Therapeutic drug monitoring of polymyxin B cerebrospinal fluid concentrations in patients with carbapenem-resistant Gram-negative bacteria-induced central nervous system infection.

OBJECTIVES: Central nervous system (CNS) infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) present a major health and economic burden worldwide. This multicentre prospective study aimed to assess the feasibility and usefulness of CSF therapeutic drug monitoring (TDM) after intrathecal/intraventricular administration of polymyxin B in patients with CNS infections. METHODS: Forty-two patients treated with intrathecal/intraventricular administration of polymyxin B against CR-GNB-induced CNS infections were enrolled. CSF trough level (Cmin) was collected beginning on Day 2 post-polymyxin B initiation and thereafter. The primary outcomes were clinical cure and 28-day all-cause mortality. RESULTS: All patients started with intrathecal/intraventricular administration of polymyxin B at a dose of 5 g/day, corresponding to a median CSF Cmin of 2.93 mg/L (range, 0.21-25.74 mg/L). Clinical cure was 71.4%, and the median CSF Cmin of this group was higher than that of clinical failure group [3.31 (IQR, 1.73-5.62) mg/L versus 2.25 (IQR, 1.09-4.12) mg/L; P = 0.011]. In addition, with MICs ≤ 0.5 mg/L, maintaining polymyxin B CSF Cmin above 2.0 mg/L showed a higher clinical cure rate (P = 0.041). The 28-day all-cause mortality rate was 31.0% and had no association with CSF Cmin. CONCLUSIONS: After intrathecal/intraventricular administration of polymyxin B, CSF concentrations fluctuated considerably inter- and intra-individual. Polymyxin B CSF Cmin above 2.0 mg/L was associated with clinical cure when MICs were ≤ 0.5 mg/L, and the feasibility of TDM warrants additional clinical studies.

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.

Polymyxin B therapy based on therapeutic drug monitoring in carbapenem-resistant organisms sepsis: the PMB-CROS randomized clinical trial.

BACKGROUND: The appropriate administration regimen of polymyxin B is yet controversial. The present study aimed to explore the optimal dose of polymyxin B under therapeutic drug monitoring (TDM) guidance. METHODS: In China's Henan province, 26 hospitals participated in a randomized controlled trial. We included patients with sepsis caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) susceptible to polymyxin B. The patients were randomly divided into a high-dose (HD) group or a low-dose (LD) group and received 150 mg loading dose, 75 mg every 12 h and 100 mg loading dose, 50 mg every 12 h, respectively. TDM was employed to determine if the dose of polymyxin B needs adjustment based on the area under the concentration-time curve across 24 h at a steady state (ssAUC0-24) of 50-100 mg h/L. The primary outcome was the 14-day clinical response, and the secondary outcomes included 28- and 14-day mortality. RESULTS: This trial included 311 patients, with 152 assigned to the HD group and 159 assigned to the LD group. Intention-to-treat analysis showed that the 14-day clinical response was non-significant (p = 0.527): 95/152 (62.5%) in the HD group and 95/159 (59.7%) in the LD group. Kaplan-Meier's 180-day survival curve showed survival advantage in the HD group than in the LD group (p = 0.037). More patients achieved the target ssAUC0-24 in the HD than in the LD group (63.8% vs. 38.9%; p = 0.005) and in the septic shock subgroup compared to all subjects (HD group: 71.4% vs. 63.8%, p = 0.037; LD group: 58.3% vs. 38.9%, p = 0.0005). Also, the target AUC compliance was not correlated with clinical outcomes but with acute kidney injury (AKI) (p = 0.019). Adverse events did not differ between the HD and LD groups. CONCLUSION: A fixed polymyxin B loading dose of 150 mg and a maintenance dose of 75 mg every 12 h was safe for patients with sepsis caused by CR-GNB and improves long-term survival. The increased AUC was associated with increased incidence of AKI, and TDM results were valued to prevent AKI. Trial registration Trial registration ClinicalTrials.gov: ChiCTR2100043208, Registration date: January 26, 2021.

