The effect of type 2 diabetes mellitus on multiple obstructive coronary artery disease.

BACKGROUND: Although type 2 diabetes mellitus (T2DM) individuals easily develop three-vessel disease (3VD) coronary artery disease (CAD), there is very little information available about their left ventricle (LV) functions. The purpose of this study is to evaluate the LV function using two-dimensional speckle tracking echocardiography (2-D STE) in T2DM patients with 3VD. METHODS: One hundred and three consecutive patients with confirmed 3VD CAD were enrolled and divided into two groups, while 53 patients with DM and 50 patients without. The control group was composed of 30 age- and sex-matched healthy individuals. All patients underwent 2-D STE and standard echocardiograms. The durations of DM and the level of HbA1c were also recorded. RESULT: Between the 3VD-DM and 3VD-non-DM groups, normal echocardiography did not reveal any appreciable differences. However, patients with 3VD-DM had significantly lower global longitudinal strain (GLS) than those with 3VD-non-DM (15.87 ± 2.51 vs.17.56 ± 2.72, p < .05) by 2-D STE strain measurement. Besides, patients whose duration of DM excess 5 years showed significant lower GLS than those with less than 5 years duration (14.25 ± 2.31 vs. 16.65 ± 1.96, p = .007). However, there was no difference in GLS between the 3VD-DM patients with HbA1c ≥ 7% and HbA1c < 7%. CONCLUSIONS: Compared to patients with 3VD alone, those with 3VD-DM have a lower cardiac function. In 3VD-DM patients, the duration of DM is a significant factor that contributes to cardiac function deterioration, whereas, the glucose control state has limited influence.

Downregulation of the CD151 protects the cardiac function by the crosstalk between the endothelial cells and cardiomyocytes via exosomes.

BACKGROUND: Heart failure (HF) is the last stage in the progression of various cardiovascular diseases. Although it is documented that CD151 contributes to regulate the myocardial infarction, the function of CD151 on HF and involved mechanisms are still unclear. METHOD AND RESULTS: In the present study, we found that the recombinant adeno-associated virus (rAAV)-mediated endothelial cell-specific knockdown of CD151-transfected mice improved transverse aortic constriction (TAC)-induced cardiac function, attenuated myocardial hypertrophy and fibrosis, and increased coronary perfusion, whereas overexpression of the CD151 protein aggravated cardiac dysfunction and showed the opposite effects. In vitro, the cardiomyocytes hypertrophy induced by PE were significantly improved, while the proliferation and migration of cardiac fibroblasts (CFs) were significantly reduced, when co-cultured with the CD151-silenced endothelial cells (ECs). To further explore the mechanisms, the exosomes from the CD151-silenced ECs were taken by cardiomyocyte (CMs) and CFs, verified the intercellular communication. And the protective effects of CD151-silenced ECs were inhibited when exosome inhibitor (GW4869) was added. Additionally, a quantitative proteomics method was used to identify potential proteins in CD151-silenced EC exosomes. We found that the suppression of CD151 could regulate the PPAR signaling pathway via exosomes. CONCLUSION: Our observations suggest that the downregulation of CD151 is an important positive regulator of cardiac function of heart failure, which can regulate exosome-stored proteins to play a role in the cellular interaction on the CMs and CFs. Modulating the exosome levels of ECs by reducing CD151 expression may offer novel therapeutic strategies and targets for HF treatment.

Expression profiles and potential functions of microRNAs in heart failure patients from the Uyghur population.

