Critical care (Houten, Netherlands)最新文献

Background: Data on long-term outcomes after sepsis-associated critical illness have mostly come from small cohort studies, with no information about the incidence of new disability. We investigated whether sepsis-associated critical illness was independently associated with new disability at 6 months after ICU admission compared with other types of critical illness.

Methods: We conducted a secondary analysis of a multicenter, prospective cohort study in six metropolitan intensive care units in Australia. Adult patients were eligible if they had been admitted to the ICU and received more than 24 h of mechanical ventilation. There was no intervention.

Results: The primary outcome was new disability measured with the WHO Disability Assessment Schedule 2.0 (WHODAS) 12 level score compared between baseline and 6 months. Between enrollment and follow-up at 6 months, 222/888 (25%) patients died, 100 (35.5%) with sepsis and 122 (20.1%) without sepsis (P < 0.001). Among survivors, there was no difference for the incidence of new disability at 6 months with or without sepsis, 42/106 (39.6%) and 106/300 (35.3%) (RD, 0.00 (- 10.29 to 10.40), P = 0.995), respectively. In addition, there was no difference in the severity of disability, health-related quality of life, anxiety and depression, post-traumatic stress, return to work, financial distress or cognitive function.

Conclusions: Compared to mechanically ventilated patients of similar acuity and length of stay without sepsis, patients with sepsis admitted to ICU have an increased risk of death, but survivors have a similar risk of new disability at 6 months. Trial registration NCT03226912, registered July 24, 2017.

Background: SARS-CoV-2 infection leads to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Both clinical data and animal experiments suggest that the renin-angiotensin system (RAS) is involved in the pathogenesis of SARS-CoV-2-induced ALI. Angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2 and a crucial negative regulator of RAS. Recombinant ACE2 protein (rACE2) has been demonstrated to play protective role against SARS-CoV and avian influenza-induced ALI, and more relevant, rACE2 inhibits SARS-CoV-2 proliferation in vitro. However, whether rACE2 protects against SARS-CoV-2-induced ALI in animal models and the underlying mechanisms have yet to be elucidated.

Methods and results: Here, we demonstrated that the SARS-CoV-2 spike receptor-binding domain (RBD) protein aggravated lipopolysaccharide (LPS)-induced ALI in mice. SARS-CoV-2 spike RBD protein directly binds and downregulated ACE2, leading to an elevation in angiotensin (Ang) II. AngII further increased the NOX1/2 through AT₁R, subsequently causing oxidative stress and uncontrolled inflammation and eventually resulting in ALI/ARDS. Importantly, rACE2 remarkably reversed SARS-CoV-2 spike RBD protein-induced ALI by directly binding SARS-CoV-2 spike RBD protein, cleaving AngI or cleaving AngII.

Conclusion: This study is the first to prove that rACE2 plays a protective role against SARS-CoV-2 spike RBD protein-aggravated LPS-induced ALI in an animal model and illustrate the mechanism by which the ACE2-AngII-AT₁R-NOX1/2 axis might contribute to SARS-CoV-2-induced ALI.

Resilience is ubiquitous in everyday speech, academic literature and governmental policies. Yet it seems to have taken a narrow scope in healthcare, confined to individual and psychological resilience. This short essay aims to broaden the understanding of resilience to organisational levels and calls intensivists to take active roles in fostering resilience for their staff. The article explores firstly the background and etymology of resilience. It then challenges current approaches and briefly signposts some current work in the area. Some examples of structural factors which build individual resilience are listed, followed by a call for intensivists to take active roles to build future resilience. The need for interdisciplinary, cross-sectoral and multi-level approaches is vital to build future healthcare resilience, and we intensivists must continue to be advocates for systemic change.

Background: Interleukin (IL)-18 is a marker of inflammasome activation, and high baseline plasma IL-18 is associated with increased mortality in patients with sepsis-induced ARDS. The aim of this analysis was to determine if simvastatin was associated with benefit in patients with ARDS and high plasma IL-18.

Methods: In this secondary analysis of the HARP-2 study, we compared 28-day mortality and response to simvastatin according to baseline plasma IL-18 using cox proportional hazards analysis. Separately, monocyte-derived macrophages from healthy volunteers were pre-incubated with simvastatin or rosuvastatin before stimulation with ATP and LPS, and the effect on secreted IL-18 and IL-1β compared.

Results: 511 patients from HARP-2 had available data. High baseline plasma IL-18 (≥ 800 pg/ml) was associated with increased 28-day mortality (high IL-18 30.6% vs. low IL-18 17.5%; HR 1.89 [95% CI 1.30-2.73]; p = 0.001). Allocation to simvastatin in patients with high baseline plasma IL-18 was associated with a lower probability of 28-day mortality compared with placebo (24.0% vs 36.8%; p = 0.01). Finally, simvastatin, but not rosuvastatin, reduced stimulated macrophage secretion of IL-18 and IL-1β.

Conclusion: In patients with high baseline plasma IL-18, simvastatin is associated with a higher probability of survival, and this effect may be due to reduced inflammasome activation. These data suggest that baseline plasma IL-18 may allow a personalised treatment approach by identifying patients with ARDS who could benefit from simvastatin therapy.