Relapse factors of patients of anti-N-methyl-D-aspartate receptor encephalitis.

BACKGROUND: The factors associated with anti-N-methyl-D-aspartate (NMDA) receptor encephalitis relapse are yet to be elucidated. AIMS OF THE STUDY: To investigate the factors associated with relapse and prognosis of anti-NMDA receptor encephalitis. METHODS: This retrospective study included patients diagnosed with anti-NMDA receptor encephalitis admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to October 2019. The clinical features, auxiliary examinations, treatment regimens, and follow-up were recorded. The outcomes were relapse and 2-year disease prognosis. RESULTS: A total of 160 patients were included. Consequently, 6 (5%) deaths, 34 (25.4%) relapses, and 19 (15.2%) patients had a poor prognosis (modified Rankin score (mRS) ≥3) were recorded. The multivariable analyses showed that age (p = .011), abnormal magnetic resonance imaging (MRI) (p = .019), glucocorticoid pulse (p = .009), and intracranial pressure (p = .023) were independently associated with the relapse, while age (p = .030) and central hypoventilation (p = .020) were independently associated with a poor prognosis at 2 years. CONCLUSION: Glucocorticoid pulse therapy reduces the relapse of anti-NMDA receptor encephalitis. Age, abnormal MRI, and intracranial pressure are risk factors for relapse, while age and central hypoventilation are independently associated with poor prognosis.

An area under the concentration-time curve threshold as a predictor of efficacy and nephrotoxicity for individualizing polymyxin B dosing in patients with carbapenem-resistant gram-negative bacteria.

BACKGROUND: Evidence supports therapeutic drug monitoring of polymyxin B, but clinical data for establishing an area under the concentration-time curve across 24 h at steady state (AUCss,24 h) threshold are still limited. This study aimed to examine exposure-response/toxicity relationship for polymyxin B to establish an AUCss,24 h threshold in a real-world cohort of patients. METHODS: Using a validated Bayesian approach to estimate AUCss,24 h from two samples, AUCss,24 h threshold that impacted the risk of polymyxin B-related nephrotoxicity and clinical response were derived by classification and regression tree (CART) analysis and validated by Cox regression analysis and logical regression analysis. RESULTS: A total of 393 patients were included; acute kidney injury (AKI) was 29.0%, clinical response was 63.4%, and 30-day all-cause mortality was 35.4%. AUCss,24 h thresholds for AKI of > 99.4 mg h/L and clinical response of > 45.7 mg h/L were derived by CART analysis. Cox and logical regression analyses showed that AUCss,24 h of > 100 mg h/L was a significant predictor of AKI (HR 16.29, 95% CI 8.16-30.25, P < 0.001) and AUCss,24 h of ≥ 50 mg h/L (OR 4.39, 95% CI 2.56-7.47, P < 0.001) was independently associated with clinical response. However, these exposures were not associated with mortality. In addition, the correlation between trough concentration (1.2-2.8 mg/L) with outcomes was similar to AUCss,24 h. CONCLUSIONS: For critically ill patients, AUCss,24 h threshold of 50-100 mg h/L was associated with decreased nephrotoxicity while assuring clinical efficacy. Therapeutic drug monitoring is recommended for individualizing polymyxin B dosing.

Association between intake of sweetened beverages with all-cause and cause-specific mortality: a systematic review and meta-analysis.

BACKGROUND: Conclusions remain controversial between the consumption of sugar and artificially sweetened beverages (SSBs and ASBs) and mortality. METHODS: We systematically searched the PubMed, Embase, Cochrane Library and Web of Science databases from their inception date to 1st January 2020, prospective cohort studies researching the mortality risk and SSBs or ASBs consumption were included. Random effects meta-analyses and dose-response analyses were performed to measure the association. Subgroup analyses and sensitivity analyses were further performed to explore the source of heterogeneity. Publication bias was assessed by Funnel plots and Egger's regression test. RESULTS: Across all 15 cohorts, 1211 470 participants were included. High SSB consumption was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.06-1.19, P < 0.001; and cardiovascular disease [CVD] mortality [HR 1.20, 95% CI, 1.05-1.38, P < 0.001]), and high ASBs consumption showed similar result (HR 1.12, 95% CI, 1.04-1.21, P = 0.001 for all-cause mortality and HR 1.23, 95% CI, 1.00-1.50, P = 0.049 for CVD mortality), both showed a linear dose-response relationship. CONCLUSIONS: High consumption of both ASBs and SSBs showed significant associations with a higher risk of CVD mortality and all-cause mortality. This information may provide ideas for decreasing the global burden of diseases by reducing sweetened beverage intake.

