N6022 attenuates cerebral ischemia/reperfusion injury-induced microglia ferroptosis by promoting Nrf2 nuclear translocation and inhibiting the GSNOR/GSTP1 axis.

Stroke poses a significant risk of mortality, particularly among the elderly population. The pathophysiological process of ischemic stroke is complex, and it is crucial to elucidate its molecular mechanisms and explore potential protective drugs. Ferroptosis, a newly recognized form of programmed cell death distinct from necrosis, apoptosis, and autophagy, is closely associated with the pathophysiology of ischemic stroke. N6022, a selective inhibitor of S-nitrosoglutathione reductase (GSNOR), is a "first-in-class" drug for asthma with potential therapeutic applications. However, it remains unclear whether N6022 exerts protective effects in ischemic stroke, and the precise mechanisms of its action are unknown. This study aimed to investigate whether N6022 mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis and to elucidate the underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) cell model and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to mimic cerebral I/R injury. Our data, both in vitro and in vivo, demonstrated that N6022 effectively protected against I/R-induced brain damage and neurological deficits in mice, as well as OGD/R-induced BV2 cell damage. Mechanistically, N6022 promoted Nrf2 nuclear translocation, enhancing intracellular antioxidant capacity of SLC7A11-GPX4 system. Furthermore, N6022 interfered with the interaction of GSNOR with GSTP1, thereby boosting the antioxidant capacity of GSTP1 and attenuating ferroptosis. These findings provide novel insights, showing that N6022 attenuates microglial ferroptosis induced by cerebral I/R injury through the promotion of Nrf2 nuclear translocation and inhibition of the GSNOR/GSTP1 axis.

The application of different machine learning models based on PET/CT images and EGFR in predicting brain metastasis of adenocarcinoma of the lung.

OBJECTIVE: To explore the value of six machine learning models based on PET/CT radiomics combined with EGFR in predicting brain metastases of lung adenocarcinoma. METHODS: Retrospectively collected 204 patients with lung adenocarcinoma who underwent PET/CT examination and EGFR gene detection before treatment from Cancer Hospital Affiliated to Shandong First Medical University in 2020. Using univariate analysis and multivariate logistic regression analysis to find the independent risk factors for brain metastasis. Based on PET/CT imaging combined with EGFR and PET metabolic indexes, established six machine learning models to predict brain metastases of lung adenocarcinoma. Finally, using ten-fold cross-validation to evaluate the predictive effectiveness. RESULTS: In univariate analysis, patients with N2-3, EGFR mutation-positive, LYM%≤20, and elevated tumor markers(P<0.05) were more likely to develop brain metastases. In multivariate Logistic regression analysis, PET metabolic indices revealed that SUVmax, SUVpeak, Volume, and TLG were risk factors for lung adenocarcinoma brain metastasis(P<0.05). The SVM model was the most efficient predictor of brain metastasis with an AUC of 0.82 (PET/CT group),0.70 (CT group),0.76 (PET group). CONCLUSIONS: Radiomics combined with EGFR machine learning model as a new method have higher accuracy than EGFR mutation alone. SVM model is the most effective method for predicting brain metastases of lung adenocarcinoma, and the prediction efficiency of PET/CT group is better than PET group and CT group.

Development and validation of a nomogram superior to CHADS2 and CHA2DS2-VASc models for predicting left atrial appendage dense spontaneous echo contrast/left atrial appendage thrombus.

