Blood Urea Nitrogen for Short-Term Prognosis in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction.

Purpose: Cardiogenic shock (CS) is the leading cause of death in patients with acute myocardial infarction (AMI). Our study aimed to evaluate the short-term prognostic value of admission blood urea nitrogen (BUN) in patients with CS complicating AMI. Materials and Methods: 218 consecutive patients with CS after AMI were enrolled. The primary endpoint was 30-day mortality. The association of admission BUN and 30-day mortality and major adverse cardiovascular event (MACE) was investigated by Cox regression. The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) further examined the predictive value of BUN. Results: During a period of 30-day follow-up, 105 deaths occurred. Compared to survivors, nonsurvivors had significantly higher admission BUN (p < 0.001), creatinine (p < 0.001), BUN/creatinine (p = 0.03), and a lower glomerular filtration rate (p < 0.001). The area under the curve (AUC) of the 4 indices for predicting 30-day mortality was 0.781, 0.734, 0.588, and 0.773, respectively. When compared to traditional markers associated with CS, the AUC for predicting 30-day mortality of BUN, lactate, and left ventricular ejection fraction were 0.781, 0.776, and 0.701, respectively. The optimal cut-off value of BUN for predicting 30-day mortality was 8.95 mmol/L with Youden-Index analysis. Multivariate Cox analysis indicated BUN >8.95 mmol/L was an important independent predictor for 30-day mortality (HR 2.08, 95%CI 1.28-3.36, p = 0.003) and 30-day MACE (HR 1.85, 95%CI 1.29-2.66, p = 0.001). IDI (0.053, p = 0.005) and NRI (0.135, p = 0.010) showed an improvement in the accuracy for mortality prediction of the new model when BUN was included compared with the standard model of predictors in previous scores. Conclusion: An admission BUN >8.95 mmol/L was robustly associated with increased short-term mortality and MACE in patients with CS after AMI. The prognostic value of BUN was superior to other renal markers and comparable to traditional markers. This easily accessible index might be promising for early risk stratification in CS patients following AMI.

Prognostic value of neutrophil-lymphocyte ratio in cardiogenic shock complicating acute myocardial infarction: A cohort study.

BACKGROUNDS: Cardiogenic shock (CS) is the most severe complication after acute myocardial infarction (AMI) with mortality above 50%. Inflammatory response is involved in the pathology of CS and AMI. In this study, we aimed to evaluate the prognostic value of admission neutrophil-lymphocyte ratio (NLR) in patients with CS complicating AMI. METHODS: Two hundred and seventeen consecutive patients with CS after AMI were divided into two groups according to the admission NLR cut-off value ≤7.3 and >7.3. The primary outcome was 30-day all-cause mortality and the secondary end-point was the composite events of major adverse cardiovascular events (MACE), including all-cause mortality, ventricular tachycardia/ventricular fibrillation, atrioventricular block, gastrointestinal haemorrhage and non-fatal stroke. Cox proportional hazard models were performed to analyse the association of NLR with the outcome. NLR cut-off value was determined by Youden index. RESULTS: Patients with NLR > 7.3 were older and presented with lower lymphocyte count, higher admission heart rate, B-type natriuretic peptide, leucocyte, neutrophil and creatinine (all P < .05). During a period of 30-day follow-up after admission, mortality in patients with NLR > 7.3 was significantly higher than in patients with NLR ≤ 7.3 (73.7% vs. 26.3%, P < .001). The incidence of MACE was also remarkably higher in patients with NLR > 7.3 (87.9% vs. 53.4%, P < .001). After multivariable adjustment, NLR > 7.3 remained an independent predictor for higher risk of 30-day mortality (HR 2.806; 95%CI 1.784, 4.415, P < .001) and MACE (HR 2.545; 95%CI 1.791, 3.617, P < .001). CONCLUSIONS: Admission NLR could be used as an important tool for short-term prognostic evaluation in patients with CS complicating AMI and higher NLR is an independent predictor for increased 30-day all-cause mortality and MACE.

