Comparative effectiveness of prophylactic strategies for preeclampsia: a network meta-analysis of randomized controlled trials.

OBJECTIVE: Preeclampsia is a common disease during pregnancy that leads to fetal and maternal adverse events. Few head-to-head clinical trials are currently comparing the effectiveness of prophylactic strategies for preeclampsia. In this network meta-analysis, we aimed to compare the efficacy of prophylactic strategies for preventing preeclampsia in pregnant women at risk. DATA SOURCES: Articles published in or before September 2021 from PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, references of key articles, and previous meta-analyses were manually searched. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials comparing prophylactic strategies preventing preeclampsia with each other or with negative controls were included. METHODS: Two reviewers independently extracted data, assessed the risk of bias, and assessed evidence certainty. The efficacy of prophylactic strategies was estimated by frequentist and Bayesian network meta-analysis models. The primary composite outcome was preeclampsia/ pregnancy-induced hypertension. RESULTS: In total, 130 trials with a total of 112,916 patients were included to assess 13 prophylactic strategies. Low-molecular-weight heparin (0.60; 95% confidence interval, 0.42-0.87), vitamin D supplementation (0.65; 95% confidence interval, 0.45-0.95), and exercise (0.68; 95% confidence interval, 0.50-0.92) were as efficacious as calcium supplementation (0.71; 95% confidence interval, 0.62-0.82) and aspirin (0.79; 95% confidence interval, 0.72-0.86) in preventing preeclampsia/pregnancy-induced hypertension, with a P score ranking of 85%, 79%, 76%, 74%, and 61%, respectively. In the head-to-head comparison, no differences were found between these effective prophylactic strategies for preventing preeclampsia and pregnancy-induced hypertension, except with regard to exercise, which tended to be superior to aspirin and calcium supplementation in preventing pregnancy-induced hypertension. Furthermore, the prophylactic effects of aspirin and calcium supplementation were robust across subgroups. However, the prophylactic effects of low-molecular-weight heparin, exercise, and vitamin D supplementation on preeclampsia and pregnancy-induced hypertension varied with different risk populations, dosages, areas, etc. The certainty of the evidence was moderate to very low. CONCLUSION: Low-molecular-weight heparin, vitamin D supplementation, exercise, calcium supplementation, and aspirin reduce the risk of preeclampsia/pregnancy-induced hypertension. No significant differences between effective prophylactic strategies were found in preventing preeclampsia. These findings raise the necessity to reevaluate the prophylactic effects of low-molecular-weight heparin, vitamin D supplementation, and exercise on preeclampsia.

Comparison of intravascular ultrasound-guided with angiography-guided double kissing crush stenting for patients with complex coronary bifurcation lesions: Rationale and design of a prospective, randomized, and multicenter DKCRUSH VIII trial.

BACKGROUND: Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. TRIAL DESIGN: DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. CONCLUSIONS: DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.

Co-ordination between leaf biomechanical resistance and hydraulic safety across 30 sub-tropical woody species.

BACKGROUND AND AIMS: Leaf biomechanical resistance protects leaves from biotic and abiotic damage. Previous studies have revealed that enhancing leaf biomechanical resistance is costly for plant species and leads to an increase in leaf drought tolerance. We thus predicted that there is a functional correlation between leaf hydraulic safety and biomechanical characteristics. METHODS: We measured leaf morphological and anatomical traits, pressure-volume parameters, maximum leaf hydraulic conductance (Kleaf-max), leaf water potential at 50 % loss of hydraulic conductance (P50leaf), leaf hydraulic safety margin (SMleaf), and leaf force to tear (Ft) and punch (Fp) of 30 co-occurring woody species in a sub-tropical evergreen broadleaved forest. Linear regression analysis was performed to examine the relationships between biomechanical resistance and other leaf hydraulic traits. KEY RESULTS: We found that higher Ft and Fp values were significantly associated with a lower (more negative) P50leaf and a larger SMleaf, thereby confirming the correlation between leaf biomechanical resistance and hydraulic safety. However, leaf biomechanical resistance showed no correlation with Kleaf-max, although it was significantly and negatively correlated with leaf outside-xylem hydraulic conductance. In addition, we also found that there was a significant correlation between biomechanical resistance and the modulus of elasticity by excluding an outlier. CONCLUSIONS: The findings of this study reveal leaf biomechanical-hydraulic safety correlation in sub-tropical woody species.

