Allergens induce upregulated IL-18 and IL-18Rα expression in blood Th2 and Th17 cells of patients with allergic asthma.

Allergic asthma (AA) is closely associated with the polarization of T helper (Th)2 and Th17 cells. Interleukin (IL)-18 acts as an inducer of Th2 and Th17 cell responses. However, expressions of IL-18 and IL-18 receptor alpha (IL-18Rα) in blood Th2 and Th17 cells of patients with AA remain unclear. We therefore investigated their expressions in Th2 and Th17 cells using flow cytometric analysis, quantitative real-time PCR (qPCR), and murine AA model. We observed increased proportions of Th2, Th17, IL-18+, IL-18+ Th2, and IL-18+ Th17 cells in blood CD4+ T cells of patients with AA. Additionally, house dust mite seemed to upregulate further IL-18 expression in Th2 and Th17, and upregulate IL-18Rα expression in CD4+ T, Th2, and Th17 cells of AA patients. It was also found that the plasma levels of IL-4, IL-17A, and IL-18 in AA patients were elevated, and they were correlated between each other. In ovalbumin (OVA)-induced asthma mouse (AM), we observed that the percentages of blood CD4+ T, Th2, and Th17 cells were increased. Moreover, OVA-induced AM expressed higher level of IL-18Rα in blood Th2 cells, which was downregulated by IL-18. Increased IL-18Rα expression was also observed in blood Th2 cells of OVA-induced FcεRIα-/- mice. Collectively, our findings suggest the involvement of Th2 cells in AA by expressing excessive IL-18 and IL-18Rα in response to allergen, and that IL-18 and IL-18Rα expressing Th2 cells are likely to be the potential targets for AA therapy.

An analysis of differences in Carbapenem-resistant Enterobacterales in different regions: a multicenter cross-sectional study.

OBJECTIVE: This study aimed to explore the characteristics of carbapenem-resistant Enterobacterales (CRE) patients in the intensive care unit (ICU) in different regions of Henan Province to provide evidence for the targeted prevention and treatment of CRE. METHODS: This was a cross-sectional study. CRE screening was conducted in the ICUs of 78 hospitals in Henan Province, China, on March 10, 2021. The patients were divided into provincial capital hospitals and nonprovincial capital hospitals for comparative analysis. RESULTS: This study involved 1009 patients in total, of whom 241 were CRE-positive patients, 92 were in the provincial capital hospital and 149 were in the nonprovincial capital hospital. Provincial capital hospitals had a higher rate of CRE positivity, and there was a significant difference in the rate of CRE positivity between the two groups. The body temperature; immunosuppressed state; transfer from the ICU to other hospitals; and use of enemas, arterial catheters, carbapenems, or tigecycline at the provincial capital hospital were greater than those at the nonprovincial capital hospital (P < 0.05). However, there was no significant difference in the distribution of carbapenemase strains or enzymes between the two groups. CONCLUSIONS: The detection rate of CRE was significantly greater in provincial capital hospitals than in nonprovincial capital hospitals. The source of the patients, invasive procedures, and use of advanced antibiotics may account for the differences. Carbapenem-resistant Klebsiella pneumoniae (CR-KPN) was the most prevalent strain. Klebsiella pneumoniae carbapenemase (KPC) was the predominant carbapenemase enzyme. The distributions of carbapenemase strains and enzymes were similar in different regions.

circFLNA promotes intestinal injury during abdominal sepsis through Fas-mediated apoptosis pathway by sponging miR-766-3p.