Efficacy and Safety of Aspirin Combined with Low-Dose P2Y12 Receptor Antagonists in East Asian Patients Undergoing PCI.

Previous studies have indicated that low-dose new generation of P2Y12 receptor antagonists may be more suitable compared with clopidogrel at a standard dose for the dual antiplatelet therapy (DAPT) for East Asian patients receiving percutaneous coronary intervention (PCI). However, there remains no consensus in clinical practice. Thus, in this study, we aimed to determine the efficacy and safety of low-dose P2Y12 receptor antagonists, compared to clopidogrel at a standard dose, in DAPT in East Asian patients after PCI. We systematically searched literatures for randomized controlled trials (RCT) comparing low-dose P2Y12 receptor antagonists with standard-dose clopidogrel for the treatment of East Asian patients undergoing PCI. The endpoints of efficacy include major adverse cardiac events (MACEs), all-cause mortality, and the number of target vessel revascularization. The indicators of safety include major and minor bleeding events. Heterogeneity was evaluated by I2 statistic test. Begg's and Egger's tests were used to evaluate publication bias. In total, 2,747 subjects from 8 RCT studies were included. Low-dose new P2Y12 receptor antagonists, that is, ticagrelor or prasugrel, showed significantly lower incidence of MACEs, as compared with standard-dose clopidogrel, in the East Asian patients who are in DAPT after undergoing PCI. Further, no difference was noted for the risk of major and minor bleeding events. In East Asian patients undergoing PCI and receiving DAPT, the use of low-dose P2Y12 receptor antagonists, ticagrelor or prasugrel, has been determined to be superior than clopidogrel at standard dose; this has been evidenced by a lower incidence of MACEs without increasing the risk of bleeding.

Leukocyte and its Subtypes as Predictors of Short-Term Outcome in Cardiogenic Shock Complicating Acute Myocardial Infarction: A Cohort Study.

BACKGROUND: Patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) are at high risk of death. Inflammation is involved in both CS and AMI, and our present study aimed to investigate the changes of leukocyte and its subtypes as well as their prognostic value in patients with CS complicating AMI. METHODS: Data of 217 consecutive patients with CS complicating AMI were analyzed. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was the composite events of major adverse cardiovascular events (MACE) including 30-day all-cause mortality, ventricular tachycardia/ventricular fibrillation, atrioventricular block, gastrointestinal hemorrhage and nonfatal stroke. The association of leukocyte and its subtypes with the endpoints was analyzed by Cox regression analysis. RESULTS: Leukocyte and its subtypes including neutrophil, eosinophil, lymphocyte, monocyte and basophil were all statistically significant between survivors and nonsurvivors (all P < 0.05). Among the leukocyte subtypes, eosinophil had the highest predictive value for 30-day all-cause mortality (AUC = 0.799) and the composite of leukocyte and its subtypes improved the predictive power (AUC = 0.834). The 30-day mortality and MACE K-M curves of leukocyte and its subtypes reveal a distinct trend based on the cut-off value determined by Youden Index (all log rank P < 0.001). After multivariable adjustment, high leukocyte (>11.6 × 109/L) (HR 1.815; 95%CI 1.134, 2.903; P = 0.013), low eosinophil (<0.3%) (HR 2.562; 95%CI 1.412, 4.648; P = 0.002) and low basophil (≤0.1%) (HR 1.694; 95%CI 1.106, 2.592; P = 0.015) were independently associated with increased risk of 30-day mortality. Similarly, high leukocyte (>11.6 × 109/L) (HR 1.894; 95%CI 1.285, 2.791; P = 0.001), low eosinophil (<0.3%) (HR 1.729; 95%CI 1.119, 2.670; P = 0.014) and low basophil (≤0.1%) (HR 1.560; 95%CI 1.101, 2.210; P = 0.012) were independently associated with increased risk of 30-day MACE. CONCLUSIONS: Leukocyte and its subtypes changed significantly in patients with CS complicating AMI. In addition to leukocyte, eosinophil and basophil also served as independent prognostic factors for 30-day outcomes. Moreover, as the composite of leukocyte and its subtypes increased the predictive power, thus leukocyte and its subtypes, especially eosinophil and basophil should be taken into consideration for the current risk stratification model.

