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PurposeDevelopment of targeted biological therapies for COVID-19 requires reliable biomarkers that could help indicate the responding patients. Hyperactivation of the inflammasome by SARS-CoV2 virus is hypothesized to contribute to severe course of the COVID-19 disease. Therefore, we aimed to evaluate the prognostic value of several inflammasome-related cytokines and proteins at the admission to the intensive care unit (ICU).Patients and methodsPlasma samples were obtained from 45 critically ill COVID-19 patients and from 10 patients any without any signs of infection (TBI, traumatic brain injury) on admission to the ICU. The concentration of IL-1α, IL-1β, IL-18, IL-1RA, galectin-1, ASC, LDH, ferritin, and gasdermin D were analyzed. A novel cell-free caspase-1 plasma assay was developed by inhibitor-based immunoprecipitation followed by Western Blot. Demographic and clinical characteristics were recorded.ResultsIn-hospital mortality in COVID-19 patients reached 62%. Galectin-1 was 1.8-fold lower in COVID-19 than in TBI patients (17101.84 vs. 30764.20 pg/ml, p=0.007), but other inflammasome-related biomarkers were at similar concentrations. Patients with SOFA score of >9 on admission who were at high risk of death had significantly higher galectin-1 but lower IL-1RA in comparison to low-risk patients (25551.3 pg/ml vs 16302.7 pg/ml, p=0.014; 14.5 pg/ml vs 39.4 pg/ml, p=0.04, respectively). Statistically significant correlations were observed between: IL-1α and platelets (r=-0.37), IL-1β and platelets (r=-0.36), ferritin and INR (r=0.39). Activated caspase-1 p35 was detectable in 12/22 COVID-19 patients but in none of the TBI patients. Its presence was related with higher fibrinogen and lower D-dimers. Moreover, the densitometric analysis showed a significantly higher amount of p35 in patients with SOFA> 9.ConclusionOur results indicate that the systemic markers of activation of the inflammasome in critically ill COVID-19 patients is not directly related with outcome. Therefore, potential interventions aimed at the inflammasome pathway in this group of patients may be of limited effectiveness and should be biomarker-guided.

Background In Poland, little is known about the most serious cases of influenza that need admittance to the intensive care unit (ICU), as well as the use of extracorporeal respiratory support. Methods This was an electronic survey comprising ICUs in two administrative regions of Poland. The aim of the study was to determine the number of influenza patients with respiratory failure admitted to the ICU in the autumn–winter season of 2018/2019. Furthermore, respiratory support, outcome and other pathogens detected in the airways were investigated. Results Influenza infection was confirmed in 76 patients. The A(H1N1)pdm09 strain was the most common. 34 patients died (44.7%). The median age was 62 years, the median sequential organ failure assessment (SOFA) score was 11 and was higher in patients who died (12 vs. 10, p = 0.017). Mechanical ventilation was used in 75 patients and high flow nasal oxygen therapy in 1 patient. Extracorporeal membrane oxygenation (ECMO) was used in 7 patients (6 survived), and extracorporeal carbon dioxide removal (ECCO2R) in 2 (1 survived). The prone position was used in 16 patients. In addition, other pathogens were detected in the airways on admittance to the ICU. Conclusion A substantial number of influenza infections occurred in the autumn–winter season of 2018/2019 that required costly treatment in the intensive care units. Upon admission to the ICU, influenza patients had a high degree of organ failure as assessed by the SOFA score, and the mortality rate was 44.7%. Advanced extracorporeal respiratory techniques offer real survival opportunities to patients with severe influenza-related ARDS. The presence of coinfection should be considered in patients with influenza and respiratory failure.

The dysregulation of both the innate and adaptive responses to SARS-CoV-2 have an impact on the course of COVID-19, and play a role in the clinical outcome of the disease. Here, we performed a comprehensive analysis of peripheral blood lymphocyte subpopulations in 82 patients with COVID-19, including 31 patients with a critical course of the disease. In COVID-19 patients who required hospitalization we analyzed T cell subsets, including Treg cells, as well as TCRα/β and γ/δ, NK cells, and B cells, during the first two weeks after admission to hospital due to the SARS-CoV-2 infection, with marked reductions in leukocytes subpopulations, especially in critically ill COVID-19 patients. We showed decreased levels of Th, Ts cells, Treg cells (both naïve and induced), TCRα/β and γ/δ cells, as well as CD16+CD56+NK cells in ICU compared to non-ICU COVID-19 patients. We observed impaired function of T and NK cells in critically ill COVID-19 patients with extremely low levels of secreted cytokines. We found that the IL-2/INFγ ratio was the strongest indicator of a critical course of COVID-19, and was associated with fatal outcomes. Our findings showed markedly impaired innate and adaptive responses in critically ill COVID-19 patients, and suggest that the immunosuppressive state in the case of a critical course of SARS-CoV-2 infection might reflect subsequent clinical deterioration and predict a fatal outcome.