The association of baseline N-terminal pro-B-type natriuretic peptide with short and long-term prognosis following percutaneous coronary intervention in non-ST segment elevation acute coronary syndrome with multivessel coronary artery disease: a retrospective cohort study.

BACKGROUND: Several studies have shown that N-terminal pro-B-type natriuretic peptide (NT-proBNP) is strongly correlated with the complexity of coronary artery disease and the prognosis of patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS), However, it remains unclear about the prognostic value of NT-proBNP in patients with NSTE-ACS and multivessel coronary artery disease (MCAD) undergoing percutaneous coronary intervention (PCI). Therefore, this study aimed to reveal the relationship between NT-proBNP levels and the prognosis for NSTE-ACS patients with MCAD undergoing successful PCI. METHODS: This study enrolled 1022 consecutive NSTE-ACS patients with MCAD from January 2010 to December 2014. The information of NT-proBNP levels was available from these patients. The primary outcome was in-hospital all-cause death. In addition, the 3-year follow-up all-cause death was also ascertained. RESULTS: A total of 12 (1.2%) deaths were reported during hospitalization. The 4th quartile group of NT-proBNP (> 1287 pg/ml) showed the highest in-hospital all-cause death rate (4.3%) (P < 0.001). Besides, logistic analyses revealed that the increasing NT-proBNP level was robustly associated with an increased risk of in-hospital all-cause death (adjusted odds ratio (OR): 2.86, 95% confidence interval (CI) = 1.16-7.03, P = 0.022). NT-proBNP was able to predict the in-hospital all-cause death (area under the curve (AUC) = 0.888, 95% CI = 0.834-0.941, P < 0.001; cutoff: 1568 pg/ml). Moreover, as revealed by cumulative event analyses, a higher NT-proBNP level was significantly related to a higher long-term all-cause death rate compared with a lower NT-proBNP level (P < 0.0001). CONCLUSIONS: The increasing NT-proBNP level is significantly associated with the increased risks of in-hospital and long-term all-cause deaths among NSTE-ACS patients with MCAD undergoing PCI. Typically, NT-proBN P > 1568 pg/ml is related to the all-cause and in-hospital deaths.

Caffeine promotes angiogenesis through modulating endothelial mitochondrial dynamics.

Caffeine induces multiple vascular effects. In this study we investigated the angiogenic effect of physiological concentrations of caffeine with focus on endothelial cell behaviors (migration and proliferation) during angiogenesis and its mitochondrial and bioenergetic mechanisms. We showed that caffeine (10-50 µM) significantly enhanced angiogenesis in vitro, evidenced by concentration-dependent increases in tube formation, and migration of human umbilical vein endothelial cells (HUVECs) without affecting cell proliferation. Caffeine (50 µM) enhanced endothelial migration via activation of cAMP/PKA/AMPK signaling pathway, which was mimicked by cAMP analog 8-Br-cAMP, and blocked by PKA inhibitor H89, adenylate cyclase inhibitor SQ22536 or AMPK inhibitor compound C. Furthermore, caffeine (50 µM) induced significant mitochondrial shortening through the increased phosphorylation of mitochondrial fission protein dynamin-related protein 1 (Drp1) in HUVECs, which increased its activity to regulate mitochondrial fission. Pharmacological blockade of Drp1 by Mdivi-1 (10 µM) or disturbance of mitochondrial fission by Drp1 silencing markedly suppressed caffeine-induced lamellipodia formation and endothelial cell migration. Moreover, we showed that caffeine-induced mitochondrial fission led to accumulation of more mitochondria in lamellipodia regions and augmentation of mitochondrial energetics, both of which were necessary for cell migration. In a mouse model of hindlimb ischemia, administration of caffeine (0.05% in 200 mL drinking water daily, for 14 days) significantly promoted angiogenesis and perfusion as well as activation of endothelial AMPK signaling in the ischemic hindlimb. Taken together, caffeine induces mitochondrial fission through cAMP/PKA/AMPK signaling pathway. Mitochondrial fission is an integral process in caffeine-induced endothelial cell migration by altering mitochondrial distribution and energetics.

Association of in-hospital intensive statins dosage and death in arteriosclerotic cardiovascular disease with percutaneous coronary intervention: insights of multicentre cohort from China.

