ABSTRACT
Neural precursor cell expressed developmentally downregulated 4 (NEDD4), an E3 ubiquitin ligase, is commonly upregulated in human hepatocellular carcinoma (HCC) and functions as an oncogenic factor in the progression of HCC, but the molecular mechanism needs be further explored. In this study, we found that NEDD4 could facilitate the proliferation of HCC cells, which was associated with regulating the ERK signaling. Further investigation showed that protocadherin 17 (PCDH17) was a potential substrate of NEDD4, and restoration of PCDH17 could block the facilitation of ERK signaling and HCC cells proliferation induced by NEDD4 overexpression. Whereafter, we confirmed that NEDD4 interacted with PCDH17 and promoted the Lys33-linked polyubiquitination and degradation of it via the proteasome pathway. Finally, NEDD4 protein level was found to be inversely correlated with that of PCDH17 in human HCC tissues. In conclusion, these results suggest that NEDD4 acts as an E3 ubiquitin ligase for PCDH17 ubiquitination and degradation thereby promoting the proliferation of HCC cells through regulating the ERK signaling, which may provide novel evidence for NEDD4 to be a promising therapeutic target for HCC.
Subject(s)
Cadherins , Carcinoma, Hepatocellular , Liver Neoplasms , Nedd4 Ubiquitin Protein Ligases , Humans , Carcinoma, Hepatocellular/pathology , Cell Proliferation , Liver Neoplasms/pathology , Nedd4 Ubiquitin Protein Ligases/genetics , Nedd4 Ubiquitin Protein Ligases/metabolism , Ubiquitination , Cadherins/metabolismABSTRACT
As an important protein encoded by hepatitis B virus (HBV), HBV X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). It has been shown that seven in absentia homologue 1 (SIAH1) could regulates the degradation of HBx through the ubiquitin-proteasome pathway. However, as a member of SIAH family, the regulatory effects of SIAH2 on HBx remain unclear. In this study, we first confirmed that SIAH2 could reduce the protein levels of HBx depending on its E3 ligase activity. Moreover, SIAH2 interacted with HBx and induced its K48-linked polyubiquitination and proteasomal degradation. Furthermore, we provided evidence that SIAH2 inhibits HBx-associated HCC cells proliferation by regulating HBx. In conclusion, our study identified a novel role for SIAH2 in promoting HBx degradation and SIAH2 exerts an inhibitory effect in the proliferation of HBx-associated HCC through inducing the degradation of HBx. Our study provides a new idea for the targeted degradation of HBx and may have great huge significance into providing novel evidence for the targeted therapy of HBV-infected HCC.
Subject(s)
Carcinoma, Hepatocellular , Cell Proliferation , Hepatitis B virus , Liver Neoplasms , Nuclear Proteins , Proteolysis , Trans-Activators , Ubiquitin-Protein Ligases , Ubiquitination , Viral Regulatory and Accessory Proteins , Humans , Viral Regulatory and Accessory Proteins/metabolism , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/virology , Trans-Activators/metabolism , Trans-Activators/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/virology , Liver Neoplasms/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Hepatitis B virus/metabolism , Hepatitis B virus/pathogenicity , Cell Line, Tumor , Signal Transduction , Hep G2 CellsABSTRACT
SIAH1 has been reported to participate in several human cancers, including hepatocellular carcinoma (HCC). However, the effect of SIAH1 on the epithelial-mesenchymal transition (EMT) has not been reported in HCC cells. Here, we discovered the inhibitory effect of SIAH1 on HCC cell migration and invasion, which was related with regulating EMT. Molecularly, a yeast two-hybrid experiment indicated that Cln Three Requiring 9 (CTR9) was a potential interacting protein of SIAH1, which was further verified by co-immunoprecipitation assays. Furthermore, SIAH1 inhibited the EMT of HCC cells through negatively regulating CTR9. Importantly, CTR9 was ubiquitinated and degraded by SIAH1 via the proteasome pathway in HCC cells. Additionally, it was showed that SIAH1 mainly mediated the K48-linked polyubiquitination on CTR9. Finally, the protein level of CTR9 was found to be inversely correlated with SIAH1 in human HCC tissues. Summed up all together, these findings reveal that SIAH1/CTR9 axis promotes the EMT of HCC cells and is a promising therapeutic target for HCC therapy.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Epithelial-Mesenchymal Transition/genetics , Cell Line, Tumor , Cell Movement/genetics , Gene Expression Regulation, Neoplastic , Cell Proliferation/genetics , Phosphoproteins/metabolism , Transcription Factors/metabolismABSTRACT
