Prognostic significance of quantitative electrocardiographic parameters in patients with non-high-risk pulmonary embolism.

BACKGROUND: Electrocardiogram (ECG) abnormalities indicating right ventricular strain have been reported to have prognostic value in severe cases of acute pulmonary embolism (PE). We aimed to analyze the prognostic significance of other quantitative ECG parameters in non-high-risk acute PE. METHODS: Consecutive patients with non-high-risk acute PE were prospectively enrolled. The following baseline ECG parameters were collected: rhythm, heart rate, QRS axis, right bundle branch block (RBBB) pattern, S1Q3T3 pattern, T-wave inversion, ST-segment elevation, Qr in lead V1, PR Interval, QRS complex duration, QT interval, P-wave amplitude and duration, R- and S-wave amplitudes. The primary endpoint was early discharge within three days. Associations between ECG parameters and early discharge were analyzed. RESULTS: Overall, 383 patients were enrolled (median age: 67 years, 57% female): 277 (72.3%) with low-risk and 106 (27.7%) with intermediate-risk. The two groups of patients differed in several ECG signs of right ventricular strain and many other quantitative parameters like R- and S-wave amplitudes. In the multivariate logistic regression analysis, the S-wave depth in lead V5 (S-V5) was the only independent prognostic factor for early discharge (odds ratio = 0.137, 95% confidence interval = 0.031-0.613, p = 0.009). The optimum cutoff value of S-V5 for predicting early discharge derived from the receiver operative characteristic curve was 0.15 mv (c-statistic = 0.66, p =0.003). CONCLUSIONS: Several ECG signs of right ventricular strain and many other quantitative parameters were associated with disease severity in non-high-risk acute PE. An S-V5 lesser than 0.15 mv was predictive for early discharge in these patients.

SGLT2 inhibitors for the prevention of atrial fibrillation: a systemic review and meta-analysis.

AIMS: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are reported to have cardiac benefits. The effects of SGLT2 inhibitors on the prevention of atrial fibrillation (AF) remain inconclusive. We aimed to investigate whether SGLT2 inhibitors can prevent AF occurrence in patients with cardiometabolic diseases. METHODS: We searched MEDLINE, EMBASE, and the Cochrane CENTRAL database up to July 1, 2023. Randomized, placebo-controlled trials of SGLT2 inhibitors in patients with diabetes, heart failure, chronic kidney diseases, or cardiometabolic risk factors were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated in the overall population and selected subgroups. RESULTS: Forty-six trials comprising 101 100 patients were included. Overall, no significant risk reduction of AF occurrence was observed with SGLT2 inhibitors, although there was a favorable trend (RR 0.90, 95% CI 0.80-1.01). In trials with follow-up durations of over one year, a similar result was achieved (RR 0.90, 95% CI 0.80-1.01). The results were consistent across different SGLT2 inhibitors, with RRs (95%CIs) of 0.82 (0.60-1.12) for canagliflozin, 0.87 (0.73-1.03) for dapagliflozin, 0.97 (0.78-1.22) for empagliflozin, 0.99 (0.66-1.50) for sotagliflozin, and 0.87 (0.58-1.29) for ertugliflozin. Analyses in different doses of SGLT2 inhibitors yielded similar results. The associations between SGLT2 inhibitors and AF occurrence were also absent in patients with diabetes, heart failure, and chronic kidney diseases. CONCLUSION: For patients with cardiometabolic diseases or risk factors, SGLT2 inhibitors did not decrease the risk of AF occurrence, regardless of follow-up duration, type or dose of the drug, or the patient population.

The effects of SGLT2 inhibitors on the prevention of atrial fibrillation (AF) remain inconclusive. For patients with cardiometabolic diseases or risk factors, SGLT2 inhibitors did not decrease the risk of AF occurrence, regardless of follow-up duration, type or dose of the drug, or the patient population. Further research is warranted to investigate the potential benefit of SGLT2 inhibitors in AF.

Exogenous NADPH exerts a positive inotropic effect and enhances energy metabolism via SIRT3 in pathological cardiac hypertrophy and heart failure.