PURPOSE: In-hospital statin dosage-related effect remains unknown for patients with arteriosclerotic cardiovascular disease (ASCVD). This study aimed to determine the associations of different in-hospital intensive statins dosages with the prognosis for patients in the era of percutaneous coronary intervention (PCI). METHODS: From January 2010 to December 2014, consecutive ASCVD patients receiving PCI were enrolled from five centres in China. All the enrolled patients were classified into high-dose (40 mg atorvastatin or 20 mg rosuvastatin) or low-dose (20 mg atorvastatin or 10 mg rosuvastatin) intensive statin group. In-hospital all-cause death was the primary outcome. RESULTS: Of the 7008 patients included in this study, 5248 received low-dose intensive statins (mean age, 64.28 ± 10.39; female, 25.2%), whereas 1760 received high-dose intensive statins (mean age, 63.68 ± 10.59; female, 23.1%). There was no significant difference in the in-hospital all-cause death between the two groups (adjusted OR, 1.27; 95% CI, 0.43-3.72; P = 0.665). All-cause death was similar between the two groups during the 30-day follow-up period (adjusted HR, 1.28; 95% CI, 0.55-2.97; P = 0.571). However, the high-dose intensive statins were tightly associated with the reduction in in-hospital dialysis (adjusted OR, 0.11; 95% CI, 0.01-0.81; P = 0.030). Besides, primary analyses were confirmed by subgroup analyses. CONCLUSIONS: The in-hospital high-dose intensive statins are not associated with the lower risk of in-hospital or 30-day all-cause death among ASCVD patients undergoing PCI. Given the robust beneficial effect of high-dose intensive statins with in-hospital dialysis, an individualized high-dose intensive statin therapy can be rational in specified populations.

Risk prediction in infective endocarditis by modified MELD-XI score.

The suitability of the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score to predict adverse outcomes in infective endocarditis (IE) patients remains uncertain. This study was performed to explore the prognostic value of the MELD-XI score and modified MELD-XI score for patients with IE. A total of 858 patients with IE were consecutively enrolled and classified into two groups: MELD-XI ≤ 10 (n = 588) and MELD-XI > 10 (n = 270). Multivariate analysis was performed to determine risk factors independent of MELD-XI score. Higher MELD-XI score was associated with higher in-hospital mortality (15.6 vs. 4.8%, p < 0.001) and major adverse clinical events (33.3 vs. 18.4%, p < 0.001). MELD-XI score was an independent predictor of in-hospital death (odds ratio [OR] = 1.06, 95% CI, 1.02-1.10, p = 0.005). Based on a multivariate analysis, NYHA class III or IV (3 points), C-reactive protein > 9.5 mg/L (4 points), and non-surgical treatment (6 points) were added to MELD-XI score. Modified MELD-XI score produced higher predictive power than previous (AUC 0.823 vs. 0.701, p < 0.001). The cumulative incidence of long-term mortality (median 29 months) was significantly higher in patients with modified MELD-XI score > 13 than those without (log-rank = 25.30, p < 0.001). Modified MELD-XI score was independently associated with long-term mortality (hazard ratio = 1.08, 95% CI, 1.04-1.12, p < 0.001). MELD-XI score could be used as a risk assessment tool in IE. Furthermore, modified MELD-XI score remained simple and more effective in predicting poor prognosis.

Novel Risk Biomarker for Infective Endocarditis Patients With Normal Left Ventricular Ejection Fraction　- Monocyte to High-Density Lipoprotein Cholesterol Ratio.