Background: Atrial fibrillation (AF) is one of the most frequently encountered arrhythmias in clinical practice, with stroke triggered by detachment of left atrial appendage thrombus (LAAT) after AF being its most critical complication. The purpose of this study was to construct a nomogram model for forecasting left atrial appendage (LAA) dense spontaneous echo contrast (SEC) and LAAT to accurately identify patients at high risk for stroke. Methods: A retrospective analysis was conducted on 433 patients with AF receiving transesophageal echocardiography (TEE) in the First Affiliated Hospital of Soochow University from October 2019 to July 2022. These patients were assigned into a non-dense SEC/LAAT group or a dense SEC/LAAT group. We constructed a nomogram model dependent on the odds ratios (ORs) of logistic regression and subsequently compared its performance with two models, CHADS2 and CHA2DS2-VASc. Results: Female gender, high D-dimer level, low left ventricular ejection fraction, low left atrial ejection fraction, and low left atrial reservoir strain rate were found to be independent factors for predicting LAA SEC/LAAT, with OR values and 95% confidence intervals of 2.811 (1.445-5.469), 2.460 (1.230-4.921), 0.961 (0.927-0.996), 0.950 (0.932-0.967), and 0.173 (0.035-0.848), respectively. The consistency statistic of the nomogram based on these given predictive factors was 0.921, and the calibrated consistency statistic was 0.903. According to receiver operation curve analysis and decision curve analysis, the nomogram was demonstrated to be superior to the CHADS2 and CHA2DS2-VASc models in predicting LAA dense SEC/LAAT. The net reclassification improvement and integrated discrimination improvement of the nomogram were 0.449 (0.324-0.575) and 0.461 (0.408-0.515), when compared with the CHADS2 model, and were 0.521 (0.411-0.632), and 0.432 (0.400-0.504), respectively, when compared with the CHA2DS2-VASc models. Conclusions: The nomogram model constructed in this study demonstrated excellent performance in predicting LAA dense SEC/LAAT, displaying a superior ability to that of the CHADS2 and CHA2DS2-VASc models.

A randomized, double-blind, placebo-controlled, phase IIa, clinical study on investigating the efficacy and safety of SPH3127 tablet in patients with essential hypertension.

Around 70% of patients diagnosed with hypertension exhibit increased levels of renin. SPH3127, an inventive renin inhibitor, has shown favorable tolerability and sustained pharmacodynamic inhibitory impact on plasma renin activity (PRA) during previous phase I trials. This phase II study was conducted to investigate the efficacy and safety of SPH3127 in patients with essential hypertension. This study was conducted in patients with mild to moderate essential hypertension, utilizing a randomized, double-blind, placebo-controlled design. The patients were administered either tablet of SPH3127 at doses of 50 mg, 100 mg, or 200 mg, or a placebo. A total of 122 patients were included in the study, with 121 patients included in the full analysis set. Among these patients, there were 30 individuals in each subgroup receiving different dosage regimens of SPH3127, and 31 patients in the placebo group. The reductions in mean sitting diastolic blood pressure (msDBP) after 8 weeks compared to baseline were 5.7 ± 9.5, 8.6 ± 8.8, and 3.8 ± 10.6 mmHg in the SPH3127 50-, 100-, and 200 mg groups, respectively. In the placebo group, the reduction was 3.1 ± 8.4 mmHg. The corresponding reductions in mean sitting systolic blood pressure (msSBP) were 11.8 ± 13.0, 13.8 ± 11.2, 11.1 ± 13.1, and 7.7 ± 9.7 mmHg in each respective group. SPH3127 is a promising drug for the treatment of patients with essential hypertension. The recommended dosage is 100 mg daily.Clinical trial registration: This study was registered in ClinicalTrials.gov (NCT03756103).

Efficiency and Durability of EIVOM on Acute Reconnection After Mitral Isthmus Bidirectional Block.

BACKGROUND: Reconnection after mitral isthmus (MI) block with radiofrequency ablation is common. OBJECTIVES: The aim of this study was to investigate the effects of ethanol infusion in the vein of Marshall (EIVOM) on acute reconnection after MI bidirectional block. METHODS: Patients with persistent atrial fibrillation who were scheduled to receive radiofrequency ablation for the first time were randomly assigned to the radiofrequency catheter ablation (RFCA) group (n = 44) or the EIVOM group (n = 45). The RFCA group's strategy was bilateral pulmonary vein ablation and linear ablation; in the EIVOM group, EIVOM was performed first. The primary endpoint was acute reconnection 30 minutes after MI bidirectional block. RESULTS: A total of 89 patients (average age 62.9 years; 57.3% male) were enrolled. The average duration for persistent atrial fibrillation was 2.3 years. Before observation, all patients in the EIVOM group achieved MI bidirectional block (45 of 45 [100%]), compared with 84.1% (37 of 44) in the RFCA group. After the observation, 3 cases of MI reconnection occurred in the EIVOM group and 13 cases in the RFCA group (6.7% vs 35.1%; P < 0.05). After additional ablation, the final MI block rates in the EIVOM and RFCA groups were 97.8% (44 of 45) and 72.7% (32 of 44), respectively. During a 1-year follow-up, 8 of 45 patients who underwent EIVOM had recurrent atrial fibrillation, compared with 14 of 44 in the RFCA group (17.8% vs 31.8%; P < 0.01). CONCLUSIONS: EIVOM can reduce acute reconnection after MI bidirectional block and significantly increase first-pass MI block.

