Comparison of the effects of albumin and crystalloid on mortality among patients with septic shock: systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: This study aimed to compare the effects on mortality of albumin and crystalloid, used for fluid resuscitation among adult patients with septic shock, through conducting a meta-analysis and trial sequential analysis (TSA). DESIGN AND SETTING: Meta-analysis and TSA conducted at Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. METHODS: Data were collected from several major databases including MEDLINE, EMBASE, Clinical Trials.gov and Cochrane Central Register of Controlled Trials. Studies that compared the effects of albumin therapy versus crystalloid therapy on mortality among adult septic shock patients were eligible for inclusion in the analyses. The study name, year of publication, country of the trial, albumin concentration, type of crystalloid and all reported mortalities at different follow-up endpoints were extracted. RESULTS: Compared with crystalloid, albumin did not decrease all-cause mortality at the final follow-up. However, in TSA, the required information size was not achieved in all groups, which means that the effect size was not definitive and further RCTs are needed to confirm or deny these findings. CONCLUSIONS: Compared with crystalloid solutions, albumin was unable to decrease all-cause mortality. However, TSA indicated that these results could be false-negative. Additional randomized controlled trials are needed to clarify this discrepancy.

Comparison of the effects of albumin and crystalloid on mortality among patients with septic shock: systematic review with meta-analysis and trial sequential analysis

ABSTRACT BACKGROUND: This study aimed to compare the effects on mortality of albumin and crystalloid, used for fluid resuscitation among adult patients with septic shock, through conducting a meta-analysis and trial sequential analysis (TSA). DESIGN AND SETTING: Meta-analysis and TSA conducted at Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. METHODS: Data were collected from several major databases including MEDLINE, EMBASE, Clinical Trials.gov and Cochrane Central Register of Controlled Trials. Studies that compared the effects of albumin therapy versus crystalloid therapy on mortality among adult septic shock patients were eligible for inclusion in the analyses. The study name, year of publication, country of the trial, albumin concentration, type of crystalloid and all reported mortalities at different follow-up endpoints were extracted. RESULTS: Compared with crystalloid, albumin did not decrease all-cause mortality at the final follow-up. However, in TSA, the required information size was not achieved in all groups, which means that the effect size was not definitive and further RCTs are needed to confirm or deny these findings CONCLUSIONS: Compared with crystalloid solutions, albumin was unable to decrease all-cause mortality. However, TSA indicated that these results could be false-negative. Additional randomized controlled trials are needed to clarify this discrepancy.

Rac2 deficiency attenuates CCl4-induced liver injury through suppressing inflammation and oxidative stress.

Oxidative stress is a leading cause to liver injury. Rac2 is a Ras-associated guanosine triphosphatase, an important molecule modulating a large number of cells and involved in the regulation of reactive oxygen species (ROS). For the study described here, we supposed that Rac2 knockout protects mice against CCl4-induced acute liver injury. We found that Rac2 expressed highly in CCl4-induced liver tissues. CCl4-treated Rac2 knockout (Rac2-/-) mice had reduced CD24 levels and steatosis. In addition, CCl4-induced high expression of pro-inflammatory cytokines and chemokine were reversed by Rac2 deficiency compared to CCl4-treated wild type (WT) mice. We also found that fibrosis-related signals of MMP-9, MMP-2 and TGF-ß1 were also down-regulated in Rac2 knockout mice induced by CCl4. Significantly, oxidative stress induced by CCl4 was also suppressed owing to the lack of Rac2, evidenced by enhanced superoxide dismutase (SOD) activity, and reduced malondialdehyde (MDA) levels, superoxide radical, H2O2, xanthine oxidase (XO), xanthine dehydrogenase (XDH) and XO/XDH ratio. Moreover, c-Jun N-terminal protein kinase mitogen-activated protein kinases (JNK MAPK) was activated by CCl4, which was reversed in the liver of Rac2-/- mice through western blot and immunohistochemical analysis. In vitro, endotoxin (LPS) was treated to hepatocytes isolated from WT mice and Rac2-/- mice. The data further confirmed the role of Rac2 deficiency suppressed pro-inflammatory cytokines and chemokine, as well as fibrosis-related signals. Of note, production of ROS induced by LPS was reduced in Rac2-/- cells, accompanied with enhanced SOD1, SOD2 and reduced XO and phosphorylated-JNK expressions. Our results indicated that Rac2 played an essential role in acute liver injury induced by CCl4, providing the compelling information of the effects of Rac2 on liver injury, and revealing a novel regulatory mechanism for acute liver injury.