Incidence, Clinical Characteristics and Short-Term Prognosis in Patients With Cardiogenic Shock and Various Left Ventricular Ejection Fractions After Acute Myocardial Infarction.

The 2016 European Society of Cardiology Guidelines introduced a new term, mid-range left ventricular ejection fraction (mrEF) heart failure, however, the clinical characteristics and short-term outcomes in cardiogenic shock patients with mrEF after acute myocardial infarction remain unclear. This retrospective study analyzed the baseline characteristics, management, and outcomes according to the left ventricular ejection fraction (LVEF), reduced LVEF (rEF) ≤40%, mrEF 41% to 49%, and preserved LVEF (pEF) ≥50% in patients with acute myocardial infarction complicated by cardiogenic shock. The primary end point was 30-day all-cause mortality and the secondary end point was the composite events of major adverse cardiovascular events (MACEs). In 218 patients, 71 (32.6%) were patients with mrEF. Compared with those with pEF, patients with mrEF had some similar clinical characteristics to that of rEF. The 30-day all-cause mortality in patients with rEF, mrEF, and pEF were 72.7%, 56.3%, and 32.0%, respectively (p = 0.001). The 30-day MACE were 90.9%, 69.0%, and 60.2%, respectively (p = 0.001). After multivariable adjustment, patients with mrEF and rEF had comparable 30-day all-cause mortality (hazard ratio [HR] = 0.81, 95% confidence interval [CI] 0.50 to 1.33, p = 0.404), and pEF was associated with decreased risk of 30-day all-cause mortality compared with rEF (HR = 0.41, 95% CI 0.24 to 0.71, p = 0.001). In contrast, the risk of 30-day MACE in mrEF and pEF were lower than that of rEF (HR = 0.62, 95% CI 0.40 to 0.96, p = 0.031 and HR = 0.53, 95% CI 0.34 to 0.80, p = 0.003, respectively). In conclusion, 1/3 of patients with acute myocardial infarction complicated by cardiogenic shock were mrEF. The clinical characteristics and short-term mortality in patients with mrEF were inclined to that of rEF and the occurrence of early left ventricular systolic dysfunction is of prognostic significance.

Macrophages regulate vascular smooth muscle cell function during atherosclerosis progression through IL-1ß/STAT3 signaling.

Vascular smooth muscle cells (VSMCs) play a central role in atherosclerosis progression, but the functional changes in VSMCs and the associated cellular crosstalk during atherosclerosis progression remain unknown. Here we show that scRNA-seq analysis of proximal adjacent (PA) and atherosclerotic core (AC) regions of human carotid artery plaques identifies functional alterations in macrophage-like VSMCs, elucidating the main state differences between PA and AC VSMCs. And, IL-1ß mediates macrophage-macrophage-like VSMC crosstalk through regulating key transcription factors involved in macrophage-like VSMCs functional alterations during atherosclerosis progression. In vitro assays reveal VSMCs trans-differentiated into a macrophage-like phenotype and then functional alterations in response to macrophage-derived stimuli. IL-1ß promots the adhesion, inflammation, and apoptosis of macrophage-like VSMCs in a STAT3 dependent manner. The current findings provide interesting insight into the macrophages-macrophage-like VSMC crosstalk, which would drive functional alterations in the latter cell type through IL-1ß/STAT3 axis during atherosclerosis progression.

The Relationship Between Resilience and Posttraumatic Growth Among the Primary Caregivers of Children With Developmental Disabilities: The Mediating Role of Positive Coping Style and Self-Efficacy.