Objectives: Despite restrictions, mercury continues to pose a health concern. Mercury has the ability to deposit in most parts of the body and can cause a wide range of unspecific symptoms leading to diagnostic mistakes. Methods and results: We report the case of severe mercury vapour poisoning after occupational exposure in a chloralkali plant worker that resulted in life-threatening respiratory failure, pneumomediastinum and quadriparesis. Conclusions: Prolonged mechanical ventilation and treatment with penicillamine and spironolactone was used with successful outcome.

To examine the effect of endotoxemia on the procalcitonin (PCT) serum levels and mortality rates of adult patients with septic shock diagnosed on the day of admission to the intensive care unit (ICU). A retrospective observational study was performed over a 2-year period. Levels of PCT were compared for septic shock patients with and without endotoxemia on admission to the ICU. Endotoxemia was identified with an Endotoxin Activity Assay. One hundred fifty-seven patients with septic shock were enrolled into the study. Group 1 consisted of patients with elevated endotoxin activity (EA) (n = 95, EA = 0.57 endotoxin activity unit [EAU] [0.46–0.67]) and Group 2 consisted of patients with low EA (n = 62, EA = 0.27 EAU [0.17–0.36]). Acute Physiology And Chronic Health Evaluation II (APACHE II) score and SOFA score were similar in both groups (APACHE II = 23 [16–29] and 19 [16–25]; Sequential Organ Failure Assessment [SOFA] = 10 [7–13] and 11 [8–12] in Groups 1 and 2, respectively) (nonsignificant). The PCT level was 6 times higher in Group 1 than in Group 2 (19.6 ng/mL vs. 3.1 ng/mL, P

Endotoxin, a key component on the outer membrane of Gram-negative bacteria, is considered to be the most important toxin involved in the development of septic shock, and procalcitonin (PCT) serum concentration has been strongly associated with the severity of sepsis. The effect of elevated endotoxin activity (EA) on PCT serum level, organ function and mortality of patients with septic shock was evaluated on the day of admission to the ICU.

Endotoxin, a component of the outer membrane of Gram-negative bacteria, is considered an important factor in pathogenesis of septic shock [1]. The aim of our study was to determine whether endotoxin elimination treatment added to the standard treatment would improve organ function in patients with septic shock.

To evaluate the effectiveness of endotoxin elimination with an adsorption column in patients with septic shock and endotoxemia. The elimination therapy was guided by a new bedside method of measuring endotoxin activity (EA). Intensive care unit (ICU) patients with septic shock and suspected Gram-negative infection were consecutively added to the study group within the first 24 h. Endotoxin elimination was performed using hemoperfusion with the Alteco LPS Adsorber. The primary endpoint was improvement in organ function within the first 24 h of treatment. A secondary objective was to assess the usefulness of a new method of measuring EA to help guide endotoxin elimination therapy. Out of 64 patients 18 had a high baseline EA [0.70 EA units (0.66–0.77)]. Those patients had endotoxin elimination treatment in addition to conventional medical therapy. At 24 h after endotoxin elimination, the EA had decreased to 0.56 EA units (0.43–0.77), (p = 0.005); MAP increased from 69 (62–80) to 80 mm Hg (68–88), (p = 0.002), and noradrenaline use decreased from 0.28 (0.15–0.80) to 0.1 μg/kg/min (0.00–0.70) at the same time (p = 0.04). The SOFA score had decreased from 11 (9–15) to 9 (7–14) points 24 h after endotoxin elimination (p = 0.01) with a median delta SOFA –2 points. Endotoxin elimination did not have a significant effect on the ICU length of stay or ICU mortality. Effective endotoxin elimination resulted in a significant improvement in hemodynamic parameters and of organ function. The application of the EA assay was useful for the bedside monitoring of endotoxemia in critically ill ICU patients.

Many symptoms of septic shock are due to the presence of endotoxin in the bloodstream. The biological activity of endotoxins is associated with lipopolysaccharide (LPS). LPS induces systemic inflammatory response and a high level of endotoxin in blood is associated with worse clinical outcome. Reduction of the level of circulating endotoxins with hemoperfusion through the filter with high affinity for LPS could potentially interrupt the biological cascade of sepsis. The aim of the study was to evaluate the efficiency of extracorporeal endotoxin elimination in patients with Gram-negative septic shock.