Wound hygiene survey: awareness, implementation, barriers and outcomes.

OBJECTIVE: In light of the COVID-19 pandemic, which has resulted in changes to caseload management, access to training and education, and other additional pressures, a survey was developed to understand current awareness and implementation of the wound hygiene concept into practice one year on from its dissemination. Barriers to implementation and outcomes were also surveyed. METHOD: The 26-question survey, a mixture of multiple choice and free-text, was developed by the Journal of Wound Care projects team, in consultation with ConvaTec, and distributed globally via email and online; the survey was open for just over 12 weeks. Due to the exploratory nature of the research, non-probability sampling was used. The authors reviewed the outputs of the survey to draw conclusions from the data, with the support of a medical writer. RESULTS: There were 1478 respondents who agreed to the use of their anonymised aggregated data. Nearly 90% were from the US or UK, and the majority worked in wound care specialist roles, equally distributed between community and acute care settings; 66.6% had been in wound care for more than 8 years. The respondents work across the spectrum of wound types. More than half (57.4%) had heard of the concept of wound hygiene, of whom 75.3% have implemented it; 78.7% answered that they 'always' apply wound hygiene and 20.8% 'sometimes' do so. The top three barriers to adoption were confidence (39.0%), the desire for more research (25.7%) and competence (24.8%). Overall, following implementation of wound hygiene, 80.3% reported that their patients' healing rates had improved. CONCLUSION: Respondents strongly agreed that implementing wound hygiene is a successful approach for biofilm management and a critical component for improving wound healing rates in hard-to-heal wounds. However, the barriers to its uptake and implementation demonstrate that comprehensive education and training, institutional support for policy and protocol changes, and more clinical research are needed to support wound hygiene.

Proteomic analysis of intraluminal thrombus highlights complement activation in human abdominal aortic aneurysms.

OBJECTIVE: To identify proteins related to intraluminal thrombus biological activities that could help to find novel pathological mechanisms and therapeutic targets for human abdominal aortic aneurysm (AAA). APPROACH AND RESULTS: Tissue-conditioned media from patients with AAA were analyzed by a mass spectrometry-based strategy using liquid chromatography coupled to tandem mass spectrometry. Global pathway analysis by Ingenuity software highlighted the presence of several circulating proteins, among them were proteins from the complement system. Complement C3 concentration and activation were assessed in plasma from AAA patients (small AAA, AAA diameter=3-5 cm and large AAA, AAA diameter >5 cm), showing decreased C3 levels and activation in large AAA patients. No association of a combination of single-nucleotide polymorphisms in complement genes between large and small AAA patients was observed. Intense extracellular C3 inmunostaining, along with C9, was observed in AAA thrombus. Analysis of C3 in AAA tissue homogenates and tissue-conditioned media showed increased levels of C3 in AAA thrombus, as well as proteolytic fragments (C3a/C3c/C3dg), suggesting its local deposition and activation. Finally, the functional role of local complement activation in polymorphonuclear (PMN) cell activation was tested, showing that C3 blockade by anti-C3 antibody was able to decrease thrombus-induced neutrophil chemotaxis and reactive oxygen species production. CONCLUSIONS: A decrease of systemic C3 concentration and activity in the later stages of AAA associated with local complement retention, consumption, and proteolysis in the thrombus could induce PMN chemotaxis and activation, playing a detrimental role in AAA progression.

Potential protective role of let-7d-5p in atherosclerosis progression reducing the inflammatory pathway regulated by NF-κB and vascular smooth muscle cells proliferation.

