Sex differences in the associations between relative fat mass and all-cause and cardiovascular mortality: A population-based prospective cohort study.

BACKGROUND AND AIMS: The novel sex-specific anthropometric equation relative fat mass (RFM) is a new estimator of whole-body fat %. The study aimed to investigate the predictive role of RFM in cardiometabolic abnormalities, cardiovascular disease (CVD), all-cause and cardiovascular mortality, and explored potential sex differences. METHODS AND RESULTS: The study analyzed data from 26,754 adults in NHANES 1999-2010, with a median follow-up of 13.8 years. The correlation between RFM and body composition as well as fat distribution assessed by dual-energy X-ray absorptiometry was investigated. Weighted multivariable generalized linear models, Cox proportional hazards models and restricted cubic spline were applied to investigate the predictive role of RFM in metabolic markers, cardiovascular risk factors, CVD, all-cause and cardiovascular mortality. RFM exhibited a robust correlation with both whole-body fat % and trunk fat %. Higher RFM exhibited a stronger association with impaired glucose homeostasis, serum lipids, the incidence of hypertension, and coronary heart disease in males, while a stronger association with C-reactive protein in females. A U-shaped association between RFM and all-cause mortality was observed only in males. The hazard ratio (HR) of all-cause and cardiovascular mortality in males increased rapidly when RFM exceeded 30. However, in females, the HR of all-cause and cardiovascular mortality fluctuated until RFM exceeded 45, after which it increased rapidly. CONCLUSION: RFM was a sex-specific estimator for both general and central obesity, sex-specific differences in predicting cardiometabolic abnormalities and adverse events using RFM might be partially attributed to differences in body composition and fat distribution between sexes.

Comprehensively evaluating the relationships between marital status and other family factors with cardiovascular disease and long-term overall mortality in the elderly: a study of 48 510 Chinese individuals.

BACKGROUND: Marital status is associated with cardiovascular disease (CVD) incidence and overall mortality, yet limited research on this topic in elderly individuals is available. Our aim was to comprehensively assess the impact of marital status and other family factors on CVD incidence and long-term mortality among elderly people. METHODS: Data from the Chinese Longitudinal Healthy Longevity Survey (2002/2005/2008-2018) for participants aged ≥60 years were analysed. A cross-sectional study initially examined the correlation between spouses, offspring, living arrangements, and CVD using logistic regression. Subsequently, a retrospective cohort study investigated the long-term associations of these factors with overall mortality via Kaplan-Meier and Cox regression analyses. RESULTS: The study involved 48 510 subjects (average age: 87 years). The cross-sectional analysis revealed a correlation between living with a spouse and an increased incidence of heart disease (adjusted OR 1.27, 95% CI 1.04-1.55) and cerebrovascular disease/stroke (adjusted OR 1.26, 95% CI 1.11-1.42). According to the retrospective cohort analysis, living with a spouse significantly reduced overall mortality (adjusted HR 0.84, 95% CI 0.80-0.87), irrespective of marital relationship quality. Conversely, living with offspring (adjusted HR 1.12, 95% CI 1.08-1.16), having more children (adjusted Pnonlinearity = 0.427) or cohabitants (adjusted Pnonlinearity < 0.0001) were associated with increased overall mortality. CONCLUSION: In the elderly population, being married and living with a spouse were not significantly associated with a decrease in CVD incidence but were associated with a reduction in long-term overall mortality. Living with offspring, having more children, or having a larger family size did not replicate the protective effect but indicated greater overall mortality.

Machine learning for the prediction of 1-year mortality in patients with sepsis-associated acute kidney injury.

