Impact of albumin infusion on prognosis of intensive care unit patients with congestive heart failure-hypoalbuminemia overlap: a retrospective cohort study.

Background: Hypoalbuminemia is common in congestive heart failure (CHF) patients. Serum albumin is associated with the prognosis of CHF patients. Impact of albumin infusion on prognosis of patients with CHF-hypoalbuminemia overlap remains unclear. We retrospectively investigated the impact of albumin infusion on prognosis of intensive care unit (ICU) patients with CHF-hypoalbuminemia overlap. Methods: We enrolled all patients whose diagnosis included CHF [ICD-9 (international classification of diseases 9) code =428.0] at first ICU admission from the MIMIC III (Medical Information Mart for Intensive Care III) database, and excluded those with missing serum albumin values, with serum albumin >3.4 g/dL or <18 years old. According to the exposure of albumin infusion during hospitalization, patients were stratified into non-albumin and albumin groups. Propensity-score matching (PSM) was performed (1:1 ratio) to control for baseline confounding. Outcome measures were in-hospital mortality as well as length of stay in the ICU (ICU LOS) and the hospital (hospital LOS). Results: There were 3,190 eligible patients in the initial search. Patients with albumin infusion had markedly higher in-hospital mortality (36.42% vs. 21.81%, P<0.001), longer ICU LOS [median 6.93 (3.39-14.82) vs. 3.84 (1.96-8.00) days, P<0.001], and longer hospital LOS [median 17.46 (11.45-28.33) vs. 10.92 (6.81-18.00) days, P<0.001] than those without albumin infusion. The multivariate logistic regression analysis revealed that albumin infusion [odds ratio (OR), 1.509; 95% confidence interval (CI), 1.164-1.957; P=0.002] was significantly associated with increased risk of in-hospital mortality. After PSM, a cohort of 429 pairs of patients was included in the final analysis. Patients with albumin infusion had markedly higher in-hospital mortality (34.97% vs. 27.27%, P=0.015), longer ICU LOS [median 8.43 (4.33-16.28) vs. 6.43 (3.07-13.66) days, P<0.001], and longer hospital LOS [median 16.92 (11.27-28.06) vs. 13.33 (8.00-21.10) days, P<0.001] than those without albumin infusion. The multivariate logistic regression analysis revealed that albumin infusion (OR, 1.594; 95% CI, 1.143-2.223; P=0.006) was significantly associated with increased risk of in-hospital mortality. Conclusions: Albumin infusion increased in-hospital mortality, ICU LOS, and hospital LOS in ICU patients with CHF-hypoalbuminemia overlap.

Metabolomic study on the protective effect of isoorientin against myocardial infarction.

Myocardial infarction has become one of the largest threats to human life. Myocardial ischemia and hypoxia caused by myocardial infarction are important causes of myocardial cell injury. Compared with chemical drugs, botanical drugs that are natural antioxidants have relatively few toxic side effects. Isoorientin (ISO), a C-glucosyl flavone with a chemical nomenclature, exists in the human diet and has antioxidant and anti-inflammatory effects in other diseases. However, its role in myocardial infarction has not been reported. In this study, we investigated the effects of ISO administration on cardiac function in mice after myocardial infarction, on ROS levels in H9C2 myocardial cells after hypoxia in vitro, and on metabolomic changes in mice after myocardial infarction. We found that ISO improved cardiac function in mice after myocardial infarction and inhibited hypoxia-induced oxidative stress injury in H9C2 cells in vitro. We also found through metabolomic analysis and KEGG enrichment analysis that ISO significantly changed metabolic pathways in mice after myocardial infarction, including histidine metabolism, arachidonic acid metabolism, renin secretion and other pathways. These results lay a foundation for further exploration of the protective effect of ISO against myocardial infarction and the development of related drugs.

Folic Acid Attenuates Contrast-Induced Nephropathy in Patients With Hyperhomocysteinemia Undergoing Coronary Catheterization: A Randomized Controlled Trial.

Background: Hyperhomocysteinemia is a risk factor for contrast-induced nephropathy. Folic acid can attenuate such nephropathies in rats. The protective effect of folic acid against contrast-induced nephropathy has not been studied in humans. We aimed to investigate the effect of folic acid on the incidence of contrast-induced nephropathy (CIN) after coronary catheterization in patients with hyperhomocysteinemia. Methods: This was a single-center, prospective, double-blind, randomized controlled trial (ClinicalTrials.gov, NCT02444013). In total, 412 patients (mean age: 65 ± 12 years, 268 male) with plasma homocysteine ≥15 µM, who underwent coronary arteriography (CAG) or percutaneous coronary intervention (PCI) from May 2015 to August 2018, were enrolled. Patients were randomly assigned to two groups: a treatment group (n = 203), taking 5 mg of folic acid (orally, three times/day) immediately after enrollment and for 72 h after operation, and a control group (n = 209), taking placebo. Contrast-induced nephropathy was defined as an increase in serum creatinine of >25% or 44 µM within 48 or 72 h after contrast medium administration. Results: In total, 50 (12%) patients developed CIN after 48 h after catheterization, including 16 (8%) in the treatment group and 34 (16%) in the control group (P = 0.009). Meanwhile, 53 (13%) patients developed CIN after 72 h of CAG/PCI, including 18 (9%) in the treatment group and 35 (17%) in the control group (P = 0.017). The incidence of contrast-induced nephropathy in the treatment group was lower than that in the control group (P = 0.017). Logistic regression analysis confirmed that administration of folic acid was a protective factor against contrast-induced nephropathy (RD = 0.0788, 95%CI: 0.0105-0.1469, P = 0.019). We found no serious adverse events associated with folic acid. No death or hemodialysis occurred in either group. Conclusions: Perioperative administration of folic acid attenuates the incidence of contrast-induced nephropathy after coronary catheterization in patients with hyperhomocysteinemia. Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT02444013].

Inhaled Beta2-Agonists Increase In-Hospital Mortality in ICU Patients with Heart Failure.

The impact of beta2-agonists (B2As) on heart failure (HF) remains controversial. This study aimed to investigate whether inhaled B2As increased in-hospital mortality in ICU patients with HF.The Multiparameter Intelligent Monitoring in Intensive Care III database was initially searched to identify adult patients (≥ 18 years old) with HF in ICU. Then, patients using or not using inhaled B2As were matched using propensity score matching on a 1:1 basis to control for baseline confounders. In-hospital mortality was compared between the two groups, and logistic regression analysis was performed to assess the association between B2As and in-hospital mortality.The initial search retrieved 2345 eligible patients with HF from the database. After propensity score matching, 705 pairs of patients were included in the final analysis. Patients using B2As had markedly higher in-hospital mortality than those not using B2As (4.68% versus 2.27%; P = 0.013). In the multivariate logistic regression analysis, B2A use (odd ratios (OR), 2.471; 95% confidence interval (CI), 1.289-4.734; P = 0.006), stroke (OR, 4.581; 95% CI, 1.621-12.948; P = 0.004), and simplified acute physiology score II (SAPS-II) scores (OR, 1.090; 95% CI, 1.064-1.116; P < 0.001) were significantly associated with increased risk of in-hospital mortality, whereas renin angiotensin system inhibitor use (OR, 0.396; 95% CI, 0.202-0.778; P = 0.007) was significantly associated with decreased risk of in-hospital mortality. Subgroup analysis further indicated that the association between B2A use and mortality was significant only in patients with HF without chronic pulmonary disease (OR, 2.427; 95% CI, 1.351-4.362; P = 0.003), but not in those with chronic pulmonary disease (OR, 2.094; 95% CI, 0.582-7.537; P = 0.258).In ICU patients with HF but without chronic pulmonary disease, the use of inhaled B2As is associated with increased in-hospital mortality.

Atrial fibrillation increases inpatient and 4-year all-cause mortality in critically ill patients with liver cirrhosis.

BACKGROUND: The association between atrial fibrillation (AF) and cirrhosis is unclear. Therefore, the aim of the present study was to determine the association between AF and short-term and 4-year mortality in critically ill patients with cirrhosis using a large database. METHODS: The Medical Information Mart for Intensive Care III (MIMIC III) database was used to identify patients with cirrhosis hospitalized in an intensive care unit from 2001 to 2012. Demographic and clinical data were extracted from the database. Clinical data and demographic information were collected for each patient in our study. Kaplan-Meier analysis and multivariate Cox regression models were performed to examine the relation between atrial fibrillation and in-hospital and 4-year all-cause mortality. RESULTS: A total of 1,481 patients (mean age: 58 years, 68% male) with liver cirrhosis were included in the analysis, and the prevalence of AF was 14.18%. The inpatient all-cause mortality rate was 26.6%, and patients who died in hospital had a significantly higher rate of AF (21.57% vs. 11.50%, P<0.001). Multivariate Cox regression analysis indicated that AF was significantly associated with inpatient all-cause mortality [hazard ratio (HR): 1.52, 95% confidence interval (CI): 1.19-1.95, P<0.001], and 4-year all-cause mortality (HR: 1.55, 95% CI: 1.12-2.13, P=0.008). Kaplan-Meier survival analysis showed that patients with AF had a significantly higher inpatient and 4-year all-cause mortality. CONCLUSIONS: Critically ill patients with liver cirrhosis have a high rate of AF, and the presence of AF is an independent risk factor for inpatient and 4-year all-cause mortality.