BACKGROUND: The monocyte to high-density lipoprotein cholesterol ratio (MHR) appears to be a newly emerging inflammatory marker. However, its prognostic value in patients with infective endocarditis (IE) and normal left ventricular ejection fraction (LVEF) has been unclear.Methods and Results:We enrolled consecutive patients with IE and normal LVEF and divided into 3 groups based on the tertiles of MHR. Of 698 included patients, 44 (6.3%) died while in hospital. The occurrence of in-hospital death (3.9%, 4.3%, and 10.8%, P=0.003) and of major adverse clinical events (MACEs) (15.6%, 20.9%, and 30.6%, P<0.001) increased from the lowest to the highest MHR tertiles, respectively. Receiver-operating characteristic analysis demonstrated that MHR had good predictive value for in-hospital death (area under the curve [AUC] 0.670, 95% confidence interval [CI] 0.58-0.76, P<0.001) and was similar to C-reactive protein (AUC 0.670 vs. 0.702, P=0.444). Furthermore, MHR >21.3 had a sensitivity of 74.4% and specificity of 57.6% for predicting in-hospital death. Multiple analysis showed that MHR >21.3 was an independent predictor of both in-hospital (odds ratio 3.98, 95% CI 1.91-8.30, P<0.001) and long-term death (hazard ratio 2.29, 95% CI 1.44-3.64, P<0.001) after adjusting for age, female, diabetes mellitus, estimated glomerular filtration rate <90 mL/min/1.73 m2, and surgical treatment. Kaplan-Meier survival curves showed that patients with MHR >21.3 had an increased rate of long-term death compared to those without (P=0.002). CONCLUSIONS: Elevated MHR was independently associated with in-hospital and long-term death in patients with IE and normal LVEF.

The impact of admission neutrophil-to-platelet ratio on in-hospital and long-term mortality in patients with infective endocarditis.

BACKGROUND: Infective endocarditis (IE) is associated with increased neutrophil and reduced platelet counts. We assessed the relationship between the neutrophil-to-platelet ratio (NPR) on admission and adverse outcomes in patients with IE. METHODS: Patients diagnosed with IE between January 2009 and July 2015 (n=1293) were enrolled, and 1046 were finally entered into the study. Study subjects were categorized into four groups according to NPR quartiles: Q1<18.9 (n=260); Q2: 18.9-27.7 (n=258); Q3: 27.7-43.3 (n=266); and Q4>43.3 (n=262). Cox proportional hazards regression was performed to identify risk factors for long-term mortality; the optimal cut-off was evaluated by receiver operating characteristic curves. RESULTS: Risk of in-hospital death increased progressively with NPR group number (1.9 vs. 5.0 vs. 9.8 vs. 14.1%, p<0.001). The follow-up period was a median of 28.8 months, during which 144 subjects (14.3%) died. Long-term mortality increased from the lowest to the highest NPR quartiles (7.6, 11.8, 17.4, and 26.2%, respectively, p<0.001). Multivariate Cox proportional hazard analysis revealed that lgNPR (HR=2.22) was an independent predictor of long-term mortality. Kaplan-Meier survival curves showed that subjects in Q4 had an increased long-term mortality compared with the other groups. CONCLUSIONS: Increased NPR was associated with in-hospital and long-term mortality in patients with IE. As a simple and inexpensive index, NPR may be a useful and rapid screening tool to identify IE patients at high risk of mortality.

The 100 most-cited articles on aortic dissection.

BACKGROUND: To identify and characterize the most frequently cited articles that have been published on aortic dissection. METHODS: A list of the 100 most frequently cited publications (T100) about aortic dissection was generated by performing a searching of the Science Citation Index--Expanded using "aortic dissection" as the search term. Basic information about the articles was recorded, including number of citations, journal title, journal impact factor, time since publication, first author's country, topic/subspecialty of the research, and publication type. RESULTS: We finally included 180 articles on aortic dissection, from which we identified the 100 most frequently cited articles (T100). The most frequently cited article received 1079 citations, while the least frequently cited article received 68 (mean140.5 citations per article). The T100 originated from 19 countries, with more than half of them originating from the USA (n = 97). The T100 articles were published from 1955 to 2013, with 79% published during the period 1990-2009. In addition, there were 40 different journals with Circulation having the most citations (n = 38). Regarding the article type, there were 21 basic and 140 clinical research articles, one meta-analysis, and 18 review articles. Reviews had the highest mean number of citations (mean 235.5 citations per article). CONCLUSIONS: Our study provides a historical perspective on the progress of dissection research, and helps to identify the quality of the work, the discoveries made, and the trends steering the studies.

Additive prognostic value of left ventricular ejection fraction to the TIMI risk score for in-hospital and long-term mortality in patients with ST segment elevation myocardial infarction.

