Persistence, effectiveness and safety of dabigatran in "real-world" Chinese patients with nonvalvular atrial fibrillation.

The purpose of this study is to provide detailed data on treatment persistence and clinical outcomes in Chinese patients with nonvalvular atrial fibrillation (NVAF). A single-center retrospective observational study was conducted. A total of 26,663 NVAF patients were enrolled from January 1, 2014 to December 31, 2017, clinical information of whom were from inpatient and outpatients data system was collected. The 1-year treatment persistence rates of 11,350 dabigatran users were 24.5% in 2014, 36.6% in 2015, 37.7% in 2016 and 51.8% in 2017. The predominant reason of non-persistence patients was the cost of treatment. Incidence rates of all-cause death, ischemic stroke and embolism were 1.99/100 person-years, 2.56/100 person-years and 0.77/100 person-years, respectively. Incidence rates of minor bleeding events, intracranial hemorrhage and gastrointestinal hemorrhage were 10.05/100 person-years, 0.51/100 person-years and 0.85/100 person-years, respectively. In conclusion, it is of importance for Chinese clinicians to know about these information because dabigatran is a relatively new drug in China. Compared with other reported data, patients of this study have (1) lower dabigatran persistence and lower incident rates of all-cause death, systemic embolism, minor bleeding events and gastrointestinal hemorrhage and (2) higher incident rates of ischemic stroke and intracranial hemorrhage.

Plasma CADM1 promoter hypermethylation and D-dimer as novel metastasis predictors of cervical cancer.

AIM: Cervical cancer (CC) is the fourth malignant tumor in women worldwide. The metastasis is still the major reason for the treatment failures of most CC patients. Cell adhesion molecule 1 (CADM1) promoter methylation and plasma D-dimer levels have been reported to be increased in many types of cancers. The purpose of this study was to investigate the value of combinatorial assay of plasma CADM1 promoter hypermethylation and D-dimer as a metastasis marker in CC. METHODS: Two hundred and ninety-two patients with newly diagnosed cervical diseases and 70 healthy women were enrolled. A validation set comprised 36 Stage I CC patients and followed for 3 years. Plasma CADM1 promoter methylation and D-dimer levels were detected. RESULTS: The total coincidence rate of CADM1 promoter methylation status was 93.3% between 45 pair-matched tissue and plasma samples. Plasma CADM1 methylation levels in CC patients were higher than other benign disease groups (P = 0.000). Plasma CADM1 methylation levels had statistically differences between CC patients with and without lymph node metastasis (P = 0.049) or in CC patients with and without distant metastasis (P = 0.000). Similarly, plasma D-dimer levels in CC patients were higher than other benign disease groups (P < 0.05). D-dimer levels were only statistically different between CC patients with and without distant metastasis (P = 0.003). Combined assay of the two parameters for metastasis prediction has high sensitivity (80.4%) and specificity (90.5%). CONCLUSION: Combinatorial assay of plasma CADM1 methylation and D-dimer is a promising metastasis marker in cervical cancer.

Dissecting the Association of Apolipoprotein E Gene Polymorphisms With Type 2 Diabetes Mellitus and Coronary Artery Disease.

Background: Apolipoprotein E (APOE) gene mediates lipoprotein clearance and is one of the most studied candidate genes for type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). This study was performed to determine the association between APOE polymorphisms and T2DM with and without CAD, and its effect on plasma lipid levels in a Chinese population. Methods: A total of 1,414 subjects involving 869 patients and 545 health individuals were recruited. These patients were categorized into three distinct groups: 264 in T2DM group, 401 in CAD group, and 204 in T2DM+CAD group. Logistic regression analysis was used to obtain odds ratio (OR) and 95% confidence interval (CI) in predicting the risk probability of APOE. Besides, a meta-analysis was preformed to integrate an evaluation index to evaluate their associations. Results: Genotype frequency ratio of genotype ϵ3/4 and allele ϵ4 among the CAD patients with or without T2DM was obviously increased. Compared with ϵ3/3 genotype, the ϵ3/4 genotype had a significant increased risk of CAD (adjusted OR = 1.90, 95% CI = 1.30-2.77) and T2DM+CAD (adjusted OR = 1.95, 95% CI = 1.24-3.08). In the meta-analysis, four studies were included and provided a strong evidence for the APOE ϵ4 mutation elevating the risk of CAD in patients with T2DM (ϵ3/ϵ4+ϵ4/ϵ4 vs. ϵ3/ϵ3, OR = 1.51, 95% CI = 1.13-2.02). In the T2DM group, the plasma levels of low-density lipoprotein cholesterol (LDL-C) showed significant difference among the three APOE isoforms. The high-density lipoprotein cholesterol (HDL-C) levels of CAD patients with ϵ4-bearing genotypes were lower than those with ϵ3/3 genotype. Conclusions: Our results indicate that APOE gene polymorphisms are related to CAD with or without T2DM and have influence on lipid profiles in both T2DM and CAD patients.

