Increased thrombin generation in COVID-19 is mediated by platelet-dependent and-independent mechanisms

Background : Severe COVID-19 leads to inflammation and coagulopathy with progression to multiple organ failure. Several prothrombotic mechanisms have been proposed, including platelet hyperactivation, elevation in procoagulant microvesicles and tissue factor (TF), and NETosis with release of citrullinated histones. The contribution of these factors to enhanced thrombin generation in COVID-19 remains elusive. Aims : We hypothesized that plasma from COVID-19 patients enhances thrombin generation through both platelet-dependent and -independent mechanisms. Methods : Platelet poor plasma (PPP) was isolated from 136 COVID-19 patients enrolled in a multicenter randomized clinical trial comparing standard prophylactic dose to intermediate dose enoxaparin in hospitalized patients with severe COVID-19 (NCT04360824). Samples were also collected from healthy control subjects ( n = 33). Thrombin generation was triggered by either tissue factor (TF), phospholipids, or both, and was measured in a calibrated automated thrombogram. Citrullinated histone H3 (H3Cit) and tissue factor pathway inhibitor (TFPI) were measured by immunoassay. Results : When thrombin generation in PPP was triggered with TF and phospholipids, samples from COVID-19 patients exhibited higher endogenous thrombin potential (ETP), peak thrombin, and velocity index, and a delayed lag time compared to controls. The delayed lag time correlated with increased levels of TFPI in COVID-19 samples ( P = 0.01). Significant increases in thrombin generation in COVID-19 samples also occurred in response to phospholipids or TF alone, suggesting the presence of endogenous TF-positive microvesicles in COVID-19 plasma. To examine platelet-dependent thrombin generation, control platelets were incubated with PPP prior to measurement of thrombin generation triggered by TF. Significantly higher peak thrombin was observed with platelets incubated with plasma from COVID-19 patients;this effect was decreased by the histone aptamer KU7, suggesting histone-mediated platelet-dependent thrombin generation. Conclusions : These findings suggest that in COVID-19, histones mechanistically drive increased thrombin generation via platelets;and microvesicles and TF contributes to thrombin generation in a platelet-independent manner.

Using visual art for patient, family and staff education in the pediatric intensive care unit: A case study

AIMS & OBJECTIVES: A child's stay in the PICU is accompanied by major changes in their routine, which can have negative short-term and long-term consequences for their health-related quality of life. The use of visual learning tools in pediatric critical care can help in education and promotion of strategies to limit these effects by closing gaps in understanding and encouraging engagement of children, their families, and healthcare workers. METHODS: In 2019, we began an initiative in our tertiary care children's hospital to utilize art to optimize PICU Liberation education for critically ill children, their families, and Pediatric Intensive Care Unit (PICU) Staff. An interprofessional champion team determined the highest priorities for education and obtained feedback from their own discipline's stakeholders: 1) Education about sleep hygiene (Figure 1) and 2) Promoting early mobility (Figure 2). With the emergence of the COVID-19 pandemic, there was an additional urgent need identified for education about personal protective equipment to optimize safe mobility (Figure 3). The visual artist generated several drafts for review and feedback by the team and the final art was disseminated broadly throughout the PICU hallways, patient rooms, and entrances. RESULTS: The visual art was highly received by staff, patients, and families. CONCLUSIONS: As a learning tool, visual art can be used to increase awareness and address timely PICU topics. It should be explored further as an educational tool to help establish shared understanding between PICU staff, patients, and their families in a way that can transcend communication barriers while remaining engaging for all ages.

Social media as the rising voice of ICU nutrition

INTRODUCTION: Twitter has become an information source for healthcare professionals on a variety of critical care topics. The role Twitter plays as a resource for evidence to guide nutrition therapy is unknown. The purpose of this study is to describe dissemination of Pediatric and Adult critical care nutrition knowledge via Twitter, including frequency, scope of network, disciplines involved, and citation of literature. METHODS: Symplur Analytics was used to analyze the digital footprint of nutrition using the #ICU and #PedsICU hashtags between July 1, 2019 through June 30th, 2020. The top 1000 hashtags and keywords used in combination with #ICU or #PedsICU were examined to identify the most common nutrition related terms. RESULTS: The final dataset included 2837 tweets by 1349 users resulting in 7.5 million impressions. Data is presented as n (%). Most users tweeted once, with 222 users tweeting more than one tweet. Over half of tweeters were female [n=710 (53%)]. Most nutrition tweeters were non-physician healthcare providers [n=297 (22%)] with the next highest profession being doctors [n= 228 (17%)]. Fifty users tweeted 21% of the tweets (range 4-96 tweets/user);16 of these were dietitians, 13 physicians, and 12 organizations. Geographic data was available on 451 of the users;most tweets emanated from the US (n=149), the UK (n=132), Australia (n=20) and Canada (n=16). The most common hashtags used in this dataset were #COVID19, #FOAMcc and #CriticalCare and the most common keywords, ?enteral?, ?patients?, and ?early?. Eight of the 11 most tweeted links were journal articles and webinars from professional societies, and 3 were industry sponsored podcasts/webinars. CONCLUSIONS: This is the first analysis of the role Twitter plays in the dissemination of critical care nutrition therapy information. A limitation to this approach is variability in spelling across the globe. Future research should focus on identifying and analyzing those spellings not represented here to formulate a more comprehensive approach to information sharing. Identification and promotion of a single hashtag may further enhance the usability of ICU and Peds ICU nutrition knowledge internationally.

Live-tweeting the discovery of the new multisystem inflammatory syndrome in children (MIS-C)

INTRODUCTION: In April 2020, the COVID-19 pandemic saw a rise in the number of children with a multi-system hyperinflammatory disease with myocardial involvement and characteristics of toxic shock syndrome, Kawasaki Disease Shock Syndrome, atypical Kawasaki disease. Clinicians turned to social media to discuss what they were seeing and several names for this new syndrome were used, including Paediatric Multisystem Inflammatory Syndrome - Temporally Associated with SARSCoV- 2 and MIS-C. The use of these different names and hashtags may have affected the discussion and ability to share information. Our goal was to examine the real-time conversation on Twitter related to the discovery of this new syndrome. METHODS: We examined conversations occurring on Twitter in the pediatric critical care (PCC) community by examining hashtags associated with #PedsICU. Symplur Signals was used to identify the MIS-C related hashtags. We examined the digital footprint containing those hashtags including stakeholders, frequency of use, and the most commonly tweeted links. RESULTS: Between April 1st and July 21st 2020, there were 50,628 tweets by 13,411 users in the #PedsICU dataset resulting in 128,609,673 impressions. Thirteen new hashtags were identified related to MIS-C in 3664 tweets by 1391 users;#PIMSTS and #MISC were the most commonly used in 3085 (84%) of these tweets. Although #PIMSTS was promoted more in the UK and #MISC in the US, there were no significant differences in usage by country. Of the users tweeting with these MIS-C related hashtags, 39% were healthcare providers, 23% were physicians, and 6% were healthcare organizations. The five most commonly shared links were shared 248 times and included links to research articles, government guidelines, news articles, and a review blog. Peaks of usage of these hashtags coincided with the publication of research articles. CONCLUSIONS: New hashtags like #PIMSTS and #MISC have been used in the PCC community to focus and disseminate contents related to a novel pediatric syndrome related to COVID19. The evolving definitions and names used for this new entity are converging, but early confusion in names may have hampered discussion on Twitter and curation of reliable content.