SOFA in sepsis: with or without GCS.

PURPOSE: Sepsis is a global public health burden. The sequential organ failure assessment (SOFA) is the most commonly used scoring system for diagnosing sepsis and assessing severity. Due to the widespread use of endotracheal intubation and sedative medications in sepsis, the accuracy of the Glasgow Coma Score (GCS) is the lowest in SOFA. We designed this multicenter, cross-sectional study to investigate the predictive efficiency of SOFA with or without GCS on ICU mortality in patients with sepsis. METHODS: First, 3048 patients with sepsis admitted to Peking Union Medical College Hospital (PUMCH) were enrolled in this survey. The data were collected from June 8, 2013 to October 12, 2022. Second, 18,108 patients with sepsis in the eICU database were enrolled. Third, 2397 septic patients with respiratory system ≥ 3 points in SOFA in the eICU database were included. We investigated the predictive efficiency of SOFA with or without GCS on ICU mortality in patients with sepsis in various ICUs of PUMCH, and then we validated the results in the eICU database. MAIN RESULTS: In data of ICUs in PUMCH, the predictive efficiency of SOFA without GCS (AUROC [95% CI], 24 h, 0.724 [0.688, 0.760], 48 h, 0.734 [0.699, 0.769], 72 h, 0.748 [0.713, 0.783], 168 h, 0.781 [0.747, 0.815]) was higher than that of SOFA with GCS (AUROC [95% CI], 24 h, 0.708 [0.672, 0.744], 48 h, 0.721 [0.685, 0.757], 72 h, 0.735 [0.700, 0.757], 168 h, 0.770 [0.736, 0.804]) on ICU mortality in patients with sepsis, and the difference was statistically significant (P value, 24 h, 0.001, 48 h, 0.003, 72 h, 0.004, 168 h, 0.005). In septic patients with respiratory system ≥ 3 points in SOFA in the eICU database, although the difference was not statistically significant (P value, 24 h, 0.148, 48 h, 0.178, 72 h, 0.132, 168 h, 0.790), SOFA without GCS (AUROC [95% CI], 24 h, 0.601 [0.576, 0.626], 48 h, 0.625 [0.601, 0.649], 72 h, 0.639 [0.615, 0.663], 168 h, 0.653 [0.629, 0.677]) had a higher predictive efficiency on ICU mortality than SOFA with GCS (AUROC [95% CI], 24 h, 0.591 [0.566, 0.616], 48 h, 0.616 [0.592, 0.640], 72 h, 0.628 [0.604, 0.652], 168 h, 0.651 [0.627, 0.675]). CONCLUSIONS: In severe sepsis, it is realistic and feasible to discontinue the routine GCS for SOFA in patients with a respiratory system ≥ 3 points, and even better predict ICU mortality.

Association of medical care capacity and the patient mortality of septic shock: a cross-sectional study.

BACKGROUND: Hospitals with higher septic shock case volume demonstrated lower hospital mortality. We conducted this study to investigate whether this phenomenon was only caused by the increase in the number of admissions or the need to improve the medical care capacity in septic shock at the same time. METHODS: Seven-hundred and eighty-seven hospitals from China collected in a survey from January 1, 2021 to December 31, 2021. Medical care capacity for septic shock was explored by patients with septic shock in intensive care units (ICU) divided into beds, intensivists, and nurses respectively. MAIN RESULTS: The proportion of ICU patients with septic shock was negatively associated with the patient mortality of septic shock (Estimate [95%CI], -0.2532 [-0.5038, -0.0026]) (p-value 0.048). The ratios of patients with septic shock to beds, intensivists, and nurses were negatively associated with mortality of septic shock (Estimate [95%CI], -0.370 [-0.591, -0.150], -0.136 [-0.241, -0.031], and -0.774 [-1.158, -0.389]) (p-value 0.001, 0.011 and < 0.001). Severe pneumonia, the most common infection that caused a septic shock, correlated positively with its mortality (Estimate [95%CI], 0.1002 [0.0617, 0.1387]) (p-value < 0.001). CONCLUSIONS: Hospitals with higher medical care capacity for septic shock were associated with lower hospital mortality.

Factors influencing DVT formation in sepsis.

