Gut microbiota composition and changes in patients with sepsis: potential markers for predicting survival.

BACKGROUND: Sepsis can cause immune dysregulation and multiple organ failure in patients and eventually lead to death. The gut microbiota has demonstrated its precise therapeutic potential in the treatment of various diseases. This study aimed to discuss the structural changes of the gut microbiota in patients with sepsis and to analyze the differences in the gut microbiota of patients with different prognoses. METHODS: We conducted a multicenter study in which rectal swab specimens were collected on the first and third days of sepsis diagnosis. A total of 70 specimens were collected, and gut microbiota information was obtained by 16S rRNA analysis. RESULTS: The relative abundance of Enterococcus decreased in rectal swab specimens during the first three days of diagnosis in patients with sepsis, while the relative abundance of inflammation-associated Bacillus species such as Escherichia coli, Enterobacteriaceae, and Bacteroidetes increased. By comparing the differences in the flora of the survival group and the death group, we found that the abundance of Veillonella and Ruminococcus in the death group showed an increasing trend (p < 0.05), while the abundance of Prevotella_6 and Prevotella_sp_S4_BM14 was increased in surviving patients (p < 0.05). CONCLUSIONS: The Firmicutes/Bacteroidetes ratio, reflecting overall gut microbial composition, was significantly lower on day three of sepsis diagnosis. Changes in the abundance of specific gut microbiota may serve as prognostic markers in patients with sepsis.

Effect of early serum phosphate disorder on in-hospital and 28-day mortality in sepsis patients: a retrospective study based on MIMIC-IV database.

BACKGROUND: This study aims to assess the influence of early serum phosphate fluctuation on the short-term prognosis of sepsis patients. METHODS: This retrospective study used the Medical Information Mart for Intensive Care IV database to analyze serum phosphate levels in sepsis patients within 3 days of ICU admission. According to the absolute value of delta serum phosphate (the maximum value minus the minimum value of serum phosphorus measured within three days), the patients were divided into four groups, 0-1.3, 1.4-2.0, 2.1-3.1, and ≥ 3.2 mg/dl. Meanwhile, the direction of delta serum phosphate was compared. With the serum phosphate change group of 0-1.3 mg/dl as the reference group, the relationship between delta serum phosphate and in-hospital mortality and 28-day mortality was analyzed by multivariate Logistics regression analysis. RESULTS: The study involved 1375 sepsis patients. Serum phosphate changes (0-1.3, 1.4-2.0, 2.1-3.1, and ≥ 3.2 mg/dl) correlated with in-hospital and 28-day mortality variations (p = 0.005, p = 0.008). Much higher serum phosphate fluctuation elevated in-hospital and 28-day mortality. Compared to the 0-1.3 mg/dl change group, adjusted odds ratios (OR) in other groups for in-hospital mortality were 1.25 (0.86-1.81), 1.28 (0.88-1.86), and 1.63 (1.10-2.43), and for 28-day mortality were 1.21 (0.86-1.72), 1.10 (0.77-1.57), and 1.49 (1.03-2.19). Under the trend of increasing serum phosphate, the ORs of in-hospital mortality and 28-day mortality in ≥ 3.2 mg/dl group were 2.52 and 2.01, respectively. CONCLUSION: In conclude, the delta serum phosphate ≥ 3.2 mg/dl was associated with in-hospital mortality and 28-day mortality in patients with sepsis.

Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients.

