Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly recognized for their role in reducing the risk and improving the prognosis of heart failure (HF). However, the precise mechanisms involved remain to be fully delineated. Evidence points to their potential anti-inflammatory pathway in mitigating the risk of HF. METHODS: A two-sample, two-step Mendelian Randomization (MR) approach was employed to assess the correlation between SGLT-2 inhibition and HF, along with the mediating effects of inflammatory biomarkers in this relationship. MR is an analytical methodology that leverages single nucleotide polymorphisms as instrumental variables to infer potential causal inferences between exposures and outcomes within observational data frameworks. Genetic variants correlated with the expression of the SLC5A2 gene and glycated hemoglobin levels (HbA1c) were selected using datasets from the Genotype-Tissue Expression project and the eQTLGen consortium. The Genome-wide association study (GWAS) data for 92 inflammatory biomarkers were obtained from two datasets, which included 14,824 and 575,531 individuals of European ancestry, respectively. GWAS data for HF was derived from a meta-analysis that combined 26 cohorts, including 47,309 HF cases and 930,014 controls. Odds ratios (ORs) and 95% confidence interval (CI) for HF were calculated per 1 unit change of HbA1c. RESULTS: Genetically predicted SGLT-2 inhibition was associated with a reduced risk of HF (OR 0.42 [95% CI 0.30-0.59], P < 0.0001). Of the 92 inflammatory biomarkers studied, two inflammatory biomarkers (C-X-C motif chemokine ligand 10 [CXCL10] and leukemia inhibitory factor) were associated with both SGLT-2 inhibition and HF. Multivariable MR analysis revealed that CXCL10 was the primary inflammatory cytokine related to HF (MIP = 0.861, MACE = 0.224, FDR-adjusted P = 0.0844). The effect of SGLT-2 inhibition on HF was mediated by CXCL10 by 17.85% of the total effect (95% CI [3.03%-32.68%], P = 0.0183). CONCLUSIONS: This study provides genetic evidence supporting the anti-inflammatory effects of SGLT-2 inhibitors and their beneficial impact in reducing the risk of HF. CXCL10 emerged as a potential mediator, offering a novel intervention pathway for HF treatment.

Metastasis patterns and prognosis in young gastric cancer patients: A propensity score­matched SEER database analysis.

BACKGROUND: Whether young patients with metastatic gastric cancer (GC) had distinct metastasis patterns and survival outcomes from older patients remains controversial. The aim of the present study was to explore the metastasis patterns and prognostic factors in young patients and evaluate the survival outcome in comparison to their older counterparts. MATERIALS AND METHODS: We identified patients with metastatic GC in the surveillance, epidemiology, and end results (SEER) database from 2010 to 2015. The patients were divided into two groups based on age at diagnosis: younger (≤40 years old) and older (>40 years old). We employed the chi-squared test to compare the clinicopathological characteristics between the two age groups. Furthermore, we conducted survival analyses using Kaplan-Meier and Cox regression analyses. To balance disparities in baseline characteristics, we employed propensity score matching (PSM). RESULTS: We identified 5,580 metastatic GC patients from the SEER database, with 237 (4.2%) classified as younger and 5343 (95.8%) as older patients. A total of 237 pairs of patients were generated after adjustment by PSM. Patients in the younger group exhibited a higher proportion of bone-only metastases and a lower proportion of liver-only metastases compared with patients in the older group. Multivariate Cox regression analysis demonstrated that youth was an independent protective factor for overall survival (OS) before and after PSM, but not for gastric cancer-specific survival (GCSS). Among the younger group, patients with liver-only metastasis demonstrated the best prognosis, whereas patients with lung-only metastasis exhibited significantly worse survival outcomes compared with liver-only metastases, even comparable to that of bone metastasis. CONCLUSIONS: Compared with the older group, the metastatic GC patients in the younger group exhibited more aggressive tumors but better prognoses. The metastasis pattern and its effect on the prognosis of GC varied by age group.

Relationship between the health poverty vulnerability and multimorbidity patterns identified with latent class analysis aged 45 years or more adults in Northwestern China: A cross-section study.