INTRODUCTION: Sepsis is a global public health burden. Deep vein thrombosis (DVT) is the third most common cause of death from cardiovascular disease after heart attacks and strokes. We designed this experiment to investigate the factors influencing DVT formation in patients with sepsis. METHODS: In this survey, 918 septic patients admitted to Peking Union Medical College Hospital, who underwent DVT screening were enrolled. The data were collected from June 8, 2013 to October 12, 2022. The differences between septic patients with and without DVT were studied from following aspects: basic information, comorbidities, inflammatory cytokines, albumin, source of infection, sequential organ failure assessment (SOFA) score, coagulation and prognosis. MAIN RESULTS: In this study, the prevalence of DVT in patients with sepsis was 0.23. Elderly patients with sepsis were prone to DVT (p value < 0.001). In terms of comorbidities, septic patients with hypertension and atrial fibrillation were prone to DVT (p value 0.045 and 0.048). Inflammatory cytokines, such as procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, had no significant correlation with DVT in patients with sepsis (p value 0.364, 0.882, 0.912, 0.789, 0.245, and 0.780). Levels of serum albumin correlated with DVT in patients with sepsis (p value 0.003). The SOFA total score had no relationship with DVT formation (p value 0.254). Coagulation and respiration function were negatively correlated with DVT (p value 0.018). Liver function was positively correlated with DVT (p value 0.020). Patients in the DVT group had longer duration of mechanical ventilation and longer intensive care unit (ICU) stays (p value < 0.001 and 0.006). There was no significant difference in survival in septic patients with and without DVT (p value 0.868). CONCLUSIONS: The SOFA total score had no relationship with DVT formation. The function of each organ had different effects on DVT formation. Better coagulation and respiration function, easier DVT formation. Poorer liver function, easier DVT formation. DVT was associated with longer duration of mechanical ventilation and longer ICU stays.

Health economic analysis and medical cost analysis of children with severe hepatitis B in China: A retrospective study from 2016 to 2022.

BACKGROUND: Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China. METHODS: Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran's I  analysis. RESULTS: The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603,) of total cases and cirrhosis cases accounted for 11.23% (180/1603,). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (GDP, Moran's I <0) and percentage of urban population (Moran's I <0), and positively correlated with the number of pediatric beds per million population (Moran's I >0). CONCLUSION: The number of severe hepatitis B cases is low in areas with high GDP levels and high urban population ratios, and health care costs have been declining over the years.

Association between ICU quality and in-hospital mortality of V-V ECMO-supported patients-the ECMO quality improvement action (EQIA) study: a national cohort study in China from 2017 to 2019.

This cohort study was performed to explore the influence of intensive care unit (ICU) quality on in-hospital mortality of veno-venous (V-V) extracorporeal membrane oxygenation (ECMO)-supported patients in China. The study involved all V-V ECMO-supported patients in 318 of 1700 tertiary hospitals from 2017 to 2019, using data from the National Clinical Improvement System and China National Critical Care Quality Control Center. ICU quality was assessed by quality control indicators and capacity parameters. Among the 2563 V-V ECMO-supported patients in 318 hospitals, a significant correlation was found between ECMO-related complications and prognosis. The reintubation rate within 48 hours after extubation and the total ICU mortality rate were independent risk factors for higher in-hospital mortality of V-V ECMO-supported patients (cutoff: 1.5% and 7.0%; 95% confidence interval: 1.05-1.48 and 1.04-1.45; odds ratios: 1.25 and 1.23; P = 0.012 and P = 0.015, respectively). Meanwhile, the V-V ECMO center volume was a protective factor (cutoff of ≥ 50 cases within the 3-year study period; 95% confidence interval: 0.57-0.83, odds ratio: 0.69, P = 0.0001). The subgroup analysis of 864 patients in 11 high-volume centers further strengthened these findings. Thus, ICU quality may play an important role in improving the prognosis of V-V ECMO-supported patients.

Measuring the worldwide spread of COVID-19 using a comprehensive modeling method.

