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The COVID-19 crisis impacted emergency departments (ED) unexpectedly and exposed teams to major issues within a constantly changing environment. We implemented post-shift clinical debriefings (CDs) from the beginning of the crisis to cope with adaptability needs. As the crisis diminished, clinicians voiced a desire to maintain the post-shift CD program, but it had to be reshaped to succeed over the long term. A strategic committee, which included physician and nurse leadership and engaged front-line staff, designed and oversaw the implementation of CD. The CD structure was brief and followed a debriefing with a good judgment format. The aim of our program was to discover and integrate an organizational learning strategy to promote patient safety, clinicians' wellbeing, and engagement with the post-shift CD as the centerpiece. In this article, we describe how post-shift CD process was performed, lessons learned from its integration into our ED strategy to ensure value and sustainability and suggestions for adapting this process at other institutions. This novel application of debriefing was well received by staff and resulted in discovering multiple areas for improvement ranging from staff interpersonal interactions and team building to hospital wider quality improvement initiatives such as patient throughput.

Here, the authors show that HPV infection leads to downregulation of host mucosal innate peptides, which are in turn used by predominant Lactobacillus species as amino acid source, promoting ultimately an imbalance in the vaginal flora.

Abstract Aim Due to improved therapy in childhood, many patients with congenital heart disease reach adulthood and are termed adults with congenital heart disease (ACHD). ACHD often develop heart failure (HF) as a consequence of initial palliative surgery or complex anatomy and subsequently require advanced HF therapy. ACHD are usually excluded from trials evaluating heart failure therapies, and in this context, more data about heart failure trajectories in ACHD are needed to guide the management of ACHD suffering from HF. Methods and results The pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA‐R) will collect data from ACHD evaluated or listed for heart or heart‐combined organ transplantation from 16 countries in Europe and the Asia/Pacific region. We plan retrospective collection of data from 1989–2020 and will include patients prospectively. Additional organizations and hospitals in charge of transplantation of ACHD will be asked in the future to contribute data to the register. The primary outcome is the combined endpoint of delisting due to clinical worsening or death on the waiting list. The secondary outcome is delisting due to clinical improvement while on the waiting list. All‐cause mortality following transplantation will also be assessed. The data will be entered into an electronic database with access to the investigators participating in the register. All variables of the register reflect key components important for listing of the patients or assessing current HF treatment. Conclusion The ARTORIA‐R will provide robust information on current management and outcomes of adults with congenital heart disease suffering from advanced heart failure.

To date, it is still largely unclear how the changes, as a result of Covid-19, affect the work environment and the perceived organizational and managerial context (OMC). Through a mixed methods design, this study aims, (1) to identify changes in the hospital OMC before and during the first wave of the Covid-19 crisis; (2) to further analyze and compare the impact of the crisis on the perceptions of the staff. For the quantitative phase, questionnaire measuring the OMC was used in Covid and Non-Covid wards. For the qualitative phase, we performed semi-structured interviews to identify positive and negative elements from the crisis management. Results from linear mixed models highlighted multiple tendencies following the Covid crisis. Differences appeared between Covid and Non-Covid units, with the latter showing greater difficulties following the crisis. A significant increase in participants' scores on interprofessional relationships was reported (P < 0.05). We found a significant decrease in job satisfaction (P < 0.001), absence of burnout (P = 0.001) and perceived efficiency of the service (P < 0.001). These findings suggest that hospital management strategies should aim at providing transformational leadership and information flow, as well as equal support for all working units, so that healthcare professionals feel motivated and work towards a shared meaning. [ABSTRACT FROM AUTHOR]

Abstract Background There are limited data on Coronavirus disease 2019 (COVID-19) in solid organ transplant patients, especially in heart transplant recipients, with only a few case reports and case series described so far. Heart transplant recipients may be at particular high risk due to their comorbidities and immunosuppressed state. Case presentation This report describes the clinical course and the challenging management of early COVID-19 infection in two heart transplant recipients who tested positive for the SARS-CoV-2 virus in the perioperative period of the transplant procedure. The two patients developed a severe form of the disease and ultimately died despite the initiation of an antiviral monotherapy with hydroxychloroquine coupled with the interruption of mycophenolate mofetil. Conclusions These two cases illustrate the severity and poor prognosis of COVID-19 in the perioperative period of a heart transplant. Thorough screening of donors and recipients is mandatory, and the issue of asymptomatic carriers needs to be addressed.

