Altered intestinal microbiome and metabolome correspond to the clinical outcome of sepsis.

BACKGROUND: The gut microbiome plays a pivotal role in the progression of sepsis. However, the specific mechanism of gut microbiota and its metabolites involved in the process of sepsis remains elusive, which limits its translational application. METHOD: In this study, we used a combination of the microbiome and untargeted metabolomics to analyze stool samples from patients with sepsis enrolled at admission, then microbiota, metabolites, and potential signaling pathways that might play important roles in disease outcome were screened out. Finally, the above results were validated by the microbiome and transcriptomics analysis in an animal model of sepsis. RESULTS: Patients with sepsis showed destruction of symbiotic flora and elevated abundance of Enterococcus, which were validated in animal experiments. Additionally, patients with a high burden of Bacteroides, especially B. vulgatus, had higher Acute Physiology and Chronic Health Evaluation II scores and longer stays in the intensive care unit. The intestinal transcriptome in CLP rats illustrated that Enterococcus and Bacteroides had divergent profiles of correlation with differentially expressed genes, indicating distinctly different roles for these bacteria in sepsis. Furthermore, patients with sepsis exhibited disturbances in gut amino acid metabolism compared with healthy controls; namely, tryptophan metabolism was tightly related to an altered microbiota and the severity of sepsis. CONCLUSION: Alterations in microbial and metabolic features in the gut corresponded with the progression of sepsis. Our findings may help to predict the clinical outcome of patients in the early stage of sepsis and provide a translational basis for exploring new therapies.

Association between albumin or prealbumin levels at different stages and prognosis in severe acute pancreatitis: a 5-year retrospective study.

Severe acute pancreatitis (SAP) is a common abdominal disorder contributing to high mortality and open laparotomy rates. The role of exogenous infused albumin in fluid resuscitation or continuous therapy has always been an unanswered question. In early stage after onset, SAP patients with higher serum albumin or prealbumin show a better prognosis. In this study, we tried to disclose the linkage between albumin/prealbumin and SAP prognosis and establish a new goal-directed therapy involving albumin and prealbumin. Pearson's chi-squared test and the Mann-Whitney U test were used to compare the descriptive data between surviving and non-surviving patients. Three days, 4-7 days, 8-14 days and 15-28 days after SAP onset were defined as stages 1-4. The average concentrations of albumin and prealbumin were calculated, and receiver operating characteristic (ROC) curves were drawn to screen out the best cutoff values associated with poor prognostic outcomes, including laparotomy and failure to survive. Kaplan-Meier survival curves and log-rank tests were used to validate the effect of the cut-off values. A total of 199 admitted patients were enrolled in this study. According to the analysis of the ROC curve, the serum albumin value should be raised to 35, 37, 40 and 42 g/L in the 1-4 stage after onset. Serum prealbumin values should be raised to 108, 180, and 181 g/L in stages 2-4 after onset. The validity of the above data was confirmed by Kaplan-Meier survival curves. Serum albumin and prealbumin levels in the early stage of SAP are significantly relevant to prognosis. Albumin should be infused from the fluid resuscitation stage to continuous therapy in order to reach the targets mentioned above. The increase in prealbumin depends on the early initiation of enteral nutrition and this also helps to ameliorate the prognosis.

High-dose vitamin C on sepsis: Protocol of a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study.

Background: Sepsis is an inflammatory syndrome with life-threatening organ dysfunction and high mortality. In the recent 10 years, high-dose intravenous injection of vitamin C, the first-line antioxidant of humans, has received highlighted attention in the field of critical care. The study aims to examine the efficacy and safety of high-dose intravenous injection of vitamin C in the treatment of sepsis. Methods and design: Here, we are conducting a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study named High-Dose Vitamin C on Sepsis (HDVCOS). A total of 620 participants diagnosed with sepsis in four participating sites across China that satisfy the eligibility criteria will be randomized at a ratio of 1:1 to receive treatment with a high-dose intravenous injection of vitamin C (200 mg/kg/24 h) or placebo (saline) for 4 days. The primary outcome is 28 days of mortality. The secondary outcomes include the incidence of organ failure, Sequential Organ Failure Assessment (SOFA) score change, organ support, the relationship between plasma vitamin C concentration and outcomes, and adverse events. Conclusion: The findings of this study will provide potential evidence for high-dose intravenous injection of vitamin C in the treatment of sepsis. Clinical trial registration: [http://www.chictr.org.cn/showprojen.aspx?proj=29851], identifier [ChiCTR1800017633].

