Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Effect of Hydroalcoholic Extract of Boerhaavia Diffusa Linn against Cisplatin Induced Nephrotoxicity

Conclusion: The results indicate that the aerial parts of Boerhaavia diffusa are endowed with Nephroprotective effect

How to Improve the Interaction Design of NFC Payment Terminals?

Part 1: E-commerceInternational audienceNear field communication (NFC) payments also popularly known as contactless payments are increasingly used in retails shops like supermarkets and cafes nowadays. User studies on NFC payments show that NFC payments fail to provide users with the appropriate user experience. In this paper, we aimed to redesign the existing NFC payment experience design by altering 5 factors namely the audio feedback, the visual feedback, the haptic feedback, the screen design of the payment terminal and the NFC component. The results show that altering the aforementioned factors increase the usability of NFC payments and provides users with privacy and security-enhanced experience. We also framed 5 guidelines based on our evaluation results which will aid designers while designing or redesigning any system. We also believe that our research methods and guidelines contribute to the researches in the HCI community

Synergistic Innovations: Organometallic Frameworks on Graphene Oxide for Sustainable Eco-Energy Solutions

Combining organometallic frameworks with graphene oxide presents a fresh strategy to enhance the electrochemical capabilities of supercapacitors, contributing to the advancement of sustainable energy solutions. Continued refinement of materials and device design holds promise for broader applications across energy storage and conversion systems. This featured application underscores the inventive utilization of organometallic frameworks on graphene oxide, shedding light on the creation of superior energy storage devices for eco-friendly solutions. This review article delves into the synergistic advancements resulting from the fusion of organometallic frameworks with graphene oxide, offering a thorough exploration of their utility in sustainable eco-energy solutions. This review encompasses various facets, including synthesis methodologies, amplified catalytic performances, and structural elucidations. Through collaborative efforts, notable progressions in photocatalysis, photovoltaics, and energy storage are showcased, illustrating the transformative potential of these hybrids in reshaping solar energy conversion and storage technologies. Moreover, the environmentally conscious features of organometallic–graphene oxide hybrids are underscored through their contributions to environmental remediation, addressing challenges in pollutant elimination, water purification, and air quality enhancement. The intricate structural characteristics of these hybrids are expounded upon to highlight their role in tailoring material properties for specific eco-energy applications. Despite promising advancements, challenges such as scalability and stability are candidly addressed, offering a pragmatic view of the current research landscape. The manuscript concludes by providing insights into prospective research avenues, guiding the scientific community towards surmounting hurdles and fully leveraging the potential of organometallic–graphene oxide hybrids for a sustainable and energy-efficient future

TGF-β Determines the Pro-migratory Potential of bFGF Signaling in Medulloblastoma

The microenvironment shapes cell behavior and determines metastatic outcomes of tumors. We addressed how microenvironmental cues control tumor cell invasion in pediatric medulloblastoma (MB). We show that bFGF promotes MB tumor cell invasion through FGF receptor (FGFR) in vitro and that blockade of FGFR represses brain tissue infiltration in vivo. TGF-β regulates pro-migratory bFGF function in a context-dependent manner. Under low bFGF, the non-canonical TGF-β pathway causes ROCK activation and cortical translocation of ERK1/2, which antagonizes FGFR signaling by inactivating FGFR substrate 2 (FRS2), and promotes a contractile, non-motile phenotype. Under high bFGF, negative-feedback regulation of FRS2 by bFGF-induced ERK1/2 causes repression of the FGFR pathway. Under these conditions, TGF-β counters inactivation of FRS2 and restores pro-migratory signaling. These findings pinpoint coincidence detection of bFGF and TGF-β signaling by FRS2 as a mechanism that controls tumor cell invasion. Thus, targeting FRS2 represents an emerging strategy to abrogate aberrant FGFR signaling

Endothelial CaMKII as a regulator of eNOS activity and NO-mediated vasoreactivity

<div><p>The multifunctional Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase important in transducing intracellular Ca²⁺ signals. While <i>in vitro</i> data regarding the role of CaMKII in the regulation of endothelial nitric oxide synthase (eNOS) are contradictory, its role in endothelial function <i>in vivo</i> remains unknown. Using two novel transgenic models to express CaMKII inhibitor peptides selectively in endothelium, we examined the effect of CaMKII on eNOS activation, NO production, vasomotor tone and blood pressure. Under baseline conditions, CaMKII activation was low in the aortic wall. Consistently, systolic and diastolic blood pressure, heart rate and plasma NO levels were unaltered by endothelial CaMKII inhibition. Moreover, endothelial CaMKII inhibition had no significant effect on NO-dependent vasodilation. These results were confirmed in studies of aortic rings transduced with adenovirus expressing a CaMKII inhibitor peptide. In cultured endothelial cells, bradykinin treatment produced the anticipated rapid influx of Ca²⁺ and transient CaMKII and eNOS activation, whereas CaMKII inhibition blocked eNOS phosphorylation on Ser-1179 and dephosphorylation at Thr-497. Ca²⁺/CaM binding to eNOS and resultant NO production <i>in vitro</i> were decreased under CaMKII inhibition. Our results demonstrate that CaMKII plays an important role in transient bradykinin-driven eNOS activation <i>in vitro</i>, but does not regulate NO production, vasorelaxation or blood pressure <i>in vivo</i> under baseline conditions.</p></div