OBJECTIVE: To explore the current situation and influencing factors of quality of life of septic patients in intensive care unit (ICU) after discharge, and to provide theoretical basis for clinical early psychological intervention and continuity of care. METHODS: A prospective observational study was conducted. The septic patients who were hospitalized in the department of critical care medicine of the Affiliated Hospital of Jining Medical University and discharged with improvement from January 1 to December 31, 2022 were selected as the research objects. The demographic information, basic diseases, infection site, vital signs at ICU admission, severity scores of the condition within 24 hours after ICU admission, various biochemical indexes, treatment process, and prognostic indexes of all the patients were recorded. All patients were assessed by questionnaire at 3 months of discharge using the 36-item short-form health survey scale (SF-36 scale), the activities of daily living scale (ADL scale), and the Montreal cognitive assessment scale (MoCA scale). Multiple linear regression was used to analyze the factors influencing the quality of life of septic patients after discharge from the hospital. RESULTS: A total of 200 septic patients were discharged with improvement and followed up at 3 months of discharge, of which 150 completed the questionnaire. Of the 150 patients, 57 had sepsis and 93 had septic shock. The total SF-36 scale score of septic patients at 3 months of discharge was 81.4±23.0, and the scores of dimensions were, in descending order, role-emotional (83.4±23.0), mental health (82.9±23.6), bodily pain (82.8±23.3), vitality (81.6±23.2), physical function (81.4±23.5), general health (81.1±23.3), role-physical (79.5±27.0), and social function (78.8±25.2). There was no statistically significant difference in the total SF-36 scale score between the patients with sepsis and septic shock (82.6±22.0 vs. 80.7±23.6, P > 0.05). Incorporating the statistically significant indicators from linear univariate analysis into multiple linear regression analysis, and the results showed that the factors influencing the quality of life of septic patients at 3 months after discharge included ADL scale score at 3 months after discharge [ß= 0.741, 95% confidence interval (95%CI) was 0.606 to 0.791, P < 0.001], length of ICU stay (ß= -0.209, 95%CI was -0.733 to -0.208, P = 0.001), duration of mechanical ventilation (ß= 0.147, 95%CI was 0.122 to 0.978, P = 0.012), total dosage of norepinephrine (ß= -0.111, 95%CI was -0.044 to -0.002, P = 0.028), mean arterial pressure (MAP) at ICU admission (ß= -0.102, 95%CI was -0.203 to -0.007, P = 0.036) and body weight (ß= 0.097, 95%CI was 0.005 to 0.345, P = 0.044). CONCLUSIONS: The quality of life of patients with sepsis at 3 months after discharge is at a moderately high level. The influencing factors of the quality of life of patients with sepsis at 3 months after discharge include the ADL scale score at 3 months after discharge, the length of ICU stay, the duration of mechanical ventilation, the total dosage of norepinephrine, MAP at ICU admission and body weight, and healthcare professionals should enhance the treatment and care of the patients during their hospitalization based on the above influencing factors, and pay attention to early psychological intervention and continued care for such patients.
Subject(s)
Sepsis , Shock, Septic , Humans , Shock, Septic/therapy , Quality of Life , Activities of Daily Living , Sepsis/psychology , Intensive Care Units , Prognosis , Norepinephrine , Survivors , Body WeightABSTRACT
OBJECTIVE: To investigate the risk factors of lower extremity deep venous thrombosis (LEDVT) in patients with sepsis during hospitalization in intensive care unit (ICU), and to construct a nomogram prediction model of LEDVT in sepsis patients in the ICU based on the critical care scores combined with inflammatory markers, and to validate its effectiveness in early prediction. METHODS: 726 sepsis patients admitted to the ICU of the Affiliated Hospital of Jining Medical University from January 2015 to December 2021 were retrospectively included as the training set to construct the prediction model. In addition, 213 sepsis patients admitted to the ICU of the Affiliated Hospital of Jining