Comparing the Population Pharmacokinetics of and Acute Kidney Injury Due to Polymyxin B in Chinese Patients with or without Renal Insufficiency.

Despite excellent bactericidal effect, dosing adjustment of polymyxin B for patients with renal insufficiency and polymyxin B-related nephrotoxicity is still a major concern to clinicians. The aim of this study was to compare the population pharmacokinetics (PK) properties of polymyxin B in Chinese patients with different renal functions and to investigate the relationship between PK parameters and polymyxin B-related acute kidney injury (AKI). A total of 37 patients with normal renal function (creatinine clearance ≥ 80 ml/min) and 33 with renal insufficiency (creatinine clearance < 80 ml/min) were included. In the two-compartment population PK models, the central compartment clearance (CL) (2.19 liters/h versus 1.58 liters/h; P < 0.001) and intercompartmental clearance (Q) (13.83 liters/h versus 10.28 liters/h; P < 0.001) values were significantly different between the two groups. The simulated values for AUC across 24 h at steady state (AUCss,24h) for patients with normal renal function were higher than those for patients with renal insufficiency. However, renal dosing adjustment of polymyxin B seemed not to be necessary. In addition, during the treatment, AKI occurred in 23 (32.86%) patients. The polymyxin B AUCss,24h in patients with AKI was significantly higher than that in patients without AKI (108.66 ± 70.10 mg · h/liter versus 66.18 ± 34.79 mg · h/liter; P = 0.001). Both the receiver operating characteristic (ROC) curve and logistic regression analysis showed that an AUCss,24h of >100 mg · h/liter was a good predictor for the probability of nephrotoxicity.

Clinical outcomes and safety of polymyxin B in the treatment of carbapenem-resistant Gram-negative bacterial infections: a real-world multicenter study.

BACKGROUND: High morbidity and mortality due to carbapenem-resistant Gram-negative bacilli (CR-GNB) has led to the resurgence of polymyxin B (PMB) use in the last decade. The aim of our multicenter, real-world study was to evaluate the effectiveness and safety of PMB in the treatment of CR-GNB infections. METHODS: The real-world study included patients treated with intravenous PMB for at least 7 days during the period of October 2018 through June 2019. Associations between these clinical features and 28-day mortality or all-cause hospital mortality were explored through univariate analyses and multivariable logistic regression. RESULTS: The study included 100 patients. Many patients presented with combined chronic conditions, septic shock, mechanical ventilation, and the presence of Klebsiella pneumoniae. The mean duration of PMB therapy was 11 days (range 7-38 days). Temperature (38 °C vs 37.1 °C), white blood cells (14.13 × 109/l vs 9.28 × 109/l), C-reactive protein (103.55 ug/l vs 47.60 ug/l), procalcitonin (3.89 ng/ml vs 1.70 ng/ml) and APACHE II levels (17.75 ± 7.69 vs 15.98 ± 7.95) were significantly decreased after PMB treatment. The bacteria eradication rate was 77.65%. The overall mortality at discharge was 15%, and 28-day mortality was 40%. Major adverse reactions occurred in 16 patients. Nephrotoxicity was observed in 7 patients (7%). CONCLUSIONS: Our results provide positive clinical and safety outcomes for PMB in the treatment of CR-GNB. Timely and appropriate use of PMB may be particularly useful in treating patients with sepsis in CR-GNB infections.

Paraquat promotes acute lung injury in rats by regulating alveolar macrophage polarization through glycolysis.

The present study investigates whether paraquat (PQ) regulates polarization of alveolar macrophages through glycolysis and promotes the occurrence of acute lung injury in rats. In vivo, the PQ intraperitoneal injection was used to construct a model of acute lung injury in rats. In vitro, the study measured the effect of different concentrations of PQ on the viability of the alveolar macrophages, and explored the polarization and glycolysis metabolism of alveolar macrophages at different time points after PQ intervention. Compared with the normal control (NC) group, the lung pathological damage in rats increased gradually after PQ poisoning, reaching a significant degree at 48 h after poisoning. The PQ-poisoned rat serum showed increased expressions of interleukin-6 (IL-6), tumor necrosis factor- α (TNF-α), and M1 macrophage marker, iNOS, while the expression of interleukin-10 (IL-10) and M2 macrophage marker, Arg1, decreased. The toxic effect of PQ on alveolar macrophages was dose- and time-dependent. Compared with the NC group, IL-6 and TNF-α in the cell supernatant gradually increased after PQ intervention, while the IL-10 content gradually decreased. The PQ intervention in alveolar macrophages increased the expression of intracellular glycolysis rate-limiting enzyme pyruvate kinase isozymes M1/M2 (PKM1/M2), lactate, lactate/pyruvate ratio, and the polarization of alveolar macrophage towards M1. Inhibition of cellular glycolysis significantly reduced the PQ-induced alveolar macrophage polarization to M1 type. Thus, PQ induced increased polarization of lung macrophages toward M1 and decreased polarization toward M2, promoting acute lung injury. Therefore, it can be concluded that PQ regulates the polarization of alveolar macrophages through glycolysis.

The association between serum adipocyte fatty acid-binding protein and 3-month disability outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Adipocyte fatty acid-binding protein (FABP4) is an adipokine that plays an important role in development of cardiovascular and metabolic diseases. The aim of this study was to assess the 3-month prognostic value of serum levels of FABP4 in Chinese patients with aneurysmal subarachnoid hemorrhage (aSAH) on hospital admission. METHODS: This was a prospective observational study from a stroke treatment center in Zhengzhou, China. From October 2016 to May 2018, patients with aSAH who were hospitalized within 24 h were included. In addition, 202 age- and gender-matched healthy volunteers were assigned to the healthy control group. At admission, serum levels of FABP4 were measured, and patients' characteristics, Hunt-Hess grade, and modified Fisher grade evaluated. At 3-month follow-up, functional outcome (Glasgow Outcome Scale score; dichotomized as poor [score 1-3] or good [score 4-5]) and all-cause mortality were recorded. Univariate and multivariate logistic regression models were used to investigate the association of FABP4 with the two endpoints. RESULTS: A total of 418 patients with aSAH were included in this study. The median age was 58 years (interquartile range, 49-66 years), and 57.9% were women. FABP4 serum levels were related to Hunt-Hess score (r[Spearman] = 0.381; P < 0.001). Patients with a poor outcome and non-survivors had significantly increased serum FABP4 levels on admission (P < 0.001 for all). In multivariate logistic regression analysis, FABP4 was an independent predictor of poor outcome and mortality, with increased risks of 7% (odds ratios 1.07, 95% confidence interval [CI] 1.02-1.13; P = 0.001) and 5% (odds ratio 1.05, 95% CI, 1.01-1.12; P = 0.003), respectively. Receiver operating characteristics to predict functional outcome and mortality were significantly different between conventional risk factors (difference area under the curve 0.024, 95% CI 0.018-0.032) and FABP4 plus conventional risk factors (area under the curve 0.015, 95%CI 0.011-0.020). After FABP4 was added to the existing risk factors, mortality was better reclassified and was associated with the net reclassification improvement statistic (P = 0.009), while poor outcome was better reclassified and associated with both the integrated discrimination improvement and net reclassification improvement statistics (P < 0.05 for all). CONCLUSIONS: Elevated serum FABP4 levels were related to poor outcome and mortality in a cohort of patients with aSAH.

Incidence and outcomes of acute respiratory distress syndrome in intensive care units of mainland China: a multicentre prospective longitudinal study.

OBJECTIVES: To evaluate the incidence and mortality of acute respiratory distress syndrome (ARDS) in medical/respiratory intensive care units (MICUs/RICUs) to assess ventilation management and the use of adjunct therapy in routine clinical practice for patients fulfilling the Berlin definition of ARDS in mainland China. METHODS: This was a multicentre prospective longitudinal study. Patients who met the Berlin definition of ARDS were included. Baseline data and data on ventilator management and the use of adjunct therapy were collected. RESULTS: Of the 18,793 patients admitted to participating ICUs during the study timeframe, 672 patients fulfilled the Berlin ARDS criteria and 527 patients were included in the analysis. The most common predisposing factor for ARDS in 402 (77.0) patients was pneumonia. The prevalence rates were 9.7% (51/527) for mild ARDS, 47.4% (250/527) for moderate ARDS, and 42.9% (226/527) for severe ARDS. In total, 400 (75.9%) patients were managed with invasive mechanical ventilation during their ICU stays. All ARDS patients received a tidal volume of 6.8 (5.8-7.9) mL/kg of their predicted body weight and a positive end-expository pressure (PEEP) of 8 (6-12) cmH2O. Recruitment manoeuvres (RMs) and prone positioning were used in 61 (15.3%) and 85 (16.1%) ventilated patients, respectively. Life-sustaining care was withdrawn from 92 (17.5%) patients. When these patients were included in the mortality analysis, 244 (46.3%) ARDS patients (16 (31.4%) with mild ARDS, 101 (40.4%) with moderate ARDS, and 127 (56.2%) with severe ARDS) died in the hospital. CONCLUSIONS: Among the 18 ICUs in mainland China, the incidence of ARDS was low. The rates of mortality and withdrawal of life-sustaining care were high. The recommended lung protective strategy was followed with a high degree of compliance, but the implementation of adjunct treatment was lacking. These findings indicate the potential for improvement in the management of patients with ARDS in China. TRIAL REGISTRATION: Clinicaltrials.gov NCT02975908 . Registered on 29 November 2016-retrospectively registered.

Adipose-derived mesenchymal stem cells ameliorate acute liver injury in rat model of CLP induced-sepsis via sTNFR1.

Sepsis is characterized as exceed inflammation response and multiple organs dysfunction. Many articles suggested that mesenchymal stem cells can alleviate the inflammation and improve the survival rate of inflammatory animal models, however, the mechanism is still unclear. This study aimed to test the hypothesis that rat adipose-derived mesenchymal stem cells (ADMSCs) produce a amount of soluble tumour necrosis factor receptor 1 (sTNFR1), which ameliorated liver injury and inflammation and increased the survival rate of septic rat model.120 adult male Sprague-Dawley rats were randomly divided into 4 groups: sham-operated (Sham), sepsis-induced by cecal ligation and puncture (CLP), shNC (injected 1 × 106 ADMSCs with transfected with scramble shRNA 1 h after CLP), and shsTNFR1 (injected 1 × 106 ADMSCs with transfected with sTNFR1 1 h after CLP). The serum sTNFR1 levels were the lowest in Sham and highest in shNC group. ADMSCs could decrease the levels of pro-inflammatory cytokines such as TNF-α, IL-6, AP-1 c-jun and NF-κB p56 after CLP administration, whereas this result was weaken by shsTNFR1 administration. Moreover, shNC had an increased levels of the anti-inflammatory factor IL-10 compared with CLP, and this change could be weakened in shsTNFR1 administration. More importantly, ADMSCs could improve the survival rate of CLP-induced septic rats. Therapeutically administered ADMSCs secrete sTNFR1, which alleviated the liver injury and inflammatory response. Additionally, ADMSCs also ameliorated the systematic inflammation and increased the survival rate of septic rats.

Klebsiella pneumoniae: an increasing threat to public health.