BACKGROUND: With the global spread of COVID-19, detecting high-risk countries/regions timely and dynamically is essential; therefore, we sought to develop automatic, quantitative and scalable analysis methods to observe and estimate COVID-19 spread worldwide and further generate reliable and timely decision-making support for public health management using a comprehensive modeling method based on multiple mathematical models. METHODS: We collected global COVID-19 epidemic data reported from January 23 to September 30, 2020, to observe and estimate its possible spread trends. Countries were divided into three outbreak levels: high, middle, and low. Trends analysis was performed by calculating the growth rate, and then country grouping was implemented using group-based trajectory modeling on the three levels. Individual countries from each group were also chosen to further disclose the outbreak situations using two predicting models: the logistic growth model and the SEIR model. RESULTS: All 187 observed countries' trajectory subgroups were identified using two grouping strategies: with and without population consideration. By measuring epidemic trends and predicting the epidemic size and peak of individual countries, our study found that the logistic growth model generally estimated a smaller epidemic size than the SEIR model. According to SEIR modeling, confirmed cases in each country would take an average of 9-12 months to reach the outbreak peak from the day the first case occurred. Additionally, the average number of cases at the peak time will reach approximately 10-20% of the countries' populations, and the countries with high trends and a high predicted size must pay special attention and implement public health interventions in a timely manner. CONCLUSIONS: We demonstrated comprehensive observations and predictions of the COVID-19 outbreak in 187 countries using a comprehensive modeling method. The methods proposed in this study can measure COVID-19 development from multiple perspectives and are generalizable to other epidemic diseases. Furthermore, the methods also provide reliable and timely decision-making support for public health management.

Carbapenem is not always the best choice in the treatment of septic shock.

BACKGROUND: Septic shock is a global public health burden. In addition to the improvement of the level of individual care, the improvement of the overall hospital quality control management is also an essential key aspect of the Surviving Sepsis Campaign (SSC). Using of antibiotics is a cornerstone in the treatment of septic shock, so we conducted this study to investigate the influence of antibiotics and pathogenic bacteria on the mortality of septic shock at the level of overall hospital in China. METHODS: This was an observational database study in 2021 enrolled the data of 787 hospitals from 31 provinces/municipalities/autonomous regions of Mainland China collected in a survey from January 1, 2021 to December 31, 2021. RESULTS: The proportion of ICU patients with septic shock was 3.55%, while the patient mortality of septic shock was 23.08%. While carbapenem was the most preferred antibiotic medication used in 459 of the 782 hospitals, the preference for carbapenem did not show significant effect on the patient mortality in the treatment of septic shock (p-value 0.59). Compared with patients with fermenting bacteria as the most common pathogenic bacteria causing septic shock, patients with non-fermenting bacteria had a higher mortality (p-value 0.01). CONCLUSIONS: Whether using carbapenem as the preferred antibiotic or not, did not show effect on the patient mortality of septic shock. Compared with patients with fermenting bacteria as the most common pathogenic bacteria, patients of septic shock with non-fermenting bacteria had a higher mortality.

Evaluation of ICUs and weight of quality control indicators: an exploratory study based on Chinese ICU quality data from 2015 to 2020.

This study aimed to explore key quality control factors that affected the prognosis of intensive care unit (ICU) patients in Chinese mainland over six years (2015-2020). The data for this study were from 31 provincial and municipal hospitals (3425 hospital ICUs) and included 2 110 685 ICU patients, for a total of 27 607 376 ICU hospitalization days. We found that 15 initially established quality control indicators were good predictors of patient prognosis, including percentage of ICU patients out of all inpatients (%), percentage of ICU bed occupancy of total inpatient bed occupancy (%), percentage of all ICU inpatients with an APACHE II score ⩾15 (%), three-hour (surviving sepsis campaign) SSC bundle compliance (%), six-hour SSC bundle compliance (%), rate of microbe detection before antibiotics (%), percentage of drug deep venous thrombosis (DVT) prophylaxis (%), percentage of unplanned endotracheal extubations (%), percentage of patients reintubated within 48 hours (%), unplanned transfers to the ICU (%), 48-h ICU readmission rate (%), ventilator associated pneumonia (VAP) (per 1000 ventilator days), catheter related blood stream infection (CRBSI) (per 1000 catheter days), catheter-associated urinary tract infections (CAUTI) (per 1000 catheter days), in-hospital mortality (%). When exploratory factor analysis was applied, the 15 indicators were divided into 6 core elements that varied in weight regarding quality evaluation: nosocomial infection management (21.35%), compliance with the Surviving Sepsis Campaign guidelines (17.97%), ICU resources (17.46%), airway management (15.53%), prevention of deep-vein thrombosis (14.07%), and severity of patient condition (13.61%). Based on the different weights of the core elements associated with the 15 indicators, we developed an integrated quality scoring system defined as F score=21.35%xnosocomial infection management + 17.97%xcompliance with SSC guidelines + 17.46%×ICU resources + 15.53%×airway management + 14.07%×DVT prevention + 13.61%×severity of patient condition. This evidence-based quality scoring system will help in assessing the key elements of quality management and establish a foundation for further optimization of the quality control indicator system.

Effect of ICU quality control indicators on VAP incidence rate and mortality: a retrospective study of 1267 hospitals in China.