BACKGROUND: Intra-abdominal infections are the second most common cause of sepsis in the intensive care unit. Intestinal epithelial injury due to abdominal sepsis results in a variety of pathological changes, such as intestinal bacteria and toxins entering the blood, leading to persistent systemic inflammation and multiple organ dysfunction. The increased apoptosis of intestinal epithelial cells induced by sepsis further exacerbates the progression of sepsis. Although several studies have revealed that circRNAs are involved in intestinal epithelial injury in sepsis, few studies have identified the roles of circRNAs in intestinal epithelial apoptosis. METHODS: We used laser capture microdissection to obtain purified epithelial cells located in intestinal crypts from four patients with abdominal sepsis induced by intestinal perforation and four samples from age and sex-matched non-septic patients. Microarray analysis of circRNAs was conducted to assess differentially expressed circRNAs between patients with and without sepsis. Lastly, in vitro and in vivo assays were performed to study the mechanism of circFLNA in intestinal epithelial apoptosis during sepsis. RESULTS: circFLNA was upregulated in the intestinal epithelium after abdominal sepsis induced by intestinal perforation. Inhibition of miR-766-3p impaired si-circFLNA-mediated inhibition of apoptosis and inflammation factor levels in lipopolysaccharide (LPS)-treated HIEC-6 cells. circFLNA aggravated apoptosis and inflammation through the Fas-mediated apoptosis pathway in both LPS-treated HIEC-6 cells and a mouse cecal ligation and puncture model. CONCLUSION: Our findings showed that circFLNA promotes intestinal injury in abdominal sepsis through the Fas-mediated apoptosis pathway by sponging miR-766-3p. The circFLNA/miR-766-3p/Fas axis has potential as a novel therapeutic target for treating intestinal injury in sepsis.

The Epidemiology of Sepsis in Chinese ICUs: A National Cross-Sectional Survey.

OBJECTIVES: We performed a national cross-sectional survey to determine the epidemiologic characteristics of patients with sepsis in ICU in China. DESIGN: A cross-section survey study. SETTING: Forty-four hospitals in mainland China from December 1, 2015, to January 31, 2016. PATIENTS: All septic patients diagnosed according sepsis-1 criteria admitted to participating ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We recorded demographic, physiologic, and microbiological data with follow-up for 90 days or death, if sooner. The frequency of sepsis and 90-day mortality rate were computed, and the relationship with gross domestic product determined. Multivariate logistic regression analysis was used to determine risk factors for 90-day mortality in patients with sepsis. Two-thousand three-hundred twenty-two patients with sepsis were included in the analysis, of whom 786 patients (33.9%) had hospital-acquired sepsis. The most common infection site was the lung (68.2%), followed by abdomen (26.6%) and bloodstream (7.8%). The frequency of sepsis in the ICU was 20.6 cases per 100 ICU admissions (95% CI, 15.8-25.4) with a 90-day mortality of 35.5%. The proportion of sepsis, severe sepsis, and septic shock were 3.10%, 43.6%, and 53.3% with a 90-day mortality of 2.78%, 17.69%, and 51.94%, respectively. Older age, low body weight, higher Sequential Organ Failure Assessment score, the number of systemic inflammatory response syndrome criteria, comorbid with heart failure, hematologic cancer, immunosuppression, higher level of lactate, infection site (pneumonia and bloodstream) were associated with 90-day mortality. CONCLUSIONS: Sepsis affects a fifth of patients admitted to ICUs in mainland China with a 90-day mortality rate of 35.5%. Our findings indicate that a large burden of sepsis, and we need to focus on sepsis as a quality improvement target in China given the high mortality. In addition, further studies are needed to delineate the epidemiology of sepsis outside the ICU.

The Current Epidemiological Landscape of Ventilator-associated Pneumonia in the Intensive Care Unit: A Multicenter Prospective Observational Study in China.

Background: Ventilator-associated pneumonia (VAP) is among the most important hospital-acquired infections in the intensive-care unit setting. However, clinical data regarding the epidemiology of VAP in China are limited. Methods: A multicenter, longitudinal, observational study was performed from March 2013 to December 2015 to prospectively collect data on patients diagnosed with VAP. Specifically, patients supported by invasive mechanical ventilation for longer than 48 hours were included. Clinical data were recorded for each VAP patient. The exact pathogen distribution and the incidence of VAP were calculated. Risk factors associated with mortality were analyzed using univariate and multivariate regression analyses. Results: A total of 2492 patients received mechanical ventilation for longer than 48 hours and were enrolled in the study. A total of 129 (5.0%) patients fulfilled the VAP criteria, and 38 (29.5%) patients were diagnosed with early-onset VAP. The incidence of VAP was 4.5 per 1000 ventilation days, with a 28-day mortality rate of 45%. Individual pathogens, including 115 bacteria and 2 fungi, were identified in 117 (90.7%) enrollees, and 87 (75.7%) bacteria were multidrug-resistant organisms. Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most commonly detected pathogens causing VAP. No difference in the distribution of pathogens was observed between early- and late-onset VAP or between surviving and non-surviving patients. Multivariate regression revealed that older ages and Sequential Organ Failure Assessment Scores were correlated with increased 28-day mortality rates. Conclusions: High pathogen resistance and mortality were found in both early- and late-onset VAP. Clinical Trials Registration: NCT01943331.