BACKGROUND AND PURPOSE: Existing studies have shown that circulating miRNA can be used as biomarkers of heart failure (HF). However, the circulating miRNA expression profile in Uyghur HF patients is unclear. In this study, we identified the miRNA profiles in the plasma of Uyghur HF patients and preliminarily explored their potential functions to provide new ideas for the diagnosis and treatment of HF. METHODS: Totally, 33 Uyghur patients with HF with reduced ejection fraction (<40%) were included in the HF group and 18 Uyghur patients without HF were included in the control group. First, high-throughput sequencing was used to identify differentially expressed miRNAs in the plasma of heart failure patients (n = 3) and controls (n = 3). Second, the differentially expressed miRNAs were annotated with online software and bioinformatics analysis was used to explore the critical roles of these circulating miRNAs in HF. Moreover, four selected differentially expressed miRNAs were validated by quantitative real-time PCR (qRT-PCR) in 15 controls and 30 HF patients. The diagnostic value of three successfully validated miRNAs for heart failure was assessed using receiver operating characteristic curve (ROC) analysis. Finally, to explore the expression levels of the three successfully validated miRNAs in HF hearts, thoracic aortic constriction (TAC) mice models were constructed and their expression in mice hearts was detected by qRT-PCR. RESULTS: Sixty-three differentially expressed miRNAs were identified by high-throughput sequencing. Of these 63 miRNAs, most were located on chromosome 14, and the OMIM database showed that 14 miRNAs were associated with HF. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that the target genes were mostly involved in ion or protein binding, the calcium signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, inositol phosphate metabolism, autophagy, and focal adhesion. Of the four selected miRNAs, hsa-miR-378d, hsa-miR-486-5p and hsa-miR-210-3p were successfully validated in the validation cohort and hsa-miR-210-3p had the highest diagnostic value for HF. Meanwhile, miR-210-3p was found to be significantly upregulated in the hearts of TAC mice. CONCLUSION: A reference set of potential miRNA biomarkers that may be involved in HF is constructed. Our study may provide new ideas for the diagnosis and treatment of HF.

Serum myoglobin modulates kidney injury via inducing ferroptosis after exertional heatstroke.

Background and Objectives: Myoglobin released by rhabdomyolysis (RM) is considered to be involved in pathogenesis of kidney disease caused by crush injury, but whether high level of serum myoglobin predisposes patients to acute kidney injury (AKI) and its molecular mechanisms are still unclear in exertional heatstroke (EHS). We aimed to determine the association and potential mechanism of myoglobin and AKI, and further investigate the targeted therapeutic agents for myoglobinemia. Methods: Serum myoglobin concentrations in patients with EHS were measured at admission, 24 h and 48 h after admission and discharge. The risk of AKI at 48 h was the primary outcome; the secondary outcome was composite outcome events with myoglobin levels and AKI at discharge and death at 90 days. In experimental studies, we further investigated the mechanisms of human kidney proximal tubular (HK-2) cells that were exposed to human myoglobin under heat stress conditions and the effect of baicalein. Results: Our measurements showed that the highest myoglobin quartile (vs. the lowest) had an adjusted odds ratio (OR) of 18.95 (95% confidence interval [CI], 6.00-59.83) for AKI and that the OR (vs. quartile 2) was 7.92 (95% CI, 1.62-38.89) for the secondary outcome. The survival rate of HK-2 cells treated with myoglobin under heat stress was significantly decreased, and the production of Fe2+ and reactive oxygen species (ROS) was markedly increased, accompanied by changes in ferroptosis proteins, including increased p53, decreased SLC7A11 and GPX4, and alterations in endoplasmic reticulum stress (ERS) marker proteins. Treatment with baicalein attenuated HK-2 cell ferroptosis induced by myoglobin under heat stress through inhibition of ERS. Conclusions: High myoglobin was associated with AKI in the EHS, and its mechanisms involved ERS-associated ferroptosis. Baicalein may be a potential therapeutic drug for the treatment of AKI in patients with high myoglobin induced by rhabdomyolysis following EHS.

Effectiveness of early heparin therapy on outcomes in critically ill patients with sepsis-induced coagulopathy.

Background: This study aimed to investigate whether early unfractionated heparin (UFH) administration provides a survival advantage for patients with sepsis-induced coagulopathy (SIC). Methods: Patients hospitalized with sepsis-induced coagulopathy from the Medical Information Mart for Intensive Care (MIMIC)-IV database were identified. Patients were divided into two groups, who received unfractionated heparin (UFH) subcutaneously within 24 h after intensive care unit (ICU) admission, and the control group, who received not. The primary endpoint was intensive care unit mortality, the secondary outcomes were 7, 14, and 28-day and hospital mortality. Propensity score matching (PSM) the marginal structural Cox model (MSCM) and E-value analysis were used to account for baseline differences, time-varying and unmeasured confounding factors. Results: A total of 3,377 patients with sepsis-induced coagulopathy were enrolled in the study, of which 815 in unfractionated heparin group and 2,562 in control group. There was significant effect on primary and secondary outcomes with unfractionated heparin after propensity score matching (intensive care unit mortality, hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.52-0.92; 7-day, HR 0.70, 95% CI 0.49-0.99; 14-day, HR 0.68.95% CI 0.50-0.92; 28-day, HR 0.72, 95% CI 0.54-0.96; hospital mortality, HR 0.74, 95% CI 0.57-0.96), marginal structural Cox model manifested unfractionated heparin associated with decreased intensive care unit mortality in all populations (HR 0.64, 95% CI 0.49-0.84), and stratification with the marginal structural Cox model indicated analysis further indicated the survival advantage only among patients with an sepsis-induced coagulopathy score of 4 (HR 0.56, 95% CI 0.38-0.81). Further analysis showed that treatment with 6,250-13750 IU/day of unfractionated heparin associated with a decreased risk of intensive care unit mortality. Similar results were replicated in subgroup analysis with propensity score matching only for patients with an sepsis-induced coagulopathy score of 4 (intensive care unit mortality, HR 0.51, 95% CI 0.34-0.76). Conclusion: This study found early unfractionated heparin therapy to patients with sepsis-induced coagulopathy appears to be associated with improved outcomes. Subgroup analysis further demonstrates heparin therapy decreased intensive care unit mortality primarily in patients only with SIC score of 4.

