Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in pediatric sepsis by integrating bioinformatics and machine learning.

BACKGROUND: Pediatric sepsis is a complicated condition characterized by life-threatening organ failure resulting from a dysregulated host response to infection in children. It is associated with high rates of morbidity and mortality, and rapid detection and administration of antimicrobials have been emphasized. The objective of this study was to evaluate the diagnostic biomarkers of pediatric sepsis and the function of immune cell infiltration in the development of this illness. METHODS: Three gene expression datasets were available from the Gene Expression Omnibus collection. First, the differentially expressed genes (DEGs) were found with the use of the R program, and then gene set enrichment analysis was carried out. Subsequently, the DEGs were combined with the major module genes chosen using the weighted gene co-expression network. The hub genes were identified by the use of three machine-learning algorithms: random forest, support vector machine-recursive feature elimination, and least absolute shrinkage and selection operator. The receiver operating characteristic curve and nomogram model were used to verify the discrimination and efficacy of the hub genes. In addition, the inflammatory and immune status of pediatric sepsis was assessed using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). The relationship between the diagnostic markers and infiltrating immune cells was further studied. RESULTS: Overall, after overlapping key module genes and DEGs, we detected 402 overlapping genes. As pediatric sepsis diagnostic indicators, CYSTM1 (AUC = 0.988), MMP8 (AUC = 0.973), and CD177 (AUC = 0.986) were investigated and demonstrated statistically significant differences (P < 0.05) and diagnostic efficacy in the validation set. As indicated by the immune cell infiltration analysis, multiple immune cells may be involved in the development of pediatric sepsis. Additionally, all diagnostic characteristics may correlate with immune cells to varying degrees. CONCLUSIONS: The candidate hub genes (CD177, CYSTM1, and MMP8) were identified, and the nomogram was constructed for pediatric sepsis diagnosis. Our study could provide potential peripheral blood diagnostic candidate genes for pediatric sepsis patients.

Tai Chi Exercise for Patients with Chronic Heart Failure: A Meta-analysis of Randomized Controlled Trials.

AIM: This meta-analysis aimed to update and evaluate evidence from randomized controlled trials of tai chi for patients with chronic heart failure. METHOD: Both English and Chinese databases were searched from their inception to June 2, 2016 (PubMed, EMBASE, Cochrane Central Register of Controlled Trials for English publications and China Knowledge Resource Integrated, Wanfang, and Weipu databases for Chinese publication). Titles, abstracts, and full-text articles were screened against study inclusion criteria: randomized controlled trials studying tai chi intervention for patients with chronic heart failure. The meta-analysis was conducted with Revman 5.3 or STATA 12. RESULT: Thirteen randomized controlled trials were included. Tai chi induced significant improvement in 6-min walking distance (51.01 m; 30.49-71.53; P < 0.00). Moreover, tai chi was beneficial for quality of life (-10.37 points; -14.43 to -6.32; P = 0.00), left ventricular ejection fraction (7.72%; 3.58-11.89; P = 0.003), and B-type natriuretic peptide (-1.01; -1.82 to -0.19; P = 0.02). CONCLUSION: Despite heterogeneity and risk of bias, this meta-analysis further confirms that tai chi may be an effective cardiac rehabilitation method for patients with chronic heart failure. Larger, well-designed randomized controlled trials are needed to exclude the risk of bias.

Impact of operation timing on post-operative infections following colorectal cancer surgery.

BACKGROUND: To investigate the impact of operation timing on post-operative infections in a cohort of patients undergoing colorectal cancer surgery. METHODS: We prospectively analysed surgical outcomes in patients who underwent colorectal cancer surgery at the First Affiliated Hospital, College of Medicine, Zhejiang University, from January to December in 2014. In this non-randomized trial, patients were divided into three groups according to the surgery start time: CT1 (07:00 to 12:00 h), CT2 (12:01 to 18:00 h), and CT3 (18:01 h to midnight). The primary outcome was the proportion of patients developing infections within 4 weeks of the surgical procedure. RESULTS: Out of 756 patients that were enrolled in the study, 118 developed post-operative infections. The results from blood and pus culture showed 97.1% specimen as being pathogen-free. The overall incidence of post-operative infection was 14.5% (38 of 262), 15.3% (46 of 300) and 17.5% (34 of 194) in the CT1, CT2 and CT3 group, respectively, with no significant inter-group differences. However, white blood cell counts, C-reactive protein and glucose levels at 24 h after the surgical procedure showed significant differences between the three groups (one-way ANOVA, P < 0.05). CONCLUSION: The occurrence of post-operative infection in patients undergoing colorectal cancer surgery was not associated with operation timing. The expression of several inflammatory markers, such as white blood cell counts, C-reactive protein and blood glucose levels tended to correlate with the surgery start time.