BACKGROUND: Chimeric antigen receptor T (CAR-T) cell therapy, a new adoptive cell therapy, has been widely used to treat lymphoma patients. Immune checkpoint blockade may improve the cytotoxicity of CAR-T cells by reducing the failure of CAR-T cells and improving antitumor activity. It has shown promising efficacy. METHOD: We searched PubMed, the Cochrane Library, Embase and Web of Science from January 2012 to August 2022 to find data reporting the results of CAR-T cells therapy combined with PD-1 in tumor patients. An updated search was conducted in October 2023. The partial response rate (PR), complete response rate (CR), objective response rate (ORR), mortality rate, and incidence of adverse reactions were calculated. RESULTS: We analyzed 57 lymphoma patients from 5 clinical trials. The pooled partial, complete and overall response rates were 21% (95% CI 0.06-0.39, I2 = 0.37%), 27% (95% CI 0.03-0.60, I2 = 60.43%) and 65% (95% CI 0.23-0.98, I2 = 76.31%), respectively. The pooled incidence of cytokine release syndrome, neutropenia, fever, and fatigue was estimated to be 57% (95% CI 0.08-0.99, I2 = 85.20%), 47% (95% CI 0.14-0.81, I2 = 74.17%), 59% (95% CI 0.27-0.89, I2 = 60.23%), and 50% (95% CI 0.13-0.87, I2 = 73.89%), respectively. CONCLUSION: CAR-T-cell therapy combined with anti-PD-1 immunotherapy in the treatment of lymphoma patients has efficacy, and the most common adverse effect is fever. REGISTRATION: The protocol was registered in prospero, with the registration number CRD42022342647.

Effects of carrimycin on biomarkers of inflammation and immune function in tumor patients with sepsis: A multicenter double-blind randomized controlled trial.

Carrimycin is a potential immune-regulating agent for sepsis in patients with tumors. In this study, we investigated its effects on inflammation and immune function in tumor patients with sepsis. In total, 120 participants were randomized to receive either carrimycin treatment (400 mg/day) (n = 62) or placebo (n = 58) for 7 days. The primary outcomes were immune-related indicators. Subsequently, patients were stratified into two subgroups (CD4 < 38.25% and CD8 < 25.195%). Ninety-nine participants were analyzed: 47 and 52 in the carrimycin and placebo groups, respectively. HLA-DR levels were rapidly increased in the carrimycin group; however, the placebo group initially experienced a decline in HLA-DR level at 1 day after administration. In the subgroup with CD4 < 38.25%, the carrimycin group exhibited significantly higher HLA-DR levels than the placebo group (2.270, P = 0.023) 1 day after administration and the degree of increase in HLA-DR in the carrimycin group was higher than that in the placebo group (2.057, P = 0.040). In the CD8 < 25.195% subgroup, the carrimycin group demonstrated significantly higher levels of CD8+ T cells than the placebo group at 3 (2.300,P = 0.027) and 5 (2.106, P = 0.035) days after administration. Carrimycin intervention led to significant reductions in the SOFA, APACHE II, PCT, and CRP levels. No adverse events were observed. In tumor patients with sepsis, particularly in those experiencing immunological suppression, carrimycin effectively regulates immune responses by increasing HLA-DR and CD8+ T cell levels and plays an anti-infective role, reducing disease severity. (Chictr.org.cn, ID Number: ChiCTR2000032339).

Gut microbiota disruption during sepsis and the influence of innate metabolites on sepsis prognosis.

Sepsis causes high mortality in intensive care units. Although there have been many studies on the gut microbiota in patients with sepsis, the impact of sepsis on the gut microbiota has not been directly determined because the treatment of sepsis also affects the gut microbiota. Therefore, we designed this animal experiment to explore gut microbiota alterations during sepsis. Mice were divided into two groups, mice that survived less than 3 days and mice that survived more than 3 days. Fecal samples collected on the day of cecal ligation and puncture (CLP), as well as on the 3rd and 7th days after CLP, were subjected to microbial community analysis and nontargeted metabolomics analysis. The results showed significantly lower bacterial diversity in fecal samples after CLP. At the genus level, the fecal samples obtained on the 3rd and 7th days after CLP exhibited significantly increased relative abundances of Bacteroides, Helicobacter, etc., and significantly decreased relative abundances of Alloprevotella, Prevotella, etc. Innate metabolite levels were significantly different in mice that survived less than 3 days and mice that survived more than 3 days. In conclusion, CLP-induced sepsis in mice changes the structure of the gut microbiome, and innate metabolites affect the prognosis of septic mice.

Early gut microbiological changes and metabolomic changes in patients with sepsis: a preliminary study.