Enteral nutrition feeding in Chinese intensive care units: a cross-sectional study involving 116 hospitals.

BACKGROUND: There is a lack of large-scale epidemiological data on the clinical practice of enteral nutrition (EN) feeding in China. This study aimed to provide such data on Chinese hospitals and to investigate factors associated with EN delivery. METHODS: This cross-sectional study was launched in 118 intensive care units (ICUs) of 116 mainland hospitals and conducted on April 26, 2017. At 00:00 on April 26, all patients in these ICUs were included. Demographic and clinical variables of patients on April 25 were obtained. The dates of hospitalization, ICU admission and nutrition initiation were reviewed. The outcome status 28 days after the day of investigation was obtained. RESULTS: A total of 1953 patients were included for analysis, including 1483 survivors and 312 nonsurvivors. The median study day was day 7 (IQR 2-19 days) after ICU entry. The proportions of subjects starting EN within 24, 48 and 72 h after ICU entry was 24.8% (84/352), 32.7% (150/459) and 40.0% (200/541), respectively. The proportion of subjects receiving > 80% estimated energy target within 24, 48, 72 h and 7 days after ICU entry was 10.5% (37/352), 10.9% (50/459), 11.8% (64/541) and 17.8% (162/910), respectively. Using acute gastrointestinal injury (AGI) 1 as the reference in a Cox model, patients with AGI 2-3 were associated with reduced likelihood of EN initiation (HR 0.46, 95% CI 0.353-0.599; p < 0.001). AGI 4 was significantly associated with lower hazard of EN administration (HR 0.056; 95% CI 0.008-0.398; p = 0.004). In a linear regression model, greater Sequential Organ Failure Assessment scores (coefficient - 0.002, 95% CI - 0.008 to - 0.001; p = 0.024) and male gender (coefficient - 0.144, 95% CI - 0.203 to - 0.085; p < 0.001) were found to be associated with lower EN proportion. As compared with AGI 1, AGI 2-3 was associated with lower EN proportion (coefficient - 0.206, 95% CI - 0.273 to - 0.139; p < 0.001). CONCLUSIONS: The study showed that EN delivery was suboptimal in Chinese ICUs. More attention should be paid to EN use in the early days after ICU admission.

Invasive candidiasis in intensive care units in China: in vitro antifungal susceptibility in the China-SCAN study.

OBJECTIVES: The objectives of this study were to determine species distribution and in vitro antifungal susceptibility of Candida isolates identified in the multicentre China-SCAN study of invasive Candida infection (ICI) in intensive care units (ICUs) across China. METHODS: Candida isolates from patients in the China-SCAN study with documented ICI were evaluated by a central laboratory. Species were identified using chromogenic culture media or the API 20C AUX kit. Susceptibility to fluconazole, voriconazole, itraconazole, caspofungin and amphotericin B was determined using the CLSI broth microdilution method (M27-A3) and updated clinical breakpoints or epidemiological cut-off values. RESULTS: A total of 389 isolates from 244 patients were analysed. Species identified most frequently were Candida albicans (40.1%), Candida parapsilosis (21.3%), Candida tropicalis (17.2%) and Candida glabrata (12.9%). Rarer species such as Lodderomyces elongisporus and Candida ernobii were also identified. Fluconazole susceptibility was evident in 85.9% (134/156) of C. albicans, 62.7% (42/67) of C. tropicalis and 48.2% (40/83) of C. parapsilosis isolates. Susceptibility to voriconazole was ≥ 90% among all species. All isolates were susceptible to amphotericin B and caspofungin except C. glabrata [86.0% (43/50) susceptible to caspofungin]. Cross-resistance between fluconazole and voriconazole was observed for C. parapsilosis and C. glabrata. CONCLUSIONS: Although C. albicans was the predominant single species, non-albicans species constituted >50% of isolates. Fluconazole susceptibility was lower in most non-albicans species, indicating that fluconazole resistance should be closely monitored. Susceptibility to voriconazole, amphotericin B and caspofungin is encouraging. Differences between these data and those from other regions emphasize the importance of assessing regional variations.

