The association between cerebral blood flow variations during on-pump coronary artery bypass grafting surgery and postoperative delirium.

INTRODUCTION: Postoperative delirium (POD) has a major impact on patient recovery after cardiac surgery. Although its pathophysiology remains unclear, there could be a correlation between cerebral blood flow (CBF) variations during cardio-pulmonary bypass (CPB) and POD. Our study aimed to evaluate whether variations in on-pump CBF, compared to pre-anesthesia and pre-CPB values, are associated with POD following coronary artery bypass grafting (CABG) surgery. METHODS: This prospective observational cohort study included 95 adult patients undergoing elective on-pump CABG surgery. Right middle cerebral artery blood flow velocity (MCAV) was assessed using Transcranial Doppler before anesthesia induction, before CPB and every fifteen minutes during CPB. Pre-anesthesia and pre-CPB values were chosen as baselines. Individual values, measured during CPB, were converted as percentage changes relative to these baselines and named as %MCAV0 and %MCAV1, respectively. POD was assessed using the Confusion Assessment Method for ICU (CAM-ICU) during the first 48 post-operative hours and with the 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) on the fifth post-surgical day. RESULTS: Overall POD incidence was 17.9%. At 30 minutes of CPB, %MCAV0 was higher in POD group than in no-POD group (p = .05). %MCAV0 at 45 minutes of CPB was significantly higher in POD group (87 (±17) %) than in no-POD group (68 (±24) %), p = .04. %MCAV1 at 30 and 45 minutes of CPB were higher in POD group than in no-POD group, at the limit of statistical significance. We found %MCAV1 > 100% in POD group, but not in no-POD group. CONCLUSIONS: Significant differences in %MCAV0 became evident after 30 minutes of CPB, whereas differences in %MCAV1 at 45 minutes of CPB were at limit of statistical significance. In POD group %MCAV1 was higher than 100% at 30 and 45 minutes of CPB, which is supposed to be a sign of cerebral hyperperfusion. Monitoring CBF during CPB could have prognostic value for POD.

Too much tolerance for hyperoxemia in mechanically ventilated patients with SARS-CoV-2 pneumonia? Report from an Italian intensive care unit.

Background: In COVID-19 patients requiring mechanical ventilation, the administration of high oxygen (O2) doses for prolonged time periods may be necessary. Although life-saving in most cases, O2 may exert deleterious effects if administered in excessive concentrations. We aimed to describe the prevalence of hyperoxemia and excessive O2 administration in mechanically ventilated patients with SARS-CoV-2 pneumonia and determine whether hyperoxemia is associated with mortality in the Intensive Care Unit (ICU) or the onset of ventilator-associated pneumonia (VAP). Materials and methods: Retrospective single-center study on adult patients with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation for ≥48 h. Patients undergoing extracorporeal respiratory support were excluded. We calculated the excess O2 administered based on the ideal arterial O2 tension (PaO2) target of 55-80 mmHg. We defined hyperoxemia as PaO2 > 100 mmHg and hyperoxia + hyperoxemia as an inspired O2 fraction (FiO2) > 60% + PaO2 > 100 mmHg. Risk factors for ICU-mortality and VAP were assessed through multivariate analyses. Results: One hundred thirty-four patients were included. For each day of mechanical ventilation, each patient received a median excess O2 of 1,121 [829-1,449] L. Hyperoxemia was found in 38 [27-55]% of arterial blood gases, hyperoxia + hyperoxemia in 11 [5-18]% of cases. The FiO2 was not reduced in 69 [62-76]% of cases of hyperoxemia. Adjustments were made more frequently with higher PaO2 or initial FiO2 levels. ICU-mortality was 32%. VAP was diagnosed in 48.5% of patients. Hyperoxemia (OR 1.300 95% CI [1.097-1.542]), time of exposure to hyperoxemia (OR 2.758 [1.406-5.411]), hyperoxia + hyperoxemia (OR 1.144 [1.008-1.298]), and daily excess O2 (OR 1.003 [1.001-1.005]) were associated with higher risk for ICU-mortality, independently of age, Sequential Organ failure Assessment score at ICU-admission and mean PaO2/FiO2. Hyperoxemia (OR 1.033 [1.006-1.061]), time of exposure to hyperoxemia (OR 1.108 [1.018-1.206]), hyperoxia + hyperoxemia (OR 1.038 [1.003-1.075]), and daily excess O2 (OR 1.001 [1.000-1.001]) were identified as risk factors for VAP, independently of body mass index, blood transfusions, days of neuromuscular blocking agents (before VAP), prolonged prone positioning and mean PaO2/FiO2 before VAP. Conclusion: Excess O2 administration and hyperoxemia were common in mechanically ventilated patients with SARS-CoV-2 pneumonia. The exposure to hyperoxemia may be associated with ICU-mortality and greater risk for VAP.

