Background and Aims The triggering factors of sepsis-induced myocardial dysfunction (SIMD) are poorly understood and are not addressed by current treatments. S100A8/A9 is a pro-inflammatory alarmin abundantly secreted by activated neutrophils during infection and inflammation. We investigated the efficacy of S100A8/A9 blockade as a potential new treatment in SIMD. Methods The relationship between plasma S100A8/A9 and cardiac dysfunction was assessed in a cohort of 62 patients with severe sepsis admitted to the intensive care unit of Linköping University Hospital, Sweden. We used S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 and S100A9−/− mice for therapeutic and mechanistic studies on endotoxemia-induced cardiac dysfunction in mice. Results In sepsis patients, elevated plasma S100A8/A9 was associated with left-ventricular (LV) systolic dysfunction and increased SOFA score. In wild-type mice, 5 mg/kg of bacterial lipopolysaccharide (LPS) induced rapid plasma S100A8/A9

Background Response to prophylactic platelet transfusion is suspected to be inconsistent in critically ill patients questioning how to optimize transfusion practices. This study aimed to describe prophylactic platelet transfusion response, to identify factors associated with a suboptimal response, to analyse the correlation between corrected count increment and platelet count increment and to determine the association between poor platelet transfusion response and clinical outcomes. Methods This prospective multicentre observational study recruited patients who received at least one prophylactic platelet transfusion in one of the nine participating intensive care units for a period up to 16 months. Poor platelet transfusion response was defined as a corrected count increment (CCI) that adjusts for platelet dose and body surface area, less than 7 at 18–24 h after platelet transfusion. Factors associated with poor platelet transfusion response were assessed in a mixed-effect model. Sensi

Background Sepsis-induced immunosuppression is a frequent cause of opportunistic infections and death in critically ill patients. A better understanding of the underlying mechanisms is needed to develop targeted therapies. Circulating bile acids with immunosuppressive effects were recently identified in critically ill patients. These bile acids activate the monocyte G-protein coupled receptor TGR5, thereby inducing profound innate immune dysfunction. Whether these mechanisms contribute to immunosuppression and disease severity in sepsis is unknown. The aim of this study was to determine if immunosuppressive bile acids are present in endotoxemia and septic shock and, if so, which patients are particularly at risk. Methods To induce experimental endotoxemia in humans, ten healthy volunteers received 2 ng/kg E. coli lipopolysaccharide (LPS). Circulating bile acids were profiled before and after LPS administration. Furthermore, 48 patients with early (shock onset within < 24 h) and severe

Background The effects of awake prone position on the breathing pattern of hypoxemic patients need to be better understood. We conducted a crossover trial to assess the physiological effects of awake prone position in patients with acute hypoxemic respiratory failure. Methods Fifteen patients with acute hypoxemic respiratory failure and PaO2/FiO2 < 200 mmHg underwent high-flow nasal oxygen for 1 h in supine position and 2 h in prone position, followed by a final 1-h supine phase. At the end of each study phase, the following parameters were measured: arterial blood gases, inspiratory effort (ΔPES), transpulmonary driving pressure (ΔPL), respiratory rate and esophageal pressure simplified pressure–time product per minute (sPTPES) by esophageal manometry, tidal volume (VT), end-expiratory lung impedance (EELI), lung compliance, airway resistance, time constant, dynamic strain (VT/EELI) and pendelluft extent through electrical impedance tomography. Results Compared to supine position, pro