Research on multi-model imaging machine learning for distinguishing early hepatocellular carcinoma.

OBJECTIVE: To investigate the value of differential diagnosis of hepatocellular carcinoma (HCC) and non-hepatocellular carcinoma (non-HCC) based on CT and MR multiphase radiomics combined with different machine learning models and compare the diagnostic efficacy between different radiomics models. BACKGROUND: Primary liver cancer is one of the most common clinical malignancies, hepatocellular carcinoma (HCC) is the most common subtype of primary liver cancer, accounting for approximately 90% of cases. A clear diagnosis of HCC is important for the individualized treatment of patients with HCC. However, more sophisticated diagnostic modalities need to be explored. METHODS: This retrospective study included 211 patients with liver lesions: 97 HCC and 124 non-hepatocellular carcinoma (non-HCC) who underwent CT and MRI. Imaging data were used to obtain imaging features of lesions and radiomics regions of interest (ROI). The extracted imaging features were combined to construct different radiomics models. The clinical data and imaging features were then combined with radiomics features to construct the combined models. Support Vector Machine (SVM), K-nearest Neighbor (KNN), RandomForest (RF), eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), Multilayer Perceptron (MLP) six machine learning models were used for training. Five-fold cross-validation was used to train the models, and ROC curves were used to analyze the diagnostic efficacy of each model and calculate the accuracy rate. Model training and efficacy test were performed as before. RESULTS: Statistical analysis showed that some clinical data (gender and concomitant cirrhosis) and imaging features (presence of envelope, marked enhancement in the arterial phase, rapid contouring in the portal phase, uniform density/signal and concomitant steatosis) were statistical differences (P < 0.001). The results of machine learning models showed that KNN had the best diagnostic efficacy. The results of the combined model showed that SVM had the best diagnostic efficacy, indicating that the combined model (accuracy 0.824) had better diagnostic efficacy than the radiomics-only model. CONCLUSIONS: Our results demonstrate that the radiomic features of CT and MRI combined with machine learning models enable differential diagnosis of HCC and non-HCC (malignant, benign). The diagnostic model with dual radiomic had better diagnostic efficacy. The combined model was superior to the radiomic model alone.

Postprocedural Anticoagulation After Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction: A Multicenter, Randomized, Double-Blind Trial.

BACKGROUND: Postprocedural anticoagulation (PPA) is frequently administered after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction, although no conclusive data support this practice. METHODS: The RIGHT trial (Comparison of Anticoagulation Prolongation vs no Anticoagulation in STEMI Patients After Primary PCI) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, superiority trial conducted at 53 centers in China. Patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomly assigned by center to receive low-dose PPA or matching placebo for at least 48 hours. Before trial initiation, each center selected 1 of 3 PPA regimens (40 mg of enoxaparin once daily subcutaneously; 10 U·kg·h of unfractionated heparin intravenously, adjusted to maintain activated clotting time between 150 and 220 seconds; or 0.2 mg·kg·h of bivalirudin intravenously). The primary efficacy objective was to demonstrate superiority of PPA to reduce the primary efficacy end point of all-cause death, nonfatal myocardial infarction, nonfatal stroke, stent thrombosis (definite), or urgent revascularization (any vessel) within 30 days. The key secondary objective was to evaluate the effect of each specific anticoagulation regimen (enoxaparin, unfractionated heparin, or bivalirudin) on the primary efficacy end point. The primary safety end point was Bleeding Academic Research Consortium 3 to 5 bleeding at 30 days. RESULTS: Between January 10, 2019, and September 18, 2021, a total of 2989 patients were randomized. The primary efficacy end point occurred in 37 patients (2.5%) in both the PPA and placebo groups (hazard ratio, 1.00 [95% CI, 0.63 to 1.57]). The incidence of Bleeding Academic Research Consortium 3 to 5 bleeding did not differ between the PPA and placebo groups (8 [0.5%] vs 11 [0.7%] patients; hazard ratio, 0.74 [95% CI, 0.30 to 1.83]). CONCLUSIONS: Routine PPA after primary percutaneous coronary intervention was safe but did not reduce 30-day ischemic events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03664180.