PURPOSE: To investigate the effects of ICU quality control indicators on the VAP incidence rate and mortality in China throughout 2019. METHODS: This was a retrospective study. A total of 1267 ICUs from 30 provinces in mainland China were included. Data were collected using the National Clinical Improvement System Data that report ICU information. Ten related quality control indicators were analyzed, including 5 structural factors (patient-to-bed ratio, physician-to-bed ratio, nurse-to-bed ratio, patient-to-physician ratio, and patient-to-nurse ratio), 3 process factors (unplanned endotracheal extubation rate, reintubation rate within 48 h, and microbiology detection rate before antibiotic use), and 2 outcome factors (VAP incidence rate and mortality). The information on the most common infectious pathogens and the most commonly used antibiotics in ICU was also collected. The Poisson regression model was used to identify the impact of factors on the incidence rate and mortality of VAP. RESULTS: The incidence rate of VAP in these hospitals in 2019 was 5.03 (2.38, 10.25) per 1000 ventilator days, and the mortality of VAP was 11.11 (0.32, 26.00) %. The most common causative pathogen was Acinetobacter baumannii (in 39.98% of hospitals), followed by Klebsiella pneumoniae (38.26%), Pseudomonas aeruginosa, and Escherichia coli. In 26.90% of hospitals, third-generation cephalosporin was the most used antibiotic, followed by carbapenem (24.22%), penicillin and beta-lactamase inhibitor combination (20.09%), cephalosporin with beta-lactamase inhibitor (17.93%). All the structural factors were significantly associated with VAP incidence rate, but not with the mortality, although the trend was inconsistent. Process factors including unplanned endotracheal extubation rate, reintubation rate in 48 h, and microbiology detection rate before antibiotic use were associated with higher VAP mortality, while unplanned endotracheal extubation rate and reintubation rate in 48 h were associated with higher VAP mortality. Furthermore, K. pneumoniae as the most common pathogen was associated with higher VAP mortality, and carbapenems as the most used antibiotics were associated with lower VAP mortality. CONCLUSION: This study highlights the association between the ICU quality control (QC) factors and VAP incidence rate and mortality. The process factors rather than the structural factors need to be further improved for the QC of VAP in the ICU.

Association of annual hospital septic shock case volume and hospital mortality.

BACKGROUND: The burden of sepsis remains high in China. The relationship between case volume and hospital mortality among patients with septic shock, the most severe complication of sepsis, is unknown in China. METHODS: In this retrospective cohort study, we analyzed surveillance data from a national quality improvement program in intensive care units (ICUs) in China in 2020. Association between septic shock case volume and hospital mortality was analyzed using multivariate linear regression and restricted cubic splines. RESULTS: We enrolled a total of 134,046 septic shock cases in ICUs from 1902 hospitals in China during 2020. In this septic shock cohort, the median septic shock volume per hospital was 33 cases (interquartile range 14-76 cases), 41.4% were female, and more than half of the patients were over 61 years old, with average hospital mortality of 21.2%. An increase in case volume was associated with improved survival among septic shock cases. In the linear regression model, the highest quartile of septic shock volume was associated with lower hospital mortality compared with the lowest quartile (ß - 0.86; 95% CI - 0.98, - 0.74; p < 0.001). Similar differences were found in hospitals of respective geographic locations and hospital levels. With case volume modeled as a continuous variable in a restricted cubic spline, a lower volume threshold of 40 cases before which a substantial reduction of the hospital mortality rate was observed. CONCLUSIONS: The findings suggest that hospitals with higher septic shock case volume have lower hospital mortality in China. Further research is needed to explain the mechanism of this volume-outcome relationship.

Association between hospital and ICU structural factors and patient outcomes in China: a secondary analysis of the National Clinical Improvement System Data in 2019.