The gut microbiota is closely related to the development of sepsis. The aim of this study was to explore changes in the gut microbiota and gut metabolism, as well as potential relationships between the gut microbiota and environmental factors in the early stages of sepsis. Fecal samples were collected from 10 septic patients on the first and third days following diagnosis in this study. The results showed that in the early stages of sepsis, the gut microbiota is dominated by microorganisms that are tightly associated with inflammation, such as Escherichia-Shigella, Enterococcus, Enterobacteriaceae, and Streptococcus. On sepsis day 3 compared to day 1, there was a significant decrease in Lactobacillus and Bacteroides and a significant increase in Enterobacteriaceae, Streptococcus, and Parabacteroides. Culturomica_massiliensis, Prevotella_7 spp., Prevotellaceae, and Pediococcus showed significant differences in abundance on sepsis day 1, but not on sepsis day 3. Additionally, 2-keto-isovaleric acid 1 and 4-hydroxy-6-methyl-2-pyrone metabolites significantly increased on sepsis day 3 compared to day 1. Prevotella_7 spp. was positively correlated with phosphate and negatively correlated with 2-keto-isovaleric acid 1 and 3-hydroxypropionic acid 1, while Prevotella_9 spp. was positively correlated with sequential organ failure assessment score, procalcitonin and intensive care unit stay time. In conclusion, the gut microbiota and metabolites are altered during sepsis, with some beneficial microorganisms decreasing and some pathogenic microorganisms increasing. Furthermore, Prevotellaceae members may play different roles in the intestinal tract, with Prevotella_7 spp. potentially possessing beneficial health properties and Prevotella_9 spp. potentially playing a promoting role in sepsis.

The accuracy of artificial intelligence in predicting COVID-19 patient mortality: a systematic review and meta-analysis.

BACKGROUND: The purpose of this paper was to systematically evaluate the application value of artificial intelligence in predicting mortality among COVID-19 patients. METHODS: The PubMed, Embase, Web of Science, CNKI, Wanfang, China Biomedical Literature, and VIP databases were systematically searched from inception to October 2022 to identify studies that evaluated the predictive effects of artificial intelligence on mortality among COVID-19 patients. The retrieved literature was screened according to the inclusion and exclusion criteria. The quality of the included studies was assessed using the QUADAS-2 tools. Statistical analysis of the included studies was performed using Review Manager 5.3, Stata 16.0, and Meta-DiSc 1.4 statistical software. This meta-analysis was registered in PROSPERO (CRD42022315158). FINDINGS: Of 2193 studies, 23 studies involving a total of 25 AI models met the inclusion criteria. Among them, 18 studies explicitly mentioned training and test sets, and 5 studies did not explicitly mention grouping. In the training set, the pooled sensitivity was 0.93 [0.87, 0.96], the pooled specificity was 0.94 [0.87, 0.97], and the area under the ROC curve was 0.98 [0.96, 0.99]. In the validation set, the pooled sensitivity was 0.84 [0.78, 0.88], the pooled specificity was 0.89 [0.85, 0.92], and the area under the ROC curve was 0.93 [1.00, 0.00]. In the subgroup analysis, the areas under the summary receiver operating characteristic (SROC) curves of the artificial intelligence models KNN, SVM, ANN, RF and XGBoost were 0.98, 0.98, 0.94, 0.92, and 0.91, respectively. The Deeks funnel plot indicated that there was no significant publication bias in this study (P > 0.05). INTERPRETATION: Artificial intelligence models have high accuracy in predicting mortality among COVID-19 patients and have high prognostic value. Among them, the KNN, SVM, ANN, RF, XGBoost, and other models have the highest levels of accuracy.

Efficacy and Safety of SARS-CoV-2 Neutralizing Antibody JS016 in Hospitalized Chinese Patients with COVID-19: a Phase 2/3, Multicenter, Randomized, Open-Label, Controlled Trial.