OBJECTIVES: This review fills the paucity of information on K. pneumoniae as a nosocomial pathogen by providing pooled data on epidemiological risk factors, resistant trends and profiles and resistant and virulent genes of this organism in Asia. METHODS: Exhaustive search was conducted using PubMed, Web of Science, and Google scholar for most studies addressing the prevalence, risk factors, drug resistant-mediated genes and/or virulent factors of K. pneumoniae in Asia. Data extracted for meta-analysis were analyzed using comprehensive meta-analysis version 3. Trends data for the isolation rate and resistance rates were entered into Excel spread sheet and the results were presented in graphs. RESULTS: The prevalence rate of drug resistance in K. pneumoniae were; amikacin (40.8%) [95% CI 31.9-50.4], aztreonam (73.3%) [95% CI 59.9-83.4], ceftazidime (75.7%) [95% CI 65.4-83.6], ciprofloxacin (59.8%) [95% CI 48.6-70.1], colistin (2.9%) [95% CI 1.8-4.4], cefotaxime (79.2%) [95% CI 68.0-87.2], cefepime (72.6) [95% CI 57.7-83.8] and imipenem (65.6%) [95% CI 30.8-89.0]. TEM (39.5%) [95% CI 15.4-70.1], SHV-11 (41.8%) [95% CI 16.2-72.6] and KPC-2 (14.6%) [95% CI 6.0-31.4] were some of the resistance mediated genes observed in this study. The most virulent factors utilized by K. pneumoniae are; hypermucoviscous phenotype and mucoviscosity-related genes, genes for biosynthesis of lipopolysaccharide, iron uptake and transport genes and finally, adhesive genes. CONCLUSION: It can be concluded that, antimicrobial resistant in K. pneumoniae is a clear and present danger in Asia which needs strong surveillance to curb this menace. It is very important for public healthcare departments to monitor and report changes in antimicrobial-resistant isolates.

Nurse-led psychological intervention reduces anxiety symptoms and improves quality of life following percutaneous coronary intervention for stable coronary artery disease.

OBJECTIVE: To study the effect of nurse-led counselling on the anxiety symptoms and the quality of life following percutaneous coronary intervention for stable coronary artery disease. DESIGN: Randomised control trial. SETTING: Rural and remote China. PARTICIPANTS: Rural and remote patients were consecutively recruited from a medical centre located in China between January and December 2014. INTERVENTIONS: The control group received standard pre-procedure information from a ward nurse on the processes of the hospitalisation and percutaneous coronary intervention, and post-procedural care. The intervention group received a structured 30-minute counselling session the day before and 24 hours after the percutaneous coronary intervention, by nurse consultants with qualifications in psychological therapies and counselling. The health outcomes were assessed by a SF-12 scale and the Seattle Angina Questionnaire at 6 and 12 months after percutaneous coronary intervention. The anxiety and depression symptoms were evaluated by a Zung anxiety and depression questionnaire. MAIN OUTCOME MEASURES: Cardiac outcomes, quality of life and mental health status. RESULTS: Eighty patients were randomly divided into control (n = 40) and intervention groups (n = 40). There was a significant increase in the scores of the three domains of Seattle Angina Questionnaire 12 months after percutaneous coronary intervention in the intervention group (P < .01). The mental health and physical health scores also increased (P < .01). In the control group, the mean scores of Zung self-rating anxiety scale 12 months following percutaneous coronary intervention were higher than the baseline scores, and higher than in the intervention group (P < .01). CONCLUSIONS: Counselling by a clinician qualified in psychological therapies and counselling significantly reduces anxiety symptoms and improves quality of life.

A novel microRNA signature predicts vascular invasion in hepatocellular carcinoma.

Vascular invasion (VI) in hepatocellular carcinoma (HCC) is an important clinical parameter to predict survival. In this study, we collected microRNA (miRNA) expression data from HCC patients using The Cancer Genome Atlas database and identified a novel miRNA signature associated with VI. First, we categorized HCC patients into groups with or without VI (VI+ and VI-). We identified three miRNAs (miRNA-210, miRNA-10b, and miRNA-9-1) that were associated with VI according to a Kaplan-Meier analysis. This three-miRNA signature exhibited good predictive ability for VI in patients with HCC according to a receiver operating characteristic curve analysis at 1, 3, and 5 years. Patients with HCC with a high risk score exhibited a trend toward worse outcomes as determined by multivariable Cox regression and stratified analyses. This three-miRNA signature provides an accurate prediction of VI and can be used as an independent prognostic indicator for predicting VI in HCC patients.