BACKGROUND: Therapies are urgently required to ameliorate pathological cardiac hypertrophy and enhance cardiac function in heart failure. Our preliminary experiments have demonstrated that exogenous NADPH exhibits a positive inotropic effect on isolated heart. This study aims to investigate the positive inotropic effects of NADPH in pathological cardiac hypertrophy and heart failure, as well as the underlying mechanisms involved. METHODS: Endogenous plasma NADPH contents were determined in patients with chronic heart failure and control adults. The positive inotropic effects of NADPH were investigated in isolated toad heart or rat heart. The effects of NADPH were investigated in isoproterenol (ISO)-induced cardiac hypertrophy or transverse aortic constriction (TAC)-induced heart failure. The underlying mechanisms of NADPH were studied using SIRT3 knockout mice, echocardiography, Western blotting, transmission electron microscopy, and immunoprecipitation. FINDINGS: The endogenous NADPH content in the blood of patients and animals with pathological cardiac hypertrophy or heart failure was significantly reduced compared with age-sex matched control subjects. Exogenous NADPH showed positive inotropic effects on the isolated normal and failing hearts, while antagonism of ATP receptor partially abolished the positive inotropic effect of NADPH. Exogenous NADPH administration significantly reduced heart weight indices, and improved cardiac function in the mice with pathological cardiac hypertrophy or heart failure. NADPH increased SIRT3 expression and activity, deacetylated target proteins, improved mitochondrial function and facilitated ATP production in the hypertrophic myocardium. Importantly, inhibition of SIRT3 abolished the positive inotropic effect of NADPH, and the anti-heart failure effect of NADPH was significantly reduced in the SIRT3 Knockout mice. INTERPRETATION: Exogenous NADPH shows positive inotropic effect and improves energy metabolism via SIRT3 in pathological cardiac hypertrophy and heart failure. NADPH thus may be one of the potential candidates for the treatment of pathological cardiac hypertrophy or heart failure. FUNDING: This work was supported by grants from the National Natural Science Foundation of China (No. 81973315, 82173811, 81730092), Natural Science Foundation of Jiangsu Higher Education (20KJA310008), Jiangsu Key Laboratory of Neuropsychiatric Diseases (BM2013003) and the Priority Academic Program Development of the Jiangsu Higher Education Institutes (PAPD).

The deficiency of 5-methylcytosine (5mC) and its ramification in the occurrence and prognosis of colon cancer.

The incidence and mortality of colon cancer are increasing, and effective biomarkers for its diagnosis are limited. 5-methylcytosine (5mC), a vital DNA methylation marker, plays important roles in gene expression, genomic imprinting, and transposon inhibition. This study aimed to identify the predictors of colon cancer prognosis and lay the foundation for research on therapeutic targets by detecting the levels of 5mC, 5-hydroxymethylcytosine (5hmC), 5-formyl cytosine (5fC), and 5-carboxylcytosine (5caC) in colon cancer and adjacent non-tumor tissues. A tissue microarray including 100 colon cancer tissue samples and 60 adjacent non-tumor tissue samples was used. The expression levels of 5mC and its ramifications were assessed by immunohistochemistry. According to the expression levels, patients were divided into moderately positive and strongly positive groups, and the correlation between clinicopathological characteristics and methylation marks was assessed using 2-sided chi-square tests. The prognostic values of 5mC, 5hmC, 5fC, and 5caC were tested using Kaplan-Meier analyses. Compared with adjacent non-tumor tissues, the overall levels of DNA methylation were lower in colon carcinoma lesions. However, the clinical parameters were not significantly associated with these methylation markers, except for 5hmC, which was associated with the age of cancer patients (P value = .043). Kaplan-Meier analysis disclosed that moderate positive group had a significantly shorter disease specific survival than strong positive group for patients with different levels of 5mC (65.2 vs 95.2 months, P = .014) and 5hmC (71.2 vs 97.5 months, P = .045). 5mC and its ramifications (5hmC, 5fC, and 5caC) can serve as biomarkers for colon cancer. 5mC and 5hmC are stable predictors and therapeutic targets in colon cancer. However, further understanding of its function will help to reveal the complex tumorigenic process and identify new therapeutic strategies.

Untargeted metabolomics reveal the metabolic profile of normal pulmonary circulation.

BACKGROUND: As an important place of material exchange, the homeostasis of the pulmonary circulation environment and function lays an essential foundation for the normal execution of various physiological functions of the body. Small metabolic molecules in the circulation can reflect the corresponding state of the pulmonary circulation. METHODS: We enrolled patients with Patent Foramen Ovale and obtained blood from the pulmonary arteries and veins through heart catheterization. UPLC-MS based untargeted metabolomics was used to compare the changes and metabolic differences of plasma between pulmonary vein and pulmonary artery. RESULTS: The plasma metabolomics revealed that pulmonary artery had a different metabolomic profile compared to venous. 1060 metabolites were identified, and 61 metabolites were differential metabolites. Purine, Amino acids, Nicotinamide, Tetradecanedioic acid and Bile acid were the most markedly. CONCLUSION: The differential metabolites are mostly related to immune inflammation and damage repaired. It is suggested that the pulmonary circulation is always in a steady state of injury and repair while pathological changes may be triggered when the homeostasis is broken. These changes play an important role in revealing the development process and etiology of lung homeostasis and related diseases. Relevant metabolites can be used as potential targets for further study of pulmonary circulation homeostasis.

Characteristics of exercise intolerance in different subgroups of pulmonary arterial hypertension associated with congenital heart disease.

BACKGROUND: Exercise intolerance is a major manifestation of pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). We aimed to investigate the characteristics of exercise intolerance in different subgroups of PAH-CHD. METHODS: We retrospectively enrolled 171 adult patients with PAH-CHD and 30 age and sex-matched healthy subjects and performed cardiopulmonary exercise testing. Gas exchange parameters, including peak oxygen uptake (peak V̇o2), anaerobic threshold, and the slope of ventilatory equivalent for carbon dioxide (V̇e/V̇co2 slope), were recorded. RESULTS: The median age of patients at enrollment was 27.8 years, and 131 (76.6%) were female. Peak V̇o2 was reduced in patients compared to healthy controls (median, 14.8 ml/kg/min versus 26.9 ml/kg/min, p < 0.001). Of all 171 patients, 60 (35.1%) had Eisenmenger syndrome, 35 (20.5%) had PAH associated with systemic-to-pulmonary shunts (PAH-SP), 39 (22.8%) had PAH with small defects (PAH-SD), and 37 (21.6%) had PAH after cardiac defect correction (PAH-CD). Patients with Eisenmenger syndrome had the lowest peak V̇o2 (p = 0.003) and the highest V̇e/V̇co2 slope (p = 0.012), compared with other patients, representing the worst exercise capacity and ventilatory efficiency. Patients with PAH-SP had the best exercise capacity among the four groups, indicated by the highest peak V̇o2 (p = 0.003) compared with other patients. Peak V̇o2 was negatively correlated with pulmonary vascular resistance (r = -0.411, p < 0.001). CONCLUSIONS: Exercise capacity was severely reduced in patients with PAH-CHD. Among the four subgroups, patients with Eisenmenger syndrome had the worst exercise capacity and ventilatory efficiency.

Prevalence, Genetic Background, and Clinical Phenotype of Congenital Thrombophilia in Chronic Thromboembolic Pulmonary Hypertension.

Background: The role of congenital thrombophilia in chronic thromboembolic pulmonary hypertension (CTEPH) remains unresolved. Objectives: The purpose of this study was to investigate the prevalence, genetic background, and clinical phenotype of congenital thrombophilia in CTEPH. Methods: In total, 367 patients with CTEPH from May 2013 to December 2020 were consecutively enrolled in this cross-sectional study in FuWai Hospital and Peking Union Medical College Hospital in China. The primary outcome was the occurrence of congenital thrombophilia diagnosed through tests for congenital anticoagulants activity (including protein C, protein S, and antithrombin III), factor V Leiden and prothrombin G20210A sequence variants. Next-generation sequencing was conducted for patients with congenital thrombophilia. Clinical phenotype was compared between patients with and without thrombophilia. Results: A total of 36 (9.8%; 95% CI: 6.8%-12.9%) patients were diagnosed as congenital thrombophilia, including 13 protein C deficiency (3.5%; 95% CI: 1.6%-5.4%), 19 protein S deficiency (5.2%; 95% CI: 2.9%-7.5%), and 4 antithrombin III deficiency (1.1%; 95% CI: 0%-2.2%). No factor V Leiden or prothrombin G20210A sequence variants were identified. Genotype for patients with thrombophilia revealed that 10 (76.9%) protein C deficiency patients were PROC sequence variant carriers, 4 (21.1%) protein S deficiency were PROS1 sequence variant carriers, and 2 (50.0%) antithrombin III deficiency were SERPINC1 sequence variant carriers. In the logistic regression model, male sex (OR: 3.24; 95% CI: 1.43-7.31) and proximal lesion in pulmonary arteries (OR: 4.10; 95% CI: 1.91-8.85) had significant differences between the congenital thrombophilia and nonthrombophilia group in CTEPH patients. Conclusions: Congenital thrombophilia was not rare. Male sex and proximal lesion in pulmonary arteries might be the specific clinical phenotype for CTEPH patients with congenital thrombophilia.

Estimating disability-adjusted life years for breast cancer and the impact of screening in female populations in China, 2015-2030: an exploratory prevalence-based analysis applying local weights.

BACKGROUND: Most cancer disability-adjusted life year (DALY) studies worldwide have used broad, generic disability weights (DWs); however, differences exist among populations and types of cancers. Using breast cancer as example, this study aimed to estimate the population-level DALYs in females in China and the impact of screening as well as applying local DWs. METHODS: Using multisource data, a prevalence-based model was constructed. (1) Overall years lived with disability (YLDs) were estimated by using numbers of prevalence cases, stage-specific proportions, and local DWs for breast cancer. Numbers of females and new breast cancer cases as well as local survival rates were used to calculate the number of prevalence cases. (2) Years of life lost (YLLs) were estimated using breast cancer mortality rates, female numbers and standard life expectancies. (3) The prevalence of and mortality due to breast cancer and associated DALYs from 2020 to 2030 were predicted using Joinpoint regression. (4) Assumptions considered for screening predictions included expanding coverage, reducing mortality due to breast cancer and improving early-stage proportion for breast cancer. RESULTS: In Chinese females, the estimated number of breast cancer DALYs was 2251.5 thousand (of 17.3% were YLDs) in 2015, which is predicted to increase by 26.7% (60.3% among those aged ≥ 65 years) in 2030 (2852.8 thousand) if the screening coverage (25.7%) stays unchanged. However, if the coverage can be achieved to 40.7% in 2030 (deduced from the "Healthy China Initiative"), DALYs would decrease by 1.5% among the screened age groups. Sensitivity analyses found that using local DWs would change the base-case values by ~ 10%. CONCLUSION: Estimates of DALYs due to breast cancer in China were lower (with a higher proportion of YLDs) than Global Burden of Disease Study numbers (2527.0 thousand, 8.2% were YLDs), suggesting the importance of the application of population-specific DWs. If the screening coverage remains unchanged, breast cancer-caused DALYs would continue to increase, especially among elderly individuals.

Chronic Thromboembolic Pulmonary Hypertension in Females: Clinical Features and Survival.

Sparse data are available on the female-specific features of chronic thromboembolic pulmonary hypertension (CTEPH). We prospectively enrolled 160 consecutive female patients who were firstly diagnosed with CTEPH between 2013 and 2019 to explore their clinical phenotypes, treatment patterns, and long-term survival. The patients' mean age was 54.7 ± 13.8 years, 70.6% provided a confirmed history of venous thromboembolism, 46 (28.8%) patients underwent pulmonary endarterectomy (PEA), 65 (40.6%) received balloon pulmonary angioplasty (BPA), and 49 (30.6%) were treated with medical therapy alone. The patients were followed for a median of 51 (34-70) months; three patients were lost to follow-up, and twenty-two patients died. The estimated survival rates at 1, 3, 5, and 7 years were 98.1% (95% CI 96.0-100), 96.9% (95% CI 94.2-99.6), 85.1% (95% CI 78.1-92.2), and 76.2% (95% CI 65.2-87.2), respectively. After adjusting for the confounders, the results of the multivariate Cox analysis showed that the presence of anemia (5.56, 95% CI 1.6-19.22) was associated with an increased risk of all-cause death, and compared with medical treatment, receiving PEA and BPA decreased the risk of death by 74% (0.26, 95% CI 0.07-0.97) and 86% (0.14, 95% CI 0.04-0.57), respectively. In conclusion, in the modern era of CTEPH treatment, invasive revascularization combined with targeted therapy display good clinical outcomes for females; anemia should be actively modified, which may lead to clinical improvements. (ClinicalTrials.gov Identifier: NCT05360992).