Association between performance measures and clinical outcomes in patients with heart failure in China: Results from the HERO study.

BACKGROUND: There is great heterogeneity in the quality of care among hospitals in China, but studies on the performance measures and prognosis of patients with heart failure (HF) are still deficient. HYPOTHESIS: Performance measures have been used as a guideline to clinicans, however, the association between them and outcomes among HF patients in China remains unclear. METHODS: We analyzed 4497 patients with HF from the Heart Failure Registry of Patient Outcomes study. Performance measures were determined according to the guidelines, and the patients were divided into four groups based on a composite performance score. Multiple imputation and Cox proportional-hazard regression models were used to assess the association between the performance measures and clinical outcomes. RESULTS: Overall, only 12.5% of patients met the top 25% of the performance measures, whereas 33.5% of patients met the bottom 25% of the measures. A total of 992 (22.2%) patients died within 1 year, involving a larger proportion of patients who had met only the bottom 25% of the performance measures than had met the top 25% (27.0% vs. 16.3%, respectively). The patients who met the top 25% of the measures had a lower 1-year mortality rate (adjusted hazard ratio: 0.78, 95% confidence interval: 0.61-0.98). CONCLUSIONS: The association between performance measures and mortality appeared to follow a dose-response pattern with a larger degree of compliance with performance measures being associated with a lower mortality rate in patients with HF. Accordingly, the quality of care for patients with HF in China needs to be further improved.

Evaluation of an algorithm-guided photoplethysmography for atrial fibrillation burden using a smartwatch.

BACKGROUND: Wearable devices based on the PPG algorithm can detect atrial fibrillation (AF) effectively. However, further investigation of its application on long-term, continuous monitoring of AF burden is warranted. METHOD: The performance of a smartwatch with continuous photoplethysmography (PPG) and PPG-based algorithms for AF burden estimation was evaluated in a prospective study enrolling AF patients admitted to Beijing Anzhen Hospital for catheter ablation from September to November 2022. A continuous Electrocardiograph patch (ECG) was used as the reference device to validate algorithm performance for AF detection in 30-s intervals. RESULTS: A total of 578669 non-overlapping 30-s intervals for PPG and ECG each from 245 eligible patients were generated. An interval-level sensitivity of PPG was 96.3% (95% CI 96.2%-96.4%), and specificity was 99.5% (95% CI 99.5%-99.6%) for the estimation of AF burden. AF burden estimation by PPG was highly correlated with AF burden calculated by ECG via Pearson correlation coefficient (R2 = 0.996) with a mean difference of -0.59 (95% limits of agreement, -7.9% to 6.7%). The subgroup study showed the robust performance of the algorithm in different subgroups, including heart rate and different hours of the day. CONCLUSION: Our results showed the smartwatch with an algorithm-based PPG monitor has good accuracy and stability in continuously monitoring AF burden compared with ECG patch monitors, indicating its potential for diagnosing and managing AF.

Catheter ablation of atrial fibrillation in patients with left bundle branch block.