INTRODUCTION: Sepsis-associated acute kidney injury (SA-AKI) is strongly associated with poor prognosis. We aimed to build a machine learning (ML)-based clinical model to predict 1-year mortality in patients with SA-AKI. METHODS: Six ML algorithms were included to perform model fitting. Feature selection was based on the feature importance evaluated by the SHapley Additive exPlanations (SHAP) values. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the discriminatory ability of the prediction model. Calibration curve and Brier score were employed to assess the calibrated ability. Our ML-based prediction models were validated both internally and externally. RESULTS: A total of 12,750 patients with SA-AKI and 55 features were included to build the prediction models. We identified the top 10 predictors including age, ICU stay and GCS score based on the feature importance. Among the six ML algorithms, the CatBoost showed the best prediction performance with an AUROC of 0.813 and Brier score of 0.119. In the external validation set, the predictive value remained favorable (AUROC = 0.784). CONCLUSION: In this study, we developed and validated a ML-based prediction model based on 10 commonly used clinical features which could accurately and early identify the individuals at high-risk of long-term mortality in patients with SA-AKI.

Prognostic Value of QRS Duration in Patients with Dilated Cardiomyopathy According to Left Ventricular Ejection Fraction.

Background: The prognostic significance of QRS duration (QRSd) in patients with dilated cardiomyopathy (DCM) and a left ventricular ejection fraction (LVEF) between 30% and 50% is unclear, resulting in questions regarding eligibility for cardiac resynchronisation therapy. This study aimed to explore the prognostic role of QRSd in patients with DCM and a LVEF 30-50% or LVEF < 30. Methods: Patients hospitalised at Fuwai hospital with DCM who had a LVEF ≤ 50% were prospectively included. The primary outcomes were a composite of death, heart transplantation, and rehospitalisation for worsening heart failure. Results: Among the 633 patients included, 302 (47.7%) had a LVEF of 30-50%. The multivariable hazard ratio (HR) for QRSd ≥ 120 ms was 1.65 (95% confidence interval [CI] 1.29-2.11, p < 0.001) for overall DCM patients, 2.8 (95% CI 1.82-4.30, p < 0.001) for patients with LVEF 30-50%, and 1.41 (95% CI 1.02-1.94, p = 0.036) for patients with LVEF < 30%. QRSd ≥ 120 ms tended to be more strongly associated with outcome in patients with LVEF 30-50% than in those with LVEF < 30% despite the non-significant interaction (p = 0.067). DCM patients with QRSd ≥ 120 ms and LVEF 30-50% did not experience a significantly better outcome than those with LVEF < 30% and QRSd < 120 ms after propensity-score matching (HR 0.91, 95% CI 0.61-1.36, p = 0.645). Conclusions: QRSd independently predicts prognosis in DCM patients irrespective of LVEF and identifies a group of high-risk patients who may benefit from device implantation despite the absence of severely reduced LVEF.

Scalable Fabrication of Crystalline COF Membranes from Amorphous Polymeric Membranes.

Covalent organic framework (COF) membranes hold potential for widespread applicability, but scalable fabrication is challenging. Here, we demonstrate the disorder-to-order transformation from amorphous polymeric membrane to crystalline COF membrane via monomer exchange. Solution processing is used to prepare amorphous membrane and the replacing monomer is selected based on the chemical and thermodynamical stability of the final framework. Reversible imine bonds allow the extraneous monomers to replace the pristine monomers within amorphous membrane, driving the transformation from disordered network to ordered framework. Incorporation of intramolecular hydrogen bonds enables the crystalline COF to imprint the amorphous membrane morphology. The COF membranes harvest proton conductivity up to 0.53 S cm-1 at 80 °C. Our strategy bridges amorphous polymeric and crystalline COF membranes for large-scale fabrication of COF membranes and affords guidance on materials processing.

[Therapeutic effect of Artemisia argyi on oral ulcer in rats].