To investigate whether the addition of left ventricular ejection fraction (LVEF) to the TIMI risk score enhances the prediction of in-hospital and long-term death in ST segment elevation myocardial infarction (STEMI) patients. 673 patients with STEMI were divided into three groups based on TIMI risk score for STEMI: low-risk group (TIMI ≤3, n = 213), moderate-risk group (TIMI 4-6, n = 285), and high-risk group (TIMI ≥7, n = 175). The predictive value was evaluated using the receiver operating characteristic. Multivariate logistic regression was used to determine risk predictors. The rates of in-hospital death (0.5 vs 3.2 vs 10.3 %, p < 0.001) and major adverse cardiovascular events (14.6 vs 22.5 vs 40.6 %, p < 0.001) were significantly higher in high-risk group. Multivariate analysis showed that TIMI risk score (OR 1.24, 95 % CI 1.04-1.48, P = 0.015) and LVEF (OR 3.85, 95 % CI 1.58-10.43, P = 0.004) were independent predictors of in-hospital death. LVEF had good predictive value for in-hospital death (AUC: 0.838 vs 0.803, p = 0.571) or 1-year death (AUC: 0.743 vs 0.728, p = 0.775), which was similar to TIMI risk score. When compared with the TIMI risk score alone, the addition of LVEF was associated with significant improvements in predicting in-hospital (AUC: 0.854 vs 0.803, p = 0.033) or 1-year death (AUC: 0.763 vs 0.728, p = 0.016). The addition of LVEF to TIMI risk score enhanced net reclassification improvement (0.864 for in-hospital death, p < 0.001; 0.510 for 1-year death, p < 0.001). LVEF was associated with in-hospital and long-term mortality in STEMI patients and had additive prognostic value to TIMI risk score.

Different leaf cost-benefit strategies of ferns distributed in contrasting light habitats of sub-tropical forests.

BACKGROUND AND AIMS: Ferns are abundant in sub-tropical forests in southern China, with some species being restricted to shaded understorey of natural forests, while others are widespread in disturbed, open habitats. To explain this distribution pattern, we hypothesize that ferns that occur in disturbed forests (FDF) have a different leaf cost-benefit strategy compared with ferns that occur in natural forests (FNF), with a quicker return on carbon investment in disturbed habitats compared with old-growth forests. METHODS: We chose 16 fern species from contrasting light habitats (eight FDF and eight FNF) and studied leaf functional traits, including leaf life span (LLS), specific leaf area (SLA), leaf nitrogen and phosphorus concentrations (N and P), maximum net photosynthetic rates (A), leaf construction cost (CC) and payback time (PBT), to conduct a leaf cost-benefit analysis for the two fern groups. KEY RESULTS: The two groups, FDF and FNF, did not differ significantly in SLA, leaf N and P, and CC, but FDF had significantly higher A, greater photosynthetic nitrogen- and phosphorus-use efficiencies (PNUE and PPUE), and shorter PBT and LLS compared with FNF. Further, across the 16 fern species, LLS was significantly correlated with A, PNUE, PPUE and PBT, but not with SLA and CC. CONCLUSIONS: Our results demonstrate that leaf cost-benefit analysis contributes to understanding the distribution pattern of ferns in contrasting light habitats of sub-tropical forests: FDF employing a quick-return strategy can pre-empt resources and rapidly grow in the high-resource environment of open habitats; while a slow-return strategy in FNF allows their persistence in the shaded understorey of old-growth forests.

Brain natriuretic peptide for prevention of contrast-inducednephropathy: a meta-analysis of randomized controlled trials.

PURPOSE: Contrast-induced nephropathy (CIN) is a serious complication and associated with poor clinical outcomes. The protective value of brain natriuretic peptide (BNP) administration on CIN is still controversial in patients undergoing percutaneous coronary intervention (PCI) or coronary angiography (CAG). We performed a meta-analysis of randomized controlled trials (RCTs) for BNP in preventing CIN. METHODS: We systematically searched PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov for RCTs comparing administration of BNP versus non-BNP for preventing CIN. Publication bias was assessed by funnel plots. Relative risk (RR) was calculated for incidence of CIN and major adverse cardiovascular events (MACEs) using the random or fixed effect model according to heterogeneity analysis. RESULTS: There were five RCTs with 1441 patients in this analysis. BNP treatment was associated with lower incidence of CIN (RR = 0.38, 95 % CI 0.27-0.54, p < 0.001) and MACEs (RR = 0.47, 95 % CI 0.24-0.95, p = 0.034) with no significant heterogeneity (I 2 = 0 %, p = 0.701; I 2 = 60 %, p = 0.113, respectively). Similar results were seen in subgroup analysis. Prophylactic BNP significantly decreased the incidence of CIN after cardiac catheterization in the studies of regarding sodium chloride as placebo (I 2 = 0 %, RR = 0.39, 95 % CI 0.27-0.56, p < 0.001) or JADAD score > 3 (I 2 = 0 %, RR = 0.38, 95 % CI 0.21-0.68, p = 0.001). CONCLUSIONS: Preprocedural BNP treatment significantly decreased the incidence of CIN and short-term MACEs in patients undergoing PCI or CAG.

