The Relationship Between Sub Epidermal Moisture (SEM) Measurement and Inflammatory Markers in the Early Identification of Pressure Ulcers

Introduction: Pressure ulcer (PU) prevention in the intensive care unit (ICU) is a particularly important clinical issue as ICU patients are at high risk of developing PUs. However, current methods of PU detection are limited. The current gold standard of PU detection involves visual skin assessment (VSA). Reliance on VSA as a method of PU detection is problematic given that PUs’ often develop from within the deeper tissues at a microscopic rather than macroscopic level. Further research into the early methods of PU detection are needed in order to facilitate an objective approach to diagnosis, thus leading to the implementation of prevention strategies to prevent progression of PUs. Methods: The aim of this study was to establish the correlation between IL- 1α, total protein (TP) and Sub Epidermal Moisture (SEM) measurements in the early identification of PUs in ICU patients. This study involved the sampling of sebum using Sebutape and measurement of SEM from skin sites (sacrum, heels and a control site). SEM measurements and Sebutape samples were taken at the same time points, to assess any potential associations between these inflammatory measurement approaches in the detection of inflammation as part of the PU development phase. Five healthy volunteers were also recruited to the study. SEM and Sebutape readings were taken at the same anatomical locations as the ICU patients. Results: The study was conducted on 53 participants (equating to 783 measures) admitted to ICU in a large hospital in the Republic of Ireland. The mean baseline SEM delta measurements among the study participants indicate abnormal SEM deltas for all anatomical sites except the control site, where the reading was considered normal. Mean baseline IL-1α/TP readings were higher for the sacrum versus the right heel and left heel. Further, on average, IL-1α/TP readings were higher for the control site versus all other anatomical locations. Results demonstrated that there was very weak or weak correlations between SEM delta measurements and IL-1α/TP readings on all the study days, for all anatomical locations. Further, these correlations were not statistically significant. In the healthy volunteers, all mean SEM delta measurements were within normal limits. IL-1α/TP readings were higher for the sacrum versus the right heel and left heel. Further, IL-1α/TP readings were higher for the control site versus all other anatomical locations. Results showed a strong positive correlation between for the right heel and the left heel. Conversely, there was a very strong negative correlation for the sacrum, and a weak negative correlation for the control site. Conclusions: This study provides important information on not only the relationship between IL-1α/TP and SEM measurements as potential biomarkers in the early detection of PUs in adult ICU patients, but also sheds light on the feasibility of these methods in the ICU setting. Results from this study are consistent with findings from previous studies in terms of SEM delta measurements. There is a need for a quick, easy, and objective measure of PU development. It is evident from conducting this study that obtaining SEM measurements, is more practical and feasible than Sebutape sampling to assess for the presence of inflammation.</p

From impact factors to Altmetrics: what numbers are important in publishing your paper?

The volume of published research articles has increased exponentially over the past number of years, especially since many journals have transitioned to online open (free) access journal articles only. For this reason, it is important that academics, clinicians and researchers can quantify the impact and quality of the articles they are reading and publishing. It can become challenging to keep up to date with all of the terminology used to capture article and journal metrics. In this editorial we will present an overview of traditional metrics and newer, alternative metrics (Altmetrics) of article success and impact.</p

Reply to Blot et al. and to Inoue et al.

We thank Blot and colleagues for their interest in our article and for raising an important question regarding the suitability of IL-6 as a therapeutic target in coronavirus disease (COVID-19).In their correspondence, Blot and colleagues provide data on IL-6 levels measured in patients with a diagnosis of COVID-19 versus non–COVID-19 pneumonia. Although we believe the data presented by Blot and colleagues are valid, we suggest that the IL-6 levels depicted are, by virtue of sample timing, processing methodology, and patient severity of disease, not comparable to ours and should be interpreted in context.</p

Pressure ulcers in patients with COVID-19 acute respiratory distress syndrome undergoing prone positioning in the intensive care unit: a pre- and post-intervention study

