Impact of influenza virus infection on lung microbiome in adults with severe pneumonia.

BACKGROUND: Bacterial and viral infections are commonly implicated in the development of pneumonia. We aimed to compare the diversity and composition of lung bacteria among severe pneumonia patients who were influenza virus positive (IFVP) and influenza virus negative (IFVN). METHODS: Bronchoalveolar lavage fluid specimens were procured from patients diagnosed with severe pneumonia to investigate the microbiome utilizing 16S-rDNA sequencing. The alpha diversity of the microbiome was evaluated employing Chao1, Shannon, and Simpson indexes, while the beta diversity was assessed using principal component analysis and principal coordinate analysis. Linear discriminant analysis effect size (LEfSe) was employed to determine the taxonomic differences between the IFVP and IFVN groups. RESULTS: A total of 84 patients with 42 in the IFVP group and 42 in the IFVN group were enrolled. Slightly higher indexes of Shannon and Simpson were observed in the IFVP group without statistically significant difference. The dominant bacterial genera were Streptococcus, Klebsiella, Escherichia-Shigella in the IFVN group and Acinetobacter, Streptococcus, Staphylococcus in the IFVP group. Streptococcus pneumoniae and Acinetobacter baumannii were the most abundant species in the IFVN and IFVP groups, respectively. LEfSe analysis indicated a greater abundance of Klebsiella in the IFVN group. CONCLUSIONS: Individuals with severe pneumonia infected with IFV exhibit heightened susceptibility to certain bacteria, especially Acinetobacter baumannii, and the underlying mechanism of the interaction between IFV and Acinetobacter baumannii in the progression of pneumonia needs further investigation.

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.

Recombinant human erythropoietin attenuates neuronal apoptosis and cognitive defects via JAK2/STAT3 signaling in experimental endotoxemia.

BACKGROUND: Septic encephalopathy is characterized by changes in mental status and an increase in neuronal apoptosis. Accumulating evidence has shown that recombinant human erythropoietin (rhEPO) protects brain against ischemia and hypoxia injury. However, whether rhEPO exerts neuroprotective effects on septic encephalopathy remains unclear. We designed the current study to evaluate possible neuroprotection of rhEPO in a model of sepsis. METHODS: For this in vitro study, we determined hippocampal neuronal apoptosis by lactate dehydrogenase release, cell counting kit-8 assay, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining after treatment with lipopolysaccharide. We transfected the signal transducer and activator of transcription 3 (STAT3) short hairpin RNA at 14 d in vitro for 48 h. For the in vivo study, we performed cecal ligation and peroration surgery. We detected the expression of phospho-Janus-activated kinase 2 (JAK2), total JAK2, phospho-STAT3, total STAT3, Bax and Bcl-XL by Western blot, and examined behavior using the Morris water maze. RESULTS: Treatment with rhEPO reduces apoptosis and increases cell viability in lipopolysaccharide-treated neuronal cultures. In cecal ligation and peroration rats, rhEPO attenuated the inhibition of phospho-JAK2 and phospho-STAT3. In addition, rhEPO enhanced the expression of Bcl-XL, but depressed Bax, which was abolished by additional administration of inhibitor of JAK2/STAT3 signaling 2-cyano-3-(3,4-dihydroxyphenyl)-N-(benzyl)-2-propenamide,2-cyano-3-(3,4-dihydroxyphenyl)-N-(phenylmethyl)-2-propenamide or (E)-3(6-bromopyridin-2-yl)-2-cyano-N-([S0-1-phenylethyl]acrylamide)in vivo, and was ameliorated by STAT3 short hairpin RNA transfection in vitro. Alternatively, we confirmed the neuronal protective effect of rhEPO by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelingstaining. For the Morris water maze study, rhEPO improved learning and memory disorders without an alternation in locomotor activity. CONCLUSIONS: These results indicated that rhEPO improves brain dysfunction by reducing neuronal apoptosis, and JAK2/STAT3 signaling is likely to be involved. Application of rhEPO may serve as a potential therapy for the treatment of septic encephalopathy.