In Silico Screening of Circulating MicroRNAs as Potential Biomarkers for the Diagnosis of Ovarian Cancer.

Current screening tests for the diagnosis of ovarian cancer (OC) face enduring challenges. However, microRNAs (miRNAs) are stable in the circulation and may be promising molecular biomarkers for OC prediction. Circulating miRNA expression profiles in OC were analyzed using sequencing data from the Gene Expression Omnibus database. Differentially expressed miRNAs were generated from GSE94533, of which some were selected as candidate miRNAs based on an electronic search of the literature and comprehensive evaluation. A meta-analysis was preformed to integrate an evaluation index for these miRNAs in diagnosing OC patients. An independent validation set (GSE106817) was also conducted to further confirm the roles of these miRNAs. We identified four MIR200 members (MIR200A, MIR200B, MIR200C, and MIR429) and MIR25 as being differentially expressed among malignant or benign ovarian tumor patients and healthy controls. In the meta-analysis, these five miRNAs yielded a pooled area under the receiver operating characteristic (ROC) curve (AUC) of 0.78 (sensitivity: 64%, specificity: 88%) in discriminating OC from healthy controls, while the four MIR200 members demonstrated a summary AUC of 0.81 (sensitivity: 92%, specificity: 69%) in differing OC cases from patients with benign disease. In the validation set, differential expression and ROC curve analyses of these miRNAs were consistent except for MIR25. The circulating MIR200 family has the potential to become reliable and noninvasive biomarkers for OC diagnosis. Studies with larger cohorts are warranted to validate the applicability of these miRNAs.

Peripheral blood lymphocyte responses to cytomegalovirus seropositivity after allogeneic-hematopoietic stem cell transplantation.

BACKGROUND: The main purpose of this study was to investigate the relationship among cytomegalovirus (CMV) viremia, peripheral immune cells alternations, and leukemia prognosis. PATIENTS AND METHODS: We studied 90 leukemia patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) from 2008 to 2015. Their complete clinical laboratory data were collected until 1 year after transplantation. RESULTS: All patients were serum CMV negative before allo-HSCT. After transplantation, the CMV reactivation group showed increased peripheral CD8+ T cells and decreased CD4+ T cells and B cells. However, CD8/CD4 ratio and B cells restored by control of CMV infection due to 2 months maximum course of ganciclovir treatment. CMV seropositivity was positively related to leukemia-free survival (LFS) of all recruited leukemia types. CONCLUSION: In summary, CMV drives immune cell post-transplantation fluctuation, which also favors LFS of leukemia partly resulted from CD8+ T cells.

A novel coagulation parameter monitoring bleeding tendency of Chinese nonvalvular atrial fibrillation patients prescribing dabigatran etexilate.

The objective of this study was to find a new parameter to monitor bleeding tendency after dabigatran etexilate (Pradaxa) medication in Chinese nonvalvular atrial fibrillation patients. Blood samples of 231 nonvalvular atrial fibrillation patients were collected and five routine coagulation examinations (prothrombin time/International normalized ratio, activated partial thromboplastin time, fibrinogen assay, thrombin time and D-dimer) were assayed. After dabigatran etexilate administration, prolonged activated partial thromboplastin time and thrombin time were observed, especially TT. Derived parameter ΔTT (TT after dabigatran etexilate medication - TT before dabigatran etexilate medication) of bleeding patients was higher than nonbleeding patients (97.7 vs. 85.6 s, P = 0.038). When using ΔTT to distinguish patients with and without bleeding events, the cutoff value was 97.25 s, where sensitivity was 82.4% and specificity was 50.0%. The area under the curve was 0.786. TT is better than other routine coagulation parameters in monitoring the effect of dabigatran etexilate. ΔTT can distinguish bleeding patients from nonbleeding patients.

A 4-year surveillance of antimicