Low-Dose Colchicine Ameliorates Doxorubicin Cardiotoxicity Via Promoting Autolysosome Degradation.

BACKGROUND: The only clinically approved drug that reduces doxorubicin cardiotoxicity is dexrazoxane, but its application is limited due to the risk of secondary malignancies. So, exploring alternative effective molecules to attenuate its cardiotoxicity is crucial. Colchicine is a safe and well-tolerated drug that helps reduce the production of reactive oxygen species. High doses of colchicine have been reported to block the fusion of autophagosomes and lysosomes in cancer cells. However, the impact of colchicine on the autophagy activity within cardiomyocytes remains inadequately elucidated. Recent studies have highlighted the beneficial effects of colchicine on patients with pericarditis, postprocedural atrial fibrillation, and coronary artery disease. It remains ambiguous how colchicine regulates autophagic flux in doxorubicin-induced heart failure. METHODS AND RESULTS: Doxorubicin was administered to establish models of heart failure both in vivo and in vitro. Prior studies have reported that doxorubicin impeded the breakdown of autophagic vacuoles, resulting in damaged mitochondria and the accumulation of reactive oxygen species. Following the administration of a low dose of colchicine (0.1 mg/kg, daily), significant improvements were observed in heart function (left ventricular ejection fraction: doxorubicin group versus treatment group=43.75%±3.614% versus 57.07%±2.968%, P=0.0373). In terms of mechanism, a low dose of colchicine facilitated the degradation of autolysosomes, thereby mitigating doxorubicin-induced cardiotoxicity. CONCLUSIONS: Our research has shown that a low dose of colchicine is pivotal in restoring the autophagy activity, thereby attenuating the cardiotoxicity induced by doxorubicin. Consequently, colchicine emerges as a promising therapeutic candidate to improve doxorubicin cardiotoxicity.

Combined pesticides in field doses weaken honey bee (Apis cerana F.) flight ability and analyses of transcriptomics and metabolomics.

Imidacloprid, chlorpyrifos, and glyphosate rank among the most extensively employed pesticides worldwide. The effects of these pesticides and their combined on the flight capability of Apis cerana, and the potential underlying mechanisms remain uncertain. To investigate these effects, we carried out flight mill, transcriptome, and metabolome experiments. Our findings reveal that individual acute oral treatments with pesticides, specifically 20 µL of 10 ng/g imidacloprid (0.2 ng per bee), 30 ng/g chlorpyrifos (0.6 ng per bee), and 60 ng/g glyphosate (1.2 ng per bee), did not impact the flight capability of the bees. However, when bees were exposed to a combination of two or three pesticides, a notable reduction in flight duration and distance was observed. In the transcriptomic and metabolomic analyses, we identified 307 transcripts and 17 metabolites that exhibited differential expression following exposure to combined pesticides, primarily associated with metabolic pathways involved in energy regulation. Our results illuminate the intricate effects and potential hazards posed by combined pesticide exposures on bee behavior. These findings offer valuable insights into the synergistic potential of pesticide combinations and their capacity to impair bee behavior. Understanding these complex interactions is essential for comprehending the broader consequences of pesticide formulations on honey bee populations.

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.

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.

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.

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.

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.

Outcome of cancer patients after atrial fibrillation ablation: Insights from the China-AF registry.