Impact of early heparin therapy on mortality in critically ill patients with sepsis associated acute kidney injury: a retrospective study from the MIMIC-IV database.

Background: Inflammatory-coagulation dysfunction plays an increasingly important role in sepsis associated acute kidney injury (SAKI). This study aimed to investigate whether early heparin therapy improves survival in patients with SAKI. Methods: Patients with SAKI were identified from the Medical Information Mart for Intensive Care-IV database. The patients were divided into two groups: those who received heparin subcutaneously within 48 h after intensive care unit (ICU) admission and the control group, who received no heparin. The primary endpoint was ICU mortality, the secondary outcomes were 7-day, 14-day, 28-day, and hospital mortality. Propensity score matching (PSM), marginal structural Cox model (MSCM), and E-value analyses were performed. Results: The study included 5623 individuals with SAKI, 2410 of whom received heparin and 3213 of whom did not. There were significant effects on ICU and 28-day mortality in the overall population with PSM. MSCM further reinforces the efficacy of heparin administration reduces ICU mortality in the general population. Stratification analysis with MSCM showed that heparin administration was associated with decreased ICU mortality at various AKI stages. Heparin use was also associated with reduced 28-day mortality in patients with only female, age >60 years, and AKI stage 3, with HRs of 0.79, 0.77, and 0.60, respectively (p < 0.05). E-value analysis suggests robustness to unmeasured confounding. Conclusion: Early heparin therapy for patients with SAKI decreased ICU mortality. Further analysis demonstrated that heparin therapy was associated with reduced 28-day mortality rate in patients only among female, age > 60 years and AKI stage 3.

Impact of early heparin therapy on outcomes in patients with solid malignancy associated sepsis: a marginal structural model causal analyse.

Background: Previous studies documented that heparin can inhibit the invasion and metastasis of tumors, but its role on outcomes in patients with solid malignancy complicated sepsis remains unclear. Methods: A retrospective cohort study was conducted in critically ill patients with solid malignancy associated sepsis from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The primary endpoint was intensive care unit (ICU) mortality, secondary outcomes were thrombosis and hospital mortality. Propensity score matching (PSM), marginal structural Cox model (MSCM), cox proportional hazards model, stratification analysis and E-value were used to account for baseline differences, time-varying confounding and unmeasured variables. Results: A total of 1,512 patients with solid malignancy complicated sepsis were enrolled, of which 683 in the heparin group with intensive care unit mortality, thrombosis rate and hospital mortality were 9.7%, 5.4%, 16.1%, and 829 in the non-heparin group with ICU mortality, thrombosis rate and hospital mortality were 14.6%, 12.5%, 22.6%. Similar results were observed on outcomes for patients with PSM (ICU mortality hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.41-0.92), thrombosis rate (HR 0.42, 95% confidence interval 0.26-0.68); hospital mortality HR 0.70, 95% CI 0.50-0.99). marginal structural Cox model further reinforced the efficacy of heparin in reducing ICU mortality (HR 0.48, 95% CI 0.34-0.68). Logistic regression and Cox regression model showed heparin use also markedly reduced thrombosis (HR 0.42; 95% CI 0.26-0.68; p < 0.001) and hospital mortality (HR 0.70; 95% CI 0.50-0.99; p = 0.043). Stratification analysis with the MSCM showed an effect only those with digestive system cancer (HR 0.33, 95% CI 0.16-0.69). Conclusion: Early heparin therapy improved outcomes in critically ill patients with solid malignancy complicated sepsis. These results are evident especially in those with digestive system cancer. A prospective randomized controlled study should be designed to further assess the relevant findings.

