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 investigate time-related association between fluid balance and prognosis in sepsis patients. METHODS: A retrospective cohort study was conducted based on the data of sepsis patients in the Medical Information Database for Intensive Care-IV 2.0 (MIMIC-IV 2.0) from 2008 to 2019. Sepsis patients aged ≥ 18 years who were admitted to intensive care unit (ICU) for at least 2 days were included. The daily fluid balance and cumulative fluid balance (CFB) were calculated from days 1 to 7 after ICU admission. According to CFB,the patients were divided into negative fluid balance group (CFB% < 0%), fluid balance group (0% ≤ CFB% ≤ 10%), and fluid overload group (CFB% > 10%). In-hospital mortality was the primary outcome. Multifactorial Logistic regression was used to analyze time-related association between different CFB and the risk of in-hospital mortality in patients with sepsis during 7 days after ICU admission. In addition, subgroup analysis was performed on patients with septic shock and patients with sepsis who stayed in the ICU for 7 days or longer. RESULTS: A total of 11 437 patients with sepsis were included, of which 6 595 were male and 4 842 were female. The mean age was (64.4±16.4) years. A total of 10 253 patients (89.6%) survived and 1 184 patients (10.4%) died during hospitalization. Compared with the survival group, patients in the death group were older, lighter, had higher sequential organ failure assessment (SOFA), simplified acute physiology score II (SAPS II), longer ICU stay, higher incidence of septic shock, and higher proportion of invasive mechanical ventilation, renal replacement therapy (RRT) and vasoactive drugs. In terms of comorbidities, congestive heart failure, renal disease, liver disease, and malignancy were more common in the death group. The death group had a higher daily fluid balance than the survival group during 7 days after ICU admission, the CFB in the two groups gradually increased with length of ICU stay. After adjusting variables such as age, gender, race, SOFA score, SAPS II score, comorbidities, and the use of invasive mechanical ventilation, RRT and vasoactive drugs, multivariate Logistic regression analysis showed that fluid overload on day 1 after ICU admission was a protective factor for the reduced risk of in-hospital mortality in sepsis patients [odds ratio (OR) = 0.74, 95% confidence interval (95%CI) was 0.64-0.86, P = 0.001]. However, fluid overload on day 3 was a risk factor for in-hospital mortality in sepsis patients (OR = 1.70, 95%CI was 1.47-1.97, P < 0.001) and the risk of in-hospital mortality was significantly increased from day 4 to day 7. Furthermore, the same results were obtained in patients with septic shock and sepsis patients who stayed in the ICU for 7 days or longer. CONCLUSIONS Fluid overload on day 1 was associated with reduced in-hospital mortality. However, from the third day, fluid overload increases the risk of in-hospital mortality. Thus, managing fluid balance at different times may improve prognosis.
Humans ; Male ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Shock, Septic ; Cohort Studies ; Retrospective Studies ; Sepsis ; Intensive Care Units ; Water-Electrolyte Balance ; Heart Failure ; Prognosis

OBJECTIVE: To explore the effect of thrombocytopenia on the prognosis of patients with septic shock and its mechanism in leading to death. METHODS: A retrospective case-control study was conducted. Patients with septic shock admitted to emergency intensive care unit (EICU) and intensive care unit (ICU) in Peking University People's Hospital from April 1, 2015 to January 31, 2023 were enrolled. Patients were divided into the thrombocytopenia group and the non-thrombocytopenia group, according to whether the minimum platelet count was less than 100×10⁹/L within 24 hours after admission to ICU. The outcome index was the mortality during ICU stay. The baseline data, hospitalization information and laboratory test results of the two groups were compared, and the risk factors of in-hospital death were analyzed by Logistic regression, and the mediation effect was performed by Bootstrap method. RESULTS: A total of 301 patients with septic shock were enrolled, of which 172 (57.1%) had thrombocytopenia and 129 (42.9%) did not. There were significant differences between the two groups in age, mortality, disseminated intravascular coagulation (DIC), continuous renal replacement therapy, and level of creatinine, urea nitrogen, total bilirubin, white blood cell count, lymphocyte count, prothrombin time (PT) and activated partial thromboplastin time (APTT). Univariate Logistic regression analysis showed thrombocytopenia [odds ratio (OR) = 4.478], continuous renal replacement therapy (OR = 4.601), DIC (OR = 6.248), serum creatinine (OR = 1.005), urea nitrogen (OR = 1.126), total bilirubin (OR = 1.006) and PT (OR = 1.126) were risk factors of death during hospitalization in patients with septic shock (all P < 0.05). Multivariate Logistic regression analysis showed that thrombocytopenia [OR = 3.338, 95% confidence interval (95%CI) was 1.910-5.834, P = 0.000], continuous renal replacement therapy (OR = 3.175, 95%CI was 1.576-6.395, P = 0.001) and PT (OR = 1.077, 95%CI was 1.011-1.147, P = 0.021) were independent risk factors for in-hospital mortality in patients with septic shock. Mediation analysis showed that 51% of the deaths due to thrombocytopenia in patients with septic shock were due to coagulopathy. CONCLUSIONS Thrombocytopenia is a powerful predictor of death in septic shock patients, and half of all thrombocytopenia-related deaths may be due to abnormal coagulation function.
Humans ; Shock, Septic ; Retrospective Studies ; Case-Control Studies ; Hospital Mortality ; Prognosis ; Thrombocytopenia ; Intensive Care Units ; Bilirubin ; Nitrogen ; Urea ; Sepsis