Medical University from January 2022 to June 2023 were retrospectively included as the validation set to verify the performance of the prediction model. Clinical data of patients were collected, such as demographic information, vital signs at the time of admission to the ICU, underlying diseases, past history, various types of scores within 24 hours of admission to the ICU, the first laboratory indexes of admission to the ICU, lower extremity venous ultrasound results, treatment, and prognostic indexes. Lasso regression analysis was used to screen the influencing factors for the occurrence of LEDVT in sepsis patients, and the results of Logistic regression analysis were synthesized to construct a nomogram model. The nomogram model was evaluated by receiver operator characteristic curve (ROC curve), calibration curve, clinical impact curve (CIC) and decision curve analysis (DCA). RESULTS: The incidence of LEDVT after ICU admission was 21.5% (156/726) in the training set of sepsis patients and 21.6% (46/213) in the validation set of sepsis patients. The baseline data of patients in both training and validation sets were comparable. Lasso regression analysis showed that seven independent variables were screened from 67 parameters to be associated with the occurrence of LEDVT in patients with sepsis. Logistic regression analysis showed that the age [odds ratio (OR) = 1.03, 95% confidence interval (95%CI) was 1.01 to 1.04, P < 0.001], body mass index (BMI: OR = 1.05, 95%CI was 1.01 to 1.09, P = 0.009), venous thromboembolism (VTE) score (OR = 1.20, 95%CI was 1.11 to 1.29, P < 0.001), activated partial thromboplastin time (APTT: OR = 0.98, 95%CI was 0.97 to 0.99, P = 0.009), D-dimer (OR = 1.03, 95%CI was 1.01 to 1.04, P < 0.001), skin or soft-tissue infection (OR = 2.53, 95%CI was 1.29 to 4.98, P = 0.007), and femoral venous cannulation (OR = 3.72, 95%CI was 2.50 to 5.54, P < 0.001) were the independent influences on the occurrence of LEDVT in patients with sepsis. The nomogram model was constructed by combining the above variables, and the ROC curve analysis showed that the area under the curve (AUC) of the nomogram model for predicting the occurrence of LEDVT in patients with sepsis was 0.793 (95%CI was 0.746 to 0.841), and the AUC in the validation set was 0.844 (95%CI was 0.786 to 0.901). The calibration curve showed that its predicted probability was in good agreement with the actual probabilities were in good agreement, and both CIC and DCA curves suggested a favorable net clinical benefit. CONCLUSIONS: The nomogram model based on the critical illness scores combined with inflammatory markers can be used for early prediction of LEDVT in ICU sepsis patients, which helps clinicians to identify the risk factors for LEDVT in sepsis patients earlier, so as to achieve early treatment.
Subject(s)
Intensive Care Units , Lower Extremity , Nomograms , Sepsis , Venous Thrombosis , Humans , Venous Thrombosis/diagnosis , Venous Thrombosis/epidemiology , Sepsis/diagnosis , Lower Extremity/blood supply , Retrospective Studies , Risk Factors , Prognosis , Female , Male , Middle AgedABSTRACT
It has been shown that the formation of filopodia is a key step in tumor cell metastasis, but there is limited research regarding its mechanism. In this study, we demonstrated that fatty acid synthase (FASN) promoted filopodia formation in liver cancer cells by regulating fascin actin-bundling protein 1 (FSCN1), a marker protein for filopodia. Mechanistically, on the one hand, the accumulation of FASN is caused by the enhanced deubiquitination of FASN mediated by UCHL5 (ubiquitin c-terminal hydrolase L5). In this pathway, low expression of SIAH1 (Seven in absentia homolog 1) can decrease the ubiquitination and degradation of ADRM1 (adhesion regulating molecule 1) thereby increasing its protein level, which will recruit and activate the deubiquitination enzyme UCHL5, leading to FASN undergo deubiquitination and escape from proteasomal degradation. On the other hand, the accumulation of FASN is related to its weakened ubiquitination, where SIAH1 directly acts as a ubiquitin ligase toward FASN, and low expression of SIAH1 reduces the ubiquitination and degradation of FASN. Both the two pathways are involved in the regulation of FASN in liver cancer. Our results reveal a novel mechanism for FASN accumulation due to the low expression of SIAH1 in human liver cancer and suggest an important role of FASN in filopodia formation in liver cancer cells.