Polymorphisms of the HTR3B gene are associated with post-surgery emesis in a Chinese Han population.

WHAT IS KNOWN AND OBJECTIVES: The serotoninergic receptor 5-hydroxytryptamine (serotonin) receptor 3 (HTR3) is instrumental in the regulation of nausea and emesis (vomiting).This study investigated whether common genomic variations of the A and B subunits of HTR3 (HTR3A, HTR3B) are associated with the incidence of post-operative vomiting in a Chinese Han population. METHODS: Two hundred and thirty-one female Chinese Han patients undergoing gynaecological surgery with standardized general anaesthesia were recruited for the study. Clinical symptoms after surgery were recorded and direct DNA sequencing was performed to detect polymorphisms of HTR3A and HTR3B. RESULTS: Five single nucleotide polymorphisms (SNPs) in HTR3A and HTR3B were found, with R(2)  > 0·8 and minor allele frequency > 10%. One of these (rs3758987 in HTR3B) was statistically associated with vomiting, after adjusting for body weight, body mass index and duration of general anaesthesia in dominant and additive models (P = 0·047 and P = 0·034). WHAT IS NEW AND CONCLUSION: The HTR3B rs3758987 SNP might serve as a predictor of post-operative vomiting in Chinese Han patients undergoing gynaecological laparoscopic surgery.

Altered melatonin secretion and circadian gene expression with increased proinflammatory cytokine expression in early-stage sepsis patients.

Inflammatory and immune responses, as well as melatonin secretion, are affected by circadian regulation. Abnormal circadian rhythm of melatonin release has been reported to be associated with the later stages of sepsis; however, its role in the early stages of sepsis is unclear. We studied 11 septic and 11 non-septic patients in our intensive care unit (ICU). Peripheral blood was drawn at 4-h intervals on the first day, beginning at 2:00 p.m., over a total period of 24 h. Plasma levels of melatonin, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were measured by radioimmunoassay or enzyme-linked immunosorbent assay (ELISA). Messenger RNA levels of circadian genes Cry-1 and Per-2 were analyzed using quantitative real-time PCR. Results show the circadian rhythm of melatonin secretion was altered in the early stages of sepsis. The melatonin secretion acrophase occurred earlier in septic patients at 6:00 p.m., compared with at 2:00 a.m. in non-septic ICU patients. Compared with the non-septic group, both Cry-1 and Per-2 expression were significantly decreased while TNF-α and IL-6 expression were significantly increased in septic patients [TNF-α, 64.1 (43.6-89.1) vs. 11.4 (10.4-12.5) ng/ml; IL-6, 41.2 (35.7-50.8) vs. 19.1 (16-136.7) ng/ml; median (range), both P=0.04]. The peak concentrations of TNF-α and IL-6 were shown to be in concordance with the rhythm of melatonin secretion. The circadian rhythm of melatonin secretion and circadian gene expression were altered in the early stages of sepsis, which likely led to the changes in pro-inflammatory cytokine release. These findings shed light on the potential link between circadian rhythm and the progression of early-stage sepsis.

[The effect of two methods guided fluid therapy to the patient undergoing open gastrointestinal surgery].

OBJECTIVE: To investigate the effect of central venous blood oxygen saturation (ScvO2) and venous-arterial PCO2 (P(cv-a)CO2) guided fluid therapy on tissue perfusion, gastrointestinal function recovering and outcome of the patients who undergoing open gastrointestinal surgery. METHODS: Forty patients undergoing open gastrointestinal surgery were randomly divided into 2 groups (n = 20 each): ScvO2 guided fluid therapy (group S) and P(cv-a) CO2 guided fluid therapy (group P). All the patients were infused 10 ml/kg lactated Ringer's (LR) solution before anesthesia induction, they were all also given a continuous lactated Ringer's (LR) solution's infusion at the speed of 2 ml·kg(-1)·h(-1) during the operation. While, 6%HES 130/0.4 (free flex 6%HES 130/0.4, Fresenius Kabi) infusion was different between the 2 groups, when the patients of group S's central venous blood oxygen saturation < 75% or venous-arterial PCO2 in the patients of P group ≥6 mm Hg, then infused 6%HES 130/0.4. Arterial and central venous blood gas analyses were performed every 20 minutes after skin incision, measure the venous and arterial lactate value, and record the anal exhaust time after surgery, postoperative complications and mortality in 28 days. RESULTS: Compared with group S, the arterial lactate value in T4 (after operation began 80 min) were significantly decreased in group P (P = 0.013), and venous lactate value in T5 (after operation began 100 min) were also lower (P = 0.044), other lactate value were not different (P > 0.05) . The anal exhaust time was not different between the two groups (P = 0.673). All the patients were survival, and there were no obvious postoperative complications. CONCLUSION: Compared to group S, there was a transient improvement in tissue perfusion in group P, but there were no difference in complications and mortality.