Safety of chronic high-dose calcium channel blockers exposure in children with pulmonary arterial hypertension.

Background: Chronic calcium channel blockers (CCBs) are indicated in children with idiopathic/heritable pulmonary arterial hypertension (IPAH/HPAH) and positive response to acute vasodilator challenge. However, minimal safety data are available on the long-term high-dose exposure to CCBs in this population. Methods: Patients aged 3 months to 18 years who were diagnosed with IPAH/HPAH and treated with CCB in the past 15 years were retrospectively reviewed. The maximum tolerated dose and the long-term safety of high-dose CCBs on the cardiovascular and noncardiovascular systems were assessed. Results: Thirty-two eligible children were enrolled in the study, with a median age of 9 (6-11) years old. Thirty-one patients were treated with diltiazem after diagnosis. The median maximum tolerated dose was 12.9 (9.8-16.8) mg/kg/day. Children younger than 7 years used higher doses than children in the older age group, 16.4 (10.5-28.5) mg/kg/day vs. 12.7 (6.6-14.4) mg/kg/day, P < 0.05. Patients were followed up for a median period of 6.2 (2.6-10.8) years. One patient died from a traffic accident, and others showed a stable or improved WHO functional class status. Thirteen (40.6%) and 10 (31.3%) patients developed arrhythmias and hypotension. Nine (28.1%) patients had sinus bradycardia, five (21.9%) had first-degree or second-degree type II atrial-ventricular blocks, and two (6.3%) had second-degree type II atrial-ventricular blocks. Most of these arrhythmias were transient and relieved after CCB dose adjustment. The most reported noncardiovascular adverse effect was gingival hyperplasia (13, 40.6%), accompanied by different degrees of dental dysplasia. No liver or kidney dysfunction was reported. Conclusion: Diltiazem was used in a very high dose for eligible children with IPAH/HPAH. The toxicity of long-term CCB use on the cardiovascular system is mild and controllable. Clinicians should also monitor the noncardiovascular adverse effects associated with drug therapy.

Association Between the Use of Pre- and Post-thrombolysis Anticoagulation With All-Cause Mortality and Major Bleeding in Patients With Pulmonary Embolism.

Objective: To explore the comparative clinical efficacy and safety outcomes of anticoagulation before (pre-) or following (post-) thrombolytic therapy in systemic thrombolytic therapy for pulmonary embolism (PE). Methods: PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases were searched from inception through 1 May 2021. All randomized clinical trials comparing systemic thrombolytic therapy vs. anticoagulation alone in patients with PE and those that were written in English were eligible. The primary efficacy and safety outcomes were all-cause mortality and major bleeding, respectively. Odds ratios (OR) estimates and associated 95% confidence intervals (CIs) were calculated. A Bayesian network analysis was performed using R studio software, and then the efficacy and safety rankings were derived. Results: This network meta-analysis enrolled 15 trials randomizing 2,076 patients. According to the plot rankings, the anticoagulant therapy was the best in terms of major bleeding, and the post-thrombolysis anticoagulation was the best in terms of all-cause mortality. Taking major bleeding and all-cause mortality into consideration, the most safe-effective treatment was the post-thrombolysis anticoagulation in patients who needed thrombolytic therapy. The net clinical benefit analysis comparing associated ICH benefits vs. mortality risks of post-thrombolysis anticoagulation demonstrated a net clinical benefit of 1.74%. Conclusion: The systemic thrombolysis followed by anticoagulation had a better advantage in all-cause mortality and major bleeding than the systemic thrombolysis before anticoagulation. The adjuvant anticoagulation treatment of systemic thrombolytic therapy should be optimized.

The population-level economic burden of liver cancer in China, 2019-2030: prevalence-based estimations from a societal perspective.