OBJECTIVE: To determine bacteriostatic abilities of Artemisia argyi extracts, and to explore the effect of Artemisia argyi extracts on oral ulcer in rats.
 Methods: We extracted the mixture of Artemisia argyi volatile oils and water-extraction by leaching method and evaluated the anti-microbial effect of Artemisia argyi extracts on common oral floras in vitro. The rat cheeks were burnt by NaOH to establish the models of oral ulcer. The curative effects of crude drug of Artemisia argyi extracts at 2.0, 1.0, 0.5 g/mL on oral ulcer in rats were evaluated by measuring the oral ulcer healing time. Serum TNF-α level and expression of proliferating cell nuclear antigen (PCNA) were analyzed by ELASA and immunohistochemical staining.
 Results: Artemisia argyi extracts obviously inhibited the Staphylococcus aureus and Streptococcus. NaOH-made oral ulcer in rats were successfully established. The crude drug at 2.0 and 1.0 g/mL obviously reduced healing time, significantly inhibited the release of TNF-α, and improved the PCNA level in the ulcer tissues (All P<0.01). The extracts obviously reduced the local inflammatory reaction and promoted tissue repair of oral ulcer.
 Conclusion: Artemisia argyi extracts promote tissue repair of oral ulcer via inhibiting bacterial growth, reducing the release of TNF-α and improving the PCNA level.

Association of point-of-care testing for sST2 with clinical outcomes in patients hospitalized with heart failure.

AIMS: This study aimed to investigate the association of soluble suppression of tumorigenicity-2 (sST2) measured by point-of-care testing assay with clinical outcomes in patients hospitalized with heart failure after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). METHODS: A total of 1726 consecutive patients hospitalized with heart failure from July 2015 to December 2021 were enrolled. Baseline serum sST2 concentrations were measured by immunofluorescence assay. Primary endpoint event was the composite of all-cause death, heart transplantation, or left ventricular assist device. RESULTS: During the median follow-up duration of 682 days, 434 patients (25.1%) suffered from primary endpoint events. Baseline sST2 remained an independent predictor of the primary endpoint event in patients hospitalized with heart failure after adjusting for other predictors including NT-proBNP and hs-cTnT [per log (unit) increase, adjusted hazard ratio (HR) (95% confidence interval) (CI): 1.20 (1.09, 1.32), P < 0.001]. And baseline sST2 had a better prognostic value for patients with chronic decompensated heart failure [per log (unit) increase, adjusted HR (95% CI): 1.19 (1.07, 1.31)] than for those with acute new onset heart failure [per log (unit) increase, adjusted HR (95% CI): 1.28 (0.94, 1.75), P value for interaction <0.001], as well as a better prognostic value for patients with New York Heart Association (NYHA) functional class I-II [per log (unit) increase, adjusted HR (95% CI): 1.67 (1.11, 2.52)] than for those with NYHA functional class III-IV [per log (unit) increase, adjusted HR (95% CI): 1.18 (1.07, 1.31), P value for interaction <0.001]. Baseline sST2 was also a good predictor of the primary endpoint event in patients hospitalized with heart failure at 1 month, 3 months, 1 year and 2 years (area under the curve: 0.789, 0.775, 0.736 and 0.733, respectively), and the best cut-off values were 27.2 ng/ml, 27.1 ng/ml, 27.1 ng/ml and 25.1 ng/ml, respectively. Furthermore, baseline sST2 could provide additional prognostic value when added to baseline NT-proBNP and hs-cTnT (all P values <0.05). According to the category of elevated biomarkers (including NT-proBNP, hs-cTnT, and sST2), patients with three elevated biomarkers had a higher risk of the primary endpoint event compared with those with one or two elevated biomarkers (all P values <0.05). CONCLUSIONS: Baseline sST2 remained an independent predictor of adverse events after adjusting for other predictors including NT-proBNP and hs-cTnT, particularly in patients with chronic decompensated heart failure and NYHA functional class I-II. And in the basis of baseline NT-proBNP and hs-cTnT, adding baseline sST2 could provide additional prognostic value for patients hospitalized with heart failure.

Global trends in heart failure from 1990 to 2019: An age-period-cohort analysis from the Global Burden of Disease study.