Subject(s)
Liver Neoplasms , Microfilament Proteins , Nuclear Proteins , Pseudopodia , Ubiquitin-Protein Ligases , Ubiquitination , Humans , Pseudopodia/metabolism , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Microfilament Proteins/metabolism , Microfilament Proteins/genetics , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Carrier Proteins/metabolism , Carrier Proteins/genetics , Animals , Cell Line, Tumor , Mice, Nude , Fatty Acid Synthase, Type I/metabolism , Fatty Acid Synthase, Type I/genetics , Hep G2 Cells , MiceABSTRACT
BACKGROUND: Constitutive photomorphogenic protein 1 (COP1) plays a pivotal role in the development and progression of several human cancers and is reported to be upregulated in liver cancer. However, the role of COP1 in human liver cancer is unclear. METHODS: We analyzed the COP1 expression in normal liver and liver cancer tissue samples using western blot and immunohistochemical analysis. We overexpressed and silenced COP1 in HepG2 and Huh7 cells and analyzed the effect on liver cancer cell proliferation. Additionally, COP1 was used as a bait to screen COP1-interacting proteins in a human cDNA library in a yeast two-hybrid screen and the results were confirmed with co-immunoprecipitation (co-IP) assays. Moreover, immunofluorescence staining was performed to assess co-localization. The protein levels of COP1 and mIL1RAcP were determined in clinical samples. RESULTS: COP1 was upregulated in liver cancer samples compared to that in normal tissue samples. COP1 overexpression promoted proliferation of liver cancer cells, while COP1 knockdown exerted the opposite effect. Yeast two-hybrid screen identified interleukin-1 receptor accessory protein (IL1RAP) as a potential COP1-interacting protein. Co-IP assays further confirmed that COP1 interacts with both preIL1RAP and membrane-bound form of IL1RAP (mIL1RAP). Furthermore, COP1 upregulated mIL1RAP protein levels and promoted nuclear translocation and activation of the nuclear factor kappa B (NF-κB) (p50/p65) dimer. Additionally, we demonstrated that COP1 regulated mIL1RAP expression through K63-linked polyubiquitination, suggesting that COP1 plays a role in stabilizing mIL1RAP. Finally, the protein levels of COP1 and mIL1RAcP were found to be positively correlated in clinical samples. CONCLUSION: COP1 regulates IL1RAP, which in turn results in activation of the NF-κB signaling. Our findings suggest that the COP1/IL1RAP/NF-κB axis promotes proliferation of liver cancer cells and is a potential target for the treatment of liver cancer.
Subject(s)
Interleukin-1 Receptor Accessory Protein , Liver Neoplasms , Ubiquitin-Protein Ligases , Humans , Interleukin-1 Receptor Accessory Protein/metabolism , Liver Neoplasms/metabolism , NF-kappa B/metabolism , Signal Transduction , Ubiquitin-Protein Ligases/metabolismABSTRACT
OBJECTIVE: To analyze the risk factors of in-hospital death in patients with sepsis in the intensive care unit (ICU) based on machine learning, and to construct a predictive model, and to explore the predictive value of the predictive model. METHODS: The clinical data of patients with sepsis who were hospitalized in the ICU of the Affiliated Hospital of Jining Medical University from April 2015 to April 2021 were retrospectively analyzed,including demographic information, vital signs, complications, laboratory examination indicators, diagnosis, treatment, etc. Patients were divided into death group and survival group according to whether in-hospital death occurred. The cases in the dataset (70%) were randomly selected as the training set for building the model, and the remaining 30% of the cases were used as the validation set. Based on seven machine learning models including logistic regression (LR), K-nearest neighbor (KNN), support vector machine (SVM), decision tree (DT), random forest (RF), extreme gradient boosting (XGBoost) and artificial neural network (ANN), a prediction model for in-hospital mortality of sepsis patients was constructed. The receiver operator characteristic curve (ROC curve), calibration curve and decision curve analysis (DCA) were used to evaluate the predictive performance of the seven models from the aspects of identification, calibration and clinical application, respectively. In addition, the predictive model based on machine learning was compared with the sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) models. RESULTS: A total of 741 patients with sepsis were included, of which 390 were discharged after improvement, 351 died in hospital, and the in-hospital mortality was 47.4%. There were significant differences in gender, age, APACHE II score, SOFA score, Glasgow coma score (GCS), heart rate, oxygen index (PaO2/FiO2), mechanical ventilation ratio, mechanical ventilation time, proportion of norepinephrine (NE) used, maximum NE, lactic acid (Lac), activated partial thromboplastin time (APTT), albumin (ALB), serum creatinine (SCr), blood urea nitrogen (BUN), blood uric acid (BUA), pH value, base excess (BE), and K+ between the death group and the survival group. ROC curve analysis showed that the area under the curve (AUC) of RF, XGBoost, LR, ANN, DT, SVM, KNN models, SOFA score, and APACHE II score for predicting in-hospital mortality of sepsis patients were 0.871, 0.846, 0.751, 0.747, 0.677, 0.657, 0.555, 0.749 and 0.760, respectively. Among all the models, the RF model had the highest precision (0.750), accuracy (0.785), recall (0.773), and F1 score (0.761), and best discrimination. The calibration curve showed that the RF model performed best among the seven machine learning models. DCA curve showed that the RF model exhibited greater net benefit as well as threshold probability compared to other models, indicating that the RF model was the best model with good clinical utility. CONCLUSIONS: The machine learning model can be used as a reliable tool for predicting in-hospital mortality in sepsis patients. RF models has the best predictive performance, which is helpful for clinicians to identify high-risk patients and implement early intervention to reduce mortality.