BACKGROUND: Left bundle branch block (LBBB) and atrial fibrillation (AF) are commonly coexisting conditions. The impact of LBBB on catheter ablation of AF has not been well determined. This study aims to explore the long-term outcomes of patients with AF and LBBB after catheter ablation. METHODS: Forty-two patients with LBBB of 11,752 patients who underwent catheter ablation of AF from 2011 to 2020 were enrolled as LBBB group. After propensity score matching in a 1:4 ratio, 168 AF patients without LBBB were enrolled as non-LBBB group. Late recurrence and a composite endpoint of stroke, all-cause mortality, and cardiovascular hospitalization were compared between the two groups. RESULTS: Late recurrence rate was significantly higher in the LBBB group than that in the non-LBBB group (54.8% vs. 31.5%, p = .034). Multivariate analysis showed that LBBB was an independent risk factor for late recurrence after catheter ablation of AF (hazard ratio [HR] 2.19, 95% confidence interval [CI] 1.09-4.40, p = .031). LBBB group was also associated with a significantly higher incidence of the composite endpoint (21.4% vs. 6.5%, HR 3.98, 95% CI 1.64-9.64, p = .002). CONCLUSIONS: LBBB was associated with a higher risk for late recurrence and a higher incidence of composite endpoint in the patients underwent catheter ablation.

Edoxaban for stroke prevention in atrial fibrillation and factors associated with dosing: patient characteristics from the prospective observational ETNA-AF-China registry.

Real-world data on effectiveness and safety of a single non-vitamin K antagonist oral anticoagulant in the Chinese population with atrial fibrillation (AF) are limited. This study reports characteristics of patients treated with edoxaban and factors associated with dosing patterns from routine care in China. ETNA-AF-China (NCT04747496) is a multicentre, prospective, observational study enrolling edoxaban-treated patients from four economic regions with a targeted 2-year follow-up. Of the 4930 patients with AF (mean age: 70.2 ± 9.5 years; male, 57.1%), the mean creatinine clearance (CrCl), CHA2DS2-VASc, and HAS-BLED scores were 71.2 mL/min, 2.9, and 1.6. Overall, 6.4% of patients were perceived as frail by investigators. Available label dose reduction criteria (N = 4232) revealed that 3278 (77.5%) patients received recommended doses and 954 (22.5%) non-recommended doses. Northeast (53.0%) and West (43.1%) regions had the highest prescriptions of 60 mg and 30 mg recommended doses, respectively. Non-recommended 30 mg doses were more frequently prescribed in patients with antiplatelet use and history of heart failure than recommended 60 mg. Multivariate analysis identified advanced age as the strongest associated factor with non-recommended doses. Frailty had the strongest association with 30 mg except for age, and history of TIA was the most relevant factor associated with 60 mg. In conclusion, patients in the ETNA-AF-China study were predominantly aged 65 years and older, had mild-to-moderate renal impairment and good label adherence. Advanced age was associated with non-recommended doses, with frailty most common for non-recommended 30 mg and a history of TIA for the non-recommended 60 mg dose.

Impact of chronic exposure to field level glyphosate on the food consumption, survival, gene expression, gut microbiota, and metabolomic profiles of honeybees.

Glyphosate (GLY) is among the most widely used pesticides in the world. However, there are a lot of unknowns about chronic exposure to GLY's effects on Honeybee (HB) behavior and physiology. To address this, we carried out five experiments to study the impact of chronic exposure to 5 mg/kg GLY on sugar consumption, survival, gene expression, gut microbiota, and metabolites of HB workers. Our results find a significant decrease in sugar consumption and survival probability of HB after chronic exposure to GLY. Further, genes associated with immune response, energy metabolism, and longevity were conspicuously altered. In addition, a total of seven metabolites were found to be differentially expressed in the metabolomic profiles, mainly related the sucrose metabolism. There was no significant difference in the gut microbiota. Results suggest that chronic exposure to field-level GLY altered the health of HB and the intricate toxic mechanisms. Our data provided insights into the chronic effects of GLY on HB behavior in food intake and health, which represents the field conditions where HB are exposed to pesticides over extended periods.

Characteristics and outcome of patients with left atrial appendage closure in China: a single-center experience.