AIMS: This study aimed to analyse the global prevalence and disability trends of heart failure (HF) from 1990 to 2019, considering both sexes and country-specific economic strata. METHODS: This study conducted a secondary analysis employing data from the Global Burden of Disease (GBD) study. The analysis is stratified by sex and Socio-demographic Index (SDI) levels. Through age-period-cohort and Joinpoint regression analyses, we investigated the temporal trends in HF prevalence and years lived with disability (YLDs) during this period. RESULTS: Between 1990 and 2019, the global prevalence of HF surged by 106.3% (95% uncertainty interval: 99.3% to 114.3%), reaching 56.2 million cases in 2019. While all-age prevalence and YLDs increased over the 30 year span, age-standardized rates decreased by 2019. Countries with higher SDI experienced a more pronounced percentage decrease compared with those with lower SDI. Longitudinal analysis revealed an overall improvement in both prevalence and YLDs for HF, albeit with notable disparities between SDI quintiles and sexes. Ischaemic heart disease and hypertensive heart disease emerged as the most rapidly increasing and primarily contributing causes of HF, albeit with variations observed across different countries. The average annual percentage change for prevalence and YLDs over the period was -0.26% and -0.25%, respectively. CONCLUSIONS: This study offers valuable insights into the global burden of HF, considering factors such as population aging, regional disparities, sex differences and aetiological variations. The findings hold significant implications for healthcare planning and resource allocation. Continued assessment of these trends and innovative strategies for HF prevention and management are crucial for addressing this pressing global health concern.

Incorporating inflammatory biomarkers into a prognostic risk score in patients with non-ischemic heart failure: a machine learning approach.

Objectives: Inflammation is involved in the mechanisms of non-ischemic heart failure (NIHF). We aimed to investigate the prognostic value of 21 inflammatory biomarkers and construct a biomarker risk score to improve risk prediction for patients with NIHF. Methods: Patients diagnosed with NIHF without infection during hospitalization were included. The primary outcome was defined as all-cause mortality and heart transplantations. We used elastic net Cox regression with cross-validation to select inflammatory biomarkers and construct the best biomarker risk score model. Discrimination, calibration, and reclassification were evaluated to assess the predictive value of the biomarker risk score. Results: Of 1,250 patients included (median age, 53 years, 31.9% women), 436 patients (34.9%) experienced the primary outcome during a median of 2.8 years of follow-up. The final biomarker risk score included high-sensitivity C-reactive protein-to-albumin ratio (CAR) and red blood cell distribution width-standard deviation (RDW-SD), both of which were 100% selected in 1,000 times cross-validation folds. Incorporating the biomarker risk score into the best basic model improved the discrimination (ΔC-index = 0.012, 95% CI 0.003-0.018) and reclassification (IDI, 2.3%, 95% CI 0.7%-4.9%; NRI, 17.3% 95% CI 6.4%-32.3%) in risk identification. In the cross-validation sets, the mean time-dependent AUC ranged from 0.670 to 0.724 for the biomarker risk score and 0.705 to 0.804 for the basic model with a biomarker risk score, from 1 to 8 years. In multivariable Cox regression, the biomarker risk score was independently associated with the outcome in patients with NIHF (HR 1.76, 95% CI 1.49-2.08, p < 0.001, per 1 score increase). Conclusions: An inflammatory biomarker-derived risk score significantly improved prognosis prediction and risk stratification, providing potential individualized therapeutic targets for NIHF patients.

Spacer-Engineered Ionic Channels in Covalent Organic Framework Membranes toward Ultrafast Proton Transport.

Side-chain engineering of covalent organic frameworks as advanced ion conductors is a critical issue to be explored. Herein, ionic covalent organic framework membranes (iCOFMs) with spacer-engineered ionic channel are de novo designed and prepared. The ionic channels are decorated with side chains comprising spacers having different carbon chain lengths and the -SO3 H groups at the end. Attributed to the synergistic contribution from the spacers and the -SO3 H groups, the iCOFM with moderate-length spacer exhibit the highest through-plane proton conductivity of 889 mS cm-1 at 90 °C.

Big Endothelin-1 as a Predictor of Reverse Remodeling and Prognosis in Dilated Cardiomyopathy.