This study aims to identify multimorbidity patterns and examine whether health poverty vulnerability (HPV) varies among adults aged 45 years or more. Data from 4338 participants were extracted from a Chinese cross-sectional study. Latent class analysis was used to identify multimorbidity patterns based on 11 self-reported chronic diseases. A 3-stage feasible generalized least-squares method was used to measure the HPV. The associations and influencing factors were analyzed using the Tobit model. The mean HPV values were 0.105 ±â€…0.225 and 0.329 ±â€…0.357, based on extreme poverty and those of low- and middle-income countries' poverty line, respectively. Four latent multimorbidity patterns were identified, comprising hypertension (57.33%), cardiovascular diseases (19.94%), the musculoskeletal system (13.09%), and spine (9.64%). The HPV value from hypertension (coefficient [Coef] =0.03, 95% confidence interval (CI) = 0.00-0.05) was significantly higher than that of the musculoskeletal system based on extreme poverty. In addition, the HPV values for hypertension (Coef =0.08, 95% CI = 0.05-0.11), spine (Coef =0.06, 95% CI = 0.02-0.11), and cardiovascular diseases (Coef =0.07, 95% CI = 0.03-0.11) were significantly high based on low- and middle-income countries' poverty line. Age ≥75 years, registered poor households, catastrophic medical expenditure, and toilet style were major risk factors. Although the multimorbidity pattern-induced HPV has been significant improved on extreme poverty, it still poses a very serious challenge with regard to low- to middle-income countries' poverty line. The sensitivity analysis proved the robustness of the results. Policymakers should focus on adults with 3 multimorbidity patterns, namely, registered poor households, age ≥75 years, and catastrophic health expenditure, to adopt targeted interventions to prevent and eliminate HPV.

Housing conditions, cooking fuels, and health-related quality of life among rural middle-aged and elderly in northwest China: A ten-year balanced panel study.

To investigate the impacts of improving housing conditions and transitioning to clean cooking fuels on health-related quality of life (HRQOL) among middle-aged and elderly populations in rural China. METHODS: Using a 10-year longitudinal follow-up study, we examined changes in housing conditions, cooking fuel use, and HRQOL among 690 Chinese adults aged 45 above in rural areas. HRQOL was assessed using the European Quality of Life-5 Dimensions 3 Levels (EQ-5D-3L) questionnaire. Generalized estimating equations were utilized to analyze correlations between variables. RESULTS: Using four-period balanced panel data of 10 years, there were significant differences in the self-reporting of mobility, self-care, usual activities, pain / discomfort and anxiety / depression in rural middle-aged and elderly people (p < 0.05). In terms of the EQ-5D index score and EQ-VAS score, showed a decreasing trend (p < 0.05). The housing area, housing material type, utilization of sanitary toilets, separation of housing and kitchen were separated and non-solid fuels used as cooking fuel were significantly associated with high HRQOL (p < 0.05). CONCLUSIONS: This study found that good housing conditions and the use of non-solid cooking fuel had positive effects on health-related quality of life of middle-aged and elderly people in rural areas of northwest China.

Jiawei Taohe Chengqi decoction inhibition of the notch signal pathway affects macrophage reprogramming to inhibit HSCs activation for the treatment of hepatic fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Taohe Chengqi Tang (JTCD) is a modified formulation of Traditional Chinese Medicine (TCM) known as Taohe Chengqi Decoction, which has been described in the ancient TCM literature "Treatise on Febrile Diseases". As a formula that can activate blood circulation and eliminate blood stasis and regulate Yin and Yang in traditional Chinese medicine applications, JTCD has been reported to be effective in the treatment of chronic liver disease and hepatic fibrosis (HF). AIM OF STUDY: The current study aimed to evaluate the effectiveness of JTCD in modulating hepatic macrophages by regulating the Notch signal pathway, and to further investigate the mechanisms underlying macrophage reprogramming that leads to HF. MATERIALS AND METHODS: Molecular assays were performed using in vitro cultures of human mononuclear THP-1 cells and human-derived hepatic stellate cells LX-2. CCl4-induced mice were utilized as an in vivo model to simulate HF. RESULTS: Our results demonstrated that JTCD exhibited dual effects by inhibiting hepatic stellate cell (HSCs) activation and modulating the polarisation of macrophages towards the M2 phenotype while decreasing the M1 phenotype. Network pharmacological analyses and molecular docking studies revealed that the Notch signal pathway was significantly enriched and played a crucial role in the therapeutic response of JTCD against HF. Moreover, through the establishment of a co-culture model, we validated that JTCD inhibited the Notch signal pathway in macrophages, leading to alterations in macrophage reprogramming, subsequent inhibition of HSC activation, and ultimately exerting anti-HF effects. CONCLUSION: In conclusion, our findings provide solid evidence for JTCD in treating HF, as it suppresses the Notch signal pathway in macrophages, regulates macrophage reprogramming, and inhibits HSC activation.