Prognostic value of the albumin-bilirubin score in critically ill patients with heart failure.

BACKGROUND: This study sought to examine the association between the albumin-bilirubin (ALBI) score and short-term and 4-year all-cause mortality in critically ill patients with heart failure (HF), and to build a simple and effective new predictive model. METHODS: The Monitoring in Intensive Care Database III was used to identify patients with HF who had been admitted to the intensive care unit (ICU) from 2001 to 2012. Correlations between ALBI scores and other commonly used risk-scoring methods and short-term and 4-year all-cause mortality were examined using the Kaplan-Meier method and Cox proportional hazards-regression models. RESULTS: The data of 3,381 ICU patients were included in the study, of whom 53.7% were male. The patients had a mean age of 70.02±12.55 years, and a short-term mortality rate of 27.7%. The ALBI score of survivors [-1.80 (-2.09 to -1.44)] was significantly lower than that of non-survivors [-1.43 (-1.80 to -0.99)] (P<0.001), and independently predicted short-term all-cause mortality and higher 4-year mortality. The area under the receiver operating characteristic curve (AUC) of the ALBI score for short-term mortality was 0.676, and that of the Get With the Guidelines-Heart Failure (GWTG-HF) score was 0.643. The new model, which combined the ALBI and GWTG-HF (the GWTG-HF-ALBI), had an AUC of 0.713. The AUC of the ALBI score for predicting 4-year all-cause mortality was 0.596, that of the GWTG-HF score was 0.638, and that of the GWTG-HF-ALBI risk score was 0.650. CONCLUSIONS: The ALBI score is useful at predicting the mortality of patients with HF requiring ICU admission. The GWTG-HF-ALBI model is simpler to use than other models that contain subjective items, such as the Glasgow Coma Score, and can be used to predict the short-term and 4-year all-cause mortality of these patients.

Fabrication, Structure, Performance, and Application of Graphene-Based Composite Aerogel.

Graphene-based composite aerogel (GCA) refers to a solid porous substance formed by graphene or its derivatives, graphene oxide (GO) and reduced graphene oxide (rGO), with inorganic materials and polymers. Because GCA has super-high adsorption, separation, electrical properties, and sensitivity, it has great potential for application in super-strong adsorption and separation materials, long-life fast-charging batteries, and flexible sensing materials. GCA has become a research hotspot, and many research papers and achievements have emerged in recent years. Therefore, the fabrication, structure, performance, and application prospects of GCA are summarized and discussed in this review. Meanwhile, the existing problems and development trends of GCA are also introduced so that more will know about it and be interested in researching it.

Impact of long-term glucose variability on coronary atherosclerosis progression in patients with type 2 diabetes: a 2.3 year follow-up study.

BACKGROUND: Glycemic variability (GV) confers a risk of cardiovascular events. In this study, we aimed to investigate whether long-term GV has an impact on coronary atherosclerosis progression in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 396 patients with T2DM who had coronary computed tomography angiography and laboratory data available at baseline and for follow-up evaluations [median 2.3 (1.8-3.1) years] were included. Fasting plasma glucose (FPG) was measured every 1-3 months, and HbA1c was measured quarterly. The coefficient of variation (CV) of HbA1c and FPG were calculated as measures of GV. Quantitative assessment of coronary plaques was performed by measuring the annual change and progression rate of total plaque volume (TPV). Significant progression was defined as annual TPV progression ≥ 15%. Multivariable regression analyses were used to assess the effects of GV on atherosclerosis progression. RESULTS: In the 396 patients, the annual change in TPV was 12.35 ± 14.23 mm3, and annual progression rate was 13.36 ± 12.69%. There were 143 (36.11%) patients with significant progression, and they had a significantly higher CV-HbA1c (P < 0.001) and CV-FPG (P < 0.001) than those without significant progression. In multivariable regression analyses, both CV-HbA1c and CV-FPG were independent predictors of annual change in TPV [CV-HbA1c: ß = 0.241 (0.019-0.462), P = 0.034; CV-FPG: ß = 0.265 (0.060-0.465), P = 0.012], annual TPV progression [CV-HbA1c: ß = 0.214 (0.023-0.405), P = 0.029; CV-FPG: ß = 0.218 (0.037-0.399), P = 0.019], and significant atherosclerosis progression [CV-HbA1c: odds ratio [OR] = 1.367 (1.149-1.650), P = 0.010; CV-FPG: OR = 1.321 (1.127-1.634), P = 0.013]. CONCLUSIONS: Long-term GV is associated with accelerated progression of coronary atherosclerosis independent of conventional risk factors in patients with T2DM. Trial registration ClinicalTrials.gov (NCT02587741), October 27, 2015; retrospectively registered.