BACKGROUND: Hospital and ICU structural factors are key factors affecting the quality of care as well as ICU patient outcomes. However, the data from China are scarce. This study was designed to investigate how differences in patient outcomes are associated with differences in hospital and ICU structure variables in China throughout 2019. METHODS: This was a multicenter observational study. Data from a total of 2820 hospitals were collected using the National Clinical Improvement System Data that reports ICU information in China. Data collection consisted of a) information on the hospital and ICU structural factors, including the hospital type, number of beds, staffing, among others, and b) ICU patient outcomes, including the mortality rate as well as the incidence of ventilator-associated pneumonia (VAP), catheter-related bloodstream infections (CRBSIs), and catheter-associated urinary tract infections (CAUTIs). Generalized linear mixed models were used to analyse the association between hospital and ICU structural factors and patient outcomes. RESULTS: The median ICU patient mortality was 8.02% (3.78%, 14.35%), and the incidences of VAP, CRBSI, and CAUTI were 5.58 (1.55, 11.67) per 1000 ventilator days, 0.63 (0, 2.01) per 1000 catheter days, and 1.42 (0.37, 3.40) per 1000 catheter days, respectively. Mortality was significantly lower in public hospitals (ß = - 0.018 (- 0.031, - 0.005), p = 0.006), hospitals with an ICU-to-hospital bed percentage of more than 2% (ß = - 0.027 (- 0.034, -0.019), p < 0.001) and higher in hospitals with a bed-to-nurse ratio of more than 0.5:1 (ß = 0.009 (0.001, 0.017), p = 0.027). The incidence of VAP was lower in public hospitals (ß = - 0.036 (- 0.054, - 0.018), p < 0.001). The incidence of CRBSIs was lower in public hospitals (ß = - 0.008 (- 0.014, - 0.002), p = 0.011) and higher in secondary hospitals (ß = 0.005 (0.001, 0.009), p = 0.010), while the incidence of CAUTIs was higher in secondary hospitals (ß = 0.010 (0.002, 0.018), p = 0.015). CONCLUSION: This study highlights the association between specific ICU structural factors and patient outcomes. Modifying structural factors is a potential opportunity that could improve patient outcomes in ICUs.

Thalidomide combined with transcatheter artierial chemoembolzation for primary hepatocellular carcinoma: a systematic review and meta-analysis.

OBJECTIVE: Transcatheter arterial chemoembolization (TACE) and thalidomide have been used for treating primary hepatocellular carcinoma(HCC). This study aims to evaluate the clinical efficacy and safety of thalidomide and TACE in primary HCC. METHODS: Randomized controlled trials(RCTs) about efficacy and safety of thalidomide combined with TACE for primary HCC were identified from the Cochrane Library, Pubmed, Embase, CNKI, and Wan Fang until August, 2016. The retrieved trials were reviewed and the data were extracted by two reviewers, independently. Combined analyses of survival rates, overall response rate(ORR), disease control rate(DCR), changes of KPS, parameters of cellular immunity and vascular endothelial growth factor(VEGF), and adverse events were performed using RevMan 5.3 software. RESULTS: A total of 23 RCTs involving 1836 patients were included. The results showed that thalidomide plus TACE was significantly superior in increasing 6-month survival rate(OR=1.79, 95% CI:1.02-3.15, P=0.04), 1-year survival rate(OR=1.76, 95% CI:1.38-2.24, P<0.0001), 1.5-year survival rate(OR=4.72, 95% CI:2.64-8.43, P<0.001), 2-year survival rate(OR=1.78, 95% CI:1.37-2.30, P<0.001), ORR(OR=1.89, 95% CI:1.48-2.42, P<0.0001), DCR(OR=2.62, 95% CI:1.90-3.63, P<0.001), improvement in cellular immunity(MD=0.63, 95% CI:0.45-0.80, P<0.0001), and reduction of VEGF(MD=-119.71, 95% CI:-135.75-103.68, P<0.0001), when compared with TACE group. The incidences of gastrointestinal reactions, myelosuppression, and liver dysfunction were similar between combination group and TACE group(P>0.05). However, compared to TACE, the combination of thalidomide and TACE had a higher incidence of drug rash(OR=6.35, 95% CI:2.75-14.68, P<0.0001). CONCLUSION: Our findings suggest that thalidomide combined with TACE shows better clinical efficacy and tolerable adverse events in patients with primary HCC when compared with TACE alone.

Regulation of T helper cell differentiation by E3 ubiquitin ligases and deubiquitinating enzymes.

CD4 T cells are essential components of adaptive immunity and play a critical role in anti-pathogenic or anti-tumor responses as well as autoimmune and allergic diseases. Naive CD4 T cells differentiate into distinct subsets of T helper (Th) cells by various signals including TCR, costimulatory and cytokine signals. Accumulating evidence suggests that these signaling pathways are critically regulated by ubiquitination and deubiquitination, two reversible posttranslational modifications mediated by E3 ubiquitin ligases and deubiquitinating enzymes (DUBs), respectively. In this review, we briefly introduce the signaling pathways that control the differentiation of Th cells and then focused on the roles of E3s- and DUBs-mediated ubiquitin modification or demodification in regulating Th cell differentiation.