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.

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Purpose: To study the protective effect of interleukin-34 (IL-34) against sepsis in mice, and the mechanism involved. Methods: Ninety healthy male mice were selected and assigned to sham, model and recombinant IL-34 protein groups. The activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed. Moreover, histopathological changes in lung, liver and kidney were recorded, and levels of C-X-C Motif Chemokine Ligand 1 (CXCL1) and C-C Motif Chemokine Ligand 2 (CCL2) in each group of mice were measured. Results: Peritoneal lavage fluid and serum concentrations of AST, ALT, LDH, CXCL1 and CCL2 were significantly elevated, relative to sham mice (p < 0.05). Mice survival in the drug group was markedly increased from day 1 to day 5; also, serum ALT, LDH and AST were significantly reduced, while CXCL1 and CCL2 concentrations in serum and peritoneal lavage fluid were increased, relative to model mice (p < 0.05). Conclusion: IL-34 improves survival of septic mice by inducing CXCL1/CCL2 immune response, resulting in a protective effect on the airway. Thus, the CXCL1/CCL2 pathway mediated by IL-34 may be useful in the development of drugs for the treatment of sepsis.

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