N-terminal pro-brain natriuretic peptide improves the C-ACS risk score prediction of clinical outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: It remained unclear whether the combination of the Canada Acute Coronary Syndrome Risk Score (CACS-RS) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) could have a better performance in predicting clinical outcomes in acute ST-elevation myocardial infarction (STEMI) patients with primary percutaneous coronary intervention. METHODS: A total of 589 consecutive STEMI patients were enrolled. The potential additional predictive value of NT-pro-BNP with the CACS-RS was estimated. Primary endpoint was in-hospital mortality and long-term poor outcomes. RESULTS: The incidence of in-hospital death was 3.1%. Patients with higher NT-pro-BNP and CACS-RS had a greater incidence of in hospital death. After adjustment for the CACS-RS, elevated NT-pro-BNP (defined as the best cutoff point based on the Youden's index) was significantly associated with in hospital death (odd ratio = 4.55, 95%CI = 1.52-13.65, p = 0.007). Elevated NT-pro-BNP added to CACS-RS significantly improved the C-statistics for in-hospital death, as compared with the original score (0.762 vs. 0.683, p = 0.032). Furthermore, the addition of NT-pro-BNP to CACS-RS enhanced net reclassification improvement (0.901, p < 0.001) and integrated discrimination improvement (0.021, p = 0.033), suggesting effective discrimination and reclassification. In addition, the similar result was also demonstrated for in-hospital major adverse clinical events (C-statistics: 0.736 vs. 0.695, p = 0.017) or 3-year mortality (0.699 vs. 0.604, p = 0.004). CONCLUSIONS: Both NT-pro-BNP and CACS-RS are risk predictors for in hospital poor outcomes in patients with STEMI. A combination of them could derive a more accurate prediction for clinical outcome s in these patients.

Ticagrelor alleviates pyroptosis of myocardial ischemia reperfusion-induced acute lung injury in rats: a preliminary study.

Pulmonary infection is highly prevalent in patients with acute myocardial infarction undergoing percutaneous coronary intervention. However, the potential mechanism is not well characterized. Myocardial ischemia-reperfusion injury (MIRI) induces acute lung injury (ALI) related to pulmonary infection and inflammation. Recent studies have shown that pyroptosis mediates ALI in several human respiratory diseases. It is not known whether MIRI induces pyroptosis in the lungs. Furthermore, ticagrelor is a clinically approved anti-platelet drug that reduces ALI and inhibits the expression levels of several pyroptosis-associated proteins, but the effects of ticagrelor on MIRI-induced ALI have not been reported. Therefore, we investigated whether ticagrelor alleviated ALI in the rat MIRI model, and its effects on pyroptosis in the lungs. Sprague-Dawley rats were randomly divided into four groups: control, MIRI, MIRI plus low ticagrelor (30 mg/kg), and MIRI plus high ticagrelor (100 mg/kg). Hematoxylin and Eosin (HE) staining was performed on the lung sections, and the HE scores were calculated to determine the extent of lung pathology. The wet-to-dry ratio of the lung tissues were also determined. The expression levels of pyroptosis-related proteins such as NLRP3, ASC, and Cleaved caspase-1 were estimated in the lung tissues using the western blot. ELISA was used to estimate the IL-1ß levels in the lungs. Immunohistochemistry was performed to determine the levels of MPO-positive neutrophils as well as the total NLRP3-positive and Cleaved caspase-1-positive areas in the lung tissues. The lung tissues from the MIRI group rats showed significantly higher HE score, wet-to-dry ratio, and the MPO-positive area compared to the control group, but these effects were attenuated by pre-treatment with ticagrelor. Furthermore, lung tissues of the MIRI group rats showed significantly higher expression levels of pyroptosis-associated proteins, including NLRP3 (2.1-fold, P < 0.05), ASC (3.0-fold, P < 0.01), and Cleaved caspase-1 (9.0-fold, P < 0.01). Pre-treatment with the high-dose of ticagrelor suppressed MIRI-induced upregulation of NLRP3 (0.46-fold, P < 0.05), ASC (0.64-fold, P < 0.01), and Cleaved caspase-1 (0.80-fold, P < 0.01). Immunohistochemistry results also confirmed that pre-treatment with ticagrelor suppressed MIRI-induced upregulation of pyroptosis in the lungs. In summary, our data demonstrated that MIRI induced ALI and upregulated pyroptosis in the rat lung tissues. Pre-treatment with ticagrelor attenuated these effects.