OBJECTIVE: To explore the diagnosis and treatment of acute cerebral infarction following extracorporeal membrane oxygenation (ECMO) therapy in patients with cardiogenic shock to review the literature. METHODS: The clinical data of two patients with cardiogenic shock treated with veno-arterial ECMO (VA-ECMO) complicated with acute cerebral infarction admitted to department of intensive care unit (ICU) of Affiliated Hospital of Guizhou Medical University were retrospectively analyzed and the treatment experience was shared. RESULTS: Case 1 was a 46-year-old male patient who was admitted to the hospital on September 16, 2021, due to "repeated chest tightness, shortness of breath, syncope for 2+ years, and worsened for 15 days. Coronary artery angiography showed 3-vessel coronary artery disease lesions. On October 15, 2021, coronary artery bypass grafting (CABG), pericardial fenestration and drainage, thoracic closed drainage, femoral bypass, thoracotomy exploration, and sternal internal fixation were performed under support of extracorporeal circulation. After surgery, the heart rate was 180-200 bpm, the blood pressure could not be maintained, and the improvement was not obvious after active drug treatment. The right femoral artery and femoral vein were intubated, VA-ECMO support treatment was performed, and the patient was transferred to the ICU. Intra-aortic balloon pump (IABP) was treated on the day of transfer because the circulation could not be maintained. Due to acute cerebral infarction in the left hemisphere and right parieto-occipital lobe, subfalcine herniation, tentorial herniation, the patient ultimately died after withdrawing from ECMO. Case 2 was a 43-year-old male patient who was admitted to the hospital on June 29, 2021, with "fever for 8 days and vomiting for 4 days". Bedside ultrasound showed cardiac enlargement and diffuse wall motion reduction in the left and right ventricles. On June 30, 2021, the patient underwent catheterization through the right femoral artery and femoral vein, VA-ECMO support, and was transferred to ICU for treatment. Acute cerebral infarction on both sides of the cerebellum occurred, and after treatment, the patient was discharged with mild impairment of daily living ability. CONCLUSIONS Strengthen monitoring of anticoagulation; regular neurological examination of patients undergoing ECMO therapy; ECMO under light sedation or awake can be performed if the condition permitsif the condition permits, perform light sedation or awake ECMO, which helpful for the early detection of nervous system injury.
Male ; Humans ; Middle Aged ; Adult ; Shock, Cardiogenic/therapy* ; Extracorporeal Membrane Oxygenation ; Retrospective Studies ; Coronary Artery Bypass/adverse effects* ; Cerebral Infarction/therapy*

Severe pneumonia is one of the most common infectious diseases and the leading cause of sepsis and septic shock. Preventing infection, balancing the patient's immune status, and anti-coagulation therapy are all important elements in the treatment of severe pneumonia. As multi-target agents, Xuebijing injection (XBJ) has shown unique advantages in targeting complex conditions and saving the lives of patients with severe pneumonia. This review outlines progress in the understanding of XBJ's anti-inflammatory, endotoxin antagonism, and anticoagulation effects. From the hundreds of publications released over the past few years, the key results from representative clinical studies of XBJ in the treatment of severe pneumonia were selected and summarized. XBJ was observed to effectively suppress the release of pro-inflammatory cytokines, counter the effects of endotoxin, and assert an anticoagulation effect in most clinical trials, which are consistent with experimental studies. Collectively, this evidence suggests that XBJ could play an important and expanding role in clinical medicine, especially for sepsis, septic shock and severe pneumonia. Please cite this article as: Zhang M, Zheng R, Liu WJ, Hou JL, Yang YL, Shang HC. Xuebijing injection, a Chinese patent medicine, against severe pneumonia: Current research progress and future perspectives. J Integr Med. 2023; 21(5): 413-422.
Humans ; Nonprescription Drugs ; Shock, Septic/drug therapy* ; Sepsis/drug therapy* ; Endotoxins ; Anticoagulants/therapeutic use*