Fabrication, Characterization, and Properties of Poly (Ethylene-Co-Vinyl Acetate) Composite Thin Films Doped with Piezoelectric Nanofillers.

Ethylene vinyl acetate (EVA) is a copolymer comprehending the semi-crystalline polyethylene and amorphous vinyl acetate phases, which potentially allow the fabrication of tunable materials. This paper aims at describing the fabrication and characterization of nanocomposite thin films made of polyethylene vinyl acetate, at different polymer concentration and vinyl acetate content, doped with piezoelectric nanomaterials, namely zinc oxide and barium titanate. These membranes are prepared by solvent casting, achieving a thickness in the order of 100-200 µm. The nanocomposites are characterized in terms of morphological, mechanical, and chemical properties. Analysis of the nanocomposites shows the nanofillers to be homogeneously dispersed in EVA matrix at different vinyl acetate content. Their influence is also noted in the mechanical behavior of thin films, which elastic modulus ranged from about 2 to 25 MPa, while keeping an elongation break from 600% to 1500% and tensile strength from 2 up to 13 MPa. At the same time, doped nanocomposite materials increase their crystallinity degree than the bare ones. The radiopacity provided by the addition of the dopant agents is proven. Finally, the direct piezoelectricity of nanocomposites membranes is demonstrated, showing higher voltage outputs (up to 2.5 V) for stiffer doped matrices. These results show the potentialities provided by the addition of piezoelectric nanomaterials towards mechanical reinforcement of EVA-based matrices while introducing radiopaque properties and responsiveness to mechanical stimuli.

Induction of CD83+CD14+ nondendritic antigen-presenting cells by exposure of monocytes to IFN-alpha.

IFN-alpha is a well-known agent for treatment of viral and malignant diseases. It has several modes of actions, including direct influence on the immune system. We investigated IFN-alpha effects on PBMC in terms of dendritic cell (DC) differentiation, as PBMC are exposed to high IFN-alpha levels during treatment of infections and cancers. We show that in vitro IFN-alpha exposure induced rapid and strong up-regulation of the DC-maturation markers CD80, CD86, and CD83 in bulk PBMC. Consistently, IFN-alpha induced up-regulation of these molecules on purified monocytes within 24 h. Up-regulation of CD80 and CD83 expression was IFN-alpha concentration-dependent. In contrast to GM-CSF + IL-4-generated DCs, most of the IFN-alpha-challenged CD83(+) cells coexpressed the monocyte marker CD14. Despite a typical mature DC immunophenotype, IFN-alpha-treated monocytes conserved phagocytic activity and never acquired a dendritic morphology. In mixed lymphocyte reactions IFN-alpha-treated monocytes were less potent than GM-CSF + IL-4-generated DCs but significantly more potent than untreated monocytes to induce T cell proliferation in bulk PBMC. However, only GM-CSF + IL-4-generated DCs were able to induce a significant proliferation of naive CD4(+) T cells. Notably, autologous memory CD4(+) T cells proliferated when exposed to tetanus toxoid-pulsed IFN-alpha-treated monocytes. At variance with untreated or GM-CSF + IL-4-exposed monocytes, those challenged with IFN-alpha showed long-lasting STAT-1 phosphorylation. Remarkably, CD83(+)CD14(+) cells were present in varicella skin lesions in close contact with IFN-alpha-producing cells. The present findings suggest that IFN-alpha alone promptly generates nondendritic APCs able to stimulate memory immune responses. This may represent an additional mode of action of IFN-alpha in vivo.

Plasmacytoid dendritic cells represent a major dendritic cell subset in sentinel lymph nodes of melanoma patients and accumulate in metastatic nodes.

Plasmacytoid dendritic cells (pDC) represent the main source of interferon-alpha, a cytokine with antitumor activity. However, in vitro studies point to pDC as a key subset for induction of tolerance. Herein, we investigated pDC in sentinel lymph nodes (SLN) of melanoma patients. We report that pDC were constantly found in SLN and represented, with Langerhans cells, the most frequent dendritic cell subset. Their frequency in positive (with metastasis) SLN was significantly higher than in negative (without metastasis) SLN. PDC were observed in the T cell-rich areas of lymph nodes, particularly around high endothelial venules and, in metastatic nodes, they accumulated in close vicinity with melanoma nests. Finally, pDC capability to produce interferon-alpha in situ was impaired. Consistently, pDC expressed CD86, but neither CD80 nor CD83, suggesting a not complete activation in melanoma-draining lymph nodes. These results are consistent with the hypothesis of a tolerogenic role played by pDC in tumor immunology.