Comparative Effectiveness of Midazolam, Propofol, and Dexmedetomidine in Patients With or at Risk for Acute Respiratory Distress Syndrome: A Propensity Score-Matched Cohort Study.

Background: Sedatives are commonly used in patients with or at risk for acute respiratory distress syndrome (ARDS) during mechanical ventilation. To systematically compare the outcomes of sedation with midazolam, propofol, and dexmedetomidine in patients with or at risk for ARDS. Methods: We developed a dataset of real-world data to enable the comparison of the effectiveness and safety of sedatives and the associated outcomes from the MIMIC-III database and the eICU Collaborative Research database. We performed a systematic study with six cohorts to estimate the relative risks of outcomes among patients administered different sedatives. Propensity score matching was performed to generate a balanced 1:1 matched cohort and to identify potential prognostic factors. The outcomes included hospital mortality, duration of mechanical ventilation, length of intensive care unit stay, length of hospitalization, and likelihood of being discharged home. Results: We performed 60 calibrated analyses among all groups and outcomes with 17,410 eligible patients. Sedation with dexmedetomidine was associated with a lower in-hospital mortality rate than sedation with midazolam and propofol or sedation without dexmedetomidine (p < 0.001). When compared with no sedation, the use of midazolam, propofol or dexmedetomidine was associated with a longer ICU stay and longer hospitalization duration (p < 0.01). Patients treated with midazolam were relatively less likely to be discharged home (p < 0.05). Conclusion: Patients treated with dexmedetomidine had a reduced risk of mortality. These data suggest that dexmedetomidine may be the preferred sedative in patients with or at risk for ARDS.

Comparative Efficacy of Fentanyl and Morphine in Patients with or At Risk for Acute Respiratory Distress Syndrome: A Propensity Score-Matched Cohort Study.

INTRODUCTION: Opioids are potent painkillers but can have severe adverse effects in the intensive care unit (ICU). The aim of this study was to compare the outcomes of fentanyl and morphine use among patients at risk for and with acute respiratory distress syndrome (ARDS). METHODS: We developed a dataset of real-world data to enable the comparison of the effectiveness and safety of opioids and the associated outcomes from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC)-III database and the eICU Collaborative Research Database. Patients who were admitted to the ICU with a diagnosis of or at risk for ARDS and received mechanical ventilation for at least 12 h were included. Patients were enrolled sequentially into one of six groups in three cohorts: treated with fentanyl or not; treated with morphine or not; and treated with fentanyl or morphine. Propensity score matching and multivariable analyses were performed. RESULTS: Fentanyl was associated with higher in-hospital mortality in the propensity score-matched model but not in the linear regression model. The use of morphine was associated with a higher in-hospital mortality in both models. Both fentanyl and morphine were associated with longer duration of mechanical ventilation, ICU stay, and hospitalization and a decreased likelihood of being discharged home in both models. Notably, compared with morphine, fentanyl was associated with a lower mortality and an increased likelihood of being discharged home. CONCLUSIONS: Both fentanyl and morphine were independent risk factors for worse outcomes in patients with or at risk for ARDS. Compared with morphine, fentanyl may be preferred in these patients.

Associations Between Elevated Systolic Blood Pressure and Outcomes in Critically Ill Patients: A Retrospective Cohort Study and Propensity Analysis.

INTRODUCTION: Studies have shown nonlinear relationships between systolic blood pressure (SBP) and outcomes, with increased risk observed at both low and high blood pressure levels. However, the relationships between cumulative times at different SBP levels and outcomes in critically ill patients remain unclear. We hypothesized that an appropriate SBP level is associated with a decrease in adverse outcomes after intensive care unit (ICU) admission. METHODS: This study was a retrospective analysis of data from the Medical Information Mart for Intensive Care (MIMIC) III database, which includes more than 1,000,000 SBP records from 12,820 patients. Associations of cumulative times at four SBP ranges (<100 mm Hg, 100-120 mm Hg, 120-140 mm Hg, and ≥140 mm Hg) with mortality (12-, 3-, 1-month mortality and in-hospital mortality) were evaluated. Restricted cubic splines and multivariable Cox regression models were employed to assess associations between mortality and cumulative times at SBP levels (4 levels: <2, 2-12, 12-36, and ≥36 h) over 72 h of ICU admission. Additionally, 120 mm Hg to 140 mm Hg was subdivided into <12 h (Group L) and ≥12 h (Group M) subsets and subjected to propensity-score matching and subgroup analyses. RESULTS: At 120 mm Hg to 140 mm Hg, level-4 SBP was associated with lower adjusted risks of mortality at 12 months (OR, 0.71; CI, 0.61-0.81), 3 months (OR, 0.72; CI, 0.61-0.85), and 1 month (OR, 0.61; CI, 0.48-0.79) and in the hospital (OR, 0.71; CI, 0.58-0.88) than level-1 SBP. The cumulative times at the other 3 SBP ranges (<100 mm Hg, 100-120 mm Hg, and ≥140 mm Hg) were not independent risk predictors of prognosis. Furthermore, Group M had lower 12-month mortality than Group L, which remained in the propensity-score matched and subgroup analyses. CONCLUSIONS: SBP at 120 mm Hg to 140 mm Hg was associated with decreased adverse outcomes. Randomized trials are required to determine whether the outcomes in critically ill patients improve with early maintenance of a SBP level at 120 mm Hg to 140 mm Hg.

