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Background: Sepsis presents a challenge due to its complex immune responses, where balance between inflammation and anti-inflammation is critical for survival. Glucocorticoid-induced leucine zipper (GILZ) is key protein in achieving this balance, suppressing inflammation and mediating glucocorticoid response. This study aims to investigate GILZ transcript variants in sepsis patients and explore their potential for patient stratification and optimizing glucocorticoid therapy., Methods: Sepsis patients meeting the criteria outlined in Sepsis-3 were enrolled, and RNA was isolated from whole blood samples. Quantitative mRNA expression of GILZ transcript variants in both sepsis patient samples (n = 121) and the monocytic U937 cell line (n = 3), treated with hydrocortisone and lipopolysaccharides, was assessed using quantitative PCR (qPCR)., Results: Elevated expression of GILZ transcript variant 1 (GILZ TV 1) serves as a marker for heightened 30-day mortality in septic patients. Increased levels of GILZ TV 1 within the initial day of sepsis onset are associated with a 2.2-[95% CI 1.2-4.3] fold rise in mortality, escalating to an 8.5-[95% CI 2.0-36.4] fold increase by day eight. GILZ TV1 expression is enhanced by glucocorticoids in cell culture but remains unaffected by inflammatory stimuli such as LPS. In septic patients, GILZ TV 1 expression increases over the course of sepsis and in response to hydrocortisone treatment. Furthermore, a high expression ratio of transcript variant 1 relative to all GILZ mRNA TVs correlates with a 2.3-fold higher mortality rate in patients receiving hydrocortisone treatment., Conclusion: High expression of GILZ TV 1 is associated with a higher 30-day sepsis mortality rate. Moreover, a high expression ratio of GILZ TV 1 relative to all GILZ transcript variants is a parameter for identifying patient subgroups in which hydrocortisone may be contraindicated., (© 2024. The Author(s).)

The aim of the current paper is to summarize the results of the International CytoSorb Registry. Data were collected on patients of the intensive care unit. The primary endpoint was actual in-hospital mortality compared to the mortality predicted by APACHE II score. The main secondary endpoints were SOFA scores, inflammatory biomarkers and overall evaluation of the general condition. 1434 patients were enrolled. Indications for hemoadsorption were sepsis/septic shock (N = 936); cardiac surgery perioperatively (N = 172); cardiac surgery postoperatively (N = 67) and "other" reasons (N = 259). APACHE-II-predicted mortality was 62.0±24.8%, whereas observed hospital mortality was 50.1%. Overall SOFA scores did not change but cardiovascular and pulmonary SOFA scores decreased by 0.4 [-0.5;-0.3] and -0.2 [-0.3;-0.2] points, respectively. Serum procalcitonin and C-reactive protein levels showed significant reduction: -15.4 [-19.6;-11.17] ng/mL; -17,52 [-70;44] mg/L, respectively. In the septic cohort PCT and IL-6 also showed significant reduction: -18.2 [-23.6;-12.8] ng/mL; -2.6 [-3.0;-2.2] pg/mL, respectively. Evaluation of the overall effect: minimal improvement (22%), much improvement (22%) and very much improvement (10%), no change observed (30%) and deterioration (4%). There was no significant difference in the primary outcome of mortality, but there were improvements in cardiovascular and pulmonary SOFA scores and a reduction in PCT, CRP and IL-6 levels. Trial registration: ClinicalTrials.gov Identifier: NCT02312024 (retrospectively registered)., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: KT has received honoraria for lectures and consultations from CytoSorbents Europe (Berlin, Germany); KK has received honoraria for lectures and consultations from CytoSorbents Europe (Berlin, Germany); AF has received honoraria for lectures and consultations from CytoSorbents Europe (Berlin, Germany); FMB has received honoraria for lectures and consultations from CytoSorbents Europe (Berlin, Germany); ZM has received honoraria for lectures and consultations and he also functions as medical director at CytoSorbents Europe (Berlin, Germany). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Sepsis is often associated with liver dysfunction, which is an indicator of poor outcomes. Specific diagnostic tools that detect hepatic dysfunction in its early stages are scarce. So far, the immune modulatory effects of hemoadsorption with CytoSorb ® on liver function are unclear., Method: We assessed the hepatic function by using the dynamic LiMAx ® test and biochemical parameters in 21 patients with sepsis or septic shock receiving CytoSorb ® in a prospective, observational study. Points of measurement: T 1 : diagnosis of sepsis or septic shock; T 2 and T 3 : 24 h and 48 h after the start of CytoSorb ® ; T 4 : 24 h after termination of CytoSorb ® ., Results: The hepatic biotransformation capacity measured by LiMAx ® was severely impaired in up to 95 % of patients. Despite a rapid shock reversal under CytoSorb ® , a significant improvement in LiMAx ® values appeared from T 3 to T 4 . This decline and recovery of liver function were not reflected by common parameters of hepatic metabolism that remained mostly within the normal range., Conclusions: Hepatic dysfunction can effectively and safely be diagnosed with LiMAx ® in ventilated ICU patients under CytoSorb ® . Various static liver parameters are of limited use since they do not adequately reflect hepatic dysfunction and impaired hepatic metabolism.