Catheter-related Candida bloodstream infection in intensive care unit patients: a subgroup analysis of the China-SCAN study.

BACKGROUND: In patients hospitalized in intensive care units (ICU), Candida infections are associated with increased morbidity, mortality and costs. However, previous studies reported confused risk factors for catheter-related Candida bloodstream infection (CRCBSI). The objective was to describe the risk factors, microbiology, management and outcomes of CRCBSI in the China-SCAN population. METHODS: Patients with ≥1 Candida-positive peripheral blood culture were selected from the China-SCAN study. Peripheral and catheter blood samples were collected for Candida isolation. Patients with the same strain of Candida in peripheral and catheter blood samples were considered as being with CRCBSI, while patients with Candida-positive peripheral blood cultures only or different strains were considered as non-CRCBSI. Data were collected from the China-SCAN study. RESULTS: CRCBSI incidence in ICU was 0.03% (29/96,060), accounting for 9.86% of all candidemia observed in ICU (29/294). The proportion of CRCBSI due to Candida parapsilosis reached 33.3%, more than that of Candida albicans (28.6%). In univariate analyses, older age (P=0.028) and lower body weight (P=0.037) were associated with CRCBSI. Multivariate analysis showed that the sequential organ failure assessment (SOFA) score was independently associated with CRCBSI (odds ratio (OR)=1.142, 95% confidence interval = 1.049-1.244, P=0.002). Catheter removal and immune enhancement therapy were often used for CRCBSI treatment. CONCLUSIONS: In China, CRCBSI was more likely to occur in old patients with low body weight. SOFA score was independently associated with CRCBSI. Candida parapsilosis accounted for a high proportion of CRCBSI, but the difference from non-CRCBSI was not significant.

[Research progress of ICU-acquired weakness].

ICU-acquired weakness (ICU-AW) is a common complication in the intensive care unit (ICU). The occurrence of ICU-AW directly leads to prolonged ICU stays for critically ill patients, and in severe cases, it continues to affect their quality of life even after discharge. This article provides a comprehensive review of the research progress on ICU-AW based on domestic and foreign studies, aiming to provide a scientific overview of ICU-AW, including its definition, pathophysiology, diagnosis, screening tools, influencing factors, and potential intervention strategies, so as to promote timely planning and implementation of relevant screening and intervention measures.

Invasive candidiasis in intensive care units in China: a multicentre prospective observational study.

OBJECTIVES: To describe the epidemiology, microbiology and management of invasive Candida infection (ICI) in intensive care units (ICUs) in China. METHODS: A multicentre, prospective, observational study in 67 hospital ICUs across China. Patients were ≥18 years old with clinical signs of infection and at least one of the following diagnostic criteria: (i) histopathological, cytopathological or microscopic confirmation of yeast cells from a normally sterile site; (ii) at least one peripheral blood culture positive for Candida; and (iii) positive Candida culture from a normally sterile site. The China-SCAN study is registered with ClinicalTrials.gov (NCT T01253954). RESULTS: ICI incidence was 0.32% (306 patients/96,060 ICU admissions) and median time between ICU admission and diagnosis was 10.0 days. Candida albicans was the most prevalent single isolate (41.8% of patients), although non-albicans species accounted for the majority of infections. Diagnostic confirmation was based solely on at least one positive blood culture in 290 (94.8%) cases. Treatment was initiated after diagnostic confirmation in 166/268 (61.9%) patients. Triazoles (62.7%) and echinocandins (34.2%) were the most commonly used antifungal agents; first-line therapy was typically fluconazole (37.7%). The median duration of antifungal therapy was 14 days. The mortality rate was 36.6% (112/306); the median time between diagnosis and death was 14.5 days. Mortality was higher in older individuals, those with solid tumours, those with recent invasive mechanical ventilation and those with a higher sequential organ failure assessment score at diagnostic confirmation. Susceptibility to first-line antifungals was associated with lower mortality than dose-dependent susceptibility or complete resistance (P=0.008). CONCLUSIONS: More infections were caused by non-albicans than Candida albicans strains. The majority of patients were treated only after diagnostic confirmation, rather than empirically. First-line antifungal susceptibility was associated with lower mortality.

[Upregulation of IL-18 expression in blood CD4+ Th2 cells of patients with allergic rhinitis].

