Sigh in Patients With Acute Hypoxemic Respiratory Failure and ARDS: The PROTECTION Pilot Randomized Clinical Trial

Feasibility; Sigh; VentilationFactibilidad; Suspiro; VentilaciónFactibilitat; Sospir; VentilacióBackground Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. Research Question Is the clinical application of sigh during pressure support ventilation (PSV) feasible? Study Design and Methods We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. Results Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, –7%; 95% CI, –18% to 4%; P = .015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P = .852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P = .337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P = .300) for the sigh vs no-sigh group. Interpretation Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk.The PROTECTION trial was supported, in part, by an ESICM Clinical Research Award (ESICM, Brussels, Belgium) and by “Ricerca Corrente” of the Policlinico Hospital (Milan, Italy)

Digital for Heritage and Museums: Design-Driven Changes and Challenges

In the recent decade, cultural institutions have increasingly embraced digital technologies as key resources for accomplishing their mission and innovating their cultural activities. In the present work, we attempt to disentangle through a design-driven and multidisciplinary approach the challenges brought by digital transformation in the cultural heritage sector. A diversified research team has thus been involved to include scholars with different backgrounds around the common phenomenon of investigation of Digital (Cultural) Heritage, under the Design Think Thank project. The Introduction is followed by a Methodological section, which outlines the approach to select and review case studies from the exploratory literature for producing a state-of-the-art report and delineates the methodology to map the main user behaviours and needs in the digital experience of CH throughout the value chain. The research team identified three relevant and major themes for the investigation which are addressed in the Literature Review Section through the lenses of design research and practices; simultaneously, design knowledge emerges to have an agency in the transformation. The following section tries to triangulate the results from the literature review, and the mapping of users and stakeholders throughout the cultural institutions value chain, to track and highlight their role and interest in changing heritage panorama. The contribution of the present work wishes to consolidate the results gathered in the first phases of the TT, providing the design community of academics and practitioners with a theoretical contribution about digital changes and challenges of heritage and museums based on a design perspective

GM1 as adjuvant of innovative therapies for cystic fibrosis disease

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is expressed at the apical plasma membrane (PM) of different epithelial cells. The most common mutation responsible for the onset of cystic fibrosis (CF), F508del, inhibits the biosynthesis and transport of the protein at PM, and also presents gating and stability defects of the membrane anion channel upon its rescue by the use of correctors and potentiators. This prompted a multiple drug strategy for F508delCFTR aimed simultaneously at its rescue, functional potentiation and PM stabilization. Since ganglioside GM1 is involved in the functional stabilization of transmembrane proteins, we investigated its role as an adjuvant to increase the effectiveness of CFTR modulators. According to our results, we found that GM1 resides in the same PM microenvironment as CFTR. In CF cells, the expression of the mutated channel is accompanied by a decrease in the PM GM1 content. Interestingly, by the exogenous administration of GM1, it becomes a component of the PM, reducing the destabilizing effect of the potentiator VX-770 on rescued CFTR protein expression/function and improving its stabilization. This evidence could represent a starting point for developing innovative therapeutic strategies based on the co-administration of GM1, correctors and potentiators, with the aim of improving F508del CFTR function

The Proteomic Landscape of Human Ex Vivo Regulatory and Conventional T Cells Reveals Specific Metabolic Requirements

Human CD4(+)CD25(hi)Foxp3(+)CD127(-) Treg and CD4(+)CD25(-)Foxp3(-) Tconv cell functions are governed by their metabolic requirements. Here we report a comprehensive comparative analysis between ex vivo human Treg and Tconv cells that comprises analyses of the proteomic networks in subcellular compartments. We identified a dominant proteomic signature at the metabolic level that primarily impacted the highly-tuned balance between glucose and fatty-acid oxidation in the two cell types. Ex vivo Treg cells were highly glycolytic while Tconv cells used predominantly fatty-acid oxidation (FAO). When cultured in vitro, Treg cells engaged both glycolysis and FAO to proliferate, while Tconv cell proliferation mainly relied on glucose metabolism. Our unbiased proteomic analysis provides a molecular picture of the impact of metabolism on ex vivo human Treg versus Tconv cell functions that might be relevant for therapeutic manipulations of these cells

COVID-19 And Breast Fine Needle Aspiration Cytology Method: What Should We Change?

Air-dried slide preparation for fine needle aspiration cytology procedures, is currently considered unsafe because of the risk of infectious aerosols of Coronavirus 19. This study compares the safety and accuracy of two different protocols, one with and one without air-dried slides

TCT-509 Impact On Outcome Of Different Types Of Carotid Stents: Results From The European Registry Of Carotid Artery Stenting.

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Mechanisms of Resistance to Immunotherapy in Hepatocellular Carcinoma

: Systemic treatment for advanced hepatocellular carcinoma (HCC) has been revolutionized over the last few years following the approval of immune checkpoint inhibitors (ICI). Despite the promising survival extension seen with ICI combination regimens, responses are not universally seen and the optimal partner for programmed cell death 1 pathway inhibitors remains to be identified. Even fewer encouraging results have been demonstrated with ICI used for monotherapy. Several mechanisms of resistance have been described so far, involving characteristics of cancer cells (intrinsic mechanisms) and of the surrounding tumor microenvironment (extrinsic mechanisms). Factors related to therapy may also contribute to the development of resistance. Increasing research efforts are being dedicated to the discovery of novel approaches and targets to overcome resistance, some of which may be introduced into clinic in the future. Herein we describe a selection of resistance mechanisms that have been involved in impairing response to ICI and propose potential therapeutic approaches to overcome resistance