Downregulation of lncRNA NEAT1 alleviates sepsis-induced acute kidney injury.

Sepsis-induced acute kidney injury (AKI) is one of the important causes of increased mortality in sepsis patients. Long non-coding RNA (lncRNA) is believed to play a vital function in the progression of AKI. However, the mechanism of nuclear enriched abundant transcript 1 (NEAT1) has not been fully elucidated. NEAT1 was overexpressed and miR-22-3p was underexpressed in sepsis patients and lipopolysaccharide (LPS)-induced AKI cell models. Knockdown of NEAT1 could promote viability and suppress apoptosis and the inflammatory response in LPS-induced HK2 cells. MiR-22-3p could be sponged by NEAT1, and its inhibitor reversed the inhibition effect of NEAT1 silencing on LPS-induced HK2 cell injury. CXCL12 could be targeted by miR-22-3p, and its overexpression reversed the suppression effect of miR-22-3p on LPS-induced HK2 cell injury. Silenced NEAT1 could restrain the activity of the NF-κB signaling pathway, and miR-22-3p inhibitor or CXCL12 overexpression could reverse this effect. In addition, NEAT1 knockdown alleviated the inflammation response of cecal ligation and puncture (CLP) mouse models. In summary, our data showed that NEAT1 promoted LPS-induced HK2 cell injury via regulating the miR-22-3p/CXCL12/NF-κB signaling pathway, suggesting that NEAT1 knockdown might be a potential pathway for alleviating sepsis-induced AKI.

The effects of early restrictive fluid resuscitation on the clinical outcomes in sepsis patients.

OBJECTIVE: To investigate the effects of early restrictive fluid resuscitation (RFR) on the clinical outcomes in sepsis patients. METHODS: A total of 122 sepsis patients admitted to our hospital were recruited for this study and divided into a study group (the SG, n=56) and a control group (the CG, n=66) according to the treatment method each patient was administered. The SG was administered early RFR, and the CG was administered adequate fluid resuscitation. The clinical data were analyzed retrospectively in both groups. The total infusion volumes, the hemorrhage amounts, the urine outputs, and the Acute Physiology and Chronic Health Evaluation (APACHE II) scores were compared between the two groups. In addition, the heart rates, the mean arterial pressure levels, the central venous pressure levels, and the cardiac function indices were compared between the two groups at 1-7 days after the procedures. The survival and the complication incidence rates were followed up. RESULTS: The SG showed significantly lower heart rates and mean arterial pressure levels and higher central venous pressure levels than the CG at 1-7 days after the procedures (P<0.05). The cardiac troponin, N-terminal brain pro-natriuretic peptide, and C-reactive protein levels at 3-7 days after the procedures in the SG were significantly lower than the levels in the CG (P<0.05). The cardiac output, stroke volume, and left ventricular ejection fraction scores in the SG were significantly higher than they were in the CG (P<0.05). The survival rate in the SG was significantly higher than it was in the CG at 16, 32, and 64 days after the procedures (P<0.05). The incidence of complications in the SG was lower than it was in the CG (P<0.05). CONCLUSION: Early RFR can remarkably improve the clinical outcomes, the myocardial injury and survival rates, and the multiple complications incidence rate in sepsis patients.

Endoscopic treatment for pancreatic diseases: Needle-knife-guided cannulation via the minor papilla.

AIM: To determine the efficacy and safety of meticulous cannulation by needle-knife. METHODS: Three needle-knife procedures were used to facilitate cannulation in cases when standard cannulation techniques failed. A total of 104 cannulations via the minor papilla attempted in 74 patients at our center between January 2008 and June 2014 were retrospectively reviewed. RESULTS: Standard methods were successful in 79 cannulations. Of the 25 cannulations that could not be performed by standard methods, 19 were performed by needle-knife, while 17 (89.5%) were successful. Needle-knife use improved the success rate of cannulation [76.0%, 79/104 vs 92.3%, (79 + 17)/104; P = 0.001]. When the 6 cases not appropriate for needle-knife cannulation were excluded, the success rate was improved further (80.6%, 79/98 vs 98.0%, 96/98; P = 0.000). There were no significant differences in the rates of post-endoscopic retrograde cholangiopancreatography adverse events between the group using standard methods alone and the group using needle-knife after failure of standard methods (4.7% vs 10.5%, P = 0.301). CONCLUSION: The needle-knife procedure may be an alternative method for improving the success rate of cannulation via the minor papilla, particularly when standard cannulation has failed.