Higher versus lower mean arterial pressure target management in older patients having non-cardiothoracic surgery: A prospective randomized controlled trial.

STUDY OBJECTIVE: This study aimed to evaluate the effects of low versus high mean arterial pressure (MAP) levels on the incidence of postoperative delirium during non-cardiothoracic surgery in older patients. DESIGN: Multicenter, randomized, parallel-controlled, open-label, and assessor-blinded clinical trial. SETTING: University hospital. PATIENTS: Three hundred twenty-two patients aged ≥65 with an American Society of Anesthesiologists physical status of I-II who underwent non-cardiothoracic surgery with general anaesthesia. INTERVENTIONS: Participants were randomly assigned into a low-level MAP (60-70 mmHg) or high-level MAP (90-100 mmHg) group during general anaesthesia. The study was conducted from November 2016 to February 2020. Participants were older patients having non-cardiothoracic surgery. The follow-up period ranged from 1 to 7 days after surgery. The primary outcome was the incidence of postoperative delirium. MAIN RESULTS: In total, 322 patients were included and randomized; 298 completed in-hospital delirium assessments [median (interquartile range) age, 73 (68-77) years; 173 (58.1%) women]. Fifty-four (18.1%) patients total, including 36 (24.5%) and 18 (11.9%) in the low-level and high-level MAP groups [relative risk (RR) 0.48, 95% confidence interval (CI) 0.25 to 0.87, P = 0.02], respectively, experienced postoperative delirium. The adjusted RR was 0.34 (95% CI 0.16 to 0.70, P < 0.01) in the multiple regression analysis. High-level MAP was associated with a shorter delirium span and a higher intraoperative urine volume than low-level MAP. CONCLUSIONS: In older patients during non-cardiothoracic surgery, high-level blood pressure management might help reduce the incidence of postoperative delirium.

Preparation of Syringaldehyde from Lignin by Catalytic Oxidation of Perovskite-Type Oxides.

The influence of different reaction conditions on the yield of syringaldehyde was studied by using perovskite oxide as the catalyst. The optimal reaction conditions are as follows: 0.60 g of dealkali lignin, 0.60 g of 5 wt % theta ring-loaded LaFe0.2Cu0.8O3 catalyst, 30 mL of 1.0 mol/L NaOH solution, 160 °C reaction temperature, 0.80 MPa O2 pressure, and 2.5 h reaction time. Under these conditions, the highest syringaldehyde yield was 10.00%. The recycling performance of the catalyst was studied. It was found by XRD analysis that the catalyst maintained high catalytic activity after four times of use.

Lipoxin A4 Ameliorates Lipopolysaccharide-Induced A549 Cell Injury through Upregulation of N-myc Downstream-Regulated Gene-1.

BACKGROUND: Lipoxin A4 (LXA4) can alleviate lipopolysaccharide (LPS)-induced acute lung injury (ALI) and acute respiratory distress syndrome through promoting epithelial sodium channel (ENaC) expression in lung epithelial cells. However, how LXA4 promote ENaC expression is still largely elusive. The present study aimed to explore genes and signaling pathway involved in regulating ENaC expression induced by LXA4. METHODS: A549 cells were incubated with LPS and LXA4, or in combination, and analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) of ENaC-α/γ. Candidate genes affected by LXA4 were explored by transcriptome sequencing of A549 cells. The critical candidate gene was validated by qRT-PCR and Western blot analysis of A549 cells treated with LPS and LXA4 at different concentrations and time intervals. LXA4 receptor (ALX) inhibitor BOC-2 was used to test induction of candidate gene by LXA4. Candidate gene siRNA was adopted to analyze its influence on A549 viability and ENaC-α expression. Phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was utilized to probe whether the PI3K signaling pathway was involved in LXA4 induction of candidate gene expression. RESULTS: The A549 cell models of ALI were constructed and subjected to transcriptome sequencing. Among candidate genes, N-myc downstream-regulated gene-1 (NDRG1) was validated by real-time-PCR and Western blot. NDRG1 mRNA was elevated in a dose-dependent manner of LXA4, whereas BOC-2 antagonized NDRG1 expression induced by LXA4. NDRG1 siRNA suppressed viability of LPS-treated A549 cells (treatment vs. control, 0.605 ± 0.063 vs. 0.878 ± 0.083, P = 0.040) and ENaC-α expression (treatment vs. control, 0.458 ± 0.038 vs. 0.711 ± 0.035, P = 0.008). LY294002 inhibited NDRG1 (treatment vs. control, 0.459 ± 0.023 vs. 0.726 ± 0.020, P = 0.001) and ENaC-α (treatment vs. control, 0.236 ± 0.021 vs. 0.814 ± 0.025, P < 0.001) expressions and serum- and glucocorticoid-inducible kinase 1 phosphorylation (treatment vs. control, 0.442 ± 0.024 vs. 1.046 ± 0.082, P = 0.002), indicating the PI3K signaling pathway was involved in regulating NDRG1 expression induced by LXA4. CONCLUSION: Our research uncovered a critical role of NDRG1 in LXA4 alleviation of LPS-induced A549 cell injury through mediating PI3K signaling to restore ENaC expression.

