Glucolipotoxicity initiates pancreatic beta-cell death through TNFR5/CD40-mediated STAT1 and NF-kappa B activation

Funded by Diabetes UK, NovoNordisk UK Research Foundation, and St. Bartholomew’s & The Royal London Charitable Foundation grant awards

Impact of urea on the microstructure of commercial canola protein-carrageenan network: A research note

Biopolymer mixtures contribute to network formation in food systems. The effects of pH and urea on the structural ordering of canola protein isolate-κ-carrageenan (CPI-κ-CAR) gels were assessed using scanning electron microscopy (SEM). At pH 6, loosely-crosslinked CPI networks with large empty pores were produced whereas tightly-crosslinked structures were displayed at pH 10. The structure of CPI network was greatly improved when CPI and κ-CAR were mixed, indicating a synergistic behaviour between the two macromolecules. Urea affected the structural arrangement and interactions involved in the formation CPI-κ-CAR gels. Urea-treated gels showed excessive network disruption and breakdown. The microstructural results support the involvement of disulfide bonds and noncovalent interactions in the structural arrangement of CPI-κ-CAR networks

Better With Ultrasound: Transcranial Doppler

© 2019 American College of Chest Physicians Transcranial Doppler (TCD) ultrasound is a noninvasive method of obtaining bedside neurologic information that can supplement the physical examination. In critical care, this can be of particular value in patients who are unconscious with an equivocal neurologic examination because TCD findings can help the physician in decisions related to more definitive imaging studies and potential clinical interventions. Although TCD is traditionally the domain of sonographers and radiologists, there is increasing adoption of goal-directed TCD at the bedside in the critical care environment. The value of this approach includes round-the-clock availability and a goal-directed approach allowing for repeatability, immediate interpretation, and quick clinical integration. This paper presents a systematic approach to incorporating the highest yield TCD techniques into critical care bedside practice, and includes a series of illustrative figures and narrated video presentations to demonstrate the techniques described

Basic ultrasound head-to-toe skills for intensivists in the general and neuro intensive care unit population: consensus and expert recommendations of the European Society of Intensive Care Medicine

Purpose: To provide consensus, and a list of experts’ recommendations regarding the basic skills for head-to-toe ultrasonography in the intensive care setting. Methods: The Executive Committee of the European Society of Intensive Care (ESICM) commissioned the project and supervised the methodology and structure of the consensus. We selected an international panel of 19 expert clinicians–researchers in intensive care unit (ICU) with expertise in critical care ultrasonography (US), plus a non-voting methodologist. The panel was divided into five subgroups (brain, lung, heart, abdomen and vascular ultrasound) which identified the domains and generated a list of questions to be addressed by the panel. A Delphi process based on an iterative approach was used to obtain the final consensus statements. Statements were classified as a strong recommendation (84% of agreement), weak recommendation (74% of agreement), and no recommendation (less than 74%), in favor or against. Results: This consensus produced a total of 74 statements (7 for brain, 20 for lung, 20 for heart, 20 for abdomen, 7 for vascular Ultrasound). We obtained strong agreement in favor for 49 statements (66.2%), 8 weak in favor (10.8%), 3 weak against (4.1%), and no consensus in 14 cases (19.9%). In most cases when consensus was not obtained, it was felt that the skills were considered as too advanced. A research agenda and discussion on training programs were implemented from the results of the consensus. Conclusions: This consensus provides guidance for the basic use of critical care US and paves the way for the development of training and research projects

Initial evaluation of extracorporeal immunomodulatory therapy for the treatment of critically ill COVID-19 infected patients

Severe COVID-19 infection results in significant immune dysregulation resulting from excessive recruitment and activation of neutrophils. The aim of this study was to confirm feasibility, initial safety and detect signal of efficacy of a non-propriety device delivered using an intermittent extra-corporeal system (LMOD) allowing leucocytes modulation in the setting of Severe COVID-19 infection. Twelve patients were recruited. Inclusion criteria were \textgreater 18 years age, confirmed COVID-19, acute respiratory distress syndrome requiring mechanical support and hypotension requiring vasopressor support. Primary end point was vasopressor requirements (expressed as epinephrine dose equivalents) and principle secondary endpoints related to safety, ability to deliver the therapy and markers of inflammation assessed over five days after treatment initiation. LMOD treatment appeared safe, defined by hemodynamic stability and no evidence of white cell number depletion from blood. We demonstrated a significant decrease in vasopressor doses (-37%, p = 0.02) in patients receiving LMOD therapy (despite these patients having to tolerate an additional extracorporeal intermittent therapy). Vasopressor requirements unchanged/increasing in control group (+ 10%, p = 0.48). Although much about the use of this therapy in the setting of severe COVID-19 infection remains to be defined (e.g. optimal dose and duration), this preliminary study supports the further evaluation of this novel extracorporeal approach

Initial evaluation of extracorporeal immunomodulatory therapy for the treatment of critically ill COVID-19 infected patients

Severe COVID-19 infection results in significant immune dysregulation resulting from excessive recruitment and activation of neutrophils. The aim of this study was to confirm feasibility, initial safety and detect signal of efficacy of a non-propriety device delivered using an intermittent extra-corporeal system (LMOD) allowing leucocytes modulation in the setting of Severe COVID-19 infection. Twelve patients were recruited. Inclusion criteria were \textgreater 18 years age, confirmed COVID-19, acute respiratory distress syndrome requiring mechanical support and hypotension requiring vasopressor support. Primary end point was vasopressor requirements (expressed as epinephrine dose equivalents) and principle secondary endpoints related to safety, ability to deliver the therapy and markers of inflammation assessed over five days after treatment initiation. LMOD treatment appeared safe, defined by hemodynamic stability and no evidence of white cell number depletion from blood. We demonstrated a significant decrease in vasopressor doses (-37%, p = 0.02) in patients receiving LMOD therapy (despite these patients having to tolerate an additional extracorporeal intermittent therapy). Vasopressor requirements unchanged/increasing in control group (+ 10%, p = 0.48). Although much about the use of this therapy in the setting of severe COVID-19 infection remains to be defined (e.g. optimal dose and duration), this preliminary study supports the further evaluation of this novel extracorporeal approach