The Synergistic Effect in CdS/g-C3N4 Nanoheterojunctions Improves Visible Light Photocatalytic Performance for Hydrogen Evolution Reactions.

This study focuses on the development of heterojunction photocatalysts for the efficient utilization of solar energy to address the energy crisis and reduce environmental pollution. Cadmium sulfide (CdS)/graphite-type carbon nitride (g-C3N4) nanocomposites were synthesized using a hydrothermal method, and their photoelectrochemical properties and photocatalytic performance for hydrogen evolution reaction (HER) were characterized. Scanning electron microscope images showed the intimate interface and caviar-like nanoheterojunction of the CdS nanoparticles on g-C3N4 nanospheres, suggesting their potential involvement in the photocatalytic process. Electrochemical and spectroscopic analyses were conducted to confirm the roles of CdS in the nanoheterojunction. The results showed that 10 wt% CdS/g-C3N4 nanospheres exhibited higher photocatalytic activity than pure g-C3N4 under visible light irradiation. A HER rate of 655.5 µmol/g/h was achieved after three photocatalytic cycles, signifying good photocatalytic stability. The synergistic effect of the Z-scheme heterojunction formed by g-C3N4 and CdS was identified as the main factor responsible for the enhanced photocatalytic performance and stability. The interface engineering effect of CdS/g-C3N4 facilitated the separation of photogenerated electrons and holes. This study provides insights into the design and fabrication of efficient HER photocatalysts.

New Perspectives on Chinese Medicine in Treating Hepatic Fibrosis: Lipid Droplets in Hepatic Stellate Cells.

Hepatic fibrosis (HF) is a wound healing response featuring excessive deposition of the extracellular matrix (ECM) and activation of hepatic stellate cells (HSCs) that occurs during chronic liver injury. As an initial stage of various liver diseases, HF is a reversible pathological process that, if left unchecked, can escalate into cirrhosis, liver failure, and liver cancer. HF is a life-threatening disease presenting morbidity and mortality challenges to healthcare systems worldwide. There is no specific and effective anti-HF therapy, and the toxic side effects of the available drugs also impose a heavy financial burden on patients. Therefore, it is significant to study the pathogenesis of HF and explore effective prevention and treatment measures. Formerly called adipocytes, or fat storage cells, HSCs regulate liver growth, immunity, and inflammation, as well as energy and nutrient homeostasis. HSCs in a quiescent state do not proliferate and store abundant lipid droplets (LDs). Catabolism of LDs is characteristic of the activation of HSCs and morphological transdifferentiation of cells into contractile and proliferative myofibroblasts, resulting in the deposition of ECM and the development of HF. Recent studies have revealed that various Chinese medicines (e.g., Artemisia annua, turmeric, Scutellaria baicalensis Georgi, etc.) are able to effectively reduce the degradation of LDs in HSCs. Therefore, this study takes the modification of LDs in HSCs as an entry point to elaborate on the process of Chinese medicine intervening in the loss of LDs in HSCs and the mechanism of action for the treatment of HF.