Lipoxin A4 Preconditioning Attenuates Intestinal Ischemia Reperfusion Injury through Keap1/Nrf2 Pathway in a Lipoxin A4 Receptor Independent Manner.

Oxidative stress plays a critical role in the pathogenesis of intestinal ischemia reperfusion (IIR) injury. Enhancement in endogenous Lipoxin A4 (LXA4), a potent antioxidant and mediator, is associated with attenuation of IIR. However, the effects of LXA4 on IIR injury and the potential mechanisms are unknown. In a rat IIR (ischemia 45 minutes and subsequent reperfusion 6 hours) model, IIR caused intestinal injury, evidenced by increased serum diamine oxidase, D-lactic acid, intestinal-type fatty acid-binding protein, and the oxidative stress marker 15-F2t-Isoprostane. LXA4 treatment significantly attenuated IIR injury by reducing mucosal 15-F2t-Isoprostane and elevating endogenous antioxidant superoxide dismutase activity, accompanied with Keap1/Nrf2 pathway activation. Meanwhile, LXA4 receptor antagonist Boc-2 reversed the protective effects of LXA4 on intestinal injury but failed to affect the oxidative stress and the related Nrf2 pathway. Furthermore, Nrf2 antagonist brusatol reversed the antioxidant effects conferred by LXA4 and led to exacerbation of intestinal epithelium cells oxidative stress and apoptosis, finally resulting in a decrease of survival rate of rat. Meanwhile, LXA4 pretreatment upregulated nuclear Nrf2 level and reduced hypoxia/reoxygenation-induced IEC-6 cell damage and Nrf2 siRNA reversed this protective effect of LXA4 in vitro. In conclusion, these findings suggest that LXA4 ameliorates IIR injury by activating Keap1/Nrf2 pathway in a LXA4 receptor independent manner.

Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury: a biomechanical evaluation.

Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 µg brain-derived neurotrophic factor or 1 × 10(6) human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury.

Mapping of QTL conferring resistance to sharp eyespot (Rhizoctonia cerealis) in bread wheat at the adult plant growth stage.

KEY MESSAGE: Seven sharp eyespot resistance QTL were detected consistently across five environments and delimited to seven DNA marker intervals, respectively, six of which were independent of plant height and heading time. Sharp eyespot, caused mainly by the soil-borne fungus Rhizoctonia cerealis, is one of the important diseases of bread wheat (Triticum aestivum L.). This disease has escalated into a major threat to wheat production in some regions of the world. Wheat resistance to sharp eyespot can be a potential means to reduce the needs for application of fungicides and agricultural inputs. In the present study, the winter wheat lines, Luke and AQ24788-83, both of which possess quantitative resistance to sharp eyespot, were crossed and a population consisting 241 recombinant-inbred lines (RILs) was constructed. These RILs were assessed for sharp eyespot resistance by conducting five field and greenhouse trials during the period from 2008 to 2012, and they were genotyped with 549 simple-sequence repeat DNA markers. Seven quantitative trait loci (QTL) were detected consistently across the five trial environments to be associated with the sharp eyespot resistance. They were mapped on chromosomes 1A, 2B, 3B, 4A, 5D, 6B, and 7B. Four of these QTL are unequivocally novel, while it is possible that the other three might also be novel. Plant height and heading date of the 241 RILs were recorded in the four field trials. All of the seven disease resistance QTL were independent of plant height and heading time except one that was significantly associated with plant heading time. This association might be attributed genetically to a single QTL, or to different but closely linked QTL. In the case of single QTL, pleiotropism might be involved or the sharp eyespot resistance might be conferred in a physical instead of physiological nature.