Recombinant human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monoclonal antibody JS016 showed neutralizing and therapeutic effects in preclinical studies. The clinical efficacy and safety of the therapy needed to be evaluated. In this phase 2/3, multicenter, randomized, open-label, controlled trial, hospitalized patients with moderate or severe coronavirus disease 2019 (COVID-19) were randomly assigned in a 1:1 ratio to receive standard care or standard care plus a single intravenous infusion of JS016. The primary outcome was a six-level ordinal scale of clinical status on day 28 since randomization. Secondary outcomes include adverse events, 28-day mortality, ventilator-free days within 28 days, length of hospital stay, and negative conversion rate of SARS-CoV-2 nucleic acid on day 14. A total of 199 patients were randomized, and 197 (99 in the JS016 group and 98 in the control group) were analyzed. Most patients, 95 (96%) in the JS016 group and 97 (99%) in the control group were in the best category on day 28 since randomization. The odds ratio of being in a better clinical status was 0.31 (95% confidence interval [CI], 0.03 to 3.19; P = 0.33). Few adverse events occurred in both groups (3% in the JS016 group and 1% in the control group, respectively; P = 0.34). SARS-CoV-2 neutralizing antibody JS016 did not show clinical efficacy among hospitalized Chinese patients with moderate to severe COVID-19 disease. Further studies are needed to assess the efficacy of the neutralizing antibody to prevent disease deterioration and its benefits among groups of patients specified by disease course and severity. (This study has been registered at ClinicalTrials.gov under identifier NCT04931238.).

circ-Katnal1 Enhances Inflammatory Pyroptosis in Sepsis-Induced Liver Injury through the miR-31-5p/GSDMD Axis.

Background: Sepsis is a systemic inflammatory response that can elicit organ dysfunction as well as circulatory diseases in serious cases. When inflammatory responses are especially dysregulated, severe complications can arise, including sepsis-induced liver injury. Various microRNAs along with circular (circ) RNAs are involved in inflammatory responses; nevertheless, their functions in regulating sepsis-induced liver injury remain unknown. The cecal ligation and puncture (CLP) procedure can induce liver injury as well as polymicrobial sepsis. Methods: In this study, CLP was used to induce liver injury as well as polymicrobial sepsis. Then, liver function, inflammatory cytokine expression, and hepatic histopathology were evaluated. High-throughput sequencing was employed to investigate the abnormal hepatic circRNA expression after CLP. Raw264.7 cells were utilized to simulation an in vitro sepsis inflammation model with LPS induce. The relative mRNA as well as protein levels of TNF-α, IL-1ß, and IL-6 was explored by quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assays. We explored functional connections among circRNAs, miR-31-5p, and gasdermin D (GSDMD) using dual-luciferase reporter assays. Western blot was employed to test GSDMD, caspase-1, and NLRP3 expression in mice and cell models. Results: Our results showed that CLP-induced sepsis promoted liver injury via increasing inflammatory pyroptosis. The abnormal expression of circ-Katnal1 played an important role in CLP-induced sepsis. Downregulating circ-Katnal1 suppressed LPS-induced inflammatory pyroptosis in Raw264.7 cells. Bioinformatics and luciferase reporter results confirmed that miR-31-5p and GSDMD were downstream targets of circ-Katnal1. Inhibiting miR-31-5p or upregulating GSDMD reversed the protective effects of silencing circ-Katnal1. Conclusion: Taken together, circ-Katnal1 enhanced inflammatory pyroptosis in sepsis-induced liver injury through the miR-31-5p/GSDMD axis.

Inhibition of matrix stiffness relating integrin ß1 signaling pathway inhibits tumor growth in vitro and in hepatocellular cancer xenografts.

BACKGROUND: Cancer development is strictly correlated to composition and physical properties of the extracellular matrix. Particularly, a higher matrix stiffness has been demonstrated to promote tumor sustained growth. Our purpose was to explore the role of matrix stiffness in liver cancer development. METHODS: The matrix stiffness of tumor tissues was determined by atomic force microscopy (AFM) analysis. In vitro, we used a tunable Polyacrylamide (PA) hydrogels culture system for liver cancer cells culture. The expression level of integrin ß1, phosphorylated FAK, ERK1/2, and NF-κB in SMMC-7721 cells was measured by western blotting analysis. We performed MTT, colony formation and transwell assay to examine the tumorigenic and metastatic potential of SMMC-7721 cells cultured on the tunable PA hydrogels. SMMC-7721 cancer xenografts were established to explore the anticancer effects of integrin inhibitors. RESULTS: Our study provided evidence that liver tumor tissues from metastatic patients possessed a higher matrix stiffness, when compared to the non-metastatic group. Liver cancer cells cultured on high stiffness PA hydrogels displayed enhanced tumorigenic potential and migrative properties. Mechanistically, activation of integrin ß1/FAK/ ERK1/2/NF-κB signaling pathway was observed in SMMC-7721 cells cultured on high stiffness PA hydrogels. Inhibition of ERK1/2, FAK, and NF-κB signaling suppressed the pro-tumor effects induced by matrix stiffness. Combination of chemotherapy and integrin ß1 inhibitor suppressed the tumor growth and prolonged survival time in hepatocellular cancer xenografts. CONCLUSION: A higher matrix stiffness equipped tumor cells with enhanced stemness and proliferative characteristics, which was dependent on the activation of integrin ß1/FAK/ERK1/2/NF-κB signaling pathway. Blockade of integrin signals efficiently improved the outcome of chemotherapy, which described an innovative approach for liver cancer treatment.

