Purpose The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury. Methods We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume. Results Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01–1.38; P = 0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02–1.07; P = 0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07–3.64; P = 0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher V_T. Conclusions Higher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241).

Patients with sepsis syndrome commonly have low serum selenium levels. Several randomized controlled trials have examined the efficacy of selenium supplementation on mortality in patients with sepsis. To determine the efficacy and safety of high-dose selenium supplementation compared to placebo for the reduction of mortality in patients with sepsis. We searched Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, SciFinder, and Clinicaltrials.gov. Randomized controlled parallel group trials comparing selenium supplementation in doses greater than daily requirement to placebo on the outcome of mortality in patients with sepsis syndrome. Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcome was mortality; secondary outcomes were ICU length of stay, nosocomial pneumonia, and adverse events. Trial authors were contacted for additional or clarifying information. Nine trials enrolling a total of 792 patients were included. Selenium supplementation in comparison to placebo was associated with lower mortality (odds ratio, 0.73; 95% CI, 0.54, 0.98; p = 0.03; I = 0%). Among patients receiving and not receiving selenium, there was no difference in ICU length of stay (mean difference, 2.03; 95% CI, -0.51, 4.56; p = 0.12; I = 0%) or nosocomial pneumonia (odds ratio, 0.83; 95% CI, 0.28, 2.49; p = 0.74; I = 56%). Significant heterogeneity among trials in adverse event reporting precluded pooling of results. In patients with sepsis, selenium supplementation at doses higher than daily requirement may reduce mortality. We observed no impact of selenium on ICU length of stay or risk of nosocomial pneumonia.

Several laboratory studies suggested that induced hypothermia during hemorrhagic shock improves survival. Inhaled hydrogen sulfide (H₂S) induced hypothermia and decreased metabolism in mice and rats but not in piglets. We tested the hypothesis that i.v. H₂S will induce hypothermia, reduce oxygen consumption (VO₂), and improve outcome in prolonged hemorrhagic shock in pigs. We also assessed markers of organ injury (alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, creatinine, and troponin) and level of protein thiols to monitor H₂S metabolism. In a prospective randomized study, pigs were subjected to volume-controlled hemorrhagic shock with limited fluid resuscitation to maintain MAP 30 mmHg or greater. The study group received infusion of H₂S at 5 mg·kg⁻¹·h⁻¹; the control group received vehicle (n = 8 per group). Dose was based on the highest tolerated dose in pilot studies. Full resuscitation was initiated after 3 h. There were no differences in survival at 24 h between groups (2/8 in H₂S vs. 3/8 in control group). Heart rate increased similarly during hemorrhagic shock in both groups. Cardiac output was better preserved in the delayed phase of hemorrhagic shock in the control group. Temperature and VO₂ were similar in both groups during hemorrhagic shock and resuscitation. Markers of organ injury and protein thiols markedly increased in both groups with no differences between groups. In conclusion, we were not able to demonstrate the hypothermia-inducing effect or a reduction in VO₂ from H₂S infusion in our model of hemorrhagic shock in pigs. Our data mirror those seen in piglets and provide additional evidence of difficulty in translating the hypothermia effect of H₂S to large animals in a clinically relevant postinsult paradigm.

Introduction: Procalcitonin (PCT) and C-reactive protein (CRP) are established markers of infection in the general population. In contrast, several studies reported falsely increased PCT levels in patients receiving T-cell antibodies. We evaluated the validity of these markers in patients scheduled for hemopoietic stem cell transplantation receiving anti-thymocyte globulin (ATG) during conditioning. We also assessed renal and liver functions and their relationship to PCT and CRP changes. Methods: Twenty-six patients without clinical signs of infection were prospectively studied. ATG was administered in up to three doses over the course of 5 days. PCT, CRP, white blood cell (WBC) count, urea, creatinine, glomerular filtration rate, bilirubin, alanin amino-transferase (ALT), and gamma-glutamyl transferase (GGT) were assessed daily during ATG administration. Pharyngeal, nose, and rectal swabs and urine samples were cultured twice weekly. Blood cultures were obtained if clinical symptoms of infection were present. Results: Baseline (BL) levels of both PCT and CRP before ATG administration were normal. WBC count decreased after ATG administration (P = 0.005). One day after ATG administration, both PCT and CRP levels increased significantly, returning to BL levels on day 4. Microbiological results were clinically unremarkable. There was no interrelationship between PCT levels and BL markers of renal or liver functions (P > 0.05 for all comparisons). Bilirubin and GGT were increased on days 2 to 5 and ALT was increased on day 3 (P < 0.05 versus BL). No difference in renal functions was observed. Three patients developed bacterial infection on days 7 to 11 with different dynamics of PCT and CRP. There was no association between the number of ATG doses and PCT levels or between the risk of developing infection and previous PCT levels. Conclusions: ATG triggered a marked early surge in PCT and CRP followed by a steady decrease over the course of 3 days. The dynamics of both PCT and CRP were similar and were not associated with infection. PCT levels were independent of renal and liver functions and were not predictive of further infectious complications. A direct effect of ATG on T lymphocytes could be the underlying mechanism. Hepatotoxic effect could be a contributing factor. Neither PCT nor CRP is a useful marker that can identify infection in patients receiving ATG.