Biomarkers for the early detection of pressure ulcers in the intensive care setting: A comparison between sub-epidermal moisture measurements and interleukin-1α.

Pressure ulcer (PU) prevention in the intensive care unit (ICU) is an important clinical issue as critically unwell patients are at high risk of developing PUs. However, current methods of PU detection are limited, especially for early detection. This study aimed to establish the correlation between Interleukin-1α (IL-1α)/total protein (TP) and sub-epidermal moisture (SEM) measurements in the early identification of PUs in ICU patients. This study employed an observational research design using the STROBE guidelines. Following ethical approval, 53 participants were recruited and sebum was obtained using Sebutape from weight-bearing areas (sacrum, heels and a control site). SEM measurements were taken from the same anatomical sites. Both measures were taken at the same time and participants were followed up for 5 days, or until discharge or death. Correlations between SEM delta measurements, IL-1α, TP and PU incidence and other demographic information were explored using Spearman's correlation for data not normally distributed, and Pearson's R correlation coefficient for normally distributed data. Mean baseline SEM delta measurements indicate abnormal readings for all anatomical sites except the control site, consistent with previous studies. Mean baseline IL-1α/TP readings were higher for the sacrum versus both heels and, on average, readings were higher for the control site versus all other anatomical locations. This is conflicting, given that the control site was non-weight bearing. There were very weak or weak correlations between SEM delta measurements and IL-1α/TP readings. SEM measurements are quick and easy to obtain and results are instant, however Sebutape sampling takes significantly longer and is challenging to conduct among haemodynamically unstable patients. Obtaining SEM measurements is more practical and feasible than Sebutape sampling to assess for the presence of inflammation.

Cleavage of the extracellular domain of junctional adhesion molecule-A is associated with resistance to anti-HER2 therapies in breast cancer settings.

BACKGROUND: Junctional adhesion molecule-A (JAM-A) is an adhesion molecule whose overexpression on breast tumor tissue has been associated with aggressive cancer phenotypes, including human epidermal growth factor receptor-2 (HER2)-positive disease. Since JAM-A has been described to regulate HER2 expression in breast cancer cells, we hypothesized that JAM-dependent stabilization of HER2 could participate in resistance to HER2-targeted therapies. METHODS: Using breast cancer cell line models resistant to anti-HER2 drugs, we investigated JAM-A expression and the effect of JAM-A silencing on biochemical/functional parameters. We also tested whether altered JAM-A expression/processing underpinned differences between drug-sensitive and -resistant cells and acted as a biomarker of patients who developed resistance to HER2-targeted therapies. RESULTS: Silencing JAM-A enhanced the anti-proliferative effects of anti-HER2 treatments in trastuzumab- and lapatinib-resistant breast cancer cells and further reduced HER2 protein expression and Akt phosphorylation in drug-treated cells. Increased epidermal growth factor receptor expression observed in drug-resistant models was normalized upon JAM-A silencing. JAM-A was highly expressed in all of a small cohort of HER2-positive patients whose disease recurred following anti-HER2 therapy. High JAM-A expression also correlated with metastatic disease at the time of diagnosis in another patient cohort resistant to trastuzumab therapy. Importantly, cleavage of JAM-A was increased in drug-resistant cell lines in conjunction with increased expression of ADAM-10 and -17 metalloproteases. Pharmacological inhibition or genetic silencing studies suggested a particular role for ADAM-10 in reducing JAM-A cleavage and partially re-sensitizing drug-resistant cells to the anti-proliferative effects of HER2-targeted drugs. Functionally, recombinant cleaved JAM-A enhanced breast cancer cell invasion in vitro and both invasion and proliferation in a semi-in vivo model. Finally, cleaved JAM-A was detectable in the serum of a small cohort of HER2-positive patients and correlated significantly with resistance to HER2-targeted therapy. CONCLUSIONS: Collectively, our data suggest a novel model whereby increased expression and cleavage of JAM-A drive tumorigenic behavior and act as a biomarker and potential therapeutic target for resistance to HER2-targeted therapies.

The effectiveness of Bio-Min toothpaste in the management of white spot lesions: a randomised control trial.

BACKGROUND: White spot lesions (WSL) are common side effects of orthodontic treatment with fixed appliances, in which the surface layer of enamel is demineralised. Thus, remineralisation, that is a partial or complete reversal, of these lesions can occur as they affect the surface enamel. Remineralisation with low-dose fluoride, in addition to optimal oral hygiene and diet, has been recommended to manage WSL. The aim of the planned trial is to assess the effectiveness of a fluoride-containing bioactive glass toothpaste (BioMin™) in its ability to remineralise post-orthodontic demineralised WSL. METHODS: A single-centre, double-blind randomised clinical trial to assess intervention with Bio-Min toothpaste on WSL forming on the teeth of young people completing orthodontic treatment. DISCUSSION: Remineralisation of WSL can vary depending on the individual and the site of the lesion. There is a range of oral fluoride delivery methods which include toothpastes, oral rinses, and gel preparations, which can aid remineralisation of these lesions. Identifying effective methods of remineralisation to manage this common and unsightly complication of fixed appliance therapy can improve the health and aesthetics of dentition. TRIAL REGISTRATION: ISRCTN.com International Standard Randomised Controlled Trials Number (ISRCTN) 14479893 . Registered on 14 May 2020.

