Sepsis is a systemic inflammatory response syndrome caused by infection, with high fatality rate and complex pathogenesis. Early and accurate diagnosis is essential to improving the prognosis of patients with sepsis. This review briefly describes the basic pathogenesis of sepsis, and summarizes the current new technologies for detecting sepsis from two aspects: pathogen detection and host immune status detection, such as digital polymerase chain reaction, biosensors, fluorescent probes, single-cell RNA sequencing, and enzyme-linked immunospot assay. By comprehensively analyzing and applying these new techniques, it is helpful to improve the efficiency and accuracy of early diagnosis of sepsis and improve the clinical treatment effect of patients.
Objective To investigate the efficacy of continuous blood purification ( CBP) in the treatment of severe sepsis, and explore the related immune regulatory mechanisms. Methods Forty-eight patients with severe sepsis were randomly divided into a control group ( n =23) and a CBP group ( n =25) .CD4 + CD25 + regulatory T cells ( Treg% ) in peripheral blood and APACHEⅡ score were measured dynamically before treatment and 12, 24, 36, 48, 60, 72 hours after treatment. Meanwhile the length of ICUstay, duration of mechanical ventilation, and 28 day mortality were determined. Results Compared with the control group, the length of ICU stay, ventilator time, incidence of multiple organ failure, and mortality decreased significantly in the CBP group ( P lt; 0. 05) . And CBP also decreased Treg% and APACHEⅡ score significantly. There was a positive correlation between Treg% and APACHEⅡ score ( r =0. 804, P lt;0. 01) .Conclusion Early CBP treatment can reduce Treg%, improve cellular immunity and improve the prognosis of sepsis.
ObjectiveTo detecte the expressions of phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene and protein in peripheral blood mononuclear cells (PBMC) of patients with sepsis and to explore its role in the pathogenesis of acute obstructive suppurative cholangitis (AOSC).
MethodsThe PBMC and serum were separated from AOSC patients (n=25) before treatment and in 1 week after recure, and healthy volunteers (normal control group, n=15). The serum levels of lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α) and interleukin 10 (IL-10) were detected by enzyme linked immunosorbent assay (ELISA) methods. The mRNA and protein expression levels of PTEN, nuclear fator κB P65 (NF-κB), and inhibitor of NF-κB (IκB) were detected by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, respectively.
ResultsThe levels of LPS, TNF-α, and IL-10 before treatment were significantly higher than those of normal control group (P < 0.05), the indicators were significantly decreased and close to normal levels in 1 week after recure. The mRNA and protein expression levels of PTEN and IκB before treatment were lower than those of normal control group (P < 0.05), NF-κB P65 was higher than those of normal control group (P < 0.05), while the phosphorylation levels of PTEN and IκB were higher than those normal control group (P < 0.05), and in 1 week after recure, the above indicators returned to normal levels.
ConclusionsSepsis shift may be associated with the occurrence of intestinal LPS, and caused the imbalance between proinflammatory and anti-inflammatory cytokines in the body. PTEN for phosphorylation activation of IκB or directly activation of NF-κB participate the originating process of sepsis, hinting a therapeutic potentialities in the early stage of sepsis.
ObjectiveTo investigate the effect of polymyxin B hemoperfusion on the prognosis of patients with sepsis and septic shock by meta-analysis.MethodsSupplemented by manual search and document traceability, the US National Library of Medicine Pubmed, the Dutch Medical Abstracts Embase database, and the Cochrane clinical trial database were searched. Randomized controlled trials (RCTs) were collected from January 1998 to October 2018 for the treatment of sepsis and septic shock with polymyxin B hemoperfusion, only limited to English publications. The collected RCTs were evaluated and the prognosis of patients with sepsis and septic shock was analyzed by the Cochrane Collaboration.ResultsFinally six RCTs were included, and a total of 926 patients were analyzed, with 471 patients in the polymyxin B hemoperfusion group and 455 patients in the control group. The mortality rate was 36.3% (171/471) in the polymyxin B hemoperfusion group and 39.1% (178/455) in the control group. Hemoperfusion with polymyxin B could not reduce the patient mortality (RR=0.80, 95% CI 0.56 to 1.15, P=0.233). A subgroup analysis was taken on the patients with moderate to severe septic shock. Four RCTs were included in total and 418 patients were analyzed, with 207 patients in the polymyxin B hemoperfusion group and 211 in the control group. The mortality rate was 38.65% (80/207) in the polymyxin B hemoperfusion group and 50.71% (107/211) in the control group were. The hemoperfusion of polymyxin B could significantly reduce the mortality of patients with moderate to severe septic shock (RR=0.70, 95% CI 0.52 to 0.96, P=0.025).ConclusionsOlymyxin B hemoperfusion can not improve the prognosis of patients with sepsis and septic shock. However, compared with conventional treatment, polymyxin B hemoperfusion can improve the 28-day mortality rate of patients of severe septic shock. Due to the limit number of randomized controlled trials, more high-quality trials are needed to a further confirmation.