Early prophylactic anticoagulation with heparin alleviates mortality in critically ill patients with sepsis: a retrospective analysis from the MIMIC-IV database.

Background: Minimal data exist on anticoagulation use and timing and the dose of heparin in patients with sepsis, and whether heparin use improves sepsis survival remains largely unclear. This study was performed to assess whether heparin administration would provide a survival advantage in critically ill patients with sepsis. Methods: A retrospective cohort study of patients with sepsis in the Medical Information Mart for Intensive Care (MIMIC)-IV database was conducted. Cox proportional hazards model and propensity score matching (PSM) were used to evaluate the outcomes of prophylactic anticoagulation with heparin administered by subcutaneous injection within 48 h of intensive care unit (ICU) admission. The primary outcome was in-hospital mortality. Secondary outcomes included 60-day mortality, length of ICU stay, length of hospital stay and incidence of acute kidney injury (AKI) on day 7. E-Value analysis were used for unmeasured confounding. Results: A total of 6646 adult septic patients were included and divided into an early prophylactic heparin group (n = 3211) and a nonheparin group (n = 3435). In-hospital mortality in the heparin therapy group was significantly lower than that in the nonheparin group (prematched 14.7 vs 20.0%, hazard ratio (HR) 0.77, 95% confidence interval (CI) [0.68-0.87], p < 0.001, and postmatched 14.9 vs 18.3%, HR 0.78, 95% CI [0.68-0.89], p < 0.001). Secondary endpoints, including 60-day mortality and length of ICU stay, differed between the heparin and nonheparin groups (p < 0.01). Early prophylactic heparin administration was associated with in-hospital mortality among septic patients in different adjusted covariates (HR 0.71-0.78, p < 0.001), and only administration of five doses of heparin was associated with decreased in-hospital mortality after PSM (HR 0.70, 95% CI 0.56-0.87, p < 0.001). Subgroup analysis showed that heparin use was significantly associated with reduced in-hospital mortality in patients with sepsis-induced coagulopathy, septic shock, sequential organ failure assessment score ≥ 10, AKI, mechanical ventilation, gram-positive bacterial infection and gram-negative bacterial infection, with HRs of 0.74, 0.70, 0.58, 0.74, 0.73, 0.64 and 0.72, respectively (p <0.001). E-Value analysis suggested robustness to unmeasured confounding. Conclusions: This study found an association between early administration prophylactic heparin provided to patients with sepsis and reduced risk-adjusted mortality. A prospective randomized-controlled study should be designed to further assess the relevant findings.

Early Combination of Albumin With Crystalloid Administration Might Reduce Mortality in Patients With Cardiogenic Shock: An Over 10-Year Intensive Care Survey.

Background: In updated international guidelines, combined albumin resuscitation is recommended for septic shock patients who receive large volumes of crystalloids, but minimal data exist on albumin use and the optimal timing in those with cardiogenic shock (CS). The objective of this study was to evaluate the relationship between resuscitation with a combination of albumin within 24 h and 30-day mortality in CS patients. Methods: We screened patients with CS from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Multivariable Cox proportional hazards models and propensity score matching (PSM) were employed to explore associations between combined albumin resuscitation within 24 h and 30-day mortality in CS. Models adjusted for CS considered potential confounders. E-value analysis suggested for unmeasured confounding. Results: We categorized 1,332 and 254 patients into crystalloid-only and early albumin combination groups, respectively. Patients who received the albumin combination had decreased 30-day and 60-day mortality (21.7 vs. 32.4% and 25.2 vs. 34.2%, respectively, P < 0.001), and the results were robust after PSM (21.3 vs. 44.7% and 24.9 vs. 47.0%, respectively, P < 0.001) and following E-value. Stratified analysis showed that only ≥ 60 years old patients benefited from administration early albumin. In the early albumin combination group, the hazard ratios (HRs) of different adjusted covariates remained significant (HRs of 0.45-0.64, P < 0.05). Subgroup analysis showed that resuscitation with combination albumin was significantly associated with reduced 30-day mortality in patients with maximum sequential organ failure assessment score≥10, with acute myocardial infarction, without an Impella or intra-aortic balloon pump, and with or without furosemide and mechanical ventilation (HRs of 0.49, 0.58, 0.65, 0.40, 0.65 and 0.48, respectively; P < 0.001). Conclusion: This study found, compared with those given crystalloid-only, resuscitation with combination albumin within 24 h is associated with lower 30-day mortality of CS patients aged≥60. The results should be conducted to further assess in randomized controlled trials.