SMARCA5 reprograms AKR1B1-mediated fructose metabolism to control leukemogenesis.

A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia.

Contrast medium volume to creatinine clearance ratio: a predictor of contrast-induced nephropathy in the first 72 hours following percutaneous coronary intervention.

OBJECTIVES: To investigate the predictive value of the contrast media volume to creatinine clearance (V/CrCl) ratio for the risk of contrast-induced nephropathy (CIN) (i.e., within 48-72 hr) and to determine a relatively safe V/CrCl cut-off value to avoid CIN in patients following percutaneous coronary intervention (PCI). BACKGROUND: The V/CrCl ratio is a pharmacokinetic risk factor for an early abnormal increase in serum creatinine (i.e., within 24 hr) after PCI. METHODS: V/CrCl ratios were obtained from 1,140 consecutive consenting patients after unselective PCI. Receiver-operator characteristic (ROC) curves were used to identify the optimal sensitivity for the observed range of V/CrCl. The predictive value of V/CrCl for the risk of CIN was assessed using multivariate logistic regression. RESULTS: Fifty-five (4.8%) patients out of 1,140 developed CIN. There was a significant association between higher V/CrCl ratio values and risk of CIN in the overall population: 1.4%, 1.4%, 5.7%, and 10.9% for quartile 1 (Q1) of the V/CrCl value (<1.56, n = 283), Q2 (1.56-2.27, n = 289), Q3 (2.28-3.42, n = 282), and Q4 (>3.42, n = 285) of contrast, respectively (P < 0.001). ROC curve analysis indicated that a V/CrCl ratio of 2.62 was a fair discriminator for CIN (C-statistic 0.73). After adjusting for other known predictors of CIN, V/CrCl ratios > 2.62 remained significantly associated with CIN (odds ratio: 2.20; 95% confidence interval: 1.00-4.81, P < 0.05). CONCLUSION: A V/CrCl ratio > 2.62 was a significant and independent predictor of CIN after PCI in unselected patients.

[Increased platelet-leukocyte aggregates in patients with acute coronary syndrome].

OBJECTIVE: To compare the platelet-leukocyte-aggregates (PLAs) level among patients with acute coronary syndrome (ACS) and stable angina pectoris (SAP). METHODS: Hospitalized patients were divided into three groups [ACS group (n=86), SAP group (n=54), the control group with 46 patients without coronary artery disease]. PLAs were measured by flow cytometry at admission before coronary angiography. ACS patients were further divided into low-risk group (0-108 points) and high-risk group (>109 points) according to GRACE scores at admission. PLA, platelet-monocyte aggregations (PMA), platelet-neutrophil aggregations (PNA), platelet-lymphocyte aggregations (PlyA) and hs-CRP values were compared among groups. RESULTS: PLA (4.40%±3.08%), PMA (33.6%±21.5%), PNA (3.76%±5.06%), PLyA (2.03%±1.27%) and hs-CRP [5.75 (3.49, 9.15)] levels in ACS group were significantly higher than those in SAP and control groups (all P<0.05). PLA was also significantly higher in high-risk group than in the low-risk group (44.8%±18.0% vs. 13.0%±6.3%, P<0.01). Spearman correlation analysis showed that hs-CRP was positively correlated with PMA (r=0.547, P<0.01) and GRACE score is positively correlated with PMA, PLA, PNA and PlyA (r=0.746, 0.652, 0.460, respectively, all P<0.01). CONCLUSION: PLAs is increased in ACS patients and higher PMA level is related with the unstable coronary syndrome in ACS patients. Increased PMA, PLA, PNA and PlyA levels is associated with higher GRACE score in ACS patients.