Objective To investigate the expressions of IL-18, IL-18 binding protein isoform a (IL-18BPa) and IL-18 receptor α (IL-18Rα) in blood CD4+ Th2 cells of patients with allergic rhinitis (AR) and the effects of allergens on their expressions. Methods Blood samples of AR patients and healthy control subjects (HCs) were collected. Peripheral blood mononuclear cells (PBMCs) and CD4+ T cells sorted by immunomagnetic beads were stimulated by crude extract of Artemisia sieversiana wild allergen (ASWE), Platanus pollen (PPE) and house dust mite extract (HDME). Flow cytometry was used to detect the expression of IL-18, IL-18BPa and IL-18Rα in CD4+ Th2 cells, and BioPlex was used to detect the level of plasma IL-4 and analyze its correlation with the proportion of IL-18+ Th2 cells. Results Compared with HCs, the proportion of IL-18+ cells was increased in Th2 cells of AR patients; MFI of IL-18 was increased, while that of IL-18Rα was decreased. Moreover, allergens induced IL-18 and IL-18Rα expression in sorted CD4+ Th2 cells of HCs and induced IL-18Rα in that of AR patients. Additionally, elevated plasma IL-4 level was found in AR patients, which was moderately correlated with the percentage of IL-18+ Th2 cells. Conclusion Allergens may be involved in the pathogenesis of AR by inducing expression of IL-18 in peripheral blood CD4+ Th2 cells.

Association of lymphopenia and RDW elevation with risk of mortality in acute aortic dissection.

OBJECTIVE: The study aimed to investigate whether lymphopenia and red blood cell distribution width (RDW) elevation are associated with an increased risk of mortality in acute aortic dissection (AAD). METHODS: This multicenter retrospective cohort study enrolled patients diagnosed with AAD by aortic computed tomographic angiography (CTA) from 2010 to 2021 in five teaching hospitals in central-western China. Cox proportional hazards regression and Kaplan-Meier curves were used in univariable and multivariable models. Clinical outcomes were defined as all-cause in-hospital mortality, while associations were evaluated between lymphopenia, accompanied by an elevated RDW, and risk of mortality. RESULTS: Of 1903 participants, the median age was 53 (interquartile range [IQR], 46-62) years, and females accounted for 21.9%. Adjusted increased risk of mortality was linearly related to the decreasing lymphocyte percentage (P-non-linearity = 0.942) and increasing RDW (P-non-linearity = 0.612), and per standard deviation (SD) of increment lymphocyte percentage and RDW was associated with the 26% (0.74, 0.64-0.84) decrement and 5% (1.05, 0.95-1.15) increment in hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality, respectively. Importantly, lymphopenia and elevation of RDW exhibited a significant interaction with increasing the risk of AAD mortality (P-value for interaction = 0.037). CONCLUSIONS: Lymphopenia accompanied by the elevation of RDW, which may reflect the immune dysregulation of AAD patients, is associated with an increased risk of mortality. Assessment of immunological biomarkers derived from routine tests may provide novel perspectives for identifying the risk of mortality.

[Effect of continuous renal replacement therapy on plasma concentration, clinical efficacy and safety of colistin sulfate].

OBJECTIVE: To investigate the effects of continuous renal replacement therapy (CRRT) on plasma concentration, clinical efficacy and safety of colistin sulfate. METHODS: Clinical data of patients received with colistin sulfate were retrospectively analyzed from our group's previous clinical registration study, which was a prospective, multicenter observation study on the efficacy and pharmacokinetic characteristics of colistin sulfate in patients with severe infection in intensive care unit (ICU). According to whether patients received blood purification treatment, they were divided into CRRT group and non-CRRT group. Baseline data (gender, age, whether complicated with diabetes, chronic nervous system disease, etc), general data (infection of pathogens and sites, steady-state trough concentration, steady-state peak concentration, clinical efficacy, 28-day all-cause mortality, etc) and adverse event (renal injury, nervous system, skin pigmentation, etc) were collected from the two groups. RESULTS: A total of 90 patients were enrolled, including 22 patients in the CRRT group and 68 patients in the non-CRRT group. (1) There was no significant difference in gender, age, basic diseases, liver function, infection of pathogens and sites, colistin sulfate dose between the two groups. Compared with the non-CRRT group, the acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) were higher in the CRRT group [APACHE II: 21.77±8.26 vs. 18.01±6.34, P < 0.05; SOFA: 8.5 (7.8, 11.0) vs. 6.0 (4.0, 9.0), P < 0.01], serum creatinine level was higher [µmol/L: 162.0 (119.5, 210.5) vs. 72.0 (52.0, 117.0), P < 0.01]. (2) Plasma concentration: there was no significant difference in steady-state trough concentration between CRRT group and non-CRRT group (mg/L: 0.58±0.30 vs. 0.64±0.25, P = 0.328), nor was there significant difference in steady-state peak concentration (mg/L: 1.02±0.37 vs. 1.18±0.45, P = 0.133). (3) Clinical efficacy: there was no significant difference in clinical response rate between CRRT group and non-CRRT group [68.2% (15/22) vs. 80.9% (55/68), P = 0.213]. (4) Safety: acute kidney injury occurred in 2 patients (2.9%) in the non-CRRT group. No obvious neurological symptoms and skin pigmentation were found in the two groups. CONCLUSIONS: CRRT had little effect on the elimination of colistin sulfate. Routine blood concentration monitoring (TDM) is warranted in patients received with CRRT.