Renin-Angiotensin System Inhibitors for the Prevention of Atrial Fibrillation Recurrence After Ablation　- A Meta-Analysis.

BACKGROUND: Atrial fibrillation (AF) recurrence remains a tricky problem in patients undergoing ablation. This meta-analysis aimed to summarize the current literature to clarify whether renin-angiotensin system inhibitors (RASIs) prevent AF recurrence after ablation.Methods and Results:Relevant studies were searched on Pubmed and EMBASE through December 2019. Pooled relative risk (RR) of AF recurrence was calculated. Subgroup analyses according to study design, race, and follow-up duration were further performed. A total of 15 studies examining 4,300 patients were included, with 3 randomized controlled trials and 12 cohort studies. Overall analysis showed that RASIs significantly reduced AF recurrence after ablation (RR=0.83; 95% confidence interval (CI) 0.70-0.98, P=0.028; I2=68.9%). Subgroup analysis further indicated that positive results were found in randomized controlled trials (RR=0.51, 95% CI 0.37-0.70, P<0.001; I2=4%), studies conducted in Asia (RR=0.59, 95% CI 0.46-0.76, P<0.001; I2=30.7%), and studies with follow-up duration ≥1 year (RR=0.82, 95% CI 0.70-0.95, P=0.01; I2=59.1%); negative results were found in cohort studies, studies conducted in Europe or the USA, and studies with follow-up duration <1 year. CONCLUSIONS: RASIs can potentially prevent AF recurrence after ablation under selected conditions. However, more studies are required to confirm this finding due to the variation in current evidence.

Sleep Deprivation Selectively Down-Regulates Astrocytic 5-HT2B Receptors and Triggers Depressive-Like Behaviors via Stimulating P2X7 Receptors in Mice.

Chronic loss of sleep damages health and disturbs the quality of life. Long-lasting sleep deprivation (SD) as well as sleep abnormalities are substantial risk factors for major depressive disorder, although the underlying mechanisms are not clear. Here, we showed that chronic SD in mice promotes a gradual elevation of extracellular ATP, which activates astroglial P2X7 receptors (P2X7Rs). Activated P2X7Rs, in turn, selectively down-regulated the expression of 5-HT2B receptors (5-HT2BRs) in astrocytes. Stimulation of P2X7Rs induced by SD selectively suppressed the phosphorylation of AKT and FoxO3a in astrocytes, but not in neurons. The over-expression of FoxO3a in astrocytes inhibited the expression of 5-HT2BRs. Down-regulation of 5-HT2BsRs instigated by SD suppressed the activation of STAT3 and relieved the inhibition of Ca2+-dependent phospholipase A2. This latter cascade promoted the release of arachidonic acid and prostaglandin E2. The depression-like behaviors induced by SD were alleviated in P2X7R-KO mice. Our study reveals the mechanism underlying chronic SD-induced depression-like behaviors and suggests 5-HT2BRs as a key target for exploring therapeutic strategies aimed at the depression evoked by sleep disorders.

Fluoxetine improves behavioural deficits induced by chronic alcohol treatment by alleviating RNA editing of 5-HT2C receptors.

The alcoholism and major depressive disorder are common comorbidity, with alcohol-induced depressive symptoms being eased by selective serotonin re-uptake inhibitors (SSRIs), although the mechanisms underlying pathology and therapy are poorly understood. Chronic alcohol consumption affects the activity of serotonin 2C receptors (5-HT2CR) by regulating adenosine deaminases acting on RNA (ADARs) in neurons. Astrogliopathic changes contribute to alcohol addiction, while decreased release of ATP from astrocytes can trigger depressive-like behaviours in mice. In this study, we discovered that chronic alcohol treatment increased editing of RNA of 5-HT2CR via up-regulating the expression of ADAR2, consequently reducing the release of ATP from astrocytes induced by 5-HT2CR agonist, MK212. Moreover, SSRI antidepressant fluoxetine decreased the expression of ADAR2 through the transactivation of EGFR/PI3K/AKT/cFos signalling pathway. The increased release of astroglial ATP by MK212 which was suppressed by chronic alcohol consumption, and reduction in ADAR2 activity eliminated the RNA editing of 5-HT2CR increased by alcohol in vitro and recovered the release of ATP from astrocytes induced by MK212. Meanwhile, fluoxetine improved the behavioural and motor symptoms induced by alcohol addiction and decreased the alcohol intake. Our study suggests that the astrocytic 5-HT2CR contribute to alcohol addiction; fluoxetine thus can be used to alleviate depression, treat alcohol addiction and improve motor coordination.