Jiawei Taohe Chengqi Decoction attenuates hepatic fibrosis by preventing activation of HSCs through regulating Src/ERK/Smad3 signal pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Taohe Chengqi Decoction (JTCD) is a Traditional Chinese Medicine (TCM) formula modified from Taohe Chengqi Decoction in the classic ancient literature of TCM "Treatise on Febrile Diseases". Clinical and pharmacological studies have shown that JTCD has a therapeutic effect on hepatic encephalopathy, non-alcoholic fatty liver, cirrhotic ascites, and can alleviate acute liver injury in rats. Our previous studies confirmed that JTCD could alleviate hepatic fibrosis and activation of hepatic stellate cells (HSCs). However, its mechanism remains unclear. AIM OF THE STUDY: This study aimed to elucidate the mechanism of Src Signal on hepatic fibrosis and HSCs activation, and whether JTCD inhibited hepatic fibrosis and HSCs activation through affecting Src Signal. MATERIALS AND METHODS: In vivo, sixty specific pathogen free male C57/BL6 mice were divided into following six groups: Control group, Model group, SARA group, JTCD low dose group, JTCD medium dose group and JTCD high dose group. Then we established a carbon tetrachloride (CCL4)-induced hepatic fibrosis mice model, each JTCD group was given the corresponding dose of JTCD by gavage, the SARA group was given Saracatinib and the control group was given saline, once a day for 4 consecutive weeks. UPLC-Q-TOF-MS analyzed chemical components of JTCD. Pathological examination including Hematoxylin and Eosin (H&E), Masson and Sirius red staining was used to observe the characteristic of hepatic fibrosis. Automatic biochemical analyzer detected the levels of alanine aminotransfease (ALT), and aspartate transaminase (AST) in serum. Western-blot and immunohistochemical staining (IHC) detected protein expression. In vitro, we used shRNA to knock down the expression of Src in immortalized human hepatic stellate cell line (LX-2), then intervened with ERK1/2 agonists/inhibitors and JTCD-containing serum after transforming growth factor ß1 (TGF-ß1) treatment. Immunofluorescence and western-blot detected protein expression. The migratory characteristic of HSCs was assessed by wound-healing assay. RESULTS: We identified 135 chemical components in the water extract of JTCD, and the water extract of JTCD contains a variety of anti-hepatic fibrosis components. Compared to the model group, hepatic fibrosis performance was significantly improved, the serum levels of ALT and AST were significantly decreased in JTCD groups and SARA group, IHC staining and western blot results indicated that JTCD decreased the expressions of α-smooth muscle actin (α-SMA), phospho-Src (Tyr416), phospho-ERK1/2 and phospho-Smad3. In vitro, JTCD-containing serum could significantly decrease the protein expressions of α-SMA, phospho-Src (Tyr416), phospho-ERK1/2 and phospho-Smad3 according to the results of western-blot and immunofluorescence, in addition, JTCD-containing serum inhibited the mobility and activation of LX-2. What's more, after intervening with Src-shRNA, ERK1/2 agonists/inhibitors and JTCD-containing serum, the western-blot results showed that Src/ERK/Smad3 signal has an important role in hepatic fibrosis and HSCs, and JTCD attenuates hepatic fibrosis by preventing activation of HSCs through regulating Src/ERK/Smad3 signal pathway. CONCLUSIONS: The results showed that Src kinase promoted hepatic fibrosis and HSCs activation through the ERK/Smad3 signal pathway. More importantly, the mechanism by which JTCD attenuated hepatic fibrosis and HSCs activation was by inhibiting the Src/ERK/Smad3 signal pathway.

Clinical benefit of sodium-glucose transport protein-2 inhibitors in patients with heart failure: An updated meta-analysis and trial sequential analysis.

To assess whether the current body of accumulated data can give convincing evidence in favor of sodium-glucose transport protein-2 inhibitor (SGLT-2i) in all types of heart failure (HF). We searched for randomized controlled trials contrasting the effectiveness of SGLT-2i to placebo or other hypoglycemic medications on clinicaltrials.gov, PubMed, and the Cochrane Library database. To gauge effect size, hazard ratios (HR) were employed as measurements. The composite outcome of cardiovascular death or hospitalization owing to HF was the primary endpoint. Eleven studies were included. In comparison to the control group, the data demonstrated that SGLT-2i is related with a decreased incidence of composite outcome (HR: 0.77, 95% CIs: 0.73-0.81, I 2 = 0%, P < 0.01), CV death (HR: 0.87, 95% CIs: 0.81-0.94, I 2 = 3%, P < 0.01), all-cause mortality (HR: 0.90, 95% CIs: 0.84-0.96, I 2 = 10%, P < 0.01), and hospitalization due to HF (HHF) (HR: 0.70, 95% CIs: 0.66-0.75, I 2 = 0%, P < 0.01). The trial sequential analysis found strong evidence of a decrease in the incidence of all clinical outcomes with SGLT-2i when compared to the control group. Subgroup analysis demonstrated that the association between SGLT-2i and clinical outcome was independent of population characteristics. We confirm that the present evidence supports the use of SGLT-2i in a wide range of HF patients. Systematic review registration: [https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42022333279].