Subject(s)
Sepsis , Humans , Hospital Mortality , Retrospective Studies , ROC Curve , Prognosis , Sepsis/diagnosis , Intensive Care UnitsABSTRACT
OBJECTIVE: To assess the association between neutrophil percentage-to-albumin ratio (NPAR) and 28-day mortality in severely ill Chinese patients with sepsis. METHODS: In this retrospective, single-centre study, sepsis patients admitted to the ICU of the Affiliated Hospital of Jining Medical University between May 2015 and December 2021 were retrospectively analysed. The relationship between NPAR and 28-day mortality was examined using Cox proportional-hazards model. RESULTS: In total, 741 patients with sepsis were included. Multivariate analysis, adjusted for age, sex, body mass index (BMI), smoking and alcohol drinking history, showed an association between elevated NPAR and a high risk of 28-day mortality. After removal of additional confounders, moderate and high NPAR values remained significantly associated with 28-day mortality in comparison with low NPAR values (tertile 2 vs 1: HR, 95% CI: 1.42, 1.06-1.90; tertile 3 vs 1: HR, 95% CI: 1.35, 1.00-1.82). Survival curves stratified by NPAR groups showed that high NPAR levels had lower survival probabilities than lower NPAR levels. Subgroup analysis did not show any significant interactions between NPAR and 28-day mortality. CONCLUSIONS: Elevated NPAR values were linked to increased 28-day mortality in severely ill Chinese patients with sepsis. The findings require verification by large, prospective, multi-centre studies.
Subject(s)
Albumins , Neutrophils , Sepsis , Humans , East Asian People , Prospective Studies , Retrospective StudiesABSTRACT
Seven in absentia homolog 1 (SIAH1) was reported to be downregulated in hepatocellular carcinoma (HCC) and played an important role in HCC progression; however, the underlying reason remains unknown. Here, we found that Cathepsin K (CTSK), a protein potentially interacting with SIAH1, inhibits SIAH1 protein level. CTSK was highly expressed in HCC tissues. CTSK inhibition or downregulation suppressed HCC cell proliferation, whereas CTSK overexpression had the opposite effect; it promotes HCC cell proliferation by regulating the SIAH1/protein kinase B (AKT) pathway, wherein promotes SIAH1 ubiquitination. Neural precursor cells expressing developmentally downregulated 4 (NEDD4) was found to be a potential upstream ubiquitin ligase of SIAH1. Further, CTSK could mediate SIAH1 ubiquitination and degradation by increasing SIAH1 autoubiquitination and recruiting NEDD4 to ubiquitinate SIAH1. Finally, the roles of CTSK were confirmed in a xenograft mouse model. In conclusion, oncogenic CTSK was upregulated in human HCC tissues and accelerated HCC cell proliferation by downregulating SIAH1.
ABSTRACT
OBJECTIVE: To investigate the changes of quadriceps femoris thickness with the length of stay in intensive care unit (ICU) in patients with sepsis, and to evaluate the diagnostic value of muscle changes in mortality. METHODS: A prospective study was conducted, and 92 patients with sepsis who were admitted to the ICU of the Affiliated Hospital of Jining Medical College from January 2020 to December 2021 were enrolled. The thickness of quadriceps femoris [including the quadriceps femoris muscle thickness at the midpoint of the anterior superior iliac spine and the upper edge of the patella (M-QMLT), and at the middle and lower 1/3 of the patella (T-QMLT)] measured by ultrasound 1 day (D1), 3 days (D3), and 7 days (D7) after admission to the ICU were collected. The atrophy rate of quadriceps femoris was calculated 3 and 7 days after admission to the ICU compared with 1 day [(D3-D1)/D1 and (D7-D1)/D1, (TD3-TD1)/TD1 and (TD7-TD1)/TD1, respectively]. The demographic information, underlying diseases, vital signs when admission to the ICU and in-hospital mortality of all patients were recorded, and the differences of the above indicators between the two groupswere compared. Multivariate Logistic regression was used to analyze the influence of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of quadriceps femoris muscle thickness and atrophy rate on in-hospital mortality of septic patients. RESULTS: A total of 92 patients with severe sepsis were included, of which 41 patients died in hospital, 51 patients discharged. The in-hospital mortality was 44.6%. The muscle thickness of