BACKGROUND: Benchmark data on the population-level economic burden are critical to inform policymakers about liver cancer control. However, comprehensive data in China are currently limited. METHODS: A prevalence-based approach from a societal perspective was used to quantify the annual economic burden of liver cancer in China from 2019 to 2030. Detailed per-case data on medical/non-medical expenditure and work-loss days were extracted from a multicenter survey. The numbers/rates of new/prevalent cases and deaths, survival, and population-related parameters were extracted from the Global Burden of Disease 2019 and the literature. All expenditure data were reported in both 2019 Chinese Yuan (CNY) and United States dollar (US$, for main estimations). RESULT: The overall economic burden of liver cancer was estimated at CNY76.7/US$11.1 billion in China in 2019 (0.047% of the local GDP). The direct expenditure was CNY21.6/US$3.1 billion, including CNY19.7/US$2.9 billion for medical expenditure and CNY1.9/US$0.3 billion for non-medical expenditure. The indirect cost was CNY55.1/US$8.0 billion (71.8% of the overall burden), including CNY3.0/US$0.4 billion due to disability and CNY52.0/US$7.5 billion due to premature death. The total burden would increase to CNY84.2/US$12.2 billion, CNY141.7/US$20.5 billion, and CNY234.3/US$34.0 billion in 2020, 2025, and 2030, accounting for 0.102%, 0.138%, and 0.192% of China's GDP, respectively. However, if China achieves the goals of Healthy China 2030 or the United Nations' Sustainable Development Goals for non-communicable diseases, the burden in 2030 would be < CNY144.4/US$20.9 billion. CONCLUSIONS: The population-level economic burden of liver cancer in China is currently substantial and will consistently increase in the future. Sustainable efforts in primary and secondary interventions for liver cancer need to be further strengthened.

Association Between Anticoagulation Outcomes and Venous Thromboembolism History in Chronic Thromboembolic Pulmonary Hypertension.

Background: The association between anticoagulation outcomes and prior history of venous thromboembolism (VTE) in chronic thromboembolic pulmonary hypertension (CTEPH) has not been established. This study aimed to compare the efficacy and safety of anticoagulation treatment in CTEPH patients with and without prior history of VTE. Methods: A total of 333 CTEPH patients prescribed anticoagulants were retrospectively included from May 2013 to April 2019. The clinical characteristics were collected at their first admission. Incidental recurrent VTE and clinically relevant bleeding were recorded during follow-up. The Cox proportional regression models were used to identify potential factors associated with recurrent VTE and clinically relevant bleeding. Results: Seventy patients (21%) without a prior history of VTE did not experience recurrent VTE during anticoagulation. Compared to CTEPH patients without a prior history of VTE, those with a prior history of VTE had an increased risk of recurrent VTE [2.27/100 person-year vs. 0/100 person-year; hazard ratio (HR), 8.92; 95% confidence interval (CI), 1.18-1142.00; P = 0.029] but a similar risk of clinically relevant bleeding (3.90/100 person-year vs. 4.59/100 person-year; HR, 0.83; 95% CI, 0.38-1.78; P = 0.623). Multivariate Cox analyses suggested that a prior history of VTE and interruption of anticoagulation treatments were significantly associated with an increased risk of recurrent VTE, while anemia and glucocorticoid use were significantly associated with a higher risk of clinically relevant bleeding. Conclusions: This study is the first to reveal that a prior history of VTE significantly increases the risk of recurrent VTE in CTEPH patients during anticoagulation treatment. This finding should be further evaluated in prospective studies.

Rare variants in MTHFR predispose to occurrence and recurrence of pulmonary embolism.

BACKGROUND: Rare genetic variants play a critical role in unprovoked pulmonary embolism (PE). However, the known risk genes only account a small proportion of patients with PE. The objective of this study was to investigate the relationship between the rare variants of gene encoding methylenetetrahydrofolate reductase (MTHFR) and the initiation and long-term clinical outcomes of PE. METHODS: The rare variants of MTHFR were detected by whole exome sequencing of DNA from 258 unprovoked PE cases and 11,451 controls. Correlation of genotype and clinical phenotype and outcome were evaluated at baseline and after follow-up. RESULTS: MTHFR rare variants were found in 15 of 258 cases (5.81%) and 241 of 11,451 controls (2.10%), conferring 2.87-fold greater odds of the PE occurrence (OR = 2.87, 95% CI = 1.68-4.91, P = 5.6 × 10-5, chi-square test). The patients with MTHFR rare variants had higher plasma level of homocysteine than those without. During a follow-up of 3.0 years, a total of 84 events were identified. The recurrent PE (two or more events of PE) were significantly higher in patients carrying MTHFR rare variants (8/15, 53.3%) compared with those without (55/239, 23.0%) (P = 0.023). CONCLUSION: We speculate that MTHFR rare variants may increase the occurrence and recurrence of PE.