Identification of distinct clinical phenotypes of acute respiratory distress syndrome with differential responses to treatment.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome, and the identification of homogeneous subgroups and phenotypes is the first step toward precision critical care. We aimed to explore whether ARDS phenotypes can be identified using clinical data, are reproducible and are associated with clinical outcomes and treatment response. METHODS: This study is based on a retrospective analysis of data from the telehealth intensive care unit (eICU) collaborative research database and three ARDS randomized controlled trials (RCTs) (ALVEOLI, FACTT and SAILS trials). We derived phenotypes in the eICU by cluster analysis based on clinical data and compared the clinical characteristics and outcomes of each phenotype. The reproducibility of the derived phenotypes was tested using the data from three RCTs, and treatment effects were evaluated. RESULTS: Three clinical phenotypes were identified in the training cohort of 3875 ARDS patients. Of the three phenotypes identified, phenotype I (n = 1565; 40%) was associated with fewer laboratory abnormalities, less organ dysfunction and the lowest in-hospital mortality rate (8%). Phenotype II (n = 1232; 32%) was correlated with more inflammation and shock and had a higher mortality rate (18%). Phenotype III (n = 1078; 28%) was strongly correlated with renal dysfunction and acidosis and had the highest mortality rate (22%). These results were validated using the data from the validation cohort (n = 3670) and three RCTs (n = 2289) and had reproducibility. Patients with these ARDS phenotypes had different treatment responses to randomized interventions. Specifically, in the ALVEOLI cohort, the effects of ventilation strategy (high PEEP vs low PEEP) on ventilator-free days differed by phenotype (p = 0.001); in the FACTT cohort, there was a significant interaction between phenotype and fluid-management strategy for 60-day mortality (p = 0.01). The fluid-conservative strategy was associated with improved mortality in phenotype II but had the opposite effect in phenotype III. CONCLUSION: Three clinical phenotypes of ARDS were identified and had different clinical characteristics and outcomes. The analysis shows evidence of a phenotype-specific treatment benefit in the ALVEOLI and FACTT trials. These findings may improve the identification of distinct subsets of ARDS patients for exploration in future RCTs.

Volatile Organic Compounds to Identify Infectious (Bacteria/Viruses) Diseases of the Central Nervous System: A Pilot Study.

BACKGROUND: Central nervous system (CNS) infectious diseases are common diseases in emergency rooms and neurology departments. CNS pathogen identification methods are time consuming and expensive and have low sensitivity and poor specificity. Some studies have shown that bacteria and viruses can produce specific volatile organic compounds (VOCs). The aim of this study is to find potential biomarkers by VOC analysis of cerebrospinal fluid (CSF) in patients with bacterial and viral meningitis/encephalitis (ME). METHODS: CSF samples from 16 patients with bacterial ME and 42 patients with viral ME were collected, and solid-phase microextraction combined with gas chromatography-mass spectrometry was used to analyze the metabolites in the CSF. RESULTS: There are 2 substances (ethylene oxide and phenol) that were found to be different between the 2 groups. Ethylene oxide was significantly greater in the group of bacterial ME patients than in the viral ME group of patients (p < 0.05). In addition, phenol was remarkably increased in the group of ME patients compared with the bacterial ME patients (p < 0.05). CONCLUSIONS: Ethylene oxide and phenol may be potential biomarkers to distinguish bacterial ME and viral ME. VOC analysis of CSF may be used as a supporting tool for clinical diagnosis.