quadriceps femoris in severe septic patients decreased with the prolongation of ICU stay, and there was no significant difference between the two groups at the first and third day of ICU admission. The muscle thickness of quadriceps femoris at different measuring positions in the survival group was significantly greater than those in the death group 7 days after admission to the ICU [M-QMLT D7 (cm): 0.50±0.26 vs. 0.39±0.19, T-QMLT D7 (cm): 0.58±0.29 vs. 0.45±0.21, both P < 0.05]. The atrophy rate of quadriceps femoris muscle thickness at different measuring positions 3 and 7 days after admission to ICU in the survival group was significantly lower than those in the death group [(D3-D1)/D1: (8.33±3.44)% vs. (9.74±3.91)%, (D7-D1)/D1: (12.21±4.76)% vs. (19.80±6.15)%, (TD3-TD1)/TD1: (7.83±4.26)% vs. (10.51±4.75)%, (TD7-TD1)/TD1: (11.10±5.46)% vs. (20.22±6.05)%, all P < 0.05]. Multivariate Logistic regression analysis showed that M-QMLT D7, T-QMLT D7, (D3-D1)/D1, (D7-D1)/D1, (TD3-TD1)/TD1, (TD7-TD1)/TD1 were independent risk factors for in-hospital mortality (all P < 0.05). The results were stable after adjusting for confounding factors. ROC curve analysis showed that (TD7-TD1)/TD1 [area under the ROC curve (AUC) was 0.853, 95% confidence interval (95%CI) was 0.773-0.934] was superior to (D7-D1)/D1, T-QMLT D7, M-QMLT D7, (TD3-TD1)/TD1 and (D3-D1)/D1 [AUC was 0.821 (0.725-0.917), 0.692 (0.582-0.802), 0.683 (0.573-0.794), 0.680 (0.569-0.791), 0.622 (0.502-0.742)]. CONCLUSIONS: For septic patients in ICU, bedside ultrasound monitoring of quadriceps femoris muscle thickness and atrophy rate has a certain predictive value for in-hospital mortality, and a certain guiding significance in clinical treatment and predicting the prognosis of sepsis.
Subject(s)
Hospital Mortality , Humans , Prospective StudiesABSTRACT
OBJECTIVE: To analyze the risk factors of acute kidney injury (AKI) in patients with septic shock in intensive care unit (ICU), construct a predictive model, and explore the predictive value of the predictive model. METHODS: The clinical data of patients with septic shock who were hospitalized in the ICU of the Affiliated Hospital of Jining Medical College from April 2015 to June 2019 were retrospectively analyzed. According to whether the patients had AKI within 7 days of admission to the ICU, they were divided into AKI group and non-AKI group. 70% of the cases were randomly selected as the training set for building the model, and the remaining 30% of the cases were used as the validation set. XGBoost model was used to integrate relevant parameters to predict the risk of AKI in patients with septic shock. The predictive ability was assessed through receiver operator characteristic curve (ROC curve), and was correlated with acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), procalcitonin (PCT) and other comparative verification models to verify the predictive value. RESULTS: A total of 303 patients with septic shock were enrolled, including 153 patients with AKI and 150 patients without AKI. The incidence of AKI was 50.50%. Compared with the non-AKI group, the AKI group had higher APACHE II score, SOFA score and blood lactate (Lac), higher dose of norepinephrine (NE), higher proportion of mechanical ventilation, and tachycardiac. In the XGBoost prediction model of AKI risk in septic shock patients, the top 10 features were serum creatinine (SCr) level at ICU admission, NE use, drinking history, albumin, serum sodium, C-reactive protein (CRP), Lac, body mass index (BMI), platelet count (PLT), and blood urea nitrogen (BUN) levels. Area under the ROC curve (AUC) of the XGBoost model for predicting the risk of AKI in patients with septic shock was 0.816, with a sensitivity of 73.3%, a specificity of 71.7%, and an accuracy of 72.5%. Compared with the APACHE II score, SOFA score and PCT, the performance of the model improved significantly. The calibration curve of the model showed that the goodness of fit of the XGBoost model was higher than the other scores (the calibration curve had the lowest score, with a score of 0.205). CONCLUSIONS: Compared with the commonly used clinical scores, the XGBoost model can more accurately predict the risk of AKI in patients with septic shock, which helps to make appropriate diagnosis, treatment and follow-up strategies while predicting the prognosis of patients.