BACKGROUND: Cancer has become significant comorbidity in patients with atrial fibrillation (AF). However, little is known about the efficacy and safety of AF ablation, the first-line rhythm control strategy, in patients with cancer. This study aims to evaluate the incidence and risk of AF recurrence and safety endpoints in patients with cancer compared to the non-cancer group after ablation. METHODS: From August 2011 to December 2020, we consecutively enrolled cancer patients in the China-AF cohort. We used propensity score matching (1:3) to select the control group and assessed the risk of AF recurrence and adverse events after ablation in cancer patients using a multivariable Fine and Gray competing risk model. RESULTS: A total of 203 patients with cancer were enrolled and 21 of them were active cancer, with a median follow-up of 12.3 months. The cumulative incidence of AF recurrence was comparable between patients with and without cancer (43.8% vs. 51.1%; p = .88). No difference in the risk of AF recurrence, thromboembolism, major bleeding, and mortality was observed after adjusting confounders. Active cancer was not associated with an increased risk of AF recurrence compared to the stable disease (SHR = 1.32; 95% CI 0.72-2.43; p = .46). Cancer was associated with a low risk of cardiovascular hospitalization (SHR, 0.54; 95% CI, 0.36-0.81; p = .01). Subgroup analysis found that hematological malignancy was associated with a high risk of AF recurrence (SHR, 5.68; 95% CI, 3.00-10.8; p < .001). CONCLUSIONS: This study suggests that catheter ablation could be feasible for rhythm control of AF patients with concomitant cancer.

Impact of age on characteristics, performance measures and outcomes of inpatients for heart failure in Beijing, China.

AIMS: This study aims to provide representative information on heart failure (HF) patients in China, especially older adults aged ≥75 years. We aim to clarify the age-related discrepancies in performance measures and the modifying effect of age on the impact of HF patients' characteristics on clinical outcomes. METHODS AND RESULTS: All HF patients admitted into five tertiary and four secondary hospitals of the Capital Medical University were divided into two groups according to age: 1419 (53.3%) were <75 years, and 1244 (46.7%) were ≥75 years. Older HF patients were more likely to be women, with higher left ventricular ejection fraction, with co-morbidities including chronic obstructive pulmonary disease/asthma, anaemia, chronic kidney disease, stroke/transient ischemic attack (TIA), atrial fibrillation/atrial flutter, hypertension, and coronary artery disease, while obesity, diabetes mellitus, hypercholesterolaemia and valvular heart disease were more prevalent among younger HF patients. Left ventricular ejection fraction assessment was performed in a similar proportion of patients in the younger and older groups (81.7% vs. 80.5%, P = 0.426), while B-type natriuretic peptide/N terminal pro brain natriuretic peptide was tested in a lower proportion in the younger group (84.8% vs. 89%, P = 0.001). At discharge, HF with reduced ejection fraction patients were less likely to receive beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, or combined beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers therapy in the older group (49.74% vs. 63.2%, P = 0.002; 52.9% vs. 64.7%, P = 0.006; and 28.57% vs. 45.5%, P < 0.001, respectively) but were equally likely to receive mineralocorticoid receptor antagonists in the two age groups (80.8% vs. 84.1%, P = 0.322). Older patients with HF had higher risk of in-hospital and 1 year mortality (2.7% vs. 1.3%, P = 0.011; 21.7% vs. 12.5%; P < 0.001, respectively). Higher body mass index was associated with better outcomes in both age groups. New York Heart Association functional class IV and estimated glomerular filtration rate < 60 mL/min/1.73 m2 were independent predictors of 1 year mortality. The associations between patients' characteristics and risk of mortality were not modified by age. CONCLUSIONS: HF patients aged ≥75 years had distinct clinical profiles, received worse in-hospital therapies and experienced higher in-hospital and 1 year mortality.

Chinese expert consensus on the construction of the fluoroless cardiac electrophysiology laboratory and related techniques.

Transcatheter radiofrequency ablation has been widely introduced for the treatment of tachyarrhythmias. The demand for catheter ablation continues to grow rapidly as the level of recommendation for catheter ablation. Traditional catheter ablation is performed under the guidance of X-rays. X-rays can help display the heart contour and catheter position, but the radiobiological effects caused by ionizing radiation and the occupational injuries worn caused by medical staff wearing heavy protective equipment cannot be ignored. Three-dimensional mapping system and intracardiac echocardiography can provide detailed anatomical and electrical information during cardiac electrophysiological study and ablation procedure, and can also greatly reduce or avoid the use of X-rays. In recent years, fluoroless catheter ablation technique has been well demonstrated for most arrhythmic diseases. Several centers have reported performing procedures in a purposefully designed fluoroless electrophysiology catheterization laboratory (EP Lab) without fixed digital subtraction angiography equipment. In view of the lack of relevant standardized configurations and operating procedures, this expert task force has written this consensus statement in combination with relevant research and experience from China and abroad, with the aim of providing guidance for hospitals (institutions) and physicians intending to build a fluoroless cardiac EP Lab, implement relevant technologies, promote the standardized construction of the fluoroless cardiac EP Lab.

Epicardial connections and bi-atrial tachycardias: From anatomy to clinical practice.

Bi-atrial tachycardia (BiAT) is not rare after extensive atrial ablation or cardiac surgery. The complexity of bi-atrial reentrant circuits poses a great challenge for clinical practice. With recent advances in mapping technologies, we are now able to characterize atrial activation in detail. However, given the involvement of both atria and multiple epicardial conductions, endocardial mapping for BiATs is not easy to understand. Knowledge of the atrial myocardial architecture is the foundation for the clinical management of BiATs; as it is required to understand the possible mechanism of the tachycardia and identify the optimal target of ablation. In this review we summarize current knowledge about the anatomy of interatrial connections as well as other epicardial fibers and discuss the interpretation of electrophysiological findings and ablation strategies for BiATs.

Tortuous treatment process of a complex femoral pseudoaneurysm following atrial fibrillation ablation: a case report.

Background: Although the rate of vascular complications following catheter ablation has been decreasing in the past 10 years, it remains a common and thorny problem in clinical settings. For the majority of iatrogenic pseudoaneurysms (PSAs), non-surgical therapeutic approaches such as ultrasound-guided compression repair (UGCR) and ultrasound-guided thrombin injection (UGTI) have been used as first-line regimens. However, suitable treatment for PSA mainly depends on the characteristics of the PSA. Case summary: This report presented the case of a 75-year-old woman who suffered from a beaded multi-chamber femoral PSA combined with arteriovenous fistula between the superficial femoral artery and the common femoral vein following radiofrequency ablation of atrial fibrillation. The treatment process of the PSA was tortuous. After a UGCR attempt, the PSA was not occluded. The UGTI successfully clotted the superficial and middle chambers of the PSA. After repeat UGCR, the residual deep chamber of the PSA was expanded, and the skin deteriorated. The complicated PSA was finally treated with surgical repair. Discussion: Appropriate treatment for PSA depends on the anatomical characteristics of the PSA and indications of various treatment measures.

The value of myocardial work in patients with left ventricular hypertrophy.

Myocardial work derived from pressure-strain analysis resembles a novel non-invasive method for myocardial function evaluation. Left ventricular hypertrophy (LVH) is commonly detected in Fabry disease (FD), cardiac amyloidosis (CA) and hypertension (HTN). The study aimed to demonstrate the characteristics of myocardial work in patients with LVH suffering from FD, CA, and HTN. Echocardiography were performed in patients with LVH suffering from FD (n = 13), light chain associated cardiac amyloidosis (AL-CA) (n = 29) and HTN (n = 72), 25 healthy controls were also included in the current study. Conventional and myocardial work parameters were assessed and compared among FD, AL-CA, HTN and controls. Patients with FD and AL-CA were included in the group of infiltrative cardiomyopathy. Logistic regression analysis was used to identify independent predictors for discriminating infiltrative cardiomyopathy from hypertension. Compared with controls, HTN patients had preserved global work index (GWI) and global constructive work (GCW) and reduced global longitudinal strain (GLS) and global work efficiency (GWE) (p < 0.05), but patients with FD and AL-CA had reduced GLS, GWI, GCW and GWE and increased global wasted work (GWW) (p < 0.05). GWI and GCW could discriminate infiltrative cardiomyopathy from HTN independently with high accuracy (GWI cut-off value 1626 mmHg%, sensitivity 0.87, specificity 0.82, area under the curve 0.90; GCW cut-off value 2021 mmHg%, sensitivity 0.84, specificity 0.88, area under the curve 0.91). GWI and GCW were reduced in FD and AL-CA patients, but not in patients with HTN. Myocardial work had an addictive value in differentiating infiltrative cardiomyopathy from hypertension.

Machine learning models predict overall survival and progression free survival of non-surgical esophageal cancer patients with chemoradiotherapy based on CT image radiomics signatures.

PURPOSE: To construct machine learning models for predicting progression free survival (PFS) and overall survival (OS) with esophageal squamous cell carcinoma (ESCC) patients. METHODS: 204 ESCC patients were randomly divided into training cohort (n = 143) and test cohort (n = 61) according to the ratio of 7:3. Two radiomics models were constructed by radiomics features, which were selected by LASSO Cox model to predict PFS and OS, respectively. Clinical features were selected by univariate and multivariate Cox proportional hazards model (p < 0.05). Combined radiomics and clinical model was developed by selected clinical and radiomics features. The receiver operating characteristic curve, Kaplan Meier curve and nomogram were used to display the capability of constructed models. RESULTS: There were 944 radiomics features extracted based on volume of interest in CT images. There were six radiomics features and seven clinical features for PFS prediction and three radiomics features and three clinical features for OS prediction; The radiomics models showed general performance in training cohort and test cohort for prediction for prediction PFS (AUC, 0.664, 0.676. C-index, 0.65, 0.64) and OS (AUC, 0.634, 0.646.C-index, 0.64, 0.65). The combined models displayed high performance in training cohort and test cohort for prediction PFS (AUC, 0.856, 0.833. C-index, 0.81, 0.79) and OS (AUC, 0.742, 0.768. C-index, 0.72, 0.71). CONCLUSION: We developed combined radiomics and clinical machine learning models with better performance than radiomics or clinical alone, which were used to accurate predict 3 years PFS and OS of non-surgical ESCC patients. The prediction results could provide a reference for clinical decision.

In-hospital outcomes of ticagrelor versus clopidogrel in patients 75 years or older with acute coronary syndrome: findings from the Improving Care for Cardiovascular Disease in China (CCC)-Acute Coronary Syndrome Project.

BACKGROUND: The evidence for the comparative effectiveness and safety of ticagrelor versus clopidogrel in older patients with acute coronary syndrome (ACS) is limited, especially in the acute phase of ACS. This study aimed to compare the in-hospital outcomes of ticagrelor versus clopidogrel in older patients with ACS. METHODS: Hospitalised ACS patients aged ≥75 years who were recruited to the Improving Care for Cardiovascular Disease in China-ACS project between November 2014 and December 2019 and received aspirin and P2Y12 receptor inhibitors within 24 h after first medical contact were included. The primary outcomes were in-hospital major adverse cardiovascular events (MACE) and major bleeding. Multivariable Cox regression was performed to evaluate the comparative effectiveness and safety of ticagrelor and clopidogrel. Inverse probability of treatment weighting (IPTW) and propensity score matching analyses were performed to evaluate the robustness of the results. RESULTS: Of 18,244 ACS patients, 18.5% received ticagrelor. Multivariable-adjusted analysis revealed comparable risks of in-hospital MACE between patients receiving ticagrelor and clopidogrel (hazard ratio [HR] 1.12, 95% confidence interval [CI] 0.92-1.35). However, ticagrelor use was associated with 45% higher risk of in-hospital major bleeding compared with clopidogrel use (HR 1.45, 95% CI 1.09-1.91). Similar results were found in the IPTW analysis. CONCLUSIONS: ACS patients aged ≥75 years receiving ticagrelor during the acute phase had similar risk of in-hospital MACE, but higher risk of in-hospital major bleeding compared with those receiving clopidogrel. More evidence is needed to guide the use of P2Y12 receptor inhibitors during hospitalisation in older patients with ACS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02306616.