Health-related quality of life of patients with colorectal neoplasms in China: A multicenter cross-sectional survey.

BACKGROUND AND AIM: This study aimed to clarify health-related quality of life (HRQoL) of patients with colorectal precancer and colorectal cancer (CRC) in China and to better understand related utility scores. METHODS: A hospital-based cross-sectional survey was conducted in precancer and CRC patients from 2012 to 2014, covering 12 provinces in China. HRQoL was assessed with EuroQol 5-Dimensions 3-Levels. Utility scores were derived using Chinese value set. A multivariate regression model was established to explore potential predictors of utility scores. RESULTS: A total of 376 precancer (mean age 58.7 years, 61.2% men) and 2470 CRC patients (mean age 58.6 years, 57.6% men) were included. In five dimensions, there was a certain percentage of problem reported among precancer (range: 12.0% to 36.7%) and CRC (range: 32.4% to 50.3%) patients, with pain/discomfort being the most serious dimension. Utility scores of precancer and CRC patients were 0.870 (95% confidence interval [CI], 0.855-0.886) and 0.751 (95% CI, 0.742-0.759), both of which were lower than those of general Chinese population (0.960 [95% CI, 0.960-0.960]). Utilities for patients at stage I to stage IV were 0.742 (95% CI, 0.715-0.769), 0.722 (95% CI, 0.705-0.740), 0.756 (95% CI, 0.741-0.772), and 0.745 (95% CI, 0.742-0.767), respectively. Multivariate analysis showed that therapeutic regimen, time point of the interview, education, occupation, annual household income, and geographic region were associated with utilities of CRC patients. CONCLUSION: Health-related quality of life of both precancer and CRC patients in China declined considerably. Utility scores differed by sociodemographic and clinical characteristics, and findings of these utilities may facilitate implementation of further cost-utility evaluations.

Comparing EQ-5D-3L and EQ-5D-5L performance in common cancers: suggestions for instrument choosing.

PURPOSE: To compare the performance of three-level EuroQol five-dimensions (EQ-5D-3L) and five-level EuroQol five-dimensions (EQ-5D-5L) among common cancer patients in urban China. METHODS: A hospital-based cross-sectional survey was conducted in three provinces from 2016 to 2018 in urban China. Patients with breast cancer, colorectal cancer, or lung cancer were recruited to complete the EQ-5D-3L and EQ-5D-5L questionnaires. Response distribution, discriminatory power (indicator: Shannon index [H'] and Shannon evenness index [J']), ceiling effect (the proportion of full health state), convergent validity, and health-related quality of life (HRQoL) were compared between the two instruments. RESULTS: A total of 1802 cancer patients (breast cancer: 601, colorectal cancer: 601, lung cancer: 600) were included, with the mean age of 55.6 years. The average inconsistency rate was 4.4%. Compared with EQ-5D-3L (average: H' = 1.100, J' = 0.696), an improved discriminatory power was observed in EQ-5D-5L (H' = 1.473, J' = 0.932), especially contributing to anxiety/depression dimensions. The ceiling effect was diminished in EQ-5D-5L (26.5%) in comparison with EQ-5D-3L (34.5%) (p < 0.001), mainly reflected in the pain/discomfort and anxiety/depression dimensions. The overall utility score was 0.790 (95% CI 0.778-0.801) for EQ-5D-3L and 0.803 (0.790-0.816) for EQ-5D-5L (p < 0.001). A similar pattern was also observed in the detailed cancer-specific analysis. CONCLUSIONS: With greater discriminatory power, convergent validity and lower ceiling, EQ-5D-5L may be preferable to EQ-5D-3L for the assessment of HRQoL among cancer patients. However, higher utility scores derived form EQ-5D-5L may also lead to lower QALY gains than those of 3L potentially in cost-utility studies and underestimation in the burden of disease.

Association between congenital thrombophilia and outcomes in pulmonary embolism patients.