Subject(s)
Acute Kidney Injury , Sepsis , Shock, Septic , Acute Kidney Injury/diagnosis , Female , Humans , Intensive Care Units , Machine Learning , Male , Norepinephrine , Procalcitonin , Prognosis , ROC Curve , Retrospective Studies , Shock, Septic/diagnosisABSTRACT
OBJECTIVE: To explore the value of lactic acid (Lac), procalcitonin (PCT), sequential organ failure assessment (SOFA) score and acute physiology and chronic health evaluation II (APACHE II) score in assessing the severity and predicting the prognosis in sepsis shock. METHODS: A retrospectively study was conducted. Patients with septic shock hospitalized in the department of critical care medicine of the Affiliated Hospital of Jining Medical University from April 2015 to June 2019 were enrrolled. The patient's gender, age, body mass index (BMI), infection site, organ dysfunction status; Lac, PCT, C-reactive protein (CRP), heart rate and body temperature immediately after admission to the intensive care unit (ICU); APACHE II and SOFA scores within 24 hours, and 28-day prognosis were collected. According to the 28-day prognosis, the patients with septic shock were divided into the survival group and the death group, and the differences in the indicators between the groups were compared. Multivariate Logistic regression analysis was used to screen the risk factors of 28-day death in patients with septic shock; receiver operating characteristic curve (ROC curve) was used to analyze the value of Lac, PCT, SOFA, APACHE II, and age in predicting the 28-day prognosis of patients with septic shock. RESULTS: A total of 303 septic shock patients were enrolled, of which 124 cases survived and 179 died on the 28th day, and the 28-day mortality was 59.08%. (1) Compared with the survival group, patients in the death group were older (years old: 66.58±15.22 vs. 61.15±15.68), APACHE II, SOFA, proportion of lung infections, Lac increased [APACHE II score: 22.79±7.62 vs. 17.98±6.88, SOFA score: 9.42±3.51 vs. 5.65±1.59, proportion of lung infections: 53.63% (96/179) vs. 39.52% (49/124), Lac (mmol/L): 5.10±3.72 vs. 3.71±2.56], oxygenation index (PaO2/FiO2) and ICU body temperature decreased [PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 198.94±80.15 vs. 220.68±72.06, ICU body temperature (centigrade): 37.47±1.08 vs. 37.80±1.14], and the differences were statistically significant (all P < 0.05). (2) Multivariate Logistic regression analysis results: after adjusted for potential confounding factors, APACHE II, PCT, Lac, age and SOFA were independent risk factors for death in patients with septic shock [APACHE II: odds ratio (OR) =1.05, 95% confidence interval (95%CI) was 1.01-1.10, P = 0.039; PCT: OR = 0.99, 95%CI was 0.98-1.00, P =0.012; Lac: OR = 1.23, 95%CI was 1.08-1.40, P = 0.002; age: OR = 1.03, 95%CI was 1.01-1.05, P = 0.009; SOFA score: OR =1.88, 95%CI was 1.59-2.22, P < 0.001]. (3) ROC curve analysis showed that APACHE II, Lac, age and SOFA could predict the prognosis of patients with septic shock [APACHE II: the area under the ROC curve (AUC) = 0.682 4, 95%CI was 0.621 7-0.743 1, P = 0.000; when the best cut-off value was 18.500, its sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 72.63%, 54.84%, 69.89%, 58.12%, 1.608 1 and 0.499 2, respectively. Lac: AUC = 0.604 5, 95%CI was 0.540 8-0.668 2, P = 0.002; when the best cut-off value was 3.550 mmol/L, the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 50.84%, 73.39%, 73.39%, 50.94%, 1.910 3 and 0.669 9, respectively. Age: AUC = 0.599 1, 95%CI was 0.535 4-0.662 7, P = 0.003; when the best cut-off value was 72.500 years old, the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 42.46%, 75.00%, 71.03%, 47.45%, 1.698 3 and 0.767 2, respectively. SOFA: AUC = 0.822 3, 95%CI was 0.776 7-0.867 9, P = 0.000; when the best cut-off value was 7.500, its sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 68.72%, 87.90%, 89.13%, 66.06%, 5.680 4, 0.355 9 respectively]. The combined prediction had a good sensitivity (72.63%) and specificity (84.86%), and AUC (0.876 5) was higher than that of a single variable, suggested that the multivariate combination was more accurate in predicting the short-term outcome of septic shock. CONCLUSIONS: Lac, PCT, SOFA score, APACHE II score and age were independent risk factors for death in patients with septic shock, and the accuracy of Lac, SOFA score, APACHE II score and age in predicting short-term prognosis of septic shock was better than that of single variable, and the diagnostic value was higher.