Abstract Aim Heart failure (HF) poses a unique medical burden of high morbidity and mortality. Elevated resting heart rate (HR) is associated with worse outcomes in chronic HF, but little is known about the prognostic impact of serial HR measurement during hospital stay after acute HF. We examined the association between HR obtained at admission at Day 4 and at discharge and long‐term mortality in a cohort of 672 patients discharge from hospital after management of acute HF. Methods and results All patients examined were in sinus rhythm. HR was derived from electrocardiogram and was defined as the first reported HR in the medical record. At 1 year follow up, 60 patients died. Median HR was 86 ± 17 b.p.m. (first tertile: 75 b.p.m., third tertile: 97 b.p.m.) at admission, 76 ± 14 b.p.m. (first tertile: 67 b.p.m., third tertile 85 b.p.m.) at Day 4, and 72 ± 11 b.p.m. (first tertile: 64 b.p.m., third tertile 80 b.p.m.) at discharge. Patients who died were significantly older (75 ± 11 vs. 71 ± 12 years; P = 0.027), had more frequently a history of ischemic cardiomyopathy (n = 34/60, P = 0.012) and of chronic obstructive pulmonary disease (n = 26/60, P = 0.027), had higher admission N terminal pro brain natriuretic peptide (14 572 ± 21 600 vs. 7647 ± 7964 pg/ml; P = 0.027), had lower systolic and diastolic blood pressures (P 85 b.p.m. at Day 4 (P 80 b.p.m. at discharge (P

Abstract The functional integrity of the endothelium is essential for vascular health. In addition to maintaining a delicate balance between vasodilation and vasoconstriction, the endothelium has numerous other complex roles involved in the maintenance of vascular homeostasis. Chronic exposure to cardiovascular risk factors and oxidative stress results in an imbalance in these functions, creating an environment that favors reduced vasodilation and a proinflammatory and prothrombic state. The involvement of endothelial dysfunction in all stages of the cardiovascular continuum makes it an important target for treatment. One of the major endothelial-derived factors involved in the maintenance of endothelial function is nitric oxide (NO). Angiotensin-converting enzyme (ACE) inhibitors increase NO production both directly and indirectly by preventing production of angiotensin II (which diminishes NO production) and inhibiting the degradation of bradykinin (which stimulates local release of NO). Among the ACE inhibitors, perindopril appears to have the greatest effects on bradykinin and has demonstrated efficacy in a number of markers of endothelial dysfunction including arterial stiffness and progression of atherosclerosis. There is also strong evidence supporting the use of perindopril-based therapy for the treatment of hypertension and for reducing the risk of cardiovascular morbidity and mortality in a wide range of patients across the cardiovascular continuum. Funding: The journal’s Rapid Service Fee was funded by Servier.

Background High-mobility group box 1 (HMGB1) is a multifunctional redox-sensitive protein involved in various intracellular (eg, chromatin remodeling, transcription, autophagy) and extracellular (inflammation, autoimmunity) processes. Regarding its role in cancer development/progression, paradoxical results exist in the literature and it is still unclear whether HMGB1 mainly acts as an oncogene or a tumor suppressor.Methods HMGB1 expression was first assessed in tissue specimens (n=359) of invasive breast, lung and cervical cancer and the two distinct staining patterns detected (nuclear vs cytoplasmic) were correlated to the secretion profile of malignant cells, patient outcomes and the presence of infiltrating immune cells within tumor microenvironment. Using several orthotopic, syngeneic mouse models of basal-like breast (4T1, 67NR and EpRas) or non-small cell lung (TC-1) cancer, the efficacy of several HMGB1 inhibitors alone and in combination with immune checkpoint blockade antibodies (anti-PD-1/PD-L1) was then investigated. Isolated from retrieved tumors, 14 immune cell (sub)populations as well as the activation status of antigen-presenting cells were extensively analyzed in each condition. Finally, the redox state of HMGB1 in tumor-extruded fluids and the influence of different forms (oxidized, reduced or disulfide) on both dendritic cell (DC) and plasmacytoid DC (pDC) activation were determined.Results Associated with an unfavorable prognosis in human patients, we clearly demonstrated that targeting extracellular HMGB1 elicits a profound remodeling of tumor immune microenvironment for efficient cancer therapy. Indeed, without affecting the global number of (CD45+) immune cells, drastic reductions of monocytic/granulocytic myeloid-derived suppressor cells (MDSC) and regulatory T lymphocytes, a higher M1/M2 ratio of macrophages as well as an increased activation of both DC and pDC were continually observed following HMGB1 inhibition. Moreover, blocking HMGB1 improved the efficacy of anti-PD-1 cancer monoimmunotherapy. We also reported that a significant fraction of HMGB1 encountered within cancer microenvironment (interstitial fluids) is oxidized and, in opposite to its reduced isoform, oxidized HMGB1 acts as a tolerogenic signal in a receptor for advanced glycation endproducts-dependent manner.Conclusion Collectively, we present evidence that extracellular HMGB1 blockade may complement first-generation cancer immunotherapies by remobilizing antitumor immune response.