Efficacy and safety of colistin sulfate in the treatment of infections caused by carbapenem-resistant organisms: a multicenter retrospective cohort study.

Background: Polymyxins have become an important treatment option for carbapenem-resistant organisms (CRO) infections. However, there is a rare of clinical studies on colistin sulfate. This study sought to investigate the rate of clinical improvement and adverse reactions of colistin sulfate in the treatment of severe infections caused by CRO in critically ill patients and assess the factors associated with 28-day all-cause mortality. Methods: This multicenter retrospective cohort study included intensive care unit (ICU) patients who received colistin sulfate due to CRO infections during July 2021 and May 2022. The primary endpoint was clinical improvement at end of therapy. Secondary endpoints included adverse reactions bacterial clearance rate and 28-day all-cause mortality. Results: A total of 122 patients, who were included between July 2021 and May 2022, were included in this study, of whom 86 (70.5%) showed clinical improvement and 36 (29.5%) showed clinical failure. The comparison of the clinical data of the patients showed that the median sequential organ failure assessment (SOFA) score was higher in the failure group than the improvement group {9.5 [7, 11] vs. 7 [4, 9], P=0.002}, the proportion of patients receiving extracorporeal membrane oxygenation (ECMO) was higher in the failure group than the improvement group (27.8% vs. 12.8%, P=0.046), and the median duration of treatment was longer in the improvement group than the failure group {12 [8, 15] vs. 5.5 [4, 9.75], P<0.001}. A total of 5 (4.1%) patients suffered from acute kidney injury due to increases in creatinine during colistin sulfate treatment. The Cox regression survival analysis showed that the SOFA score [hazards ratio (HR) =1.198, P=0.001], ECMO treatment (HR =2.373, P=0.029), and duration of treatment (HR =0.736, P<0.001) were independently associated with 28-day all-cause mortality. Conclusions: Colistin sulfate is a reasonable choice for the treatment of CRO infections in the current treatment options are limited. The possible kidney injury caused by the colistin sulfate requires intensive monitoring.

Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis: The EXIT-SEP Randomized Clinical Trial.

Importance: Previous research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis. Objective: To determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis. Design, Setting, and Participants: The Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022. Interventions: The patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days. Main Outcomes and Measures: The primary outcome was 28-day mortality. Results: Among the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group. Conclusions and Relevance: In this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03238742.

[Application of quality function deployment technology in extracorporeal membrane oxygenation treatment of patients with critical cardiopulmonary disease].