OBJECTIVE: To investigate the effects of the pre-shock state on the mortality of patients with sepsis. METHODS: We enrolled patients with sepsis admitted to the medical intensive care unit of a tertiary care university hospital. These patients were then classified into three groups: sepsis, pre-shock state, and septic shock. The primary outcome was the 28-day mortality rate. The secondary outcomes were the 90-day, 180-day, and 1-year mortality rates. RESULTS: A total of 303 patients (groups: sepsis 135 [44.6%]), pre-shock state (93 [30.7%]), and septic shock (75 [24.8%]) completed the 1-year follow-up. The mortality rates at 28 days, 90 days, and 180 days and 1 year were significantly higher in the pre-shock state group than those of the sepsis group, but significantly lower than those in the septic shock group, especially among older patients. When compared with the pre-shock state group, the sepsis group had significantly lower mortality risks at 28 days, 90 days, and 180 days and 1 year, whereas the sepsis shock group had higher mortality risks at these time points. CONCLUSION The mortality rates of patients in the pre-shock state were notably different from those of patients with sepsis or septic shock. The introduction of a modified sepsis severity classification, which includes sepsis, pre-shock state, and septic shock, could offer valuable additional prognostic information.
Humans ; Shock, Septic ; Retrospective Studies ; Sepsis ; Hospitalization ; Universities

OBJECTIVE: To investigate the clinical characteristics and risk factors of acute leukemia complicated with multi-drug resistant bacterial septicemia in children. METHODS: The clinical data of children with acute leukemia complicated with septicemia admitted to the Affiliated Hospital of Guangdong Medical University from January 2013 to May 2021 were retrospectively analyzed. Their flora composition and drug resistance were also analyzed. The children were divided into multi-drug resistant bacteria (MDRB) group and non-multi-drug resistant bacteria (non-MDRB) group according to the drug sensitivity results, and the differences in clinical data between the two group were compared. RESULTS: A total of 108 children had drug sensitivity results, 47 cases in the MDRB group, including 26 strians of Gram-positive bacteria (G⁺), the most common multi-drug resistant G⁺ bacteria were coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, and the most common multi-drug resistant Gram-negative bacteria G^- bacteria were Escherichia coli and Klebsiella pneumoniae subspecies pneumoniae. Compared with non-MDRB group, children in MDRB group had higher C-reactive protein (CRP) level and mortality rate (P <0.001, P =0.009), lower initial empirical anti-infection efficiency (P <0.001), and were more likely to have septic shock (P =0.003). Logistic analysis showed that the risk factors of acute leukemia complicated with MDRB septicemia in children were previous MDRB infection (OR =6.763, 95% CI: 1.141-40.092, P =0.035), duration of agranulocytosis before infection≥7 days (OR =3.071, 95% CI: 1.139-8.282, P =0.027), and previous use of antimicrobial drugs within 90 days before infection (OR =7.675, 95% CI: 1.581-37.261, P =0.011). CONCLUSIONS The clinical features of acute leukemia complicated with MDRB septicemia in children include a heavy inflammatory response, significantly elevated CRP, susceptibility to secondary septic shock, low efficiency of initial empirical anti-infective therapy, and high mortality rate. Previous MDRB infection, duration of agranulocytosis before infection≥7 days, and previous use of antimicrobial drugs within 90 days before infection are risk factors of acute leukemia complicated with MDRB septicemia in children.
Humans ; Child ; Shock, Septic ; Retrospective Studies ; Sepsis ; Risk Factors ; Bacteria ; Leukemia, Myeloid, Acute/complications* ; Acute Disease ; Escherichia coli ; Anti-Infective Agents ; Agranulocytosis

Shock is the clinical manifestation of acute circulatory failure, which results in inadequate utilization of cellular oxygen. It is a common condition with high mortality rates in intensive care units. The intravenous administration of Shenfu Injection (SFI) may attenuate inflammation, regulate hemodynamics and oxygen metabolism; inhibit ischemia-reperfusion responses; and have adaptogenic and antiapoptotic effects. In this review, we have discussed the clinical applications and antishock pharmacological effects of SFI. Further in-depth and large-scale multicenter clinical studies are warranted to determine the therapeutic effects of SFI on shock.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Shock/drug therapy* ; Injections ; Oxygen ; Multicenter Studies as Topic