[Comparison of three different organ failure assessment score systems in predicting outcome of severe sepsis].

OBJECTIVE: To compare multiple organ dysfunction score (MODS), the sequential organ failure assessment (SOFA) and the logistic organ dysfunction score (LODS) in predicting hospital mortality in severe sepsis. METHODS: Four hundred and three patients admitted to the ICU from December 2004 to November 2007 with a diagnosis of severe sepsis were enrolled in this study. Their MODS, SOFA, LODS and Acute Physiology and Chronic Health Evaluation (APACHE) II at admission and the highest score during hospitalization were respectively recorded and collected in regard to mortality. The discrimination of three multiple organ dysfunction score systems were assessed by the areas under the receiver operating characteristic curves (AUC). RESULTS: The AUC of admission scores was 0.811 for LODS, 0.787 for SOFA, 0.725 for MODS, and 0.770 for APACHE II in predicting hospital mortality. All maximum scores had better power of discrimination than the admission scores (P < 0.01). The power of discrimination of LODS and SOFA were better than the MODS, either the admission or the highest, respectively (P < 0.01). However, no significant difference was observed between the LODS and the SOFA regarding mortality prediction (P > 0.05). The AUC value for the APACHE II score was much lower compared to LODS (P < 0.01). However, there was no difference in AUC value among APACHE II, SOFA and MODS (P > 0.05). CONCLUSION: LODS, SOFA and MODS show a good discrimination power, while maximum LODS is of the highest discrimination power to predict the outcome of patient with severe sepsis.

Protein C -1641A/-1654C haplotype is associated with organ dysfunction and the fatal outcome of severe sepsis in Chinese Han population.

Activation of protein C plays an important role in modulating coagulation as well as inflammation during severe sepsis. The baseline of activated protein C level in patients with severe sepsis showed interindividual variability between survivors and nonsurvivors, and the decreased level of protein C correlated with organ dysfunction and poor outcome. However, there are limited data concerning the genetic predisposition of individuals carrying two functional polymorphisms -1641A>G and -1654C>T within protein C gene to sepsis. Here we investigated the impact of these two variations on the development of severe sepsis in 240 patients with severe sepsis and 323 healthy controls using direct sequencing. After Bonferroni correction for multiple comparisons, -1641A/-1654C haplotype was significantly associated with the fatal outcome of severe sepsis (P = 0.008, OR 1.739, 95% CI 1.165-2.595), which was confirmed by multiple logistic regression analysis (P = 0.024, OR 2.090, 95% CI 1.101-3.967). Compared to patients without carrying -1641A/-1654C haplotype, the -1641A/-1654C haplotype carriers showed higher SOFAmax scores (10.3 +/- 5.2 vs. 9.0 +/- 4.5; P = 0.014) and more hepatic dysfunction (P = 0.004, OR 2.270, 95% CI 1.312-3.930). These findings suggest that protein C haplotype -1641A/-1654C is associated with organ dysfunction and is an independent risk factor for the fatal outcome of severe sepsis in Chinese Han population.

Impact of invasive fungal infection on outcomes of severe sepsis: a multicenter matched cohort study in critically ill surgical patients.

INTRODUCTION: Fungal infection is increasingly common in critical illness with severe sepsis, but the influence of invasive fungal infection (IFI) on severe sepsis is not well understood. The aim of this study was to investigate the impact that IFI has on the outcomes of critically ill surgical patients with severe sepsis in China by means of matched cohort analysis; we also evaluated the epidemiologic characteristics of IFI in this population. METHODS: Records for all admissions to 10 university hospital surgical intensive care units (ICUs) from December 2004 to November 2005 were reviewed. Patients who met criteria for severe sepsis were included. IFI was identified using established criteria based on microbiologic or histological evidence. A matched cohort study was conducted to analyze the relationship between IFI and outcomes of severe sepsis. RESULTS: A total of 318 patients with severe sepsis were enrolled during the study period, of whom 90 (28.3%) were identified as having IFI. A total of 100 strains of fungi (58% Candida albicans) were isolated from these patients. Independent risk factors for IFI in patients with severe sepsis included mechanical ventilation (>3 days), Acute Physiology and Chronic Health Evaluation score, coexisting infection with both gram-positive and gram-negative bacteria, and urethral catheterization (>3 days). Compared with the control cohort, IFI was associated with increased hospital mortality (P < 0.001), high hospital costs (P = 0.038), and prolonged stay in the ICU (P < 0.001) and hospital (P = 0.020). CONCLUSION: IFI is frequent in patients with severe sepsis in surgical ICUs and is associated with excess risk for hospital mortality, longer ICU and hospital stays, and greater consumption of medical resources.