Background: Prone positioning has been widely used to improve oxygenation and reduce ventilator-induced lung injury in patients with severe COVID-19 acute respiratory distress syndrome (ARDS). One major complication associated with prone positioning is the development of pressure ulcers (PUs). Aim: This study aimed to determine the impact of a prevention care bundle on the incidence of PUs in patients with COVID-19 ARDS undergoing prone positioning in the intensive care unit. Study design: This was a single-centre pre and post-test intervention study which adheres to the Standards for Reporting Implementation Studies (StaRI) guidelines. The intervention included a care bundle addressing the following: increasing frequency of head turns, use of an open gel head ring, application of prophylactic dressings to bony prominences, use of a pressure redistribution air mattress, education of staff in the early identification of evolving PUs through regular and rigorous skin inspection and engaging in bedside training sessions with nursing and medical staff. The primary outcome of interest was the incidence of PU development. The secondary outcomes of interest were severity of PU development and the anatomical location of the PUs. Results: In the pre-intervention study, 20 patients were included and 80% (n = 16) of these patients developed PUs, comprising 34 ulcers in total. In the post-intervention study, a further 20 patients were included and 60% (n = 12) of these patients developed PUs, comprising 32 ulcers in total. This marks a 25% reduction in the number of patients developing a PU, and a 6% decrease in the total number of PUs observed. Grade II PUs were the most prevalent in both study groups (65%, n = 22; 88%, n = 28, respectively). In the post-intervention study, there was a reduction in the incidence of grade III and deep tissue injuries (pre-intervention 6%, n = 2 grade III, 6% n = 2 deep tissue injuries; post-intervention no grade III ulcers, grade IV ulcers, or deep tissues injuries were recorded). However, there was an increase in the number of unstageable PUs in the post-intervention group with 6% (n = 2) of PUs being classified as unstageable, meanwhile there were no unstageable PUs in the pre-intervention group. This is an important finding to consider as unstageable PUs can indicate deep tissue damage and therefore need to be considered alongside PUs of a more severe grade (grade III, grade IV, and deep tissue injuries). Conclusion: The use of a new evidence-based care bundle for the prevention of PUs in the management of patients in the prone position has the potential to reduce the incidence of PU development. Although improvements were observed following alterations to standard practice, further research is needed to validate these findings. Relevance to clinical practice: The use of a new, evidence-based care bundle in the management of patients in the prone position has the potential to reduce the incidence of PUs.</p

Corrigendum to 'A linear prognostic score based on the ratio of interleukin-6 to interleukin-10 predicts outcomes in COVID-19'

The authors wish to correct a typographical error in the manuscript. In both the abstract and Section 3.4 of the original manuscript, a 1-point increase in the Dublin-Boston score was described as being associated with a 5.6 times increased odds (OR 5.62, 95% CI = 3.229.81, P = 1.2 £ 109 ) for a more severe outcome. While the OR and P-value stated are correct, the CI should instead have read “3.229.81”. The CI listed in Table 3 of the original manuscript, which accompanied Section 3.4, is correct. The authors regret any confusion caused, and appreciate the opportunity to correct this mistake.</div

A linear prognostic score based on the ratio of interleukin-6 to interleukin-10 predicts outcomes in COVID-19

Background: Prognostic tools are required to guide clinical decision-making in COVID-19.Methods: We studied the relationship between the ratio of interleukin (IL)-6 to IL-10 and clinical outcome in 80 patients hospitalized for COVID-19, and created a simple 5-point linear score predictor of clinical outcome, the Dublin-Boston score. Clinical outcome was analysed as a three-level ordinal variable ("Improved", "Unchanged", or "Declined"). For both IL-6:IL-10 ratio and IL-6 alone, we associated clinical outcome with a) baseline biomarker levels, b) change in biomarker level from day 0 to day 2, c) change in biomarker from day 0 to day 4, and d) slope of biomarker change throughout the study. The associations between ordinal clinical outcome and each of the different predictors were performed with proportional odds logistic regression. Associations were run both "unadjusted" and adjusted for age and sex. Nested cross-validation was used to identify the model for incorporation into the Dublin-Boston score.Findings: The 4-day change in IL-6:IL-10 ratio was chosen to derive the Dublin-Boston score. Each 1 point increase in the score was associated with a 5.6 times increased odds for a more severe outcome (OR 5.62, 95% CI -3.22-9.81, P = 1.2 × 10-9). Both the Dublin-Boston score and the 4-day change in IL-6:IL-10 significantly outperformed IL-6 alone in predicting clinical outcome at day 7.Interpretation: The Dublin-Boston score is easily calculated and can be applied to a spectrum of hospitalized COVID-19 patients. More informed prognosis could help determine when to escalate care, institute or remove mechanical ventilation, or drive considerations for therapies.</p

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

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) 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.</p

A randomised, double-blind, placebo-controlled, pilot trial of intravenous plasma purified alpha-1 antitrypsin for SARS-CoV-2-induced Acute Respiratory Distress Syndrome: a structured summary of a study protocol for a randomised, controlled trial

