Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial.

BACKGROUND: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. METHODS: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. RESULTS: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups. CONCLUSIONS: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. TRIAL REGISTRATION: ISRCTN, ISRCTN12233792 . Registered November 20th, 2017.

Rapid detection of fungi from blood samples of patients with candidemia using modified calcofluor white stain.

We reported a modified CFW assay for rapid detection of fungi in blood samples and evaluated its efficacy in vivo and in vitro. The positive rate, sensitivity, and negative predictive values of the modified CFW method were all significantly higher than those of traditional fungal culture and KOH methods.

Evaluation of Droplet Digital PCR Assay for the Diagnosis of Candidemia in Blood Samples.

Numerous studies have shown that droplet digital PCR (ddPCR) is a promising tool for the diagnosis of pathogens, especially in samples with low concentrations of pathogenic DNA. An early diagnosis of candidemia is critical for the effective treatment of patients. In this study, we evaluated the sensitivity and specificity of ddPCR assay for Candida DNA detection both in vitro by mixing fungal cells with human blood and in vivo by analyzing blood samples from infected mice and patients with suspected candidemia. The results showed that ddPCR assay could detect a minimum of 4.5 DNA copies per reaction in blood samples. ddPCR showed higher sensitivity and specificity for Candida DNA detection than traditional culture and quantitative PCR (qPCR) methods and also exhibited significantly better positive and negative predictive values than the culture and qPCR methods that were commonly used in clinical practice. Hence, our study demonstrates that ddPCR assay is a promising method for the timely diagnosis of candidemia and could be useful for monitoring the treatment of candidemia.

[Value of blood ammonia on predicting the severity and prognosis of patients with sepsis: a prospective observation study].

OBJECTIVE: To investigate the value of arterial blood ammonia on predicting the severity and prognosis of patients with sepsis. METHODS: A prospective observation study was conducted. A total of 169 patients with sepsis admitted to intensive care unit (ICU) of Jining First People's Hospital Affiliated to Jining Medical University from January 2018 to June 2019 were enrolled. Thirty-five healthy volunteers were served as controls. Demographics, acute physiology and chronic health evaluation II (APACHE II) score were recorded. At 6-8 hours after the diagnosis of sepsis, the serum levels of arteria blood ammonia and whole blood cell count were run. The septic patients were divided into the sepsis group and septic shock group according to the disease severity, and the septic patients were divided into survival group and death group according to the outcomes during 28-day hospitalization. The clinical data were compared. Spearman rank correlation was applied to determine the correlation between those variables. The predictive value of the parameters on 28-day mortality was evaluated with receiver operating characteristic (ROC) curve. Kaplan-Meier survival curve analysis was used to compare different blood ammonia levels of patients with 28-day cumulative survival rate. RESULTS: Among the 169 sepsis patients, after excluding 12 patients who did not meet the inclusion criteria and loss to follow-up, there were finally 157 patients enrolled in the analysis. Among the 157 septic patients, 71 of them were in the sepsis group, and 86 in the septic shock group. After 28-day follow-up, 115 patients survived and 42 died. No significant differences were found in age and gender among groups with different severity and clinical prognosis. Compared with the control group, the blood ammonia, counts of white blood cell (WBC) and neutrophils ratio (Neut%) in serum of sepsis patients were significantly higher [blood ammonia (µmol/L): 42.28±28.64 vs. 12.05±5.44, WBC (×109/L): 17.51±5.13 vs. 6.57±2.20, Neut%: 0.87 (0.82, 0.90) vs. 0.62 (0.59, 0.67), all P < 0.05]. Compared with the sepsis group, the APACHE II score, blood ammonia, WBC, Neut% and 28-day mortality in the septic shock group were significantly higher [APACHE II score: 24.49±6.22 vs. 14.31±3.32,blood ammonia (µmol/L): 52.93±34.11 vs. 29.38±10.37, WBC (×109/L): 20.21±3.77 vs. 14.02±4.23, Neut%: 0.89 (0.86, 0.92) vs. 0.82 (0.79, 0.89), 28-day mortality: 43.0% (37/86) vs 7.0% (5/71), all P < 0.05]. APACHE II score, blood ammonia, WBC and Neut% in the death group were significantly higher than those in the survival group [APACHE II score: 26.89±7.91 vs. 17.34±4.90, blood ammonia (µmol/L): 69.98±41.14 vs. 32.17±11.31, WBC (×109/L): 20.20±4.78 vs. 16.53±4.91, Neut%: 0.89 (0.87, 0.95) vs. 0.87 (0.82, 0.90), all P < 0.05]. Spearman rank correlation analysis showed that blood ammonia in patients with sepsis was correlated well with APACHE II score (r = 0.592, P < 0.01), and there was moderately positive correlation between blood ammonia and the counts of WBC (r = 0.343, P < 0.01). ROC curve analysis showed that the areas under ROC curve (AUC) of APACHE II score and blood ammonia for predicting 28-day mortality were 0.846 and 0.901, respectively, and there was no statistical significance (P = 0.187). The AUC of APACHE II score combined with blood ammonia was significantly higher than that of APACHE II score alone (0.913 vs. 0.846, P = 0.002), but was not higher than that of blood ammonia alone (0.913 vs. 0.901, P = 0.647). Using a blood ammonia cut-off value of > 36.50 µmol/L for predicting 28-day mortality, the sensitivity and specificity was 92.9% and 73.9%, respectively, and the positive and negative likelihood ratios were 3.56 and 0.10, respectively. Kaplan-Meier survival curve analysis indicated that the patients whose blood ammonia was higher than 36.50 µmol/L, had lower 28-day cumulative survival rate when compared with those patients with blood ammonia ≤ 36.50 µmol/L (Log-Rank test: χ2 = 9.620, P = 0.002). CONCLUSIONS: The level of arterial blood ammonia could somehow indicate the severity and prognosis of sepsis, which could provide evidence for the treatment.