Objective: To investigate the clinical characteristics, treatment experiences and prognostic factors for descending necrotizing mediastinitis (DNM). Methods: A retrospective analysis was performed on the data of 22 patients with DNM diagnosed and treated in Henan Provincial People's Hospital from January 2016 to August 2022, including 16 males and 6 females, aged 29-79 years. After admission, all patients underwent CT scanning of the maxillofacial, cervical, and thoracic regions to confirm their diagnoses. Emergency incision and drainage were performed. The neck incision was treated with continuous vacuum sealing drainage. According to the prognoses, the patients were divided into cure group and death group, and the prognostic factors were analyzed. SPSS 25.0 software was used to analyze the clinical data. Rusults: The main complaints were dysphagia (45.5%, 10/22) and dyspnea (50.0%, 11/22). Odontogenic infection accounted for 45.5% (10/22) and oropharyngeal infection accounted for 54.5% (12/22). There were 16 cases in the cured group and 6 cases in the death group, with a total mortality rate of 27.3%. The mortality rates of DNM typeⅠand typeⅡwere respectively 16.7% and 40%. Compared with the cured group, the death group had higher incidences for diabetes, coronary heart disease and septic shock (all P<0.05). There were statistically significant differences between the cure group and the death group in procalcitonin level (50.43 (137.64) ng/ml vs 2.92 (6.33) ng/ml, M(IQR), Z=3.023, P<0.05) and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score (16.10±2.40 vs 6.75±3.19, t=6.524, P<0.05). Conclution: DNM is rare, with high mortality, high incidence of septic shock, and the increased procalcitonin level and APACHE Ⅱ score combined diabetes and coronary heart disease are the poor prognostic factors for DNM. Early incision and drainage combined with continuous vacuum sealing drainage technique is a better way to treat DNM.
Male ; Female ; Humans ; Mediastinitis/diagnosis* ; Shock, Septic/complications* ; Retrospective Studies ; Procalcitonin ; Prognosis ; Drainage/adverse effects* ; Necrosis/therapy*

OBJECTIVE: To investigate the correlation of stress-inducible phosphoprotein 1 (STIP1) expression level with prognosis of different cancers and its potential role in immunotherapy. METHODS: TCGA, TARGET and GTEx databases were used for bioinformatic analysis of STIP1 expression level and its prognostic value in different cancers. We also detected STIP1 expression immunohistochemically in 10 pairs of colorectal cancer and adjacent tissues. We further analyzed the correlation of STIP1 expression level with tumor mutational burden, microsatellite instability, immune cell infiltration, immune regulators and outcomes of different cancers. STIP1- related proteins were identified using protein- protein interaction (PPI) network analysis, and functional enrichment analysis was performed to analyze the regulatory pathways involving STIP1. RESULTS: Bioinformatics analysis showed that STIP1 was highly expressed in most tumors compared with the normal tissues (P < 0.05), which was confirmed by immunohistochemistry of the 10 pairs of colorectal cancer tissues. STIP1 expression level was correlated with clinical stages of multiple cancers (P < 0.05), and in some cancer types, an upregulated STIP1 expression was correlated with a poor prognosis of the patients in terms of overall survival, disease-specific survival, disease-free survival and progression-free survival (P < 0.05). STIP1 expression was significantly correlated with tumor mutational burden, microsatellite instability, immune cell infiltration and immunomodulatory factors in most tumors (P < 0.05). PPI network analysis indicated that STIP1-related proteins included HSPA4, HSPA8, and HSP90AA1. KEGG enrichment analysis suggested that the high expression of STIP1 in liver cancer was related mainly with valerate metabolism, tryptophan metabolism, and butyrate metabolism pathways; HALLMARK enrichment analysis suggested high STIP1 expression in liver cancer was involved in bile acid and fatty acid metabolism. CONCLUSION STIP1 is up-regulated in multiple cancer types and its expression level is correlated with clinical tumor stage, tumor mutational burden, microsatellite instability, immune cell infiltration and immunomodulatory factors.
Humans ; Microsatellite Instability ; Liver Neoplasms ; Immunotherapy ; Prognosis ; Computational Biology ; Heat-Shock Proteins ; Colorectal Neoplasms