ObjectiveTo investigate the protective effects of diisopropylamini dichlorocacetas on impairment of hepatic function in patients with sepsis.
MethodsThe 60 inpatients with liver dysfunction and sepsis treated in our hospital between June 2010 and December 2012 were randomly divided into two groups: treatment group (n=30) and control group (n=30). In the treatment group, patients were treated with intravenous diisopropylamini dichlorocacetas for 7 days, while patients in the control group were treated with Vitamin C for the same period. The venous blood sample of each patient of the two groups was collected and examined for the content of alanine aminotransferase, aspartate aminotransferase, glutamyl transpeptidase, alkaline phosphatase, total bilirubin, and direct bilirubin before and after treatment, and the effective rates of the two groups were determined.
ResultsLiver function indicators after treatment of both the two groups were reduced. Compared with the control group, the liver function indicators were significantly decreased and the total effective rate was significantly higher in the treatment group (P<0.05).
ConclusionDiisopropylamini dichlorocacetas is effective in the treatment of impairment of hepatic function in patients with sepsis.
Objective
To explore the relationship between central venous-to-arterial carbon dioxide difference/arterial-to-venous oxygen difference ration [P(cv-a)CO2/C(a-cv)O2] and arterial lactate in patients with sepsis.
Methods
A retrospective analysis was carried on 36 septic patients who were admitted to the Intensive Care Unit of Nanjng Drum-tower Hospital affiliated to Medical School of Nanjing University from May 2013 to November 2013. Cardiac index was measured by transpulmonary thermodilution. At the same time, femoral artery and central venous blood were collected to measure the value of arterial lactate and central venous oxygen saturation (ScvO2) by blood gas analysis and calculate central venous-to-arterial carbon dioxide difference [P(cv-a)CO2], arterial-to-venous oxygen difference [C(a-cv)O2], and their ration [P(cv-a)CO2/C(a-cv)O2], oxygen delivery (DO2) and oxygen consumption (VO2). The subjects were divided intoahyperlactatemia group (≥2 mmol/L) andanormal lactate group (< 2 mmol/L) according to arterial lactate value. P(cv-a)CO2/C(a-cv)O2 and other oxygen metabolism parameters were compared between two groups.
Receiver
operating characteristic (ROC) curve was used to evaluate the accuracy of P(cv-a)CO2/C(a-cv)O2 and other parameters for diagnosis of hyperlactatemia. Results A total of 36 patients with 119 data were collected. Compared with the normal lactate group, P(cv-a)CO2/C(a-cv)O2 was significantly higher [(1.38±0.76)mm Hg/mL vs. (2.31±1.01) mm Hg/mL, P < 0.01], ScvO2, DO2 and VO2 were significantly lower in the hyperlactatemia group [ScvO2: (74.26±9.13)% vs. (70.29±9.72)%; DO2: (505.52±208.39) mL/(min·m2) vs. (429.98±173.63) mL/(min·m2)]; VO2: (129.01±54.94) mL/(min·m2) vs. (109.99±38.79) mL/(min·m2), P < 0.05]. P(cv-a)CO2 had no significant difference between two groups [(5.76±3.70) mm Hg vs. (6.59±3.70) mm Hg, P > 0.05]. P(cv-a)CO2/C(a-cv)O2 was positively correlated with lactate (r=0.646, P < 0.01). ScvO2 was negatively correlated with lactate (r=-0.277, P < 0.01). DO2 and VO2 had no significant correlation with lactate (P > 0.05). The area under ROC curve (AUC) of P(cv-a)CO2 /C(a-cv)O2 for diagnosis of hyperlactatemia was 0.820, with 95% confidence interval (95%CI) of 0.715 - 0.925(P < 0.001); The AUC of ScvO2 was 0.622, with 95%CI of 0.520 - 0.724(P=0.025).
Conclusion
Compared with the traditional oxygen metabolism parameters, P(cv-a)CO2/C(a-cv)O2 can accurately diagnose hyperlactatemia, and isareliable parameter to reflect oxygen metabolism in patients with sepsis.
Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection, and is the leading cause of death in intensive care unit patients due to limited therapies currently. As is known to all, endotoxin is important in the pathogenesis of sepsis, whereby infection triggers a systemic inflammatory response, resulting in release of pro- and anti-inflammatory cytokines, which are thought to be responsible for the tissue damage that occurs in sepsis patients. Therefore, removing endotoxins is considered as an effective way to improve the conditions of sepsis patients. Both Toraymaxin (PMX) and adsorptive membrane such as oXiris can remove endotoxins by adsorption, and in this review we will summarize current studies, included in vitro study, animal study, and clinical research to show the benefit from endotoxin removal by oXiris, and also give some suggestions about oXiris clinical practice from experienced experts.