Different epidermal growth factor receptor signaling pathways in neurons and astrocytes activated by extracellular matrix after spinal cord injury.

Spinal cord injury (SCI) is a serious central nervous system (CNS) trauma that results in permanent and severe disability. The extracellular matrix (ECM) can affect the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) by interacting with the ERK integrin subunits. In this study, we built a model of SCI with glial fibrillary acidic protein-green fluorescent protein (GFAP-GFP) and thymus cell antigen 1-yellow fluorescent protein-H (Thy1-YFPH) in mice that express specific transgenes in their astrocytes or neurons. Then, we collected spinal cord neurons or astrocytes by fluorescence-activated cell sorting (FACS). In this way, we investigated the SCI-induced phosphorylation of ERK1/2 and epidermal growth factor receptor (EGFR) in neurons and astrocytes, and we discovered that the SCI-induced EGFR signaling pathways differed between neurons and astrocytes. In the present study, we found that the Src-dependent phosphorylation of EGFR induced by SCI occurred only in neurons, not in astrocytes. This phenomenon may be due to the involvement of Thy-1, which promoted the binding between Src and EGFR in neurons after SCI. In addition, the expression of the integrin subunits after SCI differed between neurons and astrocytes. Our present study shows that the EGFR signaling pathway triggered by SCI in neurons differed from the EGFR signaling pathway triggered in astrocytes, a finding that may help to pave the way for clinical trials of therapies that inhibit EGFR signaling pathways after SCI.

Protective effect of leptin-mediated caveolin-1 expression on neurons after spinal cord injury.

Spinal cord injury (SCI) causes long-term disability and has no effective clinical treatment. After SCI, extracellular adenosine triphosphate (ATP) leads to an influx of extracellular Ca2+, and this Ca2+ overload causes neuronal toxicosis and apoptosis. The biological functions of leptin have been widely investigated in the central nervous system. In this study, we discovered that the administration of leptin could improve locomotor recovery following SCI. The aim of this study was to determine the neuroprotective mechanism of leptin in vivo and in vitro. The neuronal apoptosis and Ca2+ imaging signal induced by ATP were suppressed by leptin, due to elevated caveolin-1 expression. In vivo two-photon observations revealed that leptin reduced the neuronal Ca2+ imaging signal in the exposed spinal cords of live Thy1-YFP mice. In conclusion, leptin promotes locomotor functional recovery and suppresses neuronal impairment after SCI, suggesting that leptin has a promising clinical therapeutic value for treatment of SCI.

Leptin Increases Expression of 5-HT2B Receptors in Astrocytes Thus Enhancing Action of Fluoxetine on the Depressive Behavior Induced by Sleep Deprivation.

The long-lasting loss of sleep is a generally acknowledged risk factor for the occurrence of major depressive disorder (MDD), whereas sleep abnormalities being a key clinic symptom of the MDD. In our previous work, we demonstrated that the sleep deprivation (SD) stimulates activation of nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasomes as well as the release of IL-1ß and IL-18 from astrocytes. However, the underlying mechanism connecting SD and MDD still requires further study. Apart of the secretion of the pro-inflammatory cytokines, SD affects production of brain-derived neurotrophic factor (BDNF) while release of BDNF from astrocytes appears a key contributor to mood disorders. If and how the activation of NLRP3 inflammasome following SD affects the level of BDNF remains unknown. Antidepressant fluoxetine acts through astroglial 5-hydroxytryptamine receptor 2B (5-HT2B); these receptors are also related to the sleep-wake cycle. Contribution of leptin to MDD has been discovered recently, although the mechanistic links between leptin and the depressive-like behaviors has not been revealed. In this study, we discovered: (i) that activation of NLRP3 inflammasome was involved in the depressive-like behaviors induced by SD; (ii) decrease in BDNF following SD required the activation of NLRP3 inflammasomes; (iii) leptin augmented the anti-depressive action of fluoxetine through an increase in expression of astrocytic 5-HT2B receptors. We suggest that decrease in BDNF by the activated NLRP3 inflammasomes in astrocytes is the key pathological event of the depressive-like behaviors induced by SD, while the combined treatment with fluoxetine and leptin improves therapeutic outcome for the depression induced by SD.