Adipose-derived mesenchymal stem cells ameliorate the inflammatory reaction in CLP-induced septic acute lung injury rats via sTNFR1.

We hypothesized that the adipose-derived mesenchymal stem cells (ADMSCs), which secrete high amounts of soluble molecules, such as soluble tumor necrosis factor receptor 1 (sTNFR1), may ameliorate sepsis-induced acute lung injury (ALI). A total of 120 male adult Sprague-Dawley rats were separated into four groups: the sham control (SC), sepsis induced by cecal ligation and puncture (CLP), CLP-ADMSCs, and CLP-sTNFR1 small interfering RNA (siRNA) groups; CLP groups underwent CLP and then received 1 × 106 ADMSCs with or without knockdown of sTNFR1 intravenously at 1 hr after surgery. Rats were killed at 3, 6, 24, and 48 hr after the SC or CLP procedures. 5-Ethynyl-2'-deoxyuridine-labeled ADMSCs extensively colonized the lungs at 6, 24, and 72 hr after injection. The lung wet/dry (W/D) weight ratios in the CLP group were higher than those in SC group; however, ADMSCs ameliorated the W/D weight ratios following CLP, and this effect was abolished by sTNFR1 siRNA treatment. The levels of serum sTNFR1 and interleukin-10 (IL-10) were higher in the CLP-ADMSCs group and lower in the SC group than in other groups; interestingly, these levels were higher in CLP and CLP-sTNFR1 siRNA groups than in SC group. Tumor necrosis factor-α and IL-6 levels increased significantly after CLP, and ADMSCs could alleviate these changes, but the effect was weakened by sTNFR1 siRNA treatment. The lung cell apoptosis and edema levels were consistent with IL-6 levels among all groups. Therapeutically administered ADMSCs secrete sTNFR1, which most likely protects against ALI in septic rats by ameliorating inflammation and lung edema.

Predictive model for acute respiratory distress syndrome events in ICU patients in China using machine learning algorithms: a secondary analysis of a cohort study.

BACKGROUND: To develop a machine learning model for predicting acute respiratory distress syndrome (ARDS) events through commonly available parameters, including baseline characteristics and clinical and laboratory parameters. METHODS: A secondary analysis of a multi-centre prospective observational cohort study from five hospitals in Beijing, China, was conducted from January 1, 2011, to August 31, 2014. A total of 296 patients at risk for developing ARDS admitted to medical intensive care units (ICUs) were included. We applied a random forest approach to identify the best set of predictors out of 42 variables measured on day 1 of admission. RESULTS: All patients were randomly divided into training (80%) and testing (20%) sets. Additionally, these patients were followed daily and assessed according to the Berlin definition. The model obtained an average area under the receiver operating characteristic (ROC) curve (AUC) of 0.82 and yielded a predictive accuracy of 83%. For the first time, four new biomarkers were included in the model: decreased minimum haematocrit, glucose, and sodium and increased minimum white blood cell (WBC) count. CONCLUSIONS: This newly established machine learning-based model shows good predictive ability in Chinese patients with ARDS. External validation studies are necessary to confirm the generalisability of our approach across populations and treatment practices.