Vertical farming is considered as a potential solution to increase yield while decreasing resource use and pesticide impacts compared to conventional agriculture. However, the profitability of cultivating ordinary leafy green crops with low market prices in vertical farming is debated. We studied the agronomic feasibility and viability of growing a medicinal plant—Euphorbia peplus—for its ingenol-mebutate content in a modified shipping container farm as an alternative crop cultivation system. The impacts of three hydroponic substrates, three light intensities, three plant localizations and two surface areas on E. peplus yield and cost were tested in several scenarios. The optimization of biomass yield and area surface decreased the cultivation cost, with fresh crop cost per kg ranging from €185 to €59. Three ingenol-mebutate extraction methods were tested. The best extraction yields and cheapest method can both be attributed to ethyl acetate at 120 °C, with a yield of 43.8 mg/kg at a cost of €38 per mg. Modeling of the profitability of a pharmaceutical gel based on ingenol-mebutate showed that economic feasibility was difficult to reach, but some factors could rapidly increase the profitability of this production.

The pathway of selective autophagy, leading to a targeted elimination of specific intracellular components, is mediated by the ATG8 proteins, and has been previously suggested to be involved in the regulation of the Epithelial–mesenchymal transition (EMT) during cancer’s etiology. However, the molecular factors and steps of selective autophagy occurring during EMT remain unclear. We therefore analyzed a cohort of lung adenocarcinoma tumors using transcriptome analysis and immunohistochemistry, and found that the expression of ATG8 genes is correlated with that of EMT-related genes, and that GABARAPL1 protein levels are increased in EMT+ tumors compared to EMT- ones. Similarly, the induction of EMT in the A549 lung adenocarcinoma cell line using TGF-β/TNF-α led to a high increase in GABARAPL1 expression mediated by the EMT-related transcription factors of the SMAD family, whereas the other ATG8 genes were less modified. To determine the role of GABARAPL1 during EMT, we used the CRISPR/Cas9 technology in A549 and ACHN kidney adenocarcinoma cell lines to deplete GABARAPL1. We then observed that GABARAPL1 knockout induced EMT linked to a defect of GABARAPL1-mediated degradation of the SMAD proteins. These findings suggest that, during EMT, GABARAPL1 might intervene in an EMT-regulatory loop. Indeed, induction of EMT led to an increase in GABARAPL1 levels through the activation of the SMAD signaling pathway, and then GABARAPL1 induced the autophagy-selective degradation of SMAD proteins, leading to EMT inhibition.

EMT is a reversible cellular process that is linked to gene expression reprogramming, which allows for epithelial cells to undergo a phenotypic switch to acquire mesenchymal properties. EMT is associated with cancer progression and cancer therapeutic resistance and it is known that, during the EMT, many stress response pathways, such as autophagy and NMD, are dysregulated. Therefore, our goal was to study the regulation of ATG8 family members (GABARAP, GABARAPL1, LC3B) by the NMD and to identify molecular links between these two cellular processes that are involved in tumor development and metastasis formation. IHC experiments, which were conducted in a cohort of patients presenting lung adenocarcinomas, showed high GABARAPL1 and low UPF1 levels in EMT+ tumors. We observed increased levels of GABARAPL1 correlated with decreased levels of NMD factors in A549 cells in vitro. We then confirmed that GABARAPL1 mRNA was indeed targeted by the NMD in a 3′UTR-dependent manner and we identified four overlapping binding sites for UPF1 and eIF4A3 that are potentially involved in the recognition of this transcript by the NMD pathway. Our study suggests that 3′UTR-dependent NMD might be an important mechanism that is involved in the induction of autophagy and could represent a promising target in the development of new anti-cancer therapies.