The mediation path of physical multimorbidity on the vulnerability to health-related poverty of rural aging families in Ningxia, China: A cross-sectional survey.

Background: Vulnerability to health-related poverty can predict the probability of families falling into poverty due to health risk impact. In this study, we measured the vulnerability to health-related poverty and examined the mediation path of physical multimorbidity on the vulnerability to health-related poverty of rural aging families in Ningxia, China. Methods: This cross-sectional study was conducted in Ningxia, China, in February 2019. A multi-stage stratified cluster-randomized design was used to obtain a representative sample in each county. We included participants aged 60 years and older, who had lived there for more than 1 year. A total of 3,653 rural residents older than 60 years old were selected as the research subjects. The three-stage generalized least square method was used to calculate the expected vulnerability to poverty. We used mediating effect model to test the mediation path of poverty vulnerability related to the physical multimorbidity. Results: Under different poverty line standards, i.e., $1.9/day as low vs. $3.1/day as the high poverty line, the proportion of families that could fall into poverty in the future was 5.3 and 53.7%, respectively. The prevalence of chronic diseases and physical multimorbidity among rural residents >60 years old was 64.62 and 21.24%, respectively. The results of mediating effect test showed that self-rated health status (indirect effect a × b = -0.0052), non-agricultural employment (a × b= -0.0046), household cattle production (a × b = 0.0004), housing type (a × b = -0.0008), gift expenses (a × b = 0.0006) and loan for illness (a × b = 0.0034) were the mediation paths of poverty vulnerability related to the physical multimorbidity. Conclusions: Concerted efforts are needed to reduce poverty vulnerability related to the physical multimorbidity. The strategy of alleviating poverty should emphasis on promoting non-agricultural employment of vulnerable groups sustainability and developing rural economy, which are important paths to reduce family's vulnerability to health-related poverty.

Thymosin Beta 15 Alters the Spatial Development of Thymic Epithelial Cells.

The thymus is the most sensitive organ under various pathophysiological conditions, such as aging, starvation, and infection. As a key stromal cell for T cell development, it is well-known that thymic epithelial cells (TECs) play an important role in the thymus response to the external environment. Thymosin beta 15 (Tß15) is a G-actin binding protein secreted by TECs, it plays an important role in maintaining the dynamic balance of actin, angiogenesis, axonal formation, and wound healing, but the relationship between Tß15 and TECs is not clear yet. Here, we show the impact of Tß15 on the TEC's spatial development, as well as the T-cell differentiation and thymic output. As a result, TEC is the main effector cell of Tß15 in the thymus. Tß15 OX inhibits the chemotaxis of TECs to the medulla and subsequently blocks the positive selection of thymocytes from CD3+TCRß+CD4+CD8+ double positive cells to CD3+TCRß+CD4+CD8- single-positive (CD4SP) cells. Tß15-knockdown accelerates the reticular differentiation of astral TECs and medullary TECs. Importantly, mice implanted with Tß15-knockdown iTECs show high thymic output but low peripheral T cell maturity and activity. In a word, our results explain the role of Tß15 on the differentiation and function of TECs and provide a new perspective for understanding the process of thymus development and degeneration.

Benefit of sodium-glucose cotransporter-2 inhibitors on survival outcome is related to the type of heart failure: A meta-analysis.

AIMS: This meta-analysis aimed to evaluate the efficacy of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in different types of heart failure (HF). METHODS: Randomized controlled trials (RCTs) comparing SGLT-2 inhibitors with placebo in patients with HF were searched in PubMed, the Cochrane Library database, and clinicaltrials.gov. A random-effects model was used for evidence synthesis. The primary endpoint was cardiac death. RESULTS: We included 13 studies (12 RCTs). In patients with HF with preserved ejection fraction (HFpEF), SGLT-2 inhibitors reduced the composite endpoint of cardiac death or rehospitalization because of HF (HHF) (HR: 0.78, 95% CI: 0.70-0.87, I2 = 0%, P < 0.001) and that of HHF (HR: 0.74; 95% CI: 0.64-0.85, I2 = 0%, P < 0.001) but not that of cardiac death (HR: 1.01, 95% CI: 0.80-1.28, I2 = 23.9%, P = 0.943). In patients with HF with reduced EF (HFrEF), SGLT-2 inhibitors reduced the composite endpoint of cardiac death or HHF (HR: 0.75, 95% CI: 0.69-0.82, I2 = 0%, P < 0.001) and the individual endpoints of cardiac death (HR: 0.84, 95% CI: 0.75-0.95, I2 = 0%, P = 0.007) and HHF (HR: 0.69, 95% CI: 0.62-0.77, I2 = 0%, P < 0.001). CONCLUSIONS: SGLT-2 inhibitors reduced the risk of cardiac death in patients with HFrEF but not in those with HFpEF.

