Outcomes of critically ill patients according to the perception of intensivists on the appropriateness of intensive care unit admission

Background It is important for intensivists to determine which patient may benefit from intensive care unit (ICU) admission. We aimed to assess the outcomes of patients perceived as non-beneficially or beneficially admitted to the ICU and evaluate whether their prognosis was consistent with the intensivists’ perception. Methods A prospective observational study was conducted on patients admitted to the medical ICU of a tertiary referral center between February and April 2014. The perceptions of four intensivists at admission (day 1) and on day 3 were investigated as non-beneficial admission, beneficial admission, or indeterminate state. Results A total of 210 patients were enrolled. On days 1 and 3, 22 (10%) and 23 (11%) patients were judged as having non-beneficial admission; 166 (79%) and 159 (79%), beneficial admission; and 22 (10%) and 21 (10%), indeterminate state, respectively. The ICU mortality rates of each group on day 1 were 59%, 23%, and 59%, respectively; their 6-month mortality rates were 100%, 48%, and 82%, respectively. The perceptions of non-beneficial admission or indeterminate state were the significant predictors of ICU mortality (day 3; odds ratio [OR], 4.049; 95% confidence interval [CI], 1.892–8.664; P<0.001) and 6-month mortality (day 1: OR, 4.983; 95% CI, 1.260–19.703; P=0.022; day 3: OR, 4.459; 95% CI, 1.162–17.121; P=0.029). Conclusions The outcomes of patients perceived as having non-beneficial admission were extremely poor. The intensivists’ perception was important in predicting patients’ outcomes and was more consistent with long-term prognosis than with immediate outcomes. The intensivists’ role can be reflected in limited ICU resource utilization

Anti-inflammatory Role of Mesenchymal Stem Cells in an Acute Lung Injury Mouse Model

Background Mesenchymal stem cells (MSCs) attenuate injury in various lung injury models through paracrine effects. We hypothesized that intratracheal transplantation of allogenic MSCs could attenuate lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice, mediated by anti-inflammatory responses. Methods Six-week-old male mice were randomized to either the control or the ALI group. ALI was induced by intratracheal LPS instillation. Four hours after LPS instillation, MSCs or phosphate-buffered saline was randomly intratracheally administered. Neutrophil count and protein concentration in bronchoalveolar lavage fluid (BALF); lung histology; levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and macrophage inflammatory protein-2; and the expression of proliferation cell nuclear antigen (PCNA), caspase-3, and caspase-9 were evaluated at 48 hours after injury. Results Treatment with MSCs attenuated lung injury in ALI mice by decreasing protein level and neutrophil recruitment into the BALF and improving the histologic change. MSCs also decreased the protein levels of proinflammatory cytokines including IL-1β, IL-6, and TNF-α, but had little effect on the protein expression of PCNA, caspase-3, and caspase-9. Conclusions Intratracheal injection of bone marrow-derived allogenic MSCs attenuates LPS-induced ALI via immunomodulatory effects

Fever and Total Mechanical Ventilation Time in Critically Ill Patients

This research aims to investigate the impact of fever on total mechanical ventilation time (TVT) in critically ill patients. Subgroup analysis was conducted using a previous prospective, multicenter observational study. We included mechanically ventilated patients for more than 24 hours from 10 Korean and 15 Japanese intensive care units (ICU), and recorded maximal body temperature under the support of mechanical ventilation (MAXMV). To assess the independent association of MAXMV with TVT, we used propensity-matched analysis in a total of 769 survived patients with medical or surgical admission, separately. Together with multiple linear regression analysis to evaluate the association between the severity of fever and TVT, the effect of MAXMV on ventilator-free days was also observed by quantile regression analysis in all subjects including non-survivors. After propensity score matching, a MAXMV ≥ 37.5°C was significantly associated with longer mean TVT by 5.4 days in medical admission, and by 1.2 days in surgical admission, compared to those with MAXMV of 36.5°C to 37.4°C. In multivariate linear regression analysis, patients with three categories of fever (MAXMV of 37.5°C to 38.4°C, 38.5°C to 39.4°C, and ≥ 39.5°C) sustained a significantly longer duration of TVT than those with normal range of MAXMV in both categories of ICU admission. A significant association between MAXMV and mechanical ventilator-free days was also observed in all enrolled subjects. Fever may be a detrimental factor to prolong TVT in mechanically ventilated patients. These findings suggest that fever in mechanically ventilated patients might be associated with worse mechanical ventilation outcome

Pathogen-induced binding of the soybean zinc finger homeodomain proteins GmZF-HD1 and GmZF-HD2 to two repeats of ATTA homeodomain binding site in the calmodulin isoform 4 (GmCaM4) promoter

Calmodulin (CaM) is involved in defense responses in plants. In soybean (Glycine max), transcription of calmodulin isoform 4 (GmCaM4) is rapidly induced within 30 min after pathogen stimulation, but regulation of the GmCaM4 gene in response to pathogen is poorly understood. Here, we used the yeast one-hybrid system to isolate two cDNA clones encoding proteins that bind to a 30-nt A/T-rich sequence in the GmCaM4 promoter, a region that contains two repeats of a conserved homeodomain binding site, ATTA. The two proteins, GmZF-HD1 and GmZF-HD2, belong to the zinc finger homeodomain (ZF-HD) transcription factor family. Domain deletion analysis showed that a homeodomain motif can bind to the 30-nt GmCaM4 promoter sequence, whereas the two zinc finger domains cannot. Critically, the formation of super-shifted complexes by an anti-GmZF-HD1 antibody incubated with nuclear extracts from pathogen-treated cells suggests that the interaction between GmZF-HD1 and two homeodomain binding site repeats is regulated by pathogen stimulation. Finally, a transient expression assay with Arabidopsis protoplasts confirmed that GmZF-HD1 can activate the expression of GmCaM4 by specifically interacting with the two repeats. These results suggest that the GmZF-HD1 and –2 proteins function as ZF-HD transcription factors to activate GmCaM4 gene expression in response to pathogen