ObjectiveTo explore the relationship between mitochondrial function and the severity of sepsis by detecting the platelet mitochondrial permeability transition pore, transmembrane potential and adenosine triphosphate (ATP) levels in peripheral blood.
MethodsAccording to random number table, 40 male SD rats were randomly divided into three sepsis model groups (group A, B and C) and a sham group (group D). The rats in the model groups received cecal ligation and puncture (CLP) treatment with different percent of ligated length in total length of the cecum (10% in group A, 30% in group B and 50% in group C, respectively). Twenty-four hours later, peripheral blood was collected for TNF-α, IL-1βand IL-6 levels determination, also the mitochondrial permeability transition pore, transmembrane potential and ATP content were tested in the isolated platelet. One-way ANOVA test was used to determine the relevance between above indices and the severity of sepsis. Meanwhile, 29 patients with sepsis were enrolled for clinical study. After APACHEⅡscoring, platelet samples of peripheral blood in the patients were collected for mitochondrial function determination. The relationship between mitonchondrial function and APACHEⅡscore was analyzed by Spearman method.
ResultsCalcein fluorescence, membrane potential and ATP synthesis in platelet mitochondria of the rat sepsis model were gradually decreased with the increased severity of CLP, and the difference among these groups were all statistically significant (all P < 0.05). In clinical specimens, APACHEⅡscore was negatively correlated with ATP level of platelet mitochondria(r=-0.895, P < 0.05).
ConclusionMitochondrial function of platelet in peripheral blood can be used as an effective indicator for the severity of sepsis.
Objective To investigate the expression of oncostatin M (OSM) in patients with sepsis and its role in early recognition of sepsis. Methods Thirty-four patients with sepsis admitted in Shanxi Bethune Hospital fromJune 3, 2021 to January 18, 2022 were selected as a sepsis group, 15 patients with community acquired pneumonia (CAP) as a case control group, and 16 adults who underwent physical examination in the same period were selected as a healthy control group. The patients in the sepsis group were followed up for 28 days and divided into a survival group and a death group. The serum OSM level and its correlation with clinical indexes (white blood cell, neutrophil, lymphocyte, sequential organ failure assessment score and acute physiology and chronic health evaluation Ⅱ) were analyzed, and the diagnostic value of OSM expression level in the early identification of sepsis was analyzed. Results Compared with the case control group and the healthy control group, the expression level of OSM in the sepsis group was significantly higher [(502.07±209.93)pg/mL vs. (368.22±65.95)pg/mL and (382.09±73.04)pg/mL, P<0.05]. However, the high expression of OSM had no significant correlation with white blood cell, neutrophil, lymphocyte or disease severity score (P>0.05), and there was no significant difference in serum OSM level between the sepsis survival group and the death group. Compared with white blood cell count, the high expression of OSM has certain diagnostic value in the early identification of sepsis. The area under the receiver operator characteristic curve of OSM in predicting sepsis was 0.794 (95% confidence interval 0.666 - 0.922, P<0.05), with the sensitivity of 79.4% and the specificity of 73.3%. Conclusion The expression of OSM in patients with sepsis is significantly increased, and the high expression of OSM has a certain diagnostic value in the early identification of sepsis.
Objective To investigate the effects of hypertonic saline (HTS) treatment on the function and susceptibility to sepsis of reticuloendothelial system (RES) in mice with hemorrhagic shock. Methods Forty percent of total blood volume of male Balb/c mice was withdrawn by cardiac puncture. Two hours later, the mice were treated with blood infusion and normal saline (10 ml/kg) or 7.5% NaCl (10 ml/kg).The survival rate of the mice was observed after cecal ligation and puncture (CLP). The phagocytosis function of the RES was measured by carbon clearance rate(α) and carbon amount ingested by the macrophages of liver and spleen. In vitro, the peritoneal phagocyte function in solutions of different osmotic pressor was measured by assaying neutral red amount taken in. Results The survival rate after CLP in HTS treated group was 70%, whereas all the mice in the normal saline group died. At the third hour after hemorrhagic shock, the RES carbon clearance rate(α) and carbon amount ingested by the macrophages of liver in the HTS treated mice were 5.61±0.42 and 0.59±0.19 respectively, significantly higher than those in the normal saline treated mice (4.15±0.62， 0.42±0.16). In vitro, hyperosmolarity below 40 mmol/L had no significant effects on the phagocytosis activity of peritoneal macrophages in mice. Conclusion Treating hemorrhagic shock with HTS can decrease the susceptibility to sepsis and improve the RES phagocytosis function indirectly.
