Sepsis is a life-threatening organ dysfunction caused by infection that lead to dysregulation of the host response. Sepsis and septic shock with a high mortality threaten human health at present, which are important medical and health problems. Early diagnosis and treatment decision-making for sepsis and septic shock still need to be improved. Exosomes are extracellular vesicles with a diameter of 30-150 nm formed by the fusion of multi-vesicle bodies and cell membranes. Exosomes can effectively transport a variety of bioactive substances such as proteins, lipids, RNA, DNA, and participate in the regulation of inflammatory response, immune response, infection and other pathophysiological processes. In recent years, exosomes have become one of the important methods for the diagnosis and treatment of systemic inflammatory diseases. This article will focus on the basic and clinical research of sepsis, and focus on the research progress of exosomes in the diagnosis and targeted therapy of sepsis.
Humans ; Shock, Septic/therapy* ; Exosomes/metabolism* ; Sepsis/therapy* ; Extracellular Vesicles/metabolism* ; RNA/metabolism*

OBJECTIVE: To explore the expression levels and clinical significance of helper T cell 1/helper T cell 2 (Th1/Th2) cytokine and interleukin-6 (IL-6) in patients with acute leukemia (AL) complicated by infection. METHODS: 68 patients with AL complicated by infection admitted to Wuhan Fifth Hospital from May 2017 to January 2020 were enrolled as study group, 50 AL patients without infection were enrolled as AL group, and 30 healthy volunteers checked in physical examination center were enrolled as healthy control group. The levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10), and peripheral blood Th1/Th2 cells subsets were measured and compared among the three groups. The serum IL-6, IL-10, TNF-α and Th1/Th2 were compared between the patients with mild to moderate infection (n=52) and septic shock (n=16). The relationship between IL-6, IL-10, TNF-α, Th1/Th2 and AL infection was analyzed. RESULTS: The levels of IL-6, IL-10 , TNF-α, and the proportion of Th2 of the patients in study group and AL group were significantly higher than those in healthy control group (P<0.001), while the proportion of Th1 and Th1/Th2 were significantly lower than those in healthy control group (P<0.001). The levels of IL-6, IL-10 and TNF-α, and the proportion of Th2 the patients in study group were significantly higher than those in AL group (P<0.001), while the proportion of Th1 and Th1/Th2 were significantly lower than those in AL group (P<0.001). The serum IL-6, IL-10 and TNF-α level of the patients in septic shock group were significantly higher than those in mild-to-moderate infection group (P<0.001), while Th1/Th2 was lower than those in mild-to-moderate infection group (P<0.001). The results of ROC curve analysis showed that the area under the ROC curve (AUC) values of IL-6, IL-10, TNF-α and Th1/Th2 alone for the diagnosis of septic shock were 0.779, 0.761, 0.724 and 0.718, which were lower than that their combination (0.910) (P<0.05). CONCLUSION The levels of serum IL-6, IL-10 and TNF-α are high in patients with AL complicated infection and septic shock, while Th1/Th2 cell subsets is low. The combined detection of serum IL-6, IL-10, TNF-α and Th1/Th2 is a good diagnostic value for predicting the occurrence of severe septic shock.
Cytokines/metabolism* ; Humans ; Interleukin-10 ; Interleukin-6/metabolism* ; Leukemia/metabolism* ; Shock, Septic/metabolism* ; Th1 Cells/metabolism* ; Th2 Cells/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

The key to the treatment of septic shock is to provide adequate oxygen supply and improve tissue perfusion. Lactate and central venous oxygen saturation (ScvO) are commonly used as the indices of oxygen metabolism, but tissue hypoxia may still exist even when lactate and ScvOare within the normal range. Arteriovenous difference in carbon dioxide partial pressure (COgap) can accurately reflect oxygen delivery when ScvOis in the normal range. This article reviews the advantages and shortages of lactate, lactate clearance rate, ScvO, and COgap in evaluating tissue hypoxia, in order to provide a reference for treatment and severity evaluation of septic shock.
Carbon Dioxide ; blood ; Humans ; Lactic Acid ; metabolism ; Metabolic Clearance Rate ; Oxygen ; blood ; Shock, Septic ; metabolism

BACKGROUNDPrevious studies have suggested that β1-receptor blockers benefit septic shock patients. This study aimed to determine whether β1-receptor blockers benefit tissue perfusion in sepsis and to identify parameters to reduce the risk of this drug in sepsis.