Functional potential differences between Firmicutes and Proteobacteria in response to manure amendment in a reclaimed soil.

Manure amendment generally bolsters soil organisms but not all bacteria equally. To understand why different taxa respond differently, we used shotgun metagenomic approaches to profile functional potentials and correlate them with taxon abundances. A soil originally unproductive was reclaimed using commercial manure and finally became productive. The abundance of Firmicutes in the soil decreased, whereas that of Bacteroidetes and Proteobacteria increased after manure addition. Thirty-nine KEGG modules were significantly different across fertilizer treatments. These modules were mainly associated with the phosphoenolpyruvate-dependent phosphotransferase system (PTS), ATP-binding cassette (ABC) transporters, and two-component signal transduction systems. The Proteobacteria and Firmicutes mainly contributed to these modules. Correlation between the abundances of phyla and orthologs showed two distinctive patterns. One linked the Firmicutes to cell wall biosynthesis, PTS, and ABC transporters, and the other linked the Betaproteobacteria, Bacteroidetes, and Verrucomicrobia to lipopolysaccharide biosynthesis, bacterial motility, and carbon metabolism. Correlation between the abundances of phyla and Carbohydrate-Active Enzyme Database families also showed two distinctive patterns, one of them linking the Betaproteobacteria, Bacteroidetes, and Verrucomicrobia to very high abundances of glycosyltransferases and glycoside hydrolases. Overall, the Proteobacteria and Firmicutes were main drivers of functional potential differences across fertilizer treatments. The Firmicutes were enriched with genes associated with cell wall biosynthesis and membrane transports, while Proteobacteria with lipopolysaccharide biosynthesis and carbohydrate metabolism, which supports our hypothesis that the Firmicutes have a lower potential for utilizing manure-derived carbohydrates, while Proteobacteria have a higher potential. This explains why the Proteobacteria and Firmicutes responded to manure differently.

Release of volatile organic compounds (VOCs) from colorectal cancer cell line LS174T.

Colorectal cancer (CRC) is the third most common cancer worldwide. To date, no non-invasive and specific biomarkers have been identified for the diagnosis of CRC. The analysis of volatile organic compounds (VOCs) is attracting increasing attention and provides the possibility of a non-invasive diagnosis. Solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) have been used to analyze the VOCs released from the headspace gas of LS174T (Dukes' type B colorectal adenocarcinoma) cells, arsenic trioxide (ATO)-treated LS174T cells and the blood from tumor-bearing mice. The data were processed using principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA), which showed that the levels of decanal, 2,4-dimethyl- heptane, and twelve other metabolites were significantly greater in the headspace gas of the LS174T cells and blood of tumor-bearing mice. Additionally, in vivo experiments indicated that formic acid, ethenyl ester and p-trimethylsilyloxyphenyl-(trimethylsilyloxy)trimethylsilylacrylate were consumed during tumor growth. In conclusion, VOCs such as 1-methoxy-hexane and 2,4-dimethyl-heptane could be useful diagnostic markers for CRC. Further research should focus on the potential metabolic pathways associated with these profiles.

Effects of immunotherapy on mortality in neonates with suspected or proven sepsis: a systematic review and network meta-analysis.

BACKGROUND: To investigate the efficacies of different immunotherapies in neonates with suspected or proven sepsis. METHODS: We searched the Cochrane Library, EMBASE, MEDLINE, EBSCOhost, and Web of Science for studies published before May 2019 that investigated different immunotherapies in neonates with suspected or proven sepsis. Comparisons were among immunotherapies and between immunotherapy and placebo. The review was registered in the PROSPERO CRD database. RESULTS: All-cause mortality was not significantly different between patients who received the immunoglobulin (IgG), IgM-enriched immunoglobulin (IgGAM), granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) immunotherapies and those who received placebo. The RRs of the immunotherapies were 0.80 (95% CI: 0.57 to 1.1), 0.45 (95% CI: 0.17 to 1.0), 0.93 (95% CI: 0.64 to 1.2) and 0.67 (95% CI: 0.39 to 1.1), respectively. Compared with placebo, none of the interventions showed statistically significant differences in the duration of hospital stay. The MDs of the immunotherapies were - 2.7 (95% CI: - 8.4 to 3.5), - 0.18 (95% CI: - 7.3 to 7.7), - 1.7 (95% CI: - 7.3 to 3.9) and - 7.2 (95% CI: - 28 to 13), respectively. CONCLUSIONS: No significant differences in all-cause mortality or the duration of hospital stay were found in neonates with suspected or proven sepsis treated with the four types of immunotherapies and those treated with placebo.