Saikosaponin-d ameliorates dextran sulfate sodium-induced colitis by suppressing NF-κB activation and modulating the gut microbiota in mice.

Saikosaponin-d (SSd), extracts from Bupleurum falcatum L, exhibits anti-inflammatory and anti-infectious activities. However, the effect of SSd on intestinal inflammation has not been investigated. The aim of this study was to evaluate the effect of SSd on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice, and to elucidate the underlying mechanisms. UC was induced in mice by administrating 3% DSS in drinking water for 7 days. SSd (4 mg/kg and 8 mg/kg) was administered by gavage every day during the experimental process. The results showed that SSd treatment (8 mg/kg) significantly ameliorated UC mice by decreasing disease activity index (DAI), increasing colon length and improving pathological characteristics. SSd treatment (8 mg/kg) significantly suppressed the mRNA levels of pro-inflammatory cytokines including TNF-α, IL-6 and IL-1ß, increased that of anti-inflammatory cytokine IL-10. Furthermore, SSd (8 mg/kg) suppressed the activation of NF-κB by decreasing the degradation and phosphorylation of IκB. SSd (8 mg/kg) also protected the intestinal barrier by increasing the mRNA levels of mucin (Muc1 and Muc2) and the protein levels of zonula occludens-1 (ZO-1) and Claudin-1. The 16S rDNA gene high-throughput sequencing revealed that SSd treatment (8 mg/kg) increased the alpha diversity and regulated the structure of gut microbiota in UC mice. Taken together, our findings demonstrated that SSd (8 mg/kg) improved DSS-induced intestinal inflammation by inhibiting NF-κB activation and regulated the gut microbiota.

2,3,5,4'­Tetrahydroxystilbene­2­O­ß­D­glucoside inhibits septic serum­induced inflammatory injury via interfering with the ROS­MAPK­NF­κB signaling pathway in pulmonary aortic endothelial cells.

Sepsis is characterized by injury to the microvasculature and the microvascular endothelial cells, leading to barrier dysfunction. However, the specific role of injury in septic endothelial barrier dysfunction remains to be elucidated. In the present study, it was hypothesized that endothelial cell inflammatory injury is likely required for barrier dysfunction under septic conditions in vitro. 2,3,5,4'­Tetrahydroxystilbene­2­O­ß­D­glucoside (TSG), a compound extracted from Chinese herbs, is able to inhibit the inflammatory injury of septic­serum in endothelial cells. In the present study, cell viability was assayed by CCK­8 method; mRNA and protein expression was identified by RT­qPCR, western blot or Elisa, respectively and the production of reactive oxygen species was observed by a fluorescence microscope. The present study indicated that septic serum significantly decreased the cell viability of pulmonary aortic endothelial cells (PAECs) following co­cultivation for 6 h, which occurred in a time­dependent manner. TSG notably increased the viability of PAECs in a time­ and concentration­dependent manner. Further investigations revealed that septic serum increased the secretion of interleukin (IL)­1ß, IL­6 and C­reactive protein in PAECs, whereas pretreatment with TSG significantly decreased the secretion of these inflammatory factors. These data indicated that septic serum increased inflammatory injury to the PAECs, and TSG decreased this injury via the reactive oxygen species­mitogen­activated protein kinase­nuclear factor­κB signaling pathway.

Dual character of flavonoids in attenuating and aggravating ischemia-reperfusion-induced myocardial injury.

The concept that flavonoids exert cardioprotection against myocardial ischemia-reperfusion (I/R) injury has been acknowledged by a large body of evidence. However, recent studies reported cardiotoxic effects of certain flavonoids, while the underlying mechanisms have remained largely elusive. Flavonoids have been demonstrated to activate aryl hydrocarbon receptor (Ahr), which is implicated in an array of cell signaling processes. The present study examined the cardioprotective roles of quercetin (Qu) and ß-naphthoflavone (ß-NF) against I/R injury and explored whether the underlying mechanism proceeds via molecular signaling downstream of Ahr. An oxygen glucose deprivation/reoxygenation (OGD/R) model of I/R was established in myocardial H9c2 cells in the absence or presence of Qu or ß-NF. Qu as well as ß-NF reversed OGD/R-induced overproduction of reactive oxygen species by increasing the anti-oxidative capacity of the cells and protected them from lethal injury, as demonstrated by a decreased cell death rate, lactate hydrogenase leakage and caspase-3 activity as determined by flow cytometry, colorimetric assay and western blot analysis, respectively. Immunocytochemistry, co-immunoprecipitation and western blot assays collectively revealed that Qu and ß-NF engendered the translocation of Ahr from the cytoplasm into the cell nucleus, where binding of Ahr with the Ahr nuclear translocator (ARNT) blocked its binding to hypoxia-inducible factor (HIF)-1α, which inhibited the cardioprotection of HIF-1α, including the induction of nitric oxide (NO) and inhibition of vascular endothelial growth factor (VEGF) production. Ahr knockdown recovered the binding of ARNT to HIF-1α and the generation of NO and VEGF. The results of the present study suggested a dual character of Qu and ß-NF in the process of myocardial I/R.

Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China.

BACKGROUND: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. METHODS: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. RESULTS: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0-8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5-6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. CONCLUSIONS: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. TRIAL REGISTRATION: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073.