BACKGROUND: Clinical characteristics and long-term data on the safety and efficacy of LAAC in preventing cerebrovascular accident and thromboembolism among Chinese patients with non-valvular AF (NVAF) remain limited. METHODS: Data of consecutive NVAF patients who underwent LAAC at Beijing Anzhen Hospital, Capital Medical University, from June 1, 2014, to December 31, 2021, were collected and analyzed retrospectively. The primary effectiveness endpoint was the composite endpoint of stroke/transient ischemic attack, systemic embolism, and death from cardiovascular causes. The primary safety endpoint is the severe bleeding defined by the LAAC Munich consensus. RESULTS: Of the 222 patients enrolled, the mean age was 66.90 ± 9.62 years, with a majority being male (77.03%). Many patients are non-paroxysmal AF (71.19%) with a median duration of AF of 4.00 years. The mean CHA2DS2-VASc score was 3.78 ± 1.49, and the mean HAS-BLED score was 1.68 ± 0.86. Thromboembolic events (76.58%) were the most common indication for LAAC. The device, technical, and procedural success rates were 98.65%, 98.65%, and 93.69%, respectively. The anticoagulation continuation rate was 56.36%, 31.25%, and 22.60% at 3-, 6- and 12 months post-procedure, respectively. Throughout a mean 2.81 years of follow-up, the incidence of the primary efficacy endpoint was 4.27 per 100 patient-years, predominantly attributable to stroke/TIA (3.12 per 100 PYs). Five patients experienced major bleeding during the follow-up period. Post-procedure imaging revealed minimal complications, with only one substantial peri-device leak. Device-related thrombus occurred in 2.33% of patients, resolving with anticoagulation. CONCLUSION: The study demonstrates that LAAC is a safe and effective alternative option for Chinese patients with AF, with a high success rate, few complications as well as fewer long-term adverse outcome events.

Effect of Intensive Blood Pressure Control on Cardiovascular Outcomes in Cancer Survivors.

BACKGROUND: To evaluate whether cancer modifies the effect of intensive blood pressure control on major cardiovascular outcomes. METHODS: Using data of the SPRINT (Systolic Blood Pressure Intervention Trial), we compared the risk of the composite outcomes of myocardial infarction, other acute coronary syndromes, stroke, heart failure, and cardiovascular death in patients with and without a history of cancer. Using Cox proportional hazards regression, we tested interactions between history of cancer and intensive blood pressure control on major cardiovascular outcomes. RESULTS: The study included a total of 9336 patients, with a mean age of 67.9±9.4 years, among whom 2066 (22.2%) were cancer survivors. Over a median follow-up of 3.2 years, 561 primary cardiovascular outcomes were observed. Cancer survivors had a similar risk of experiencing the primary outcome compared with patients without cancer after multivariable adjustment (adjusted hazard ratio, 0.94 [95% CI, 0.77-1.15]). Intensive blood pressure control reduced risk of the primary cardiovascular outcome similarly for cancer survivors (hazard ratio, 0.70 [95% CI, 0.51-0.97]) and patients without cancer (HR, 0.76 [95% CI, 0.63-0.93]; P for interaction 0.74). CONCLUSIONS: In SPRINT study, intensive blood pressure treatment reduced the risk of major cardiovascular events in cancer survivors to a similar extent to that of patients without cancer. Cancer history not requiring active treatment in last 2 years should not be an obstacle to intensive treatment of hypertension. This post hoc analysis should be considered as hypothesis-generating and merit further clinical trial. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Characteristics, Treatment, and In-Hospital Outcomes of Older Patients With STEMI Without Standard Modifiable Risk Factors.