This study aimed to investigate the predictive value of Big endothelin-1(ET-1) for left ventricular reverse remodeling (LVRR) and prognosis in patients with dilated cardiomyopathy (DCM). Patients with DCM and a left ventricular ejection fraction (LVEF) ≤ 50% from 2008 to 2017 were included. LVRR was defined as the LVEF increased by at least 10% or follow-up LVEF increased to at least 50% with a minimum improvement of 5%; meanwhile, the index of left ventricular end-diastolic diameter (LVEDDi) decreased by at least 10% or LVEDDi decreased to ≤33 mm/m2. The composite outcome for prognostic analysis consisted of death and heart transplantations. Of the 375 patients included (median age 47 years, 21.1% female), 135 patients (36%) had LVRR after a median of 14 months of treatment. An independent association was found between Big ET-1 at baseline and LVRR in the multivariate model (OR 0.70, 95% CI 0.55-0.89, p = 0.003, per log increase). Big ET-1, body mass index, systolic blood pressure, diagnosis of type 2 diabetes mellitus (T2DM) and treatment with ACEI/ARB were significant predictors for LVRR after stepwise selection. Adding Big ET-1 to the model improved the discrimination (∆AUC = 0.037, p = 0.042 and reclassification (IDI, 3.29%; p = 0.002; NRI, 35%; p = 0.002) for identifying patients with LVRR. During a median follow-up of 39 (27-68) months, Big ET-1 was also independently associated with the composite outcome of death and heart transplantations (HR 1.45, 95% CI 1.13-1.85, p = 0.003, per log increase). In conclusion, Big ET-1 was an independent predictor for LVRR and had prognostic implications, which might help to improve the risk stratification of patients with DCM.

Afterload-related cardiac performance is a powerful hemodynamic predictor of mortality in patients with chronic heart failure.

Background: Afterload-related cardiac performance (ACP), a diagnostic parameter for septic cardiomyopathy, integrates both cardiac performance and vascular effects and could predict prognosis in septic shock. Objectives: We hypothesized that ACP would also correlate with clinical outcomes in patients with chronic heart failure (HF). Design: A retrospective study. Methods: We retrospectively studied consecutive patients with chronic HF who underwent right heart catheterization and established an expected cardiac output-systemic vascular resistance (CO-SVR) curve model in chronic HF for the first time. ACP was calculated as COmeasured/COpredicted × 100%. ACP > 80%, 60% < ACP ⩽ 80%, and ACP ⩽ 60% represented less impaired, mildly impaired, and severely impaired cardiovascular function, respectively. The primary outcome was all-cause mortality, and the secondary outcome was event-free survival. Results: A total of 965 individual measurements from 290 eligible patients were used to establish the expected CO-SVR curve model (COpredicted = 53.468 × SVR -0.799). Patients with ACP ⩽ 60% had higher serum NT-proBNP levels (P < 0.001), lower left ventricular ejection fraction (P = 0.001), and required dopamine more frequently (P < 0.001). Complete follow-up data were available in 263 of 290 patients (90.7%). After multivariate adjustment, ACP remained associated with both primary outcome (hazard ratio (HR) 0.956, 95% confidence interval (CI) 0.927-0.987) and secondary outcome (HR 0.977, 95% CI 0.963-0.992). Patients with ACP ⩽ 60% had the worst prognosis (all P < 0.001). ACP was significantly more discriminating (area under the curve of 0.770) than other conventional hemodynamic parameters in predicting mortality (Delong test, all P < 0.05). Conclusion: ACP is a powerful independent hemodynamic predictor of mortality in patients with chronic HF. ACP and the novel CO-SVR two-dimensional graph could be useful in assessing cardiovascular function and making clinical decisions. Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02664818.

Combined use of right ventricular coupling and pulmonary arterial elastance as a comprehensive stratification approach for right ventricular function.