Association of preadmission metformin use and mortality in patients with sepsis and diabetes mellitus: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Recent studies have reported that preadmission metformin users had lower mortality than non-metformin users in patients with sepsis and diabetes mellitus; however, these results are still controversial. Therefore, we conducted a systematic review and meta-analysis of published observational cohort data to determine the association between preadmission metformin use and mortality in septic adult patients with diabetes mellitus. METHODS: The MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched from their inception to September 30, 2018. Cohort studies that evaluated the use of metformin in septic adult patients with diabetes mellitus were included. The quality of outcomes was evaluated using the Newcastle-Ottawa Scale (NOS). The inverse variance method with random effects modelling was used to calculate the pooled odds ratios (ORs) and 95% CIs. RESULTS: Five observational cohort studies (1282 patients) that were all judged as having a low risk of bias were included. In this meta-analysis, metformin use was associated with a significantly lower mortality rate (OR, 0.59; 95% CI, 0.43-0.79, P = 0.001). CONCLUSIONS: This meta-analysis indicated an association between metformin use prior to admission and lower mortality in septic adult patients with diabetes mellitus. This finding suggested that the possible effect of metformin should be evaluated in future clinical trials.

A nurse-led structured education program improves self-management skills and reduces hospital readmissions in patients with chronic heart failure: a randomized and controlled trial in China.

INTRODUCTION: Patient self-management skills are an important part of heart failure (HF) management. However, there is a lack of knowledge about the effectiveness of nurse-led education on patient self-management and the associated clinical outcomes of rural Chinese patients with chronic heart failure (CHF). As such, this study was designed to evaluate the impact of a nurse-led education program on patient self-management and hospital readmissions in rural Chinese patients with CHF. METHODS: Ninety-six patients in the eastern Chinese province of Shandong with CHF were randomly divided into intervention and control groups. A structured education program was delivered to the intervention group during hospitalization and after discharge. Control group patients were managed as per clinical guidelines without structured education. Medication adherence, dietary modifications, social support, and symptom control were assessed 12 months after the educational intervention. RESULTS: The mean score of medication adherence, dietary modifications, social support and symptom control in the intervention group was higher than in the control group at the end of the study (p<0.01). The readmission rates for HF in the intervention and control group were 10.4% and 27.1%, respectively (p=0.036). CONCLUSIONS: This study has demonstrated that a structured education program was associated with a significant improvement in medication adherence, dietary modifications, social support, and symptom control in rural CHF patients. Furthermore, this program was associated with a significant reduction in hospital readmission. This study indicates that implementation of a nurse-led education program improves self-management and clinical outcomes of rural CHF patients, who may not have regular access to cardiac management services as per metropolitan populations.

Early goal-directed and lactate-guided therapy in adult patients with severe sepsis and septic shock: a meta-analysis of randomized controlled trials.

BACKGROUND: The ProCESS, ARISE, and ProMISe trials have failed to show that early goal-directed therapy (EGDT) reduces mortality in patients with severe sepsis and septic shock. Although lactate-guided therapy (LGT) has been shown to result in significantly lower mortality, its use remains controversial. Therefore, we performed a meta-analysis to evaluate EGDT vs. LGT or usual care (UC) in adult patients with severe sepsis and septic shock. METHODS: Relevant randomized controlled trials published from January 1, 2001 to March 30, 2017 were identified in PubMed, EMBASE, Web of Science, and the Cochrane Library. The primary outcome was mortality; secondary outcomes included red cell transfusions, dobutamine use, vasopressor infusion, and mechanical ventilation support within the first 6 h and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. RESULTS: Sixteen studies enrolling 5968 patients with 2956 in EGDT, 2547 in UC, and 465 in LGT were included in this meta-analysis. Compared with UC, EGDT was associated with a lower mortality (10 trials; RR 0.85, 95% CI 0.74-0.97, P = 0.01), and this difference was more pronounced in the subgroup of UC patients with mortality > 30%. In addition, EGDT patients received more red cell transfusions, dobutamine, and vasopressor infusions within the first 6 h. Compared with LGT, EGDT was associated with higher mortality (6 trials; RR 1.42, 95% CI 1.19-1.70, P = 0.0001) with no heterogeneity (P = 0.727, I2 = 0%). CONCLUSION: EGDT seems to reduce mortality in adult patients with severe sepsis and septic shock, and the benefit may primarily be attributed to red cell transfusions, dobutamine administration, and vasopressor infusions within the first 6 h. However, LGT may result in a greater mortality benefit than EGDT.