OBJECTIVE: To accurately and effectively identify the most critical needs of extracorporeal membrane oxygenation (ECMO) treatment for patients with severe cardiopulmonary diseases, and to better carry out continuous improvement of medical service quality an patients' satisfaction. METHODS: Patients who underwent ECMO and transferred from 56 medical institutions in the Henan Provincial People's Hospital Critical Care Medicine Specialist Alliance [the patients who were transported before applying quality function deployment (QFD) from June 2017 to May 2018 were enrolled as the control group, and patients who were transported after applying QFD from June 2018 to May 2019 were the observation group], medical staff in the alliance hospitals, ECMO transfer teams and transfer driver teams were enrolled as the subjects of the survey. QFD was applied to convert the collected requirements into quality improvement elements for targeted improvement measures. RESULTS: A total of 125 questionnaires were distributed in this survey, and 116 valid questionnaires were collected, including 91 from patients (including 27 from the control group and 64 from the observation group), 10 from the medical staff of the alliance hospitals, 10 from the ECMO transport teams and 5 from the transport driver teams. The questionnaire recovery rate was 92.8%. The improvement elements of ECMO treatment for patients with critical cardiopulmonary diseases were ranked according to the importance, and the top five were as follows: the accuracy of the first diagnosis, the specialization of ECMO team, the guarantee of vehicle safety, the seamless responses, and the smooth coordinated rescue protocol. CONCLUSIONS: The top five improvement elements should be prioritized in ECMO treatment of patients with critical cardiopulmonary disease in all hospitals of the Alliance to ensure more accurate and timely treatment.

[Diagnostic accuracy of muscle ultrasound and plasma monocyte chemoattractant protein-1 for ICU-acquired weakness in patients with sepsis].

OBJECTIVE: To explore the diagnostic accuracy of muscle ultrasound and plasma monocyte chemoattractant protein-1 (MCP-1) for ICU-acquired weakness (ICU-AW) in patients with sepsis. METHODS: A prospective observational study was conducted. Patients with sepsis admitted to the intensive care unit (ICU) of Henan Provincial People's Hospital from April 2021 to October 2021 were enrolled. The demographic data were collected. The enrolled patients were evaluated with Medical Research Council (MRC) score every day until discharged from ICU. During this period, patients with total MRC score < 48 (for two consecutive times and a time interval of 24 hours) were divided into ICU-AW group, those with total MRC score ≥ 48 were served as non-ICU-AW group. On the 1st, 4th and 7th day following admission into ICU, ultrasound was used to measure the muscle linear thickness of the rectus femoris (RF-MLT), the cross sectional area of the rectus femoris (RF-CSA) and the muscle linear thickness of the vastus intermedius muscle (VI-MLT). And meanwhile, the plasmas samples of patients were collected to measure MCP-1 concentration by enzyme-linked immunosorbent assay (ELISA). The difference of each index was compared between the ICU-AW group and the non-ICU-AW group. The risk factors of ICU-AW in patients with sepsis were analyzed by binary Logistic regression. Besides, receiver operator characteristic curve (ROC curve) was plotted, the diagnostic value of ultrasound parameters and plasma MCP-1 level for ICU-AW in patients with sepsis was analyzed. RESULTS: A total of 99 septic patients were enrolled, with 68 patients in the ICU-AW group and 31 patients in the non-ICU-AW group. Compared with the patients in the ICU-AW group, the patients in the non-ICU-AW group tended to be older, and had higher sequential organ failure assessment (SOFA) score, higher acute physiology and chronic health evaluation II (APACHE II) score, higher rates of septic shock, higher blood lactic acid and lower Glasgow coma score (GCS). Binary Logistic regression analysis showed that APACHE II score and septic shock were the risk factors of ICU-AW for septic patients [odds ratio (OR) and 95% confidence interval (95%CI) were 1.310 (1.138-1.509) and 0.232 (0.072-0.746), respectively, both P < 0.05]. The RF-MLT, RF-CSA and VI-MLT on the 1st, 4th and 7th ICU day was falling over time. Compared with the patients in the ICU-AW group, the patients in the non-ICU-AW group had smaller RF-MLT on the 7th day [cm: 0.32 (0.22, 0.47) vs. 0.45 (0.34, 0.63), P < 0.05] and higher 7-day RF-CSA atrophy rate [25.85% (10.37%, 34.28%) vs. 11.65% (2.28%, 22.41%), P < 0.05]. According to ROC curve analysis, 7-day RF-MLT had diagnostic value for ICU-AW of septic patients. Area under ROC curve (AUC) was 0.688 (95%CI was 0.526-0.849); when the cut-off value was 0.41 cm, the sensitivity and the specificity were 66.7% and 68.4%. The levels of plasma MCP-1 in the ICU-AW group were significantly higher than those in the non-ICU-AW group on the 1st, 4th and 7th day. ROC curve analysis showed that the plasma MCP-1 levels on the 1st, 4th and 7th day played a significant role to diagnose ICU-AW for septic patients, the AUC and 95%CI were 0.732 (0.629-0.836), 0.865 (0.777-0.953), 0.891 (0.795-0.986), respectively. When the cut-off values were 206.3, 410.9, 239.5 ng/L, the sensitivity was 87.1%, 64.0%, 82.4%, and the specificity was 54.4%, 96.1%, 86.2%, respectively. CONCLUSIONS: The muscle mass parameters on the 7th day of bedside ultrasound and plasma MCP-1 levels had certain diagnostic values for ICU-AW in patients with sepsis.