This study was conducted to investigate the relationship between posttraumatic growth (PTG), resilience, positive coping style, and self-efficacy among the primary caregivers of children with developmental disorders in Chongqing, China. A total of 198 primary caregivers (parents and grandparents) aged from 22 to 66 years old (M = 35.55, SD = 9.16), including 155 females (78.3%) and 43 males (21.7%), were enrolled. The Posttraumatic Growth Inventory, Connor-Davidson Resilience Scale-10, Simplified Coping Style Questionnaire, and General Self-Efficacy Scale were used for data collection. The results found that PTG could be positively predicted by resilience. Positive coping style and self-efficacy mediated the relationship between resilience and PTG. The different levels of PTG were determined by the resident location, monthly income and education of the primary caregivers. The results suggest that it is critical to improve the mental health of the primary caregivers (parents and grandparents) of children with developmental disabilities. Our results also provide a scientific basis for future research.

Biomimetic and bioinspired strategies for oral drug delivery.

Oral drug delivery remains the most preferred approach due to its multiple advantages. Recently there has been increasing interest in the development of advanced vehicles for oral delivery of different therapeutics. Among them, biomimetic and bioinspired strategies are emerging as novel approaches that are promising for addressing biological barriers encountered by traditional drug delivery systems. Herein we provide a state-of-the-art review on the current progress of biomimetic particulate oral delivery systems. Different biomimetic nanoparticles used for oral drug delivery are first discussed, mainly including ligand/antibody-functionalized nanoparticles, transporter-mediated nanoplatforms, and nanoscale extracellular vesicles. Then we describe bacteria-derived biomimetic systems, with respect to oral delivery of therapeutic proteins or antigens. Subsequently, yeast-derived oral delivery systems, based on either chemical engineering or bioengineering approaches are discussed, with emphasis on the treatment of inflammatory diseases and cancer as well as oral vaccination. Finally, bioengineered plant cells are introduced for oral delivery of biological agents. A future perspective is also provided to highlight the existing challenges and possible resolution toward clinical translation of currently developed biomimetic oral therapies.

The efficacy and safety of pulmonary vasodilators in patients with Fontan circulation: a meta-analysis of randomized controlled trials.

No previous meta-analysis has evaluated the efficacy and safety of pulmonary vasodilators in Fontan physiology. Recent relative trials have obtained conflicting results regarding improvements in peak oxygen consumption; the relatively small number of patients in each study may be a limiting factor. We aimed to evaluate the efficacy and safety of pulmonary vasodilators in Fontan patients. Relevant studies were identified by searching the PubMed, Embase, and Cochrane Library databases. Pooled outcomes were determined to assess the efficacy and safety of pulmonary vasodilators in Fontan patients. Nine randomized controlled studies involving 381 patients with Fontan circulation were included. Pulmonary vasodilator therapy led to significant improvement (mean difference = -0.39, 95% CI: [-0.72, -0.05]) in the New York Heart Association (NYHA) functional class. The 6-minute walking distance (6MWD) was significantly increased by 134 m (95% CI: [86.07, 181.94]), and the peak VO2 was also significantly improved (mean difference = 1.42 ml·(kg·min)-1, 95% CI: [0.21, 2.63]). Additionally, the mean pulmonary artery pressure (mPAP) was significantly reduced (mean difference = -2.25 mmHg, 95% CI: [-3.00, -1.50]). No significant change was found in mortality or in brain natriuretic peptide (BNP) or N-terminal pronatriuretic peptide (NT-proBNP). Four studies reported no side effects and good drug tolerance, and two studies reported mild adverse effects. The present meta-analysis indicated that pulmonary vasodilators (primarily the PDE-5 inhibitor and endothelin-1 receptor antagonist) significantly improved the hemodynamics of Fontan patients, reduced the NYHA functional class and increased the 6MWD. The peak oxygen consumption was also improved. No significant change was observed in mortality or in the BNP or NT-proBNP level. Overall, the pulmonary vasodilators were well tolerated. This finding needs to be confirmed in future studies.