Right ventricular (RV)-pulmonary arterial uncoupling is the consequence of increased afterload and/or decreased RV contractility. However, the combination of arterial elastance (Ea) and end-systolic elastance (Ees)/Ea ratio to assess RV function is unclear. We hypothesized that the combination of both could comprehensively assess RV function and refine risk stratification. The median Ees/Ea ratio (0.80) and Ea (0.59 mmHg/mL) were used to classify 124 patients with advanced heart failure into four groups. RV systolic pressure differential was defined as end-systolic pressure (ESP) minus beginning-systolic pressure (BSP). Patients among different subsets showed dissimilar New York Heart Association functional class (V = 0.303, p = 0.010), distinct tricuspid annular plane systolic excursion/ pulmonary artery systolic pressure (mm/mmHg; 0.65 vs. 0.44 vs. 0.32 vs. 0.26, p < 0.001), and diverse prevalence of pulmonary hypertension (33.3% vs. 35% vs. 90% vs. 97.6%, p < 0.001). By multivariate analysis, Ees/Ea ratio (hazard ratio [HR] 0.225, p = 0.004) and Ea (HR 2.194, p = 0.003) were independently associated with event-free survival. Patients with Ees/Ea ratio greater than or equal to 0.80 and Ea less than 0.59 mmHg/mL had better outcomes (p < 0.05). In patients with Ees/Ea ratio greater than or equal to 0.80, those with Ea greater than or equal to 0.59 mmHg/mL had a higher adverse outcome risk (p < 0.05). Ees/Ea ratio less than or equal to 0.80 was associated with adverse outcomes, even when Ea was less than 0.59 mmHg/mL (p < 0.05). Approximately 86% of patients with ESP-BSP greater than 5 mmHg had an Ees/Ea ratio less than or equal to 0.80 and/or an Ea greater than or equal to 0.59 mmHg/mL (V = 0.336, p = 0.001). Combined use of Ees/Ea ratio and Ea could be a comprehensive approach to assessing RV function and predicting outcomes. An exploratory analysis demonstrated that Ees/Ea ratio and Ea might be roughly estimated based on RV systolic pressure differential.

Estimated plasma volume status adds prognostic value to hemodynamic parameters in advanced heart failure.

BACKGROUND: Estimated plasma volume status (ePVS) is a marker of intravascular congestion and has prognostic value in patients with heart failure (HF). The elevation of intracardiac filling pressures is defined as hemodynamic congestion and is also associated with poor prognosis. However, the relationship between intravascular congestion and hemodynamic congestion remains unclear. This study sought to explore the correlation between ePVS and hemodynamic parameters and determine the association between ePVS and clinical outcomes in patients with advanced HF. METHODS: Patients with advanced HF underwent right heart catheterization (RHC) for hemodynamic profiles. The sum of right atrial pressure (RAP) and pulmonary arterial wedge pressure (PAWP) > 30 mmHg was considered to present with hemodynamic congestion. Blood tests were conducted within 24 h of RHC. We calculated ePVS using the Strauss-derived Duarte formula. The primary outcome was all-cause mortality. RESULTS: A total of 195 patients were divided into two groups based on the cut-off value of ePVS (4.08 dL/g) calculated from receiver operating characteristic analysis. Patients with ePVS > 4.08 dL/g were more likely to present with wet rales (21.2% vs. 9.9%, P = 0.032) and had a higher risk of death (HR 4.748, 95% CI 2.385-9.453), regardless of whether RAP + PAWP was normal or elevated (all P < 0.05). Hemodynamic parameters and ePVS were not correlated (all P > 0.05). High ePVS significantly improved the predictive value beyond the clinical plus hemodynamic prognostic model (area under the curve of 0.844, Delong test, P = 0.024). CONCLUSION: ePVS could additionally add prognostic value to hemodynamic parameters in advanced heart failure, although not correlated with hemodynamic parameters.

sST2 and Big ET-1 as Alternatives of Multi-Biomarkers Strategies for Prognosis Evaluation in Patients Hospitalized with Heart Failure.

