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The mechanisms underlying the success of propranolol in the treatment of infantile hemangioma (IH) remain elusive and do not fully explain the rapid regression of hemangiomatous lesions following drug administration. As autophagy is critically implicated in vascular homeostasis, we determined whether β-blockers trigger the autophagic flux on infantile hemangioma-derived endothelial cells (Hem-ECs) in vitro., Material and Methods: Fresh tissue specimens, surgically removed for therapeutic purpose to seven children affected by proliferative IH, were subjected to enzymatic digestion. Cells were sorted with anti-human CD31 immunolabeled magnetic microbeads. Following phenotypic characterization, expanded Hem-ECs, at P2 to P6, were exposed to different concentrations (50 μM to 150 μM) of propranolol, atenolol or metoprolol alone and in combination with the autophagy inhibitor Bafilomycin A1. Rapamycin, a potent inducer of autophagy, was also used as control. Autophagy was assessed by Lysotracker Red staining, western blot analysis of LC3BII/LC3BI and p62, and morphologically by transmission electron microscopy., Results: Hem-ECs treated with either propranolol, atenolol or metoprolol displayed positive LysoTracker Red staining. Increased LC3BII/LC3BI ratio, as well as p62 modulation, were documented in β-blockers treated Hem-ECs. Abundant autophagic vacuoles and multilamellar bodies characterized the cytoplasmic ultrastructural features of autophagy in cultured Hem-ECs exposed in vitro to β-blocking agents. Importantly, similar biochemical and morphologic evidence of autophagy were observed following rapamycin while Bafilomycin A1 significantly prevented the autophagic flux promoted by β-blockers in Hem-ECs., Conclusion: Our data suggest that autophagy may be ascribed among the mechanisms of action of β-blockers suggesting new mechanistic insights on the potential therapeutic application of this class of drugs in pathologic conditions involving uncontrolled angiogenesis., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Arrhythmogenic cardiomyopathy (ACM) is a genetic disease associated with sudden cardiac death and cardiac fibro-fatty replacement. Over the last years, several works have demonstrated that different epigenetic enzymes can affect not only gene expression changes in cardiac diseases but also cellular metabolism. Specifically, the histone acetyltransferase GCN5 is known to facilitate adipogenesis and modulate cardiac metabolism in heart failure. Our group previously demonstrated that human primary cardiac stromal cells (CStCs) contribute to adipogenesis in the ACM pathology. Thus, this study aims to evaluate the role of GCN5 in ACM intracellular lipid accumulation. To do so, CStCs were obtained from right ventricle biopsies of ACM patients and from samples of healthy cadaveric donors (CTR). GCN5 expression was increased both in ex vivo and in vitro ACM samples compared to CTR. When GCN5 expression was silenced or pharmacologically inhibited by the administration of MB-3, we observed a reduction in lipid accumulation and a mitigation of reactive oxygen species (ROS) production in ACM CStCs. In agreement, transcriptome analysis revealed that the presence of MB-3 modified the expression of pathways related to cellular redox balance. Altogether, our findings suggest that GCN5 inhibition reduces fat accumulation in ACM CStCs, partially by modulating intracellular redox balance pathways., (© 2022 EURAC Research. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: The Intensive Care Unit (ICU) Complexity Assessment and Monitoring to Ensure Optimal Outcomes (CAMEO) acuity tool quantifies patient acuity in terms of nursing cognitive workload complexity., Objectives: The aim of this study was to refine the ICU CAMEO II acuity tool. An expert panel of nursing staff from 4 pediatric ICUs convened to refine the CAMEO II across a large, freestanding children's hospital in the United States., Method: This study used a modified Delphi technique., Results: Through a series of 4 Delphi rounds, the expert panel identified Domains of Care and nursing care items that were suitable to be collapsed or bundled. The number of Domains of Care decreased from 18 to 10. Each of the expert panel members then completed the ICU CAMEO II tool and the newly revised tool, ICU CAMEO III, on 5 to 10 patients. Sixty completed ICU CAMEO II tools, and ICU CAMEO III tools were available for comparison. The average difference of the 2 tools' total scores was 5 points (minimum, 4; maximum, 7). The level of agreement between the 2 tools by CAMEO Complexity Classification level (I-V) was 90%., Discussion: The ICU CAMEO III acuity tool is a streamlined measure to describe and quantify the acuity of pediatric critical care nursing. Use of this acuity measure will support projection of staffing models, staffing assignments, and benchmarking across pediatric ICUs. Further research is underway to validate the CAMEO III for multisite use., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The Intensive Care Unit Complexity Assessment and Monitoring to Ensure Optimal Outcomes (ICU CAMEO III) acuity tool measures patient acuity in terms of the complexity of nursing cognitive workload., Objective: To validate the ICU CAMEO III acuity tool in US children's hospitals., Methods: Using a convenience sample, 9 sites enrolled children admitted to pediatric intensive care units (ICUs). Descriptive statistics were used to summarize patient, nursing, and unit characteristics. Concurrent validity was evaluated by correlating the ICU CAMEO III with the Therapeutic Intervention Scoring System-Children (TISS-C) and the Pediatric Risk of Mortality III (PRISM III)., Results: Patients (N = 840) were enrolled from 15 units (7 cardiac and 8 mixed pediatric ICUs). The mean number of ICU beds was 23 (range, 12-34). Among the patients, 512 (61%) were diagnosed with cardiac and 328 (39%) with noncardiac conditions; 463 patients (55.1%) were admitted for medical reasons, and 377 patients (44.9%) were surgical. The ICU CAMEO III median score was 99 (range, 59-163). The ICU CAMEO complexity classification was determined for all 840 patients: 60 (7.1%) with level I complexity; 183 (21.8%) with level II; 201 (23.9%), level III; 267 (31.8%), level IV; and 129 (15.4%), level V. Strong correlation was found between ICU CAMEO III and both TISS-C (ρ = .822, P < .001) and PRISM III (ρ = .607, P < .001) scores, and between the CAMEO complexity classifications and the PRISM III categories (ρ = .575, P = .001)., Conclusion: The ICU CAMEO III acuity tool and CAMEO complexity classifications are valid measures of patient acuity and nursing cognitive workload compared with PRISM III and TISS-C in academic children's hospitals., (©2022 American Association of Critical-Care Nurses.)