that HIV infection led to an increase in PD-1+ and PD-L1+ Treg cells. This upregulation correlated with disease progression and decreased under antiretroviral treatment. Treg cells from viremic individuals had a particularly high PD-1 expression and impaired proliferative capacity in comparison with Treg cells from individuals under antiretroviral treatment. PD-L1 blockade restored the proliferative capacity of Treg cells from viremic individuals but had no effect on its suppressive capacity. Moreover, it increased the viral production in cell cultures from viremic individuals. This increase in viral production correlated with an increase in Treg cell percentage and a reduction in the CD4/Treg and CD8/Treg cell ratios. In contrast to the effect of the PD-L1 blockade on Treg cells from viremic individuals, we did not observe a significant effect on the proliferative capacity of Treg cells from individuals in whom viremia was controlled (either spontaneously or by antiretroviral treatment). However, PD-L1 blockade resulted in an increased proliferative capacity of HIV-specific-CD8 T cells in all subjects. Taken together, our findings suggest that manipulating PD-L1 in vivo can be expected to influence the net gain of effector function depending on the subject’s plasma viremia.

We report the case of a 41-year-old woman admitted to the hospital due to cardiac tamponade as the first manifestation of a pulmonary neoplasm. The patient developed an early biventricular dysfunction and pulmonary edema after removal of the pericardial effusion, with complete recovery within ten days. Since transient ventricular dysfunction after pericardiocentesis is a very unusual complication, we present a review of the different mechanisms suggested in the literature to explain the pathophysiology of this rare phenomenon.

No abstract

Background and Aim: Bicuspid aortic valve (BAV) increases the risk of aortic valve dysfunction and ascending aorta aneurysm and, consequently, the need for aortic valve replacement and/or aortic repair. However, there is no universal consensus about the surgical criteria and the predictors for surgery. The aim of this study was to investigate related factors to the need for surgery in the setting of a strict long-term follow-up with relatively conservative surgical criteria.Methods: We prospectively followed 120 patients after the diagnosis of BAV. Predisposing factors for a future need for aortic valve replacement and ascending aorta repair were assessed. Aortic surgery was indicated when the ascending aorta diameter was ≥55 mm and was recommended based on patient characteristics and in the presence of a severe aortic valve dysfunction with an aortic diameter ≥50 mm.Results: During follow-up (mean, 86 months), 34 patients (28%) (mean age, 56±12 years) were surgically treated. Aortic valve dysfunction (n=22; 64%) and ascending aorta dilatation (n=12; 36%) were the indications for surgery. Aortic regurgitation was the most frequent valve dysfunction at the time of diagnosis for BAV, but aortic stenosis was the most frequent indication for surgery. The presence at surgery of either aortic regurgitation or stenosis was clearly related to age, with regurgitation predominating in patients under 55 years, and aortic stenosis in older patients.Multivariate Cox analysis showed that aortic stenosis (hazard ratio 4.1, p=0.001), indexed ascending aorta dilatation (hazard ratio 3.0, p=0.03) and left ventricular end-diastolic diameter ≥60 mm (hazard ratio=4.0, p=0.01) at diagnosis were factors associated with future surgery. Aortic dissection was not observed in patients that did not undergo surgery.Conclusions: A relatively conservative approach for the indication of ascending aortic surgery in BAV is safe. In this setting, the presence of aortic or left ventricle dilatation and aortic stenosis at diagnosis of BAV were predictive of the need for surgery in the follow-up.

No abstract