Impact of satellite blood culture on early diagnosis of sepsis.

Background: The aim of this study was to assess whether satellite blood culture (SBC) can improve turnaround times, antibiotic switching, and patient prognosis, relative to laboratory blood culture (LBC).  . Methods: Patients with sepsis treated in the intensive care units (ICUs) of Henan Provincial People's Hospital from February 5, 2018 to January 19, 2019 who met the inclusion criteria were recruited to the study and divided into the SBC group and LBC group according to different blood culture methods. Patient demographics, blood culture, antibiotic adjustment, and prognosis data were collected and compared between the two groups.  . Results: A total of 204 blood culture sets from 52 ICU patients, including 100 from the medical microbiology LBC group and 104 from the SBC group, were analyzed in this study. There was no significant difference in the positive rates between the two groups. Time from specimen collection to incubation was significantly shorter in the SBC group than that in the LBC group (1.65 h vs. 3.51 h, z=-4.09, P<0.001). The median time from specimen collection to notification of blood culture positivity was 24.83 h in the SBC group and 27.83 h in the LBC group. Median times from adjustment of antibiotics according to the first report were 26.05 h and 51.71 h in the SBC and LBC groups, respectively, while those according to the final report were 97.17 h and 111.45 h, respectively. Median ICU lengths of stay were 15.00 days and 17.00 days in the SBC and LBC groups, respectively, and median ICU lengths of stay were 18.00 days and 23.50 days, respectively. Mean hospitalization costs were 157.99 and 186.73 thousand yuan in the SBC and LBC groups, respectively.  . Conclusion: SBC can significantly reduce blood culture turnaround times; however, there were no significant differences between the two blood culture methods in initial reporting of positive cultures, time to adjustment of antibiotic therapy, or medical costs, despite a trend toward improvement.

Erratum to "Impact of satellite blood culture on early diagnosis of sepsis" [Journal of Intensive Medicine volume 2 (2022) 56-60].

[This corrects the article DOI: 10.1016/j.jointm.2021.11.003.].

MiR-6511b-5p suppresses metastasis of pMMR colorectal cancer through methylation of CD44 by directly targeting BRG1.

PURPOSE: Distal metastases are a major cause of poor prognosis in colorectal cancer patients. Approximately 95% of metastatic colorectal cancers are defined as DNA mismatch repair proficient (pMMR). Our previous study found that miR-6511b-5p was downregulated in pMMR colorectal cancer. However, the mechanism of miR-6511b-5p in pMMR colorectal cancer metastases remain unclear. METHODS: We first used quantitative real-time PCR to evaluate the role of miR-6511b-5p in colorectal cancer. Second, we conducted invasion assays and wound healing assays to investigate the role of miR-6511b-5p and CD44 in colorectal cancer cells metastases. Third, luciferase reporter assay, in situ hybridization (ISH), and immunohistochemistry assays were performed to study the relationship between miR-6511b-5p and BRG1. Finally, real-time quantitative PCR, immunohistochemistry, and chromatin immunoprecipitation (ChIP) assays were performed to analyze the relationship between BRG1 and CD44 in colorectal cancer. RESULTS: We found that lower expression of miR-6511b-5p appeared more often in pMMR colorectal cancer patients compared with dMMR (mismatch repair deficient) cases, and was positively correlated with metastases. In vitro, overexpression of miR-6511b-5p inhibited metastasis by decreasing CD44 expression via directly targeting BRG1 in colorectal cancer. Furthermore, BRG1 knockdown decreased the expression of CD44 by promoting CD44 methylation in colorectal cancer cells. CONCLUSION: Our data suggest that miR-6511b-5p may act as a promising biomarker and treatment target for pMMR colorectal cancer, particularly in metastatic patients. Mechanistically, miR-6511b-5p suppresses invasion and migration of colorectal cancer cells through methylation of CD44 via directly targeting BRG1.