Background: Strategies targeting standard modifiable cardiovascular risk factors (SMuRFs), including hypertension, diabetes, hypercholesterolemia, and smoking, have been well established to prevent coronary heart disease. However, few studies have evaluated the management and outcomes of older patients without SMuRFs after myocardial infarction. Objectives: The authors sought to evaluate the profile of patients with ST-segment elevation myocardial infarction (STEMI) aged ≥75 years without SMuRFs. Methods: This study is based on the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project. Patients aged ≥75 years with a first presentation of STEMI were enrolled in this study between November 2014 and December 2019. Modified Poisson regression was used to evaluate the association between SMuRF-less and in-hospital outcomes. Results: Among 10,775 patients with STEMI aged ≥75 years, 1,633 (15.16%) had no SMuRFs. Compared with those with SMuRF, SMuRF-less patients received less evidence-based treatment. In-hospital mortality was similar among patients with and without SMuRFs (5.44% vs 5.14%; P = 0.630). However, after adjustment for patient characteristics and treatment, being SMuRF-less was significantly associated with a reduced risk of mortality (RR: 0.80; 95% CI: 0.65-0.99; P = 0.043). SMuRF-less patients also had a significantly reduced risk of in-hospital death when only adjusting for in-hospital treatment (RR: 0.78; 95% CI: 0.63-0.98; P = 0.030), regardless of patient characteristics. Conclusions: Approximately 1 in 7 STEMI patients in China ≥75 years old had no SMuRFs. The similar mortality in patients with and without SMuRF can be partially explained by the inadequate in-hospital treatment of SMuRF-less patients. The quality of care for older patients without SMuRF should be improved. (CCC Project-Acture Coronary Syndrome; NCT02306616).

Development and validation of a 18F-FDG PET/CT radiomics nomogram for predicting progression free survival in locally advanced cervical cancer: a retrospective multicenter study.

BACKGROUND: The existing staging system cannot meet the needs of accurate survival prediction. Accurate survival prediction for locally advanced cervical cancer (LACC) patients who have undergone concurrent radiochemotherapy (CCRT) can improve their treatment management. Thus, this present study aimed to develop and validate radiomics models based on pretreatment 18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) images to accurately predict the prognosis in patients. METHODS: The data from 190 consecutive patients with LACC who underwent pretreatment 18F-FDG PET-CT and CCRT at two cancer hospitals were retrospectively analyzed; 176 patients from the same hospital were randomly divided into training (n = 117) and internal validation (n = 50) cohorts. Clinical features were selected from the training cohort using univariate and multivariate Cox proportional hazards models; radiomic features were extracted from PET and CT images and filtered using least absolute shrinkage and selection operator and Cox proportional hazard regression. Three prediction models and a nomogram were then constructed using the previously selected clinical, CT and PET radiomics features. The external validation cohort that was used to validate the models included 23 patients with LACC from another cancer hospital. The predictive performance of the constructed models was evaluated using receiver operator characteristic curves, Kaplan Meier curves, and a nomogram. RESULTS: In total, one clinical, one PET radiomics, and three CT radiomics features were significantly associated with progression-free survival in the training cohort. Across all three cohorts, the combined model displayed better efficacy and clinical utility than any of these parameters alone in predicting 3-year progression-free survival (area under curve: 0.661, 0.718, and 0.775; C-index: 0.698, 0.724, and 0.705, respectively) and 5-year progression-free survival (area under curve: 0.661, 0.711, and 0.767; C-index, 0.698, 0.722, and 0.676, respectively). On subsequent construction of a nomogram, the calibration curve demonstrated good agreement between actually observed and nomogram-predicted values. CONCLUSIONS: In this study, a clinico-radiomics prediction model was developed and successfully validated using an independent external validation cohort. The nomogram incorporating radiomics and clinical features could be a useful clinical tool for the early and accurate assessment of long-term prognosis in patients with LACC patients who undergo concurrent chemoradiotherapy.

Temporal trend in hospitalizations for malignant neoplasm and benign neoplasm: a nationwide study, China, 2004-2020.