Shexiang Baoxin Pill (MUSKARDIA) reduces major adverse cardiovascular events in women with stable coronary artery disease: A subgroup analysis of a phase IV randomized clinical trial.

Background: A previous phase IV trial revealed sex as a potential effect modifier of MUSKARDIA efficacy in stable coronary artery disease (CAD). Objective: To assess the clinical effect of MUSKARDIA as a supplemental treatment to optimal medical therapy (OMT) in stable CAD cases. Methods: This study was a subgroup analysis of a multicenter, randomized, double-blinded, placebo-controlled phase IV clinical study. Eligible individuals underwent randomization to the oral MUSKARDIA and placebo groups and were treated for 24 months. All participants received OMT according to existing guidelines. The primary composite outcome was the major adverse cardiovascular event (MACE), included cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. The secondary composite outcome encompassed all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina and/or heart failure, and undergoing coronary procedure/surgery during treatment. Safety signals, especially cardiovascular adverse events (AEs), were analyzed. Results: The female subgroup included 776 participants (384 and 392 in the MUSKARDIA and placebo groups, respectively). The occurrence of the primary composite outcome was lower in the MUSKARDIA group compared with placebo-treated individuals (HR = 0.27, 95%CI: 0.09-0.83; P = 0.02), but the secondary composite outcome showed no significant difference (HR = 0.77, 95%CI: 0.47-1.25; P = 0.29). The MUSKARDIA group had reduced incidence of cardiovascular AEs compared with placebo-treated cases (2.9% vs. 5.6%). Conclusion: As a supplemental treatment to OMT, 24-month administration of MUSKARDIA is effective and safe in female stable CAD cases. Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT01897805].

Dosimetric analysis and biological evaluation between proton radiotherapy and photon radiotherapy for the long target of total esophageal squamous cell carcinoma.

Objective: The purpose of this study is to compare the dosimetric and biological evaluation differences between photon and proton radiation therapy. Methods: Thirty esophageal squamous cell carcinoma (ESCC) patients were generated for volumetric modulated arc therapy (VMAT) planning and intensity-modulated proton therapy (IMPT) planning to compare with intensity-modulated radiation therapy (IMRT) planning. According to dose-volume histogram (DVH), dose-volume parameters of the plan target volume (PTV) and homogeneity index (HI), conformity index (CI), and gradient index (GI) were used to analyze the differences between the various plans. For the organs at risk (OARS), dosimetric parameters were compared. Tumor control probability (TCP) and normal tissue complication probability (NTCP) was also used to evaluate the biological effectiveness of different plannings. Results: CI, HI, and GI of IMPT planning were significantly superior in the three types of planning (p < 0.001, p < 0.001, and p < 0.001, respectively). Compared to IMRT and VMAT planning, IMPT planning improved the TCP (p<0.001, p<0.001, respectively). As for OARs, IMPT reduced the bilateral lung and heart accepted irradiation dose and volume. The dosimetric parameters, such as mean lung dose (MLD), mean heart dose (MHD), V 5, V 10, and V 20, were significantly lower than IMRT or VMAT. IMPT afforded a lower maximum dose (D max) of the spinal cord than the other two-photon plans. What's more, the radiation pneumonia of the left lung, which was caused by IMPT, was lower than IMRT and VMAT. IMPT achieved the pericarditis probability of heart is only 1.73% ± 0.24%. For spinal cord myelitis necrosis, there was no significant difference between the three different technologies. Conclusion: Proton radiotherapy is an effective technology to relieve esophageal cancer, which could improve the TCP and spare the heart, lungs, and spinal cord. Our study provides a prediction of radiotherapy outcomes and further guides the individual treatment.