Impact of early empirical antifungal therapy on prognosis of sepsis patients with positive yeast culture: A retrospective study from the MIMIC-IV database.

Background: Mortality and other clinical outcomes of culture-negative and culture-positive among patients with fungal sepsis have not been documented, and whether antifungal therapy prior to fungal culture reports is related to decreased mortality among patients remains largely controversial. This study aimed to determine the mortality and other clinical outcomes of patients with positive yeast cultures and further investigate the effects of initial empiric antifungal therapy. Methods: A retrospective study was conducted among septic patients using the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients with sepsis were divided into two groups based on first fungal culture status during intensive care unit (ICU) stay, and initial empirical antifungal therapy was prescribed based on physician's experience prior to fungal culture reports within 48 h. The primary outcome was in-hospital all-cause mortality. The secondary outcomes were 30-day all-cause mortality, 60-day all-cause mortality, length of ICU stay and length of hospital stay. Multivariate logistic regression, propensity score matching (PSM), subgroup analyses and survival curve analyses were performed. Results: This study included 18,496 sepsis patients, of whom 3,477 (18.8%) had positive yeast cultures. Patients with positive yeast cultures had higher in-hospital all-cause mortality, 60-day all-cause mortality, and longer lengths of ICU stay and hospital stay than those with negative yeast cultures after PSM (all p < 0.01). Multivariate logistic regression analysis revealed that positive yeast culture was a risk factor for in-hospital mortality in the extended model. Subgroup analyses showed that the results were robust among the respiratory infection, urinary tract infection, gram-positive bacterial infection and bacteria-free culture subgroups. Interestingly, empiric antifungal therapy was not associated with lower in-hospital mortality among patients with positive yeast cultures, mainly manifested in stratification analysis, which showed that antifungal treatment did not improve outcomes in the bloodstream infection (odds ratio, OR 2.12, 95% CI: 1.16-3.91, p = 0.015) or urinary tract infection groups (OR 3.24, 95% CI: 1.48-7.11, p = 0.003). Conclusion: Culture positivity for yeast among sepsis patients was associated with worse clinical outcomes, and empiric antifungal therapy did not lower in-hospital all-cause mortality in the bloodstream infection or urinary tract infection groups in the ICU.

Clinical Characteristics and Risk Factors for Critically Ill Patients with Carbapenem-Resistant Klebsiella pneumonia e (CrKP): A Cohort Study from Developing Country.

BACKGROUND: Increasing evidence indicates carbapenem-resistant Klebsiella pneumoniae (CrKP) is increasingly prevalent in intensive care unit (ICU), but its clinical characteristics and risk factors remain unknown. AIM: The aim of the present study was to evaluate clinical characteristics, risk factors in critically ill patients with CrKP infection. METHODS: A retrospective study was included in patients from January 2013 to October 2019. Clinical data were collected from CrKP patients on the day of specimen collection admitted to ICU. Multivariable logistic regression was used for risk factors. Receiver operating curve (ROC) and the area under the curve (AUC) with DeLong method of MedCalc software were used. Two-way repeated-measures ANOVA analysis was used to analyze the characteristics of independent risk factors over time. FINDINGS: A total of 147 adult patients with CrKP were screened, among them, 89 (median age 64.0 years, 66 (74.15%) males) patients with CrKP were finally included, of which 38 patients (42.7%) were non-survival group. Multivariate logistic regression analysis indicated that lactic acid (OR3.04 95% CI 1.38-6.68, P = 0.006), APACHE II score (OR 1.20, 95% CI 1.09-1.33, P < 0.001), tigecycline combined with fosfomycin treatment (OR0.15, 95% CI 0.04-0.65, P = 0.011) are independent risk factors for 28-day mortality in patients with CRKP infection (P<0.05). Combined lactic acid with APACHE II score could predict 28-day mortality, of which AUC value was 0.916 (95% CI, 0.847-0.985), with sensitivity 0.76 and specificity 0.98. ANOVA analysis showed that APACHE II score and lactic acid between the two groups at three-time points were statistically significant, which interactive with time and showed an upward and downward trend with time (P < 0.05). CONCLUSION: Therapeutic strategy based on improving lactic acid and APACHE II would contribute to the outcome in patients with CrKP infection. Tigecycline combined with fosfomycin could reduce the 28-day mortality in patients with CrKP infection in developing country.