[Research progress of survival predictive score in veno-arterial extracorporeal membrane oxygenation].

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an extracorporeal circulation technique that provides circulatory and oxygenation support, and it is currently used in the treatment of cardiogenic shock (CS), pulmonary embolism, cardiac arrest (CA), and other diseases. However, this technology is still associated with high complications and mortality. The use of predictive scores for risk stratification before VA-ECMO will be helpful to screen the optimal benefiting population, make optimal clinical decisions, and allocate medical resources reasonably. At present, there are few reports about predictive scores for VA-ECMO. This article systematically reviewed the predictive performance of various scoring tools [the survival after venoarterial ECMO (SAVE) score, prediction of cardiogenic shock outcome for acute myocardial infarction (AMI) patients salvaged by VA-ECMO (ENCOURAGE) score, model for end-stage liver disease (MELD-XI) score, post-cardiotomy extracorporeal membrane oxygenation (PC-ECMO) score, the predicting mortality in patients undergoing VA-ECMO after coronary artery bypass grafting (REMEMBER) score, predictors of mortality with VA-ECMO for acute massive pulmonary embolism, extracorporeal cardiopulmonary resuscitation (ECPR) score, the hypothermia outcome prediction after extracorporeal life support (HOPE) score] for patients receiving VA-ECMO to provide reference for clinical treatment.

The impact of healthcare reform on the dynamic changes in health service utilization and equity: a 10-year follow-up study.

In the past decade, the government of China has implemented healthcare reforms to provide universal access to healthcare by 2020. We aimed to systematically analyse the dynamic changes in health services and equity during the past 10 years to understand the correlation between health services and social-economic status. We performed a longitudinal study in which we extracted aggregated data mainly from a project (2009, 2011, 2012, 2015, 2019). A multi-stage stratified cluster randomized design was used to obtain a representative sample in each county. Concentration indexes were used to analyse the equity of the changes in utilization. We built multivariate random-effects generalized least squares regression models with the panel data to test whether the rate of receiving a medical consultation in the last 2 weeks or the rate of hospital admission or the prevalence of chronic illness was associated with social-economic status including education level and rural disposable income per capita. We found declines in both the rate of not receiving a medical consultation during the last 2 weeks (P < 0.05 intervention group) and the rate of hospital avoidance (P < 0.05) from 2009 to 2019. The equity in residents' health service utilization has improved constantly. We additionally found that rural disposable income per capita is a protective factor for the rate of a receiving a medical consultation during the last 2 weeks and the rate of hospital admission. China's 2009 healthcare reform have positively influenced utilization rates and equity in health service utilization in the past decade, a range of health service-targeted strategies are needed including strengthen the prevention and treatment of chronic diseases, focus attention on the health status of elderly residents and improve social-economic status, especially the level of education.

Comparative differences in the risk of major gastrointestinal bleeding among different direct oral anticoagulants: An updated traditional and Bayesian network meta-analysis.