Subject(s)
Sepsis , Shock, Septic , Aged , Humans , Intensive Care Units , Lactic Acid , Procalcitonin , Prognosis , ROC Curve , Retrospective Studies , Shock, Septic/diagnosisABSTRACT
BACKGROUND: Procalcitonin (PCT) is an effective and sensitive diagnostic biomarker that can facilitate the early detection of infection and septicemia, but whether it can similarly be utilized to predict the development of acute kidney injury (AKI) in patients suffering from septic shock remains to be established. Herein, the relationship between serum PCT at admission and the onset of AKI in septic shock patients was thus evaluated following adjustment for other potential covariates. METHODS: This was a retrospective cohort study of 303 septic shock patients treated in a Chinese hospital between May 2015 and May 2019. All patients in whom PCT levels were measured on admission and who did not exhibit AKI or chronic kidney disease at the time of admission were assessed for AKI development within one week following intensive care unit (ICU) admission as per the KDIGO criteria. The relationship between serum PCT at admission and AKI incidence was then assessed for these patients. RESULTS: These 303 patients were an average of 64 years old, and were 59.7% male. Of these patients, 50.5% developed AKI within the first 7 days following ICU admission. A dully-adjusted binary logistic regression analysis revealed PCT levels at admission to be associated with AKI following adjustment for potential confounding factors (odds ratio (OR) = 1.01, 95%CI (1.01,1.02), p = 0.0007). Receiver operating characteristic curve analysis further indicated that a PCT cutoff level of 52.59â ng/ml at admission was able to predict the incidence of AKI with respective sensitivity and specificity values of 50% and 84%. Interaction analysis revealed no significant interactive relationship between PCT and AKI, suggesting that serum PCT levels represent an early predictor of AKI incidence in septic shock patients. CONCLUSIONS: Serum PCT at the time of admission can be used as a predictor of AKI in patients suffering from septic shock.
Subject(s)
Acute Kidney Injury , Shock, Septic , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Female , Humans , Male , Middle Aged , Procalcitonin , Prognosis , Retrospective Studies , Shock, Septic/complicationsABSTRACT
A healthy body activates the immune response to target invading pathogens (i.e. viruses, bacteria, fungi, and parasites) and avoid further systemic infection. The activation of immunological mechanisms includes several components of the immune system, such as innate and acquired immunity. Once any component of the immune response to infections is aberrantly altered or dysregulated, resulting in a failure to clear infection, sepsis will develop through a pro-inflammatory immunological mechanism. Furthermore, the severe inflammatory responses induced by sepsis also increase vascular permeability, leading to acute pulmonary edema and resulting in acute respiratory distress syndrome (ARDS). Apparently, potential for improvement exists in the management of the transition from sepsis to ARDS; thus, this article presents an exhaustive review that highlights the previously unrecognized relationship between sepsis and ARDS and suggests a direction for future therapeutic developments, including plasma and genetic pre-diagnostic strategies and interference with proinflammatory signaling.
Subject(s)
Respiratory Distress Syndrome/prevention & control , Sepsis/prevention & control , Animals , Gene Expression Regulation , Genetic Predisposition to Disease , Genetic Testing , Humans , Phenotype , Prognosis , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/genetics , Respiratory Distress Syndrome/metabolism , Risk Factors , Sepsis/diagnosis , Sepsis/genetics , Sepsis/metabolism , Signal TransductionABSTRACT
The gut microbiota of intensive care unit (ICU) patients displays extreme dysbiosis associated with increased susceptibility to organ failure, sepsis, and septic shock. However, such dysbiosis is difficult to characterize owing to the high dimensional complexity of the gut microbiota. We tested whether the concept of enterotype can be applied to the gut microbiota of ICU patients to describe the dysbiosis. We collected 131 fecal samples from 64 ICU patients diagnosed with sepsis or septic shock and performed 16S rRNA gene sequencing to dissect their gut microbiota compositions. During the development of sepsis or septic shock and during various medical treatments, the ICU patients always exhibited two dysbiotic microbiota patterns, or ICU-enterotypes, which could not be explained by host properties such as age, sex, and body mass index, or external stressors such as infection site and antibiotic use. ICU-enterotype I (ICU E1) comprised predominantly Bacteroides and an unclassified genus of Enterobacteriaceae, while ICU-enterotype II (ICU E2) comprised predominantly Enterococcus. Among more critically ill patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores > 18, septic shock was more likely to occur with ICU E1 (P = 0.041). Additionally, ICU E1 was correlated with high serum lactate levels (P = 0.007). Therefore, different patterns of dysbiosis were correlated with different clinical outcomes, suggesting that ICU-enterotypes should be diagnosed as independent clinical indices. Thus, the microbial-based human index classifier we propose is precise and effective for timely monitoring of ICU-enterotypes of individual patients. This work is a first step toward precision medicine for septic patients based on their gut microbiota profiles.