Objective: To identify biomarkers with independent prognostic value and investigate the prognostic value of multiple biomarkers in combination in patients hospitalized with heart failure. Methods: A total of 884 consecutive patients hospitalized with heart failure from 2015 to 2017 were enrolled. Twelve biomarkers were measured on admission, and the relationships between biomarkers and outcomes were assessed. Results: During the median follow-up of 913 days, 291 patients (32.9%) suffered from primary endpoint events. Soluble suppression of tumorigenicity-2 (sST2) (per log [unit] increase, adjusted HR [95% CI]: 1.39 [1.13,1.72], P = 0.002) and big endothelin-1 (big ET-1) (per log [unit] increase, adjusted HR [95% CI]: 1.56 [1.23,1.97], P < 0.001) remained independent predictors of primary endpoint event after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). Both sST2 (C-statistic: 0.810 vs 0.801, P = 0.005, and 0.832 vs 0.826, P = 0.024, respectively) and big ET-1 (C-statistic: 0.829 vs 0.801, P = 0.001, and 0.843 vs 0.826, P < 0.001, respectively) significantly improved the predictive value for primary endpoint event at 1 year and 3 years. However, only big ET-1 (C-statistic: 0.852 vs 0.846, P = 0.014) significantly improved the predictive value at 3 months when added to clinical predictors and known biomarkers. According to the number of elevated biomarkers (including NT-proBNP, hs-cTnT, sST2, and big ET-1), patients with three or more elevated biomarkers had a higher risk of primary endpoint event compared to those with two elevated biomarkers (P = 0.001), as well as in patients with two elevated biomarkers compared to those with one elevated biomarker (P = 0.004). However, the risk of primary endpoint event was comparable between patients with one elevated biomarker and those with no elevated biomarker (P = 0.582). Conclusion: Multiple biomarkers in combination could provide a better prognostic value than a single biomarker. sST2 and big ET-1 could act as alternatives of multi-biomarkers strategies for prognosis evaluation beyond NT-proBNP and hs-cTnT in patients hospitalized with heart failure.

Improved Prognostic Performance of Right Atrial Pressure-Corrected Cardiac Power Output in Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction.

Cardiac power output (CPO) is a powerful predictor of adverse outcomes in heart failure (HF). However, the original formula of CPO included the difference between mean arterial pressure and right atrial pressure (RAP). The prognostic performance of RAP-corrected CPO (CPORAP) remains unknown in heart failure with preserved ejection fraction (HFpEF). We studied 101 HF patients with a left ventricular ejection fraction > 40% who had pulmonary hypertension due to left heart disease. CPORAP was significantly more discriminating than CPO in predicting outcomes (Delong test, P = 0.004). Twenty-five (24.8%) patients presented with dis-concordantly high CPORAP and low CPO when stratified by the identified CPORAP threshold of 0.547 W and the accepted CPO threshold of 0.803 W. These patients had the lowest RAP, and their cumulative incidence was comparable with those with concordantly high CPO and CPORAP (P = 0.313). CPORAP might identify patients with right ventricular involvement, thereby providing better prognostic performance than CPO in HFpEF.

Clinical characteristics and outcomes of patients hospitalized with heart failure with preserved ejection fraction and low NT-proBNP levels.

The aim of this study was to investigate the clinical characteristics and prognosis of patients hospitalized with heart failure with preserved ejection fraction (HFpEF) and low N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Seven hundred ninety consecutive patients hospitalized with HFpEF from 2006 to 2017 were enrolled. Clinical characteristics and outcomes were compared between low NT-proBNP group (<300 ng/L) and elevated NT-proBNP group (≥300 ng/L). 108 HFpEF patients (13.7%) presented with low NT-proBNP levels. Age, body mass index, atrial fibrillation, New York Heart Association functional class, and albumin were independent predictors of low NT-proBNP levels in HFpEF patients. During the median follow-up duration of 1103 days, 11 patients (10.2%) in low NT-proBNP group suffered from primary endpoint event. Elevated NT-proBNP group had a higher risk of all-cause death or heart transplantation than low NT-proBNP group (adjusted HR [95%CI]: 2.36 [1.24,4.49], P = .009). Stratified analyses showed that the association between NT-proBNP (elevated NT-proBNP group vs low NT-proBNP group) and risk of all-cause death or heart transplantation was stronger in non-atrial fibrillation patients than in atrial fibrillation patients (P value for interaction = .025). Furthermore, the associations between NT-proBNP and risk of all-cause death or heart transplantation were stronger in younger and male patients than in older and female patients. However, both subgroups only reached borderline significant (P values for interaction = .062 and .084, respectively). Our findings suggest that low NT-proBNP levels were common in patients hospitalized with HFpEF. Patients with HFpEF and low NT-proBNP levels had a better prognosis than those with elevated NT-proBNP levels, particularly in younger, male, and non-atrial fibrillation patients.