Background: The most favorable gastrointestinal (GI) bleeding safety profile among different types of direct oral anticoagulants (DOACs) remains controversial. This meta-analysis includes the latest studies and aims to compare GI bleeding risk associated with the use of various DOACs. Methods: PubMed, Cochrane library, and clinicaltrial.gov were searched. Randomized control trials (RCTs) evaluating the safety of DOACs were identified. The primary endpoint assessed was major GI bleeding. Results: A total of 37 RCTs were included in the analyses. Based on the traditional meta-analysis, the major GI bleeding risk was different among various DOACs (interactive p-value <.10). Network meta-analysis findings showed that no DOACs increased the risk of major GI bleeding compared with conventional therapy. Furthermore, a 10 mg daily administration of apixaban reduced the major GI bleeding risk more than daily doses of 60 mg edoxaban, ≥15 mg rivaroxaban, and 300 mg dabigatran etexilate. No difference was observed between daily doses of 300 mg dabigatran etexilate, 60 mg edoxaban, and ≥15 mg rivaroxaban. The major GI bleeding risk associated with 30 mg daily dose of edoxaban was lower than with 10 mg daily rivaroxaban, and no differences between daily 5 mg apixaban, 30 mg edoxaban, and 220 mg dabigatran etexilate were observed. Conclusion: Differences in the major GI bleeding risk were observed when various DOACs were compared. Among standard-dose DOACs, apixaban was associated with the lowest degree of major GI risk. Among low-dose DOACs, edoxaban was associated with a lower major GI bleeding risk than rivaroxaban.

Comparative Effectiveness of Complete Revascularization Strategies in Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Disease: A Bayesian Network Meta-Analysis.

Whether fractional flow reserve (FFR) should be available for revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) is controversial. We aimed to compare the efficacy of various complete revascularization (CR) regimens for STEMI patients with MVD. The PubMed and Cochrane Library databases and clinicaltrial.gov were searched for the randomized controlled trials (RCTs) comparing the FFR-guided CR, angiography-guided CR, and culprit-only revascularization (COR) strategies in STEMI patients with MVD. A Bayesian random-effect model was employed to synthesize the evidence in network meta-analysis. We used relative risk (RR) and 95% credible interval (CrI) as measures of effect size. The primary endpoint was the composite outcome of all-cause mortality or myocardial infarction (MI). Twelve RCTs were included. Angiography-guided CR showed a lower event rate of the composite outcome (RR, 0.68; 95%CrI, 0.50-0.87), all-cause mortality (RR, 0.75; 95%CrI, 0.55-0.96), MI (RR, 0.63; 95%CrI, 0.43-0.86), and repeat revascularization (RR, 0.36; 95% CrI, 0.24-0.55) compared with COR. Additionally, angiography-guided CR had a lower risk of primary outcome (RR, 0.64; 95%CrI, 0.38-0.94) and MI (RR, 0.58; 95%CrI, 0.31-0.92) than FFR-guided CR. The difference between the FFR-guided CR and COR in terms of composite outcome, all-cause mortality, and MI was similar. Angiography-guided CR was associated with the highest probability of optimal treatment for the primary outcome (98.5%), followed by FFR-guided CR (1.2%) and COR (0.3%). STEMI patients with MVD benefitted more from angiography-guided CR than from FFR-guided CR. However, only one study compared the effectiveness of FFR-guided and angiography-guided PCI; thus, the comparison between FFR-guided and angiography-guided PCI relied on indirect evidence. Therefore, further studies directly comparing the effectiveness of these two CR strategies are warranted.

Bleeding risks with novel oral anticoagulants especially rivaroxaban versus aspirin: a meta-analysis.

BACKGROUND: This pairwise meta-analysis determines the difference in bleeding risks associated with the use of novel oral anticoagulants (NOACs) and aspirin. METHODS: PubMed, the Cochrane Library database, clinicaltrial.gov , and related studies were searched for randomized control trials (RCTs) comparing NOAC and aspirin published between January 1, 2000 and May 10, 2021. The primary endpoint was intracranial hemorrhage (ICH). RESULTS: Eleven studies involving 57,645 patients were included. Compared to aspirin, rivaroxaban (5 mg/day) had a similar risk of ICH, major bleeding, and fatal bleeding; rivaroxaban (10 mg/day) had higher risks of gastrointestinal hemorrhage (OR: 1.41; 95% CI: 1.03-1.94; P = 0.032; I2 = 0%) and a similar risk of ICH, major bleeding, and fatal bleeding; and rivaroxaban (15-20 mg/day) had higher risks of ICH (OR: 3.21; 95% CI: 1.36-7.60; P = 0.008; I2 = 0%), major bleeding (OR: 2.64; 95% CI: 1.68-4.16; P < 0.001; I2 = 0%), and fatal bleeding (OR: 2.26; 95% CI: 1.25-4.08; P = 0.007; I2 = 0%) and a similar risk of gastrointestinal hemorrhage. Bleeding outcomes between other NOACs (apixaban and dabigatran etexilate) and aspirin were not different. CONCLUSIONS: The bleeding risks associated with NOACs depend on drug type and dosage. For ≥15 mg/day of rivaroxaban, the risk of ICH was significantly higher than that with aspirin. However, further studies comparing dabigatran etexilate and apixaban versus aspirin are warranted to draw a definite conclusion.