The increasing cancer burden calls for reliably assessed changes in the hospitalizations for tumors over time and space in China. This study evaluated trends in hospitalization rate, in-hospital mortality, length of stay (LOS), and medical costs for malignant and benign neoplasms. Data were derived from China Health Statistical Yearbooks from 2004 to 2020. Temporal trends in hospitalization rates and in-hospital mortality rates were assessed through the Cochran-Armitage Test. We used the linear model with continuous variables to test for the trend. The malignant neoplasm hospitalization rate increased from 1.1‰ to 5.8‰ and the benign neoplasm increased from 1.0‰ to 2.0‰. The in-hospital mortality rate due to malignant neoplasm and benign neoplasm decreased from 5.11 to 2.87% (P for trend < 0.001) and 0.14-0.01% (P for trend < 0.001), respectively. Among all patients hospitalized with malignant neoplasm, the average cost per hospitalization significantly increased during the study period (P for trend < 0.001), adjusted for the Consumer Price Index. However, the average LOS gradually decreased (P for trend < 0.001). In line with the trend of malignant neoplasm, the average cost per hospitalization increased significantly among all patients hospitalized for benign neoplasm (P for trend < 0.001), and the average LOS showed a steady downward trend (P for trend < 0.001). We found upward trends in hospitalization rates, and medical costs in neoplasms. By contrast, substantial decreases in in-hospital mortality and LOS. The hospitalization rate gap between urban and rural areas is narrowed.

Impact of diagnosis-to-ablation time on clinical outcomes in patients with early-onset atrial fibrillation.

BACKGROUND: Evidence was lacking for the early choice of radiofrequency ablation (RFA) among patients with early-onset atrial fibrillation (AF). HYPOTHESIS: This study aimed to explore whether earlier RFA was associated with better clinical outcomes among early-onset AF patients. METHODS: Patients, who were diagnosed with AF before 45 years and underwent their first RFA procedures at baseline of the China Atrial Fibrillation registry, were enrolled and divided into four diagnosis-to-ablation time (DAT) groups: DAT ≤ 1 year, 1 year < DAT ≤ 3 years, 3 years < DAT ≤ 6 years, and DAT > 6 years. Another group of nonablation patients, who were newly diagnosed with AF and younger than 45 years, were also included. Adjusted associations of groups with composite cardiovascular events (cardiovascular death, embolism, major hemorrhages, or cardiac rehospitalization) or recurrent AF were analyzed using Cox proportional hazards models. RESULTS: Among 1694 patients who underwent their first RFA at enrollment, incidences of composite cardiovascular outcomes were increasing with extension of DAT (DAT ≤ 1 year: 6.1/100 person-years, 1 year < DAT ≤ 3 years: 7.9/100 person-years, 3 years < DAT ≤ 6 years: 7.6/100 person-years, DAT > 6 years: 10.5/100 person-years; p < .001). In comparison with DAT > 6 years group, the DAT ≤ 1 year group was associated with reduced risk of cardiovascular events (adjusted hazard ratio, HR [95% confidence interval, CI] = 0.64 [0.47-0.87], p = .005) and AF recurrence (adjusted HR [95% CI] = 0.70 [0.57-0.88], p = .002). Associations remained similar after stratified by AF types. Compared to nonablation group (n = 413), DAT ≤ 1year patients tended to show lower cardiovascular risk (adjusted HR [95% CI] = 0.78 [0.58-1.05], p = .099) and lower risk of recurrent AF (adjusted HR [95% CI] = 0.46 [0.38-0.55], p < .001). CONCLUSIONS: A shorter DAT was associated with a lower risk of cardiovascular events and recurrent AF for early-onset AF patients.

Exercise Capacity in Patients With Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM Baseline Characteristics and Study Design.

Patients with obstructive hypertrophic cardiomyopathy (oHCM) have increased risk of arrhythmia, stroke, heart failure, and sudden death. Contemporary management of oHCM has decreased annual hospitalization and mortality rates, yet patients have worsening health-related quality of life due to impaired exercise capacity and persistent residual symptoms. Here we consider the design of clinical trials evaluating potential oHCM therapies in the context of SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). This large, phase 3 trial is now fully enrolled (N = 282). Baseline characteristics reflect an ethnically diverse population with characteristics typical of patients encountered clinically with substantial functional and symptom burden. The study will assess the effect of aficamten vs placebo, in addition to standard-of-care medications, on functional capacity and symptoms over 24 weeks. Future clinical trials could model the approach in SEQUOIA-HCM to evaluate the effect of potential therapies on the burden of oHCM. (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM [SEQUOIA-HCM]; NCT05186818).