Assembling covalent organic framework membranes with superior ion exchange capacity.

Ionic covalent organic framework membranes (iCOFMs) hold great promise in ion conduction-relevant applications because the high content and monodispersed ionic groups could afford superior ion conduction. The key to push the upper limit of ion conductivity is to maximize the ion exchange capacity (IEC). Here, we explore iCOFMs with a superhigh ion exchange capacity of 4.6 mmol g-1, using a dual-activation interfacial polymerization strategy. Fukui function is employed as a descriptor of monomer reactivity. We use Brønsted acid to activate aldehyde monomers in organic phase and Brønsted base to activate ionic amine monomers in water phase. After the dual-activation, the reaction between aldehyde monomer and amine monomer at the water-organic interface is significantly accelerated, leading to iCOFMs with high crystallinity. The resultant iCOFMs display a prominent proton conductivity up to 0.66 S cm-1, holding great promise in ion transport and ionic separation applications.

Cardiotoxicity of anthracycline-free targeted oncological therapies in HER2-positive breast cancer.

Anthracycline drugs are considered to be pivotal drugs in numerous chemotherapy regimens for breast cancer. However, the cardiotoxicity associated with the treatment is an important issue to be addressed. With the emergence of increasingly diverse antitumor drugs, anthracycline-free therapies are able to reduce the cardiotoxicity caused by anthracycline drugs while ensuring that a therapeutic effect is achieved. In the present review, anthracycline-free oncological therapy regimens for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and the associated cardiovascular toxicity are discussed, as well as some monitoring strategies. It is recommended that patients with HER2-positive breast cancer patients should receive adjuvant chemotherapy with single or dual-targeted therapy, with or without endocrine therapy according to the hormone receptor status determined by immunohistochemical examination. The main side effects of targeted therapy include cardiac dysfunction, hypertension and arrhythmia. According to individual risk stratification, it is recommended that patients should be periodically monitored using echocardiography, electrocardiography and serum markers, to enable the timely detection of the cardiovascular adverse reactions associated with tumor treatment, thereby preventing the morbidity and mortality caused by the cardiotoxicity of these drugs.

The Role of Cytokines in Predicting the Response and Adverse Events Related to Immune Checkpoint Inhibitors.

Recently, the overall survival (OS) and progression-free survival (PFS) of patients with advanced cancer has been significantly improved due to the application of immune checkpoint inhibitors (ICIs). Low response rate and high occurrence of immune-related adverse events (irAEs) make urgently need for ideal predictive biomarkers to identity efficient population and guide treatment strategies. Cytokines are small soluble proteins with a wide range of biological activity that are secreted by activated immune cells or tumor cells and act as a bridge between innate immunity, infection, inflammation and cancer. Cytokines can be detected in peripheral blood and suitable for dynamic detection. During the era of ICIs, many studies investigated the role of cytokines in prediction of the efficiency and toxicity of ICIs. Herein, we review the relevant studies on TNF-α, IFN-γ, IL-6, IL-8, TGF-ß and other cytokines as biomarkers for predicting ICI-related reactions and adverse events, and explore the immunomodulatory mechanisms. Finally, the most important purpose of this review is to help identify predictors of ICI to screen patients who are most likely to benefit from immunotherapy.