Corrigendum: Acute Myocardial Infarction Detection Using Deep Learning-Enabled Electrocardiograms.

[This corrects the article DOI: 10.3389/fcvm.2021.654515.].

Relationship Between the Eosinophil/Monocyte Ratio and Prognosis in Decompensated Heart Failure: A Retrospective Study.

PURPOSE: The aim of this study was to assess the value of the eosinophil/monocyte ratio (EMR) for predicting the prognosis of decompensated heart failure (HF). PATIENTS AND METHODS: This was a retrospective cohort study. We included adults (≥18 years old) diagnosed with decompensated HF for whom EMR data were available. The patients were divided into three groups according to EMR tertiles (T1 [EMR≤0.15], T2 [0.150.32]). The primary endpoint was the composite outcome of cardiovascular death or HF rehospitalization. RESULTS: Initially, the records of 2264 patients with decompensated HF were screened; 1883 of these patients had EMR data and were therefore included in the study. There were 627 patients in the T1 group, 628 in the T2 group, and 628 in the T3 group. The risk of cardiovascular death or HF rehospitalization was significantly different among the three groups (Log rank test, P=0.007). Compared with the T3 group, both the T1 group (hazard ratio [HR]: 1.50, 95% confidence interval [CI]: 1.16-1.94, P=0.002) and the T2 group (HR: 1.34, 95% CI: 1.03-1.74, P=0.030) had significantly higher rates of cardiovascular death or HF rehospitalization. A Cochran-Armitage test for trend showed a positive correlation between the EMR and the composite outcome of cardiovascular death or HF. There was a significant difference between the three groups in terms of cardiovascular death (Log rank test, P<0.001) and HF rehospitalization (Log rank test, P=0.03). CONCLUSION: The EMR is positively correlated with the risk of cardiovascular death or HF rehospitalization in patients with decompensated HF. Specifically, the lower the EMR, the higher the risk of cardiovascular death or HF rehospitalization.

Acute Myocardial Infarction Detection Using Deep Learning-Enabled Electrocardiograms.

Background: Acute myocardial infarction (AMI) is associated with a poor prognosis. Therefore, accurate diagnosis and early intervention of the culprit lesion are of extreme importance. Therefore, we developed a neural network algorithm in this study to automatically diagnose AMI from 12-lead electrocardiograms (ECGs). Methods: We used the open-source PTB-XL database as the training and validation sets, with a 7:3 sample size ratio. Twenty-One thousand, eight hundred thirty-seven clinical 12-lead ECGs from the PTB-XL dataset were available for training and validation (15,285 were used in the training set and 6,552 in the validation set). Additionally, we randomly selected 205 ECGs from a dataset built by Chapman University, CA, USA and Shaoxing People's Hospital, China, as the testing set. We used a residual network for training and validation. The model performance was experimentally verified in terms of area under the curve (AUC), precision, sensitivity, specificity, and F1 score. Results: The AUC of the training, validation, and testing sets were 0.964 [95% confidence interval (CI): 0.961-0.966], 0.944 (95% CI: 0.939-0.949), and 0.977 (95% CI: 0.961-0.991), respectively. The precision, sensitivity, specificity, and F1 score of the deep learning model for AMI diagnosis from ECGs were 0.827, 0.824, 0.950, and 0.825, respectively, in the training set, 0.789, 0.818, 0.913, and 0.803, respectively, in the validation set, and 0.830, 0.951, 0.951, and 0.886, respectively, in the testing set. The AUC for automatic AMI location diagnosis of LMI, IMI, ASMI, AMI, ALMI were 0.969 (95% CI: 0.959-0.979), 0.973 (95% CI: 0.962-0.978), 0.987 (95% CI: 0.963-0.989), 0.961 (95% CI: 0.956-0.989), and 0.996 (95% CI: 0.957-0.997), respectively. Conclusions: The residual network-based algorithm can effectively automatically diagnose AMI and MI location from 12-lead ECGs.