METHODSConsecutive septic shock patients were recruited from the Intensive Care Unit of Peking Union Medical College Hospital within 48 h of diagnosis. All patients were hemodynamically stable and satisfactorily sedated with a heart rate (HR) ≥100 beats/min. Esmolol therapy achieved the target HR of 10-15% lower than the baseline HR. Clinical and physiological data of patients were collected prospectively within 1 h prior to esmolol therapy and 2 h after achieving the targeted HR.

RESULTSSixty-three patients were recruited. After esmolol therapy, blood pressure was unaltered, whereas stroke volume (SV) was increased compared with before esmolol therapy (43.6 ± 22.7 vs. 49.9 ± 23.7 ml, t = -2.3, P = 0.047). Tissue perfusion, including lactate levels (1.4 ± 0.8 vs. 1.1 ± 0.6 mmol/L, t = 2.6, P = 0.015) and the central venous-to-arterial carbon dioxide difference (5.6 ± 3.3 vs. 4.3 ± 2.2 mmHg, t = 2.6 P = 0.016), was also significantly decreased after esmolol therapy. For patients with increased SV (n = 42), cardiac efficiency improved, and esmolol therapy had a lower risk for a decrease in cardiac output (CO). Therefore, pretreatment cardiac systolic and diastolic parameters with (n = 42)/without (n = 21) an increase in SV were compared. Mitral lateral annular plane systolic excursion (MAPSElat) in patients with increased SV was significantly higher than that in those without increased SV (1.3 ± 0.3 vs. 1.1 ± 0.2 cm, t = 2.4, P = 0.034).

CONCLUSIONSSV of septic shock patients is increased following esmolol therapy. Although CO is also decreased with HR, tissue perfusion is not worse. MAPSElat can be used to predict an increase in SV before esmolol use.

TRIAL REGISTRATIONClinicalTrials.gov, NCT01920776; https://clinicaltrials.gov/ct2/show/NCT01920776?term=NCT01920776&rank=1.

Adrenergic beta-1 Receptor Antagonists ; therapeutic use ; Adult ; Aged ; Cardiac Output ; drug effects ; Echocardiography ; Female ; Heart Rate ; drug effects ; Hemodynamics ; drug effects ; Humans ; Male ; Middle Aged ; Myocardium ; metabolism ; Propanolamines ; therapeutic use ; Shock, Septic ; drug therapy ; Stroke Volume ; drug effects

PURPOSE: High mobility group box 1 (HMGB1) plays a central role in the pathogenesis of sepsis and multiple organ dysfunction syndromes. We investigated the associations of a single nucleotide polymorphism (SNP; rs1045411) in HMGB1 with various clinical parameters, severity, and prognosis in patients with sepsis, severe sepsis, or septic shock. MATERIALS AND METHODS: We enrolled 212 adult patients followed for 28 days. All patients were genotyped for rs1045411, and the serum levels of HMGB1 and several cytokines were measured. RESULTS: The proportions of patients according to genotype were GG (71.2%), GA (26.4%), and AA (2.4%). Among patients with chronic lung disease comorbidity, patients with a variant A allele had higher positive blood culture rates and higher levels of various cytokines [interleukin (IL)-1beta, IL-6, IL-10, IL-17, and tumor necrosis factor-alpha] than those with the GG genotype. In the analysis of those with diabetes as a comorbidity, patients with a variant A allele had higher blood culture and Gram-negative culture rates than those with GG genotypes; these patients also had a higher levels of IL-17. In the analysis of those with sepsis caused by a respiratory tract infection, patients with a variant A allele had higher levels of IL-10 and IL-17 (all p<0.05). This polymorphism had no significant impact on patient survival. CONCLUSION: The variant A allele of rs1045411 appears to be associated with a more severe inflammatory response than the GG genotype under specific conditions.
Adult ; Aged ; Alleles ; Asian Continental Ancestry Group/genetics ; China/epidemiology ; Cytokines/*blood/*genetics ; Female ; Genotype ; HMGB1 Protein/blood/*genetics ; Humans ; Interleukin-10/genetics ; Interleukin-17/genetics ; Interleukin-6/blood ; Male ; Middle Aged ; Polymorphism, Genetic/*genetics ; Polymorphism, Single Nucleotide/*genetics ; Prognosis ; Republic of Korea ; Sepsis/immunology/*metabolism/mortality ; Shock, Septic/immunology/*metabolism/mortality ; Survival ; Tumor Necrosis Factor-alpha/genetics

OBJECTIVETo investigate the molecular mechanisms of continuous venovenous hemofiltration (CVVH) combined with ulinastatin (ULI) (CVVH-ULI) for the treatment of septic shock.