Evaluating the Long-, Short-, and Oblique-Axis Approaches for Ultrasound-Guided Vascular Access Cannulation.

BACKGROUND: Our goal was to conduct a network meta-analysis of randomized controlled trials to compare the effects of the long-axis (LAX), short-axis (SAX), and oblique-axis (OAX) ultrasound guidance approaches for vascular access cannulation. METHODS: We searched 5 databases, including the Cochrane Central Register of Controlled Trials in the Cochrane Library, Embase, MEDLINE, CINAHL, and Web of Science. Seven randomized clinical trials assessing ultrasound guidance for vascular access cannulation via the LAX, SAX, or OAX approach were included. The primary end point was the first-pass success rate. Secondary end points included the mean time to success and average number of attempts until success. We used random-effects models to calculate weighted mean differences with 95% confidence intervals for continuous outcomes and relative risks with 95% confidence intervals for dichotomous outcomes. RESULTS: There were no significant differences between the LAX, SAX, and OAX techniques with respect to the first-pass success rate, mean time to success, average number of attempts until success, or the incidence of hematoma. CONCLUSION: There was insufficient evidence to definitively recommend the LAX, SAX, or OAX approach for patients undergoing ultrasound-guided vascular access cannulation.

Urine volatile organic compounds as biomarkers for minimal change type nephrotic syndrome.

Urinary volatile organic compounds (VOCs) profiling has recently received considerable attention because it can be obtained noninvasively and conveniently while it can be successfully used in a variety of diseases and can provide unique biomarkers. The aim of current study was to investigate potential biomarkers between minimal change type nephrotic syndrome (MCNS) and normal. Urinary samples were collected from 38 minimal change type nephrotic syndrome patients and 15 healthy controls. Solid phase microextraction (SPME) and chromatography- mass spectrometry (GC-MS) were used to analysis the urinary metabolites. To deal with the final data, the statistical methods principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLSDA) were performed. Six specific VOC biomarkers were present at abnormal levels in the urine of MCNS patients. These VOCs included trans-2,2-dimethyl-4-decene; pyrrole; carbamic acid, monoammonium salt; 1-butyne, 3,3-dimethyl-; diisopropylamine; and 4-heptanone. These biomarkers may be useful as a new diagnostic method and for monitoring the prognosis for MCNS patients.

Volatile organic metabolites identify patients with gastric carcinoma, gastric ulcer, or gastritis and control patients.

BACKGROUND: Gastric cancer ranks 4th among the most common cancers worldwide, and the mortality caused by gastric cancer is 2nd only to lung cancer. Gastric cancer shows a lack of specific symptoms in its early stages. In addition, its clinical symptoms often do not match the corresponding stage. Upper gastrointestinal endoscopy with biopsy is the gold standard for the diagnosis of gastric cancer because of its high accuracy. However, this operation is invasive, patient compliance is poor, and high demands for medical staff and equipment are typical of this procedure. Recent studies have demonstrated a connection between specific breath volatile organic compounds (VOCs) and various forms of cancers. METHODS: We collected expired air from patients with gastric cancer, chronic atrophic gastritis or gastric ulcers as well as from healthy individuals. Solid-phase microextraction, gas chromatography-mass spectrometry and principal component analysis statistics were applied to identify potential biomarkers of gastric cancer among VOCs. RESULTS: Fourteen differential metabolites were annotated using the NIST 11 database, with a similarity threshold of 70%. Currently, the metabolic origin of VOCs remains unclear; however, several pathways might explain the decreasing or increasing trends that were observed. CONCLUSIONS: The results of this study demonstrate the existence of specific VOC profiles associated with patients with carcinoma. In addition, these metabolites may contribute to the diagnosis and screening of patients with carcinoma.