Use of a novel "Split" ventilation system in bench and porcine modeling of acute respiratory distress syndrome.

Split ventilation (using a single ventilator to ventilate multiple patients) is technically feasible. However, connecting two patients with acute respiratory distress syndrome (ARDS) and differing lung mechanics to a single ventilator is concerning. This study aimed to: (1) determine functionality of a split ventilation system in benchtop tests, (2) determine whether standard ventilation would be superior to split ventilation in a porcine model of ARDS and (3) assess usability of a split ventilation system with minimal specific training. The functionality of a split ventilation system was assessed using test lungs. The usability of the system was assessed in simulated clinical scenarios. The feasibility of the system to provide modified lung protective ventilation was assessed in a porcine model of ARDS (n = 30). In bench testing a split ventilation system independently ventilated two test lungs under conditions of varying compliance and resistance. In usability tests, a high proportion of naïve operators could assemble and use the system. In the porcine model, modified lung protective ventilation was feasible with split ventilation and produced similar respiratory mechanics, gas exchange and biomarkers of lung injury when compared to standard ventilation. Split ventilation can provide some elements of lung protective ventilation and is feasible in bench testing and an in vivo model of ARDS.

Dysregulated plasma lipid mediator profiles in critically ill COVID-19 patients.

Coronavirus disease (COVID)-19, as a result of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has been the direct cause of over 2.2 million deaths worldwide. A timely coordinated host-immune response represents the leading driver for restraining SARS-CoV-2 infection. Indeed, several studies have described dysregulated immunity as the crucial determinant for critical illness and the failure of viral control. Improved understanding and management of COVID-19 could greatly reduce the mortality and morbidity caused by SARS-CoV-2. One aspect of the immune response that has to date been understudied is whether lipid mediator production is dysregulated in critically ill patients. In the present study, plasma from COVID-19 patients with either severe disease and those that were critically ill was collected and lipid mediator profiles were determined using liquid chromatography tandem mass spectrometry. Results from these studies indicated that plasma concentrations of both pro-inflammatory and pro-resolving lipid mediator were reduced in critically ill patients when compared with those with severe disease. Furthermore, plasma concentrations of a select group of mediators that included the specialized pro-resolving mediators (SPM) Resolvin (Rv) D1 and RvE4 were diagnostic of disease severity. Interestingly, peripheral blood SPM concentrations were also linked with outcome in critically ill patients, where we observed reduced overall concentrations of these mediators in those patients that did not survive. Together the present findings establish a link between plasma lipid mediators and disease severity in patients with COVID-19 and indicate that plasma SPM concentrations may be linked with survival in these patients.

Prone positioning improves oxygenation and lung recruitment in patients with SARS-CoV-2 acute respiratory distress syndrome; a single centre cohort study of 20 consecutive patients.

OBJECTIVE: We aimed to characterize the effects of prone positioning on respiratory mechanics and oxygenation in invasively ventilated patients with SARS-CoV-2 ARDS. RESULTS: This was a prospective cohort study in the Intensive Care Unit (ICU) of a tertiary referral centre. We included 20 consecutive, invasively ventilated patients with laboratory confirmed SARS-CoV-2 related ARDS who underwent prone positioning in ICU as part of their management. The main outcome was the effect of prone positioning on gas exchange and respiratory mechanics. There was a median improvement in the PaO2/FiO2 ratio of 132 in the prone position compared to the supine position (IQR 67-228). We observed lower PaO2/FiO2 ratios in those with low (< median) baseline respiratory system static compliance, compared to those with higher (> median) static compliance (P < 0.05). There was no significant difference in respiratory system static compliance with prone positioning. Prone positioning was effective in improving oxygenation in SARS-CoV-2 ARDS. Furthermore, poor respiratory system static compliance was common and was associated with disease severity. Improvements in oxygenation were partly due to lung recruitment. Prone positioning should be considered in patients with SARS-CoV-2 ARDS.

Health food blogger: friend or foe?

Objectives The Scientific Advisory Committee on Nutrition (SACN) and the World Health Organisation (WHO) have recently updated nutritional guidelines for a reduced sugar intake. With the increased popularity of online health-food bloggers and 'refined-sugar free' recipes, this review looked to analyse recipes from popular online bloggers to validate the veracity of their 'sugar-free' and 'healthy' claims and assess their adherence to recently implemented nutritional guidelines.Method Four bloggers were randomly selected from the Amazon top 10 booklist and their online blogs were consulted for a selection of recipes which were then nutritionally analysed in relation to their sugar and fat content.Results Eighty percent of the recipes analysed contained more fat than a Mars bar and 70% contained more fat than a popular online cake recipe, while 25% of the recipes contained over half of the recommended daily sugar intake as advised by the SACN and the WHO. None of the bloggers analysed used evidence-based approaches for the advice on their blogs.Conclusion Bloggers offer an invaluable platform to disseminate dietary advice to the public; however the recipes in this analysis were not healthy alternatives. The challenge is for government and health organisations to use this platform to promote alternative healthy eating options that align to current national and international guidance.