METHODSHuman umbilical endothelial cells (HUVECs) were incubated with serums isolated from normal healthy people (control), septic shock patients treated with conventional therapy (CT) or treated with CVVH combined with ULI (CVVH-ULI). Endothelial permeability was evaluated by the leakage of FITC-labeled albumin. The morphological changes of F-actin was evaluated by Rhodamine-phalloidin. The phosphorylated levels of p38 were determined by Western blot. Cells were then treated with p38inhibitor (SB203580), or DMSO, followed by incubation with serum from septic shock patients treated with conventional therapy. Endothelial permeability and F-actin rearrangements were also evaluated as noted above.

RESULTSSerum from CT group increased endothelial permeability, F-actin rearrangements, and phosphorylated levels of p38, which were inhibited by CVVH-ULI treatment. Moreover, in CT group, the serum-induced endothelial hyperpermeability and F-actin rearrangements were inhibited by SB203580, the inhibitor of p38.

CONCLUSIONCVVH combined with ulinastatin decreases endothelial hyperpermeability induced by septic shock through inhibiting p38 MAPK pathways.

Actins ; metabolism ; Cells, Cultured ; Glycoproteins ; therapeutic use ; Hemofiltration ; methods ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Imidazoles ; MAP Kinase Signaling System ; Pyridines ; Shock, Septic ; therapy ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVETo explore the effect of Tongfu Jinghua Decoction (TJD) on hemodynamics and tissue oxygen metabolism in patients with post-traumatic sepsis shock.

METHODSTotally 60 patients were randomly assigned to the treatment group and the control group, 30 in each group. Patients in the treatment group took TJD or were administered with TJD by nasal feeding in combined with conventional Western medical treatment, while patients in the control group only received conventional Western medical treatment. Changes of each index in hemodynamics and tissue oxygen metabolism were observed before treatment, and at 6, 12, 24, and 48 h after treatment.

RESULTSCompared with before treatment in the same group, hemodynamic changes were significantly improved at each time point in the two groups. All indices of tissue oxygen metabolism at each time point of the two groups were significantly improved, except changes of O2 extraction ratio (ER) after treatment in the control group (P < 0.05, P < 0.01). Compared with the control group in the same period, heart rate (HR), systemic vascular resist- ance (SVR), and cardiac output (CO) were significantly improved with statistical difference (P < 0.05, P < 0.01). Mean arterial pressure (MAP), central venous pressure (CVP), and cardiac index (CI) were significantly improved at 6, 12, and 24 h after treatment with statistical difference (P < 0.05, P < 0.01). Each index of tissue oxygen metabolism in the treatment group were all improved at each time point with statistical difference (P < 0.05, P < 0.01).

CONCLUSIONTJD combined with conventional Western medical treatment could quickly improve hemodynamics and tissue oxygen metabolism disorder in patients with septic shock, and its curative effect was superior to that of conventional Western medical treatment alone.

Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Heart Rate ; Hemodynamics ; drug effects ; Humans ; Oxygen ; metabolism ; Sepsis ; Shock, Septic ; drug therapy ; metabolism

BACKGROUNDSevere sepsis and septic shock are the leading causes of morbidity and mortality in hospitalized patients. This study aimed to investigate the association of poly (ADP-ribose) polymerase-1 (PARP-1) activity in circulating mononuclear cells with myocardial dysfunction in patients with septic shock.

METHODSA total of 64 patients with septic shock were divided into the survival group (n = 41) and the nonsurvival group (n = 23) according to mortality at 28 days after enrollments. PARP-1 activity in circulating mononuclear cells, brain natriuretic peptide, Acute Physiology and Chronic Health Evaluation II score, the cardiac index (CI), the cardiac function index (CFI), global ejection fraction (GEF), and the left ventricular contractility index (dp/dt max) were measured after admission to the intensive care unit.

