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Additional file 1: Table 1. Baseline characteristics, lung mechanics and outcomes of included patients across the three participating study sites. Figure S1. Distribution of scores of Sequential Organ Failure Assessment (SOFA) on the day of intubation among the three study sites. Figure S2. Distribution of partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) values on the day of intubation (calculated after intubation) among the three study sites. Table S2. Univariable and multiple variable regression analysis to isolate the contribution of age, modified SOFA score on the day of intubation and study site (independent variables) to the ICU-mortality (dependent variable). Table S3. Univariable and multiple variable regression analysis to isolate the contribution of PaO2:FiO2, FiO2 and driving pressure on the day of intubation (independent variables) to the development of persistent severe ARDS (dependent variable). Table S4. Univariable and multiple variable regression analysis to isolate the contribution of age, modified SOFA score on the day of intubation and change in PaO2:FiO2 from day of intubation to the first day following intubation (independent variables) to the ICU-mortality (dependent variable). Table S5. Characteristics and outcomes of patients hospitalized in Crete with ARDS related to COVID-19 versus influenza. Table S6. Characteristics and outcomes of patients with rapidly improving ARDS due to pneumonia related or not to COVID-19.

Introduction: The endothelial protein C receptor (EPCR) is a protein that regulates the protein C anticoagulant and anti-inflammatory pathways. A soluble form of EPCR (sEPCR) circulates in plasma and inhibits activated protein C (APC) activities. The clinical impact of sEPCR and its involvement in COVID-19 has not been explored. In this study, we investigated whether sEPCR levels were related to COVID-19 patients’ requirement for hospitalization. Methods: Plasma sEPCR levels were measured on hospital admission in 84 COVID-19 patients, and in 11 non-hospitalized SARS-CoV2-positive patients approximately 6 days after reported manifestation of their symptoms. Multiple logistic regression analysis was performed to identify potential risk factors for hospitalization and receiver operating characteristic (ROC) curves were generated to assess their value. Results: In our cohort, hospitalized patients had considerably higher sEPCR levels upon admission compared with outpatients [107.5 (76.7-156.3) vs. 44.6 (12.1-84.4) ng/mL; P < 0.0001)]. The ROC curve using hospitalization as the classification variable and sEPCR levels as the prognostic variable generated an area under the curve at 0.845 (95% CI = 0.710-0.981, P < 0.001). Additionally, we investigated the predictive value of sEPCR combined with BMI, age, or D-dimers. Conclusions: In our cohort, sEPCR levels in COVID-19 patients upon hospital admission appear considerably elevated compared with outpatients; this could lead to impaired APC activities and might contribute to the pro-coagulant phenotype reported in such patients. sEPCR measurement might be useful as a point-of-care test in SARS-CoV2-positive patients.

Acute kidney injury (AKI) is one of the most common complications in critically ill patients. In recent years, studies have focused on exploring new biomarkers for the early diagnosis and prognosis of AKI. The aim of this study was to investigate serum prognostic biomarkers (neutrophil gelatinase-associated lipocalin, NGAL, and creatinine) of AKI in critically ill patients. The study included 266 critically ill, initially nonseptic, patients admitted to a multidisciplinary ICU. Serum levels of NGAL and creatinine were measured at ICU admission. ROC curves were generated to estimate the prognostic value of the biomarkers, while a logistic regression analysis was performed to assess their association with an increased AKI risk. Patients were divided in two groups based on the development (n = 98) or not (n = 168) of AKI during their ICU stay. Serum NGAL levels at ICU admission were significantly higher in those who subsequently developed AKI compared to those who did not (p < 0.0001). NGAL was shown to be more accurate in predicting AKI development than creatinine; furthermore, NGAL levels were associated with an increased risk of AKI development (1.005 (1.002-1.008), p < 0.0001). In the present study, we were able to demonstrate that increased serum NGAL levels at ICU admission might be predictive of AKI development during ICU hospitalization. Further studies are needed to support NGAL as a prognostic marker of acute kidney injury.

Studies have hypothesized a potential role of the interleukin (IL)-23/17 axis in coronavirus disease 2019 (COVID-19). However, to date, levels of IL-23 and 17 have not been compared between critically ill COVID-19 patients and critically ill non-COVID-19 patients. IL-23 and 17 were measured on admission to the intensive care unit (ICU) in critically ill COVID-19 (N = 38) and critically ill non-COVID-19 (N = 34) patients with an equal critical illness severity. Critically ill non-COVID-19 patients did not have sepsis or septic shock on ICU admission. None of the enrolled patients had previously received corticosteroids. In our study, circulating IL-17 levels were higher in the COVID-19 patients. More specifically, critically ill COVID-19 patients had levels of 0.78 (0.05-1.8) pg/mL compared to 0.11 (0.05-0.9) pg/mL in the critically ill non-COVID-19 patients (p = 0.04). In contrast, IL-23 levels were comparable between groups. A group of patients hospitalized in the specialized COVID-19 clinic (N = 16) was also used to evaluate IL-17 and IL-23 levels with respect to COVID-19 severity. Non-critically ill COVID-19 patients had undetectable levels of both cytokines. Our results support the notion of inhibiting IL-17 in critical COVID-19 infection.