The prevalence of cardiovascular diseases (CVDs) is increasing in the last decades, even is the main cause of death in first world countries being atherosclerosis one of the principal triggers. Therefore, there is an urgent need to decipher the underlying mechanisms involved in atherosclerosis progression. In this respect, microRNAs dysregulation is frequently involved in the progression of multiple diseases including CVDs. Our aim was to demonstrate that let-7d-5p unbalance could contribute to the pathophysiology of atherosclerosis and serve as a potential diagnostic biomarker. We evaluated let-7d-5p levels in vascular biopsies and exosome-enriched extracellular vesicles (EVs) from patients with carotid atherosclerosis and healthy donors. Moreover, we overexpressed let-7d-5p in vitro in vascular smooth muscle cells (VSMCs) to decipher the targets and the underlying mechanisms regulated by let-7d-5p in atherosclerosis. Our results demonstrate that let-7d-5p was significantly upregulated in carotid plaques from overweight patients with carotid atherosclerosis. Moreover, in EVs isolated from plasma, we found that let-7d-5p levels were increased in carotid atherosclerosis patients compared to control subjects specially in overweight patients. Receiver Operating Characteristic (ROC) analyses confirmed its utility as a diagnostic biomarker for atherosclerosis. In VSMCs, we demonstrated that increased let-7d-5p levels impairs cell proliferation and could serve as a protective mechanism against inflammation by impairing NF-κB pathway without affecting insulin resistance. In summary, our results highlight the role of let-7d-5p as a potential therapeutic target for atherosclerosis since its overexpression induce a decrease in inflammation and VSMCs proliferation, and also, as a novel non-invasive diagnostic biomarker for atherosclerosis in overweight patients.

Role of miR-15a-5p and miR-199a-3p in the inflammatory pathway regulated by NF-κB in experimental and human atherosclerosis.

BACKGROUND: Cardiovascular diseases (CVDs) prevalence has significantly increased in the last decade and atherosclerosis development is the main trigger. MicroRNAs (miRNAs) are non-coding RNAs that negatively regulate gene expression of their target and their levels are frequently altered in CVDs. METHODS: By RT-qPCR, we analysed miR-9-5p, miR-15a-5p, miR-16-5p and miR-199a-3p levels in aorta from apolipoprotein knockout (ApoE-/- ) mice, an experimental model of hyperlipidemia-induced atherosclerosis, and in human aortic and carotid atherosclerotic samples. By in silico studies, Western blot analysis and immunofluorescence studies, we detected the targets of the altered miRNAs. RESULTS: Our results show that miR-15a-5p and miR-199a-3p are significantly decreased in carotid and aortic samples from patients and mice with atherosclerosis. In addition, we found an increased expression in targets of both miRNAs that participate in the inflammatory pathway of nuclear factor kappa B (NF-κB), such as IKKα, IKKß and p65. In human vein endothelial cells (HUVECs) and vascular smooth muscle cells (VSMCs), the overexpression of miR-15a-5p or miR-199a-3p decreased IKKα, IKKß and p65 protein levels as well as NF-κB activation. On the other hand, miR-15a-5p and miR-199a-3p overexpression reduced ox-LDL uptake and the inflammation regulated by NF-κB in VSMCs. Moreover, although miR-15a-5p and miR-199a-3p were significantly increased in exosomes from patients with advanced carotid atherosclerosis, only in the ROC analyses for miR-15a-5p, the area under the curve was 0.8951 with a p value of .0028. CONCLUSIONS: Our results suggest that the decrease of miR-199a-3p and miR-15a-5p in vascular samples from human and experimental atherosclerosis could be involved in the NF-κB activation pathway, as well as in ox-LDL uptake by VSMCs, contributing to inflammation and progression atherosclerosis. Finally, miR-15a-5p could be used as a novel diagnostic biomarker for advanced atherosclerosis.

Statin use in aortic aneurismal disease to prevent progression and cardiovascular events: review of experimental and clinical data C.

Abdominal aortic aneurysm (AAA) is a significant health problem in the elderly. Efforts to limit the mortality rate depend on early detection and elective AAA repair. The benefit of early detection of AAAs, by ultrasound screening is limited since early repair of small AAA has been shown to provide no clinical advantage. There is currently no established pharmacotherapeutic treatment for small AAAs. In the first part of this review, we describe the potential mechanisms whereby statins can modulate the pathological processes associated to experimental and human AAA. Among them, statins are able to regulate leukocyte recruitment and immuno-inflammatory responses, platelet activation, oxidative stress, proteolysis and extracellular matrix breakdown. However, controversial results have been obtained in experimental models of AAA. In the second part of this review, we analyze the effect of statins in both, cardiovascular events on AAA patients and AAA growth. Although statin treatment is recommended for all AAA patients with the aim of reducing the incidence of cardiovascular events and death, controversial results have been shown between experimental and clinical studies regarding the potential preventive effect on AAA growth. One potential reason for these discrepancies could be related to the fact that statins reduce total cholesterol concentrations but do not modify HDL concentrations, the most sensitive predictor of AAA among lipid markers. In this respect, it could be of interest to test the effect of drugs modulating plasma HDL concentrations on AAA evolution.