RESULTSPARP-1 activity in circulating mononuclear cells of nonsurvival patients with septic shock was significantly higher than that in survival patients. PARP-1 activity in circulating mononuclear cells was strongly, negatively correlated with the CI, the CFI, GEF, and dp/dt max. Multiple Logistic regression analysis showed that PARP-1 activity in circulating mononuclear cells was an independent risk factor of myocardial dysfunction. The optimal cutoff point of PARP-1 activity for predicting 28-day mortality was 942 nmol/L with a sensibility of 78.2% and specificity of 65.1%.

CONCLUSIONPARP-1 activity in circulating mononuclear cells is significantly associated with myocardial dysfunction and may have prognostic value in patients with septic shock.

Aged ; Aged, 80 and over ; Female ; Humans ; Leukocytes, Mononuclear ; enzymology ; Male ; Middle Aged ; Poly(ADP-ribose) Polymerases ; metabolism ; Shock, Septic ; enzymology

OBJECTIVETo observe the effects of hemofiltration at early stage of septic shock with different ultrafiltration doses, including hemodynamics, oxygen metabolism, inflammatory mediator in piglet models, and to evaluate the therapeutic effects of HVHF.

METHODThe 18 healthy young piglets (Shanghai species) were divided randomly into three groups:control group (n = 6), conventional volume hemofiltration (CVVH) group [n = 6, ultrafiltration volume = 30 ml/(kg·h)] and high volume hemofiltration (HVHF) group [n = 6, ultrafiltration volume = 50 ml/(kg·h)], the animal model of septic shock was established by injection of lipopolysaccharide (LPS) (150 µg/kg) O111: B4. During the experiment, the following observations were carried out for all groups:1) Changes of hemodynamics [heart rate (HR), mean arterial pressure (MABP), cardiac output (CO), systemic vascular resistance index (SVRI), intrathoracic blood volume (ITBV)] and oxygen metabolism [oxygen delivery (DO2), oxygen consumption (VO2), oxygen extraction rate (O2ER) ] at the time of B0h, 0 h, 2 h, 4 h and 6 h.2) changes of TNF-α, IL-6, IL-10 in plasma at different time points (B0h, 0 h, 2 h, 4 h, 6 h).

RESULTSignificant difference in circulatory parameters, inflammatory mediators in plasma were found at B0h and 0 h among three groups; the CO in two treatment groups were higher than that in control group at 4 h, 6 h after model establishment (P < 0.05), and SVRI in HVHF groups were higher than that in other two groups at 4 h, 6 h after model was established (P < 0.05). The MABP in HVHF group [4 h (82 ± 17) mm Hg, 6 h (80 ± 12) mm Hg](1 mm Hg = 0.133 kPa) were higher than that in CVVH group at 4 h [(67 ± 12) mm Hg], 6 h [(69 ± 14) mm Hg] after model was established (P < 0.05). The levels of IL-6, IL-10, TNF-α in two treatment groups were lower than that in control group at 4 h and 6 h after model was established (P < 0.05), and the IL-6 [(281 ± 51) pg/ml], TNF-α [(67 ± 13) pg/ml] level in HVHF group was lower than that in CVVH group [IL-6(281 ± 51) pg/ml, TNF-α (67 ± 13) pg/ml] at 6 h (P < 0.05). The DO2 and VO2 in two treatment groups were higher than that in control group at 4 h, 6 h (P < 0.05), the O2ER in HVHF group were higher than that in CVVH group at 4 h (44% ± 3% vs. 33% ± 4%), 6 h (43% ± 5% vs. 31% ± 3%, P < 0.05).

CONCLUSIONHigh volume hemofiltration (HVHF) at early stage of septic shock piglet models was more effective in improving hemodynamics, oxygen metabolism than conventional CVVH. And HVHF eliminated blood inflammatory mediators more effectively than conventional CVVH.