The prevalence and distribution of congenital thrombophilia is still unclear in patients with pulmonary embolism (PE). We aimed to determine the prevalence and clinical characteristics of congenital thrombophilia in PE patients and their subsequent outcomes. A prospective observational study was conducted from May 2013 to June 2018. A total of 436 consecutive patients with PE were enrolled. All patients were tested for protein C, protein S, antithrombin III (ATIII), factor V Leiden, and prothrombin G20210A mutations. The median follow-up duration was ∼800 days (range, 11-1872 days). Congenital thrombophilia was diagnosed in 31 of 436 (7.1%) patients; 12 patients had protein C deficiency (2.8%), 13 had protein S deficiency (3.0%), 5 had ATIII deficiency (1.1%), and 1 had (0.2%) factor V Leiden. Age ≤50 years at the first episode (odds ratio [OR], 5.43; 95% confidence interval [CI], 2.35-13.52; P < .001) and male sex (OR, 2.67; 95% CI, 1.15-6.78; P = .03) were 2 independent predictors of congenital thrombophilia in PE patients. There was no statistically significant difference in the prevalence of congenital thrombophilia between PE patients with and without risk factors (P = .58). We also found no significant difference in the risk of having a composite outcome of death or recurrent venous thromboembolism between patients with and without congenital thrombophilia (hazard ratio, 0.18; 95% CI, 0.02-5.69; P = .08). These results suggest that age and male sex are independently associated with the occurrence of congenital thrombophilia in PE patients but that congenital thrombophilia is not associated with the risk of recurrence or death with anticoagulation therapy.

New Insights into the Use of Direct Oral Anticoagulants in Non-high Risk Thrombotic APS Patients: Literature Review and Subgroup Analysis from a Meta-analysis.

PURPOSE OF REVIEW: The efficacy of direct oral anticoagulants (DOACs) in antiphospholipid syndrome (APS) is discussed. Results from randomized controlled trials are available. It has been stated that a history of arterial thrombosis and triple positivity was associated with a higher risk of thrombosis in APS patients treated with DOACs. However, their efficacy in non-high-risk APS patients with isolated venous manifestations is unsolved. Therefore, we performed a sub-group analysis of a previously published meta-analysis after the exclusion of patients with triple positivity and those with history of arterial or small vessel thrombosis. RECENT FINDINGS: We identified 290 APS patients with previous isolated venous event treated with DOACs; among them, 25 (8.6%) patients experienced a recurrent thrombosis in comparison to 16% in the original cohort. We found that the rate of recurrent thrombosis is lower in APS patients with isolated venous manifestations than in overall APS patients including high-risk patients. Research about DOAC use in non-high-risk APS patients needs to be continued.

Lipocalin-2 Predicts Long-Term Outcome of Normotensive Patients with Acute Pulmonary Embolism.

Normotensive patients with acute pulmonary embolism (APE) are accompanied by heterogeneously adverse events. Responding to tissue injury, lipocalin-2 (LCN-2) is elevated in experimental APE model and associated with short-term prognosis. However, the prognostic value of LCN-2 in normotensive patients with APE for long-term major adverse events (MAEs) remains unknown. We evaluated the association of plasma LCN-2 levels with the median 467-day outcome in 170 normotensive patients with APE. We also assessed whether LCN-2 could improve risk stratification. MAEs consisted of mortality or recurrence of venous thromboembolism. During follow-up, 17 (10%) patients suffered from MAEs. These patients had higher LCN-2 levels compared with patients without MAEs (median: 13.97 vs. 8.55 ng/ml, P = 0.01). The proportion of MAEs in the intermediate-low-risk group (14.0%) was higher than that in the intermediate-high-risk group (5.3%). LCN-2 levels independently had prognostic value for MAEs in overall (HR = 3.40, 95% CI 1.46-7.90) and intermediate-risk group (HR = 3.88, 95% CI 1.63-9.23). LCN-2 also showed incremental value in overall (ΔC-index: 0.13, 95% CI 0.02-0.24; category-based NRI = 0.25, 95% CI 0.07-0.42) and intermediate-risk patients (ΔC-index: 0.13, 95% CI 0.05-0.31; category-based NRI = 0.44, 95% CI 0.24-0.65). Adding LCN-2 (cut-off value = 11 ng/ml) to the current risk algorithm improved MAEs of intermediate-risk reclassification (intermediate-high vs. intermediate-low = 25.6% vs. 6.0%, P = 0.002). Elevated plasma LCN-2 levels predict long-term MAEs among normotensive patients with APE. LCN-2 might be a useful biomarker for risk stratification in the intermediate-risk group.