Objectives: The primary objective is to demonstrate that, in patients with PCR-confirmed SARS-CoV-2 resulting in Acute Respiratory Distress Syndrome (ARDS), administration of 120mg/kg of body weight of intravenous Prolastin®(plasma-purified alpha-1 antitrypsin) reduces circulating plasma levels of interleukin-6 (IL-6). Secondary objectives are to determine the effects of intravenous Prolastin® on important clinical outcomes including the incidence of adverse events (AEs) and serious adverse events (SAEs). Trial design: Phase 2, randomised, double-blind, placebo-controlled, pilot trial. Participants: The study will be conducted in Intensive Care Units in hospitals across Ireland. Patients with a laboratory-confirmed diagnosis of SARS-CoV-2-infection, moderate to severe ARDS (meeting Berlin criteria for a diagnosis of ARDS with a PaO2/FiO2 ratio 18 years of age and requiring invasive or non-invasive mechanical ventilation. All individuals meeting any of the following exclusion criteria at baseline or during screening will be excluded from study participation: more than 96 hours has elapsed from onset of ARDS; age < 18 years; known to be pregnant or breastfeeding; participation in a clinical trial of an investigational medicinal product (other than antibiotics or antivirals) within 30 days; major trauma in the prior 5 days; presence of any active malignancy (other than nonmelanoma skin cancer) which required treatment within the last year; WHO Class III or IV pulmonary hypertension; pulmonary embolism prior to hospital admission within past 3 months; currently receiving extracorporeal life support (ECLS); chronic kidney disease receiving dialysis; severe chronic liver disease with Child-Pugh score > 12; DNAR (Do Not Attempt Resuscitation) order in place; treatment withdrawal imminent within 24 hours; Prisoners; non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available; IgA deficiency. Intervention and comparator: Intervention: Either a once weekly intravenous infusion of Prolastin® at 120mg/kg of body weight for 4 weeks or a single dose of Prolastin® at 120mg/kg of body weight intravenously followed by once weekly intravenous infusion of an equal volume of 0.9% sodium chloride for a further 3 weeks. Comparator (placebo): An equal volume of 0.9% sodium chloride intravenously once per week for four weeks. Main outcomes: The primary effectiveness outcome measure is the change in plasma concentration of IL-6 at 7 days as measured by ELISA. Secondary outcomes include: safety and tolerability of Prolastin® in the respective groups (as defined by the number of SAEs and AEs); PaO2/FiO2 ratio; respiratory compliance; sequential organ failure assessment (SOFA) score; mortality; time on ventilator in days; plasma concentration of alpha-1 antitrypsin (AAT) as measured by nephelometry; plasma concentrations of interleukin-1β (IL-1β), interleukin-8 (IL-8), interleukin-10 (IL-10), soluble TNF receptor 1 (sTNFR1, a surrogate marker for TNF-α) as measured by ELISA; development of shock; acute kidney injury; need for renal replacement therapy; clinical relapse, as defined by the need for readmission to the ICU or a marked decline in PaO2/FiO2 or development of shock or mortality following a period of sustained clinical improvement; secondary bacterial pneumonia as defined by the combination of radiographic findings and sputum/airway secretion microscopy and culture. Randomisation: Following informed consent/assent patients will be randomised. The randomisation lists will be prepared by the study statistician and given to the unblinded trial personnel. However, the statistician will not be exposed to how the planned treatment will be allocated to the treatment codes. Randomisation will be conducted in a 1:1:1 ratio, stratified by site and age. Blinding (masking): The investigator, treating physician, other members of the site research team and patients will be blinded to treatment allocation. The clinical trial pharmacy personnel and research nurses will be unblinded to facilitate intervention and placebo preparation. The unblinded individuals will keep the treatment information confidential. The infusion bag will be masked at the time of preparation and will be administered via a masked infusion set to maintain blinding. Numbers to be randomised (sample size): A total of 36 patients will be recruited and randomised in a 1:1:1 ratio to each of the trial arms. </p

Von Willebrand factor propeptide in severe coronavirus disease 2019 (COVID-19): evidence of acute and sustained endothelial cell activation

Endothelial cell (EC) activation plays a key role in the pathogenesis of pulmonary microvascular occlusion, which is a hallmark of severe coronavirus disease 2019 (COVID-19). Consistent with EC activation, increased plasma von Willebrand factor antigen (VWF:Ag) levels have been reported in COVID-19. Importantly however, studies in other microangiopathies have shown that plasma VWF propeptide (VWFpp) is a more sensitive and specific measure of acute EC activation. In the present study, we further investigated the nature of EC activation in severe COVID-19. Markedly increased plasma VWF:Ag [median (interquatile range, IQR) 608·8 (531–830)iu/dl] and pro-coagulant factor VIII (FVIII) levels [median (IQR) 261·9 (170–315) iu/dl] were seen in patients with severe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Sequential testing showed that these elevated VWF–FVIII complex levels remained high for up to 3 weeks. Similarly, plasma VWFpp levels were also markedly elevated [median (IQR) 324·6 (267–524) iu/dl]. Interestingly however, the VWFpp/VWF:Ag ratio was reduced, demonstrating that decreased VWF clearance contributes to the elevated plasma VWF:Ag levels in severe COVID-19. Importantly, plasma VWFpp levels also correlated with clinical severity indices including the Sequential Organ Failure Assessment (SOFA) score, Sepsis-Induced Coagulopathy (SIC) score and the ratio of arterial oxygen partial pressure to fractional inspired oxygen (P/F ratio). Collectively, these findings support the hypothesis that sustained fulminant EC activation is occurring in severe COVID-19, and further suggest that VWFpp may have a role as a biomarker in this setting