Analysis of Variance ; Animals ; Arterial Pressure ; Cardiac Output ; Disease Models, Animal ; Down-Regulation ; Female ; Hemodynamics ; Hemofiltration ; methods ; Interleukin-10 ; blood ; Interleukin-6 ; blood ; Male ; Oxygen ; blood ; metabolism ; Oxygen Consumption ; Random Allocation ; Shock, Septic ; blood ; physiopathology ; therapy ; Swine ; Time Factors ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVEPractice recommendations have evolved, and consensus now exists among leading organizations such as the American College of Critical Care Medicine (ACCM) and Surviving Sepsis Campaign that fluid infusion is best initiated with boluses of 20 ml/kg, commonly requires 40-60 ml/kg but can be as much as 200 ml/kg if the liver is not enlarged and/or rales are not heard. The present study aimed to investigate and compare the changes of the hemodynamics and extravascular lung water after higher volume fluid resuscitation in a piglet model of endotoxic shock.

METHODTwenty piglets were used for establishing animal models of endotoxic shock by intravenous infusing lipopolysaccharide (LPS). The experimental animals were divided into three groups according to the volume infused during the resuscitation. The three groups received different volume of saline in less than an hour after endotoxic shock. By the PiCCO plus system, we investigated the changes of hemodynamics and extravascular lung water.

RESULTAfter fluid resuscitation, global end diastolic volume inder, (GEDI) and intrathoracic blood volume index, (ITBI) markedly increased in the group of 80 ml/kg and 120 ml/kg, but there was no change in the group of 40 ml/kg. GEDI: Fifteen min after fluid resuscitation R1 was (261 ± 64) ml/m(2), R2 (457 ± 124) ml/m(2), R3 (413 ± 148) ml/m(2), 4 h R1 (251 ± 68) ml/m(2), R2 (422 ± 70) ml/m(2), R3 (470 ± 160) ml/m(2); ITBI: Fifteen min after fluid resuscitation R1 was (335 ± 69) ml/m(2), R2 (550 ± 179) ml/m(2), R3 (520 ± 183) ml/m(2), 4 h R1 (314 ± 84) ml/m(2), R2 (534 ± 96) ml/m(2), R3 (594 ± 200) ml/m(2) (R1 vs. R2 vs. R3, F = 26.373, P < 0.05; R1 vs. R2, R1 vs. R3, P < 0.05; R2 vs. R3, P > 0.05). CI of all three groups significantly decreased when the models were established. After fluid resuscitation, the base level was maintained in the group of 80 ml/kg and 120 ml/kg, but it was under the basic level in the group of 40 ml/kg.Fifteen min after fluid resuscitation R1 was (4.5 ± 0.7) L/(min·m(2)), R2 (6.4 ± 2.2) L/(min·m(2)), R3 (5.5 ± 0.7) L/(min·m(2)), 4 h R1 (4.1 ± 1.0) L/(min·m(2)), R2 (5.2 ± 0.9) L/(min·m(2)), R3 (5.1 ± 0.8) L/(min·m(2)). There was no significant difference in CI between these two groups (P > 0.05).ELWI of the group of 80 ml/kg and 120 ml/kg were still higher than that of the group of 40 ml/kg, 15 min after fluid resuscitation R1 was (19.2 ± 8.6) ml/kg, R2 (29.2 ± 5.5) ml/kg, R3 (23.4 ± 8.2) ml/kg, 4 h R1 (18.3 ± 6.5) ml/kg, R2 (23.8 ± 2.6) ml/kg, R3 (21.4 ± 3.9) ml/kg, but there was no significant difference in ELWI among the groups (P > 0.05).

CONCLUSIONResuscitation with higher volume of fluid infusion in the early stage of endotoxic shock was more efficient to increase the preload and maintain the cardiac output at the baseline level, and might reduce the need for vasoactive agents. Meanwhile, resuscitation with higher volume of fluid in the early stage of endotoxic shock did not sharply increase the extravascular lung water.

Animals ; Blood Volume ; Central Venous Pressure ; Disease Models, Animal ; Extravascular Lung Water ; Female ; Fluid Therapy ; methods ; Hemodynamics ; Lung ; metabolism ; physiopathology ; Male ; Random Allocation ; Resuscitation ; methods ; Shock, Septic ; metabolism ; physiopathology ; therapy ; Sodium Chloride ; administration & dosage ; therapeutic use ; Swine