Hemoadsorption with CytoSorb ® becomes increasingly established in treatment of various, predominantly inflammation-associated diseases. In septic shock, results suggest improvements in hemodynamics and organ function. However, little is known about the in vivo adsorption properties for various antibiotics. We present the case of a 61-year-old female patient with known Ulrich Turner syndrome who treated supportively with CytoSorb ® and with linezolid due to a Staphylococcus epidermidis bloodstream infection as part of her intensive care treatment for septic shock. After establishment of a new adsorber, 600 mg of linezolid administered over 1 h. Linezolid levels measured before adsorber inlet (c pre ) and after adsorber outlet (c post ) at 0, 15, 60, 120 and 480 min after starting infusion. Out of the ten samples, only the cpre samples 60 min (3.25 mg/l) and 120 min (4.7 mg/l) showed sufficiently high linezolid levels (therapeutic range 3-9 mg/l). After 480 min, cpre decreased to 2.8 mg/l, cpost increased to 1.85 mg/l, and thus clearance decreased to 67.86 ml/min (from 200 ml/min at 60 min), with greatly reduced adsorption capacity of CytoSorb ® after 8 h. A loading dose (additional 600 mg) would have been urgently needed. Linezolid therapy under hemadsorption with CytoSorb ® requires a clear indication and close monitoring of levels to avoid underdosing., (© 2021. The Author(s).)

Remifentanil is a potent synthetic opioid with sedative effects. Intravenous remifentanil provides deep sedation and analgesia in laboratory animals during experimental procedures. We hypothesized that remifentanil would provide effective analgosedation during assisted mechanical ventilation without affecting respiratory mechanics in rats. Five male Sprague- Dawley rats (weight, 400 to 450 g) were assigned to receive assisted mechanical ventilation with continuous positive airway pressure for 5 h. Remifentanil (0.4 μg/kg/min IV) was delivered for the duration of ventilation. There were no differences between baseline, 1 h, and 5 h of ventilation in the mean arterial pressure, cardiac output, heart rate, and body temperature of all rats. Similarly, no differences were observed in the tidal volume, respiratory rate and minute ventilation, and gas exchange was equal in all rats at all time points. Frequent assessment of sedation by toe pinch documented loss of the pedal withdrawal reflex in all rats. We conclude that continuous remifentanil infusion provides sufficient analgosedation for mechanically ventilated rats without compromising hemodynamics, respiratory function, or gas exchange.

Background: From March to July 2009, influenza A (H1N1) 2009 (H1N1-2009) virus emerged as a major cause of respiratory failure that required mechanical ventilation. A small proportion of patients who had this condition developed severe respiratory failure that was unresponsive to conventional therapeutic interventions. In this report, we describe characteristics, treatment, and outcomes of critically ill patients in Canada who had H1N1-2009 infection and were treated with extracorporeal lung support (ECLS)., Methods: We report the findings of a case series of six patients supported with ECLS who were included in a cohort study of critically ill patients with confirmed H1N1-2009 infection. The patients were treated in Canadian adult and pediatric intensive care units (ICUs) from April 16, 2009 to August 12, 2009. We describe the nested sample treated with ECLS and compare it with the larger sample., Results: During the study period, 168 patients in Canada were admitted to ICUs for severe respiratory failure due to confirmed H1N1-2009 infection. Due to profound hypoxemia unresponsive to conventional therapeutic interventions, six (3.6%) of these patients were treated with ECLS in four ICUs. Four patients were treated with veno-venous pump-driven extracorporeal membrane oxygenation (vv-ECMO), and two patients were treated with pumpless lung assist (NovaLung iLA). The mean duration of support was 15 days. Four of the six patients survived (66.6%), one of the surviving patients was supported with iLA and the other three surviving patients were supported with ECMO. The two deaths were due to multiorgan failure, which occurred while the patients were on ECLS., Interpretation: Extracorporeal lung support may be an effective treatment for patients who have H1N1-2009 infection and refractory hypoxemia. Survival of these patients treated with ECLS is similar to that reported for patients who have acute respiratory distress syndrome of other etiologies and are treated with ECMO.

Background: The measurement of cardiac output in critically ill patients is complicated by rapid pathophysiological changes. The aim of this study was to compare the recently developed Arterial Pressure Cardiac Output algorithm (APCO) with transpulmonary thermodilution (TDCO). Clinical and hemodynamic parameters were tested for their impact on the measurements., Material/methods: Twenty septic patients were examined. Cardiac output measurements were performed simultaneously on 3 consecutive days. The data were evaluated using regression analysis and the Bland Altman approach., Results: Bland Altman analysis presented a bias of 0.72 L/min and limits of agreement of 2.16 to 3.61 L/min for TDCO vs. APCO. Statistically significant covariables in the regression analysis were systemic vascular resistance (p<0.001), mean arterial pressure (p<0.001), cardiac function index (p=0.01), global end-diastolic index (p=0.02) and stroke volume index (p=0.005). Multiple linear regression analysis showed the residual percentage error decreased from 49.1% to 21.5%., Conclusions: The APCO algorithm provides a broad range of hemodynamic measurements with a minimally invasive approach and simple access to the patient's hemodynamic state. However, an underestimation at high cardiac output and an overestimation at low cardiac output relative to transpulmonary thermodilution were observed in septic patients. Therefore, the APCO algorithm in its current state cannot be substituted for transpulmonary thermodilution.