Introduction: A potential complication in critically ill patients is the formation of bone in soft tissues, termed heterotopic ossification. The exact pathogenetic mechanisms are still undetermined. Bone morphogenetic proteins induce bone formation, while signalling through the receptor activator of nuclear factor kappa-B (RANK) and its ligand (RANKL), regulates osteoclast formation, activation, and survival in normal bone modelling and remodelling. Osteoprotegerin protects bone from excessive bone loss by blocking RANKL from binding to RANK. Aim: The study aimed to investigate these molecules as potential prognostic biomarkers of heterotopic ossification development in critically ill patients. Materials and Methods: In this prospective observational study, BMP-2, RANKL, and osteoprotegerin were measured by ELISA in twenty-eight critically-ill, initially non-septic patients, on admission to an ICU, seven days post-admission, and thirty days after ICU discharge. Results: In the critically-ill cohort, nine of the twenty-eight patients developed heterotopic ossification up to the 30-day follow-up time-point. The patients who developed heterotopic ossification exhibited significantly reduced BMP-2 and RANKL levels on ICU admission, compared to patients who did not; Osteoprotegerin readings were similar in both groups. Conclusions: Critically-ill patients who will subsequently develop heterotopic ossification, have significantly lower BMP-2 and RANKL levels at the time of ICU admission, suggesting that these proteins may be useful as prognostic markers for this debilitating condition.

Oxygen is the most commonly used drug in emergency medicine. The aim of this study was to identify healthcare professionals' preferences regarding oxygen therapy in common medical emergencies. An online 9-part-questionnaire was distributed through Facebook to doctors and nurses working in Greek hospitals. The questionnaire included background information of the respondents and addressed individual preferences regarding best oxygenation parameter and oxygen targets in specific acute settings. We received 678 responses and we included 663 in our analysis. We found significant differences between doctors' and nurses' attitudes towards oxygenation targets in ARDS, sepsis, acute coronary syndrome, and post cardiac-arrest patients. Nurses preferred a more conservative oxygen strategy compared to doctors. Furthermore, nurses favor SaO(2) as the best oxygenation parameter, while doctors prefer PaO2. In our survey, the type of hospital and department of the respondents did not affect the preferred oxygen strategy. Social media-based survey research is feasible and effective. In this single country study, doctors showed a tendency to liberally administer oxygen in acutely ill medical patients. On the other hand, Greek nurses preferred a more conservative approach.

Widespread endothelial activation and dysfunction often precede clinical sepsis. Several endothelium-related molecules have been investigated as potential biomarkers for early diagnosis and/or prognosis of sepsis, providing different results depending on study designs. Such factors include endothelial adhesion molecules like E- and P-selectin, and the intercellular adhesion molecule-1, vascular endothelial cadherin, growth factors such as Angiopoietin-1 and -2 and vascular endothelial growth factor, as well as von Willebrand factor antigen. We sought to investigate whether circulating biomarkers of endothelial activation/dysfunction measured at ICU admission are associated with subsequent sepsis development. Eighty-nine critically-ill patients admitted to a general ICU who met no sepsis criteria were studied. Plasma or serum levels of the above-mentioned endothelium-derived molecules were measured during the first 24 h post ICU; acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, age, sex, diagnostic category, and circulating procalcitonin (PCT) and C-reactive protein (CRP) levels were additionally measured or recorded. Forty-five patients subsequently became septic and 44 did not. Soluble (s) E- and P-selectin levels, circulating PCT, SOFA score and diagnostic category were significantly different between the two groups. Multiple logistic regression analysis associated elevated SE- and sP-selectin levels and SOFA with an increased risk of developing sepsis, while multiple Cox regression analysis identified SE- and sP-selectin levels as the only parameters related to sepsis appearance with time [RR = 1.026, 95%CI = 1.008-1.045, p = 0.005; RR = 1.005 (by 10 units), 95%CI = 1.000-1.010, p = 0.034, respectively]. When trauma patients were independently analyzed, multiple Cox regression analysis revealed sE-selectin to be the only molecule associated with sepsis development with time (RR = 1.041, 95%CI: 1.019-1.065; p < 0.001). In conclusion, in our cohort of initially non-septic critically-ill patients, high levels of the circulating endothelial adhesion molecules E- and P-selectin, measured at ICU admission, appear to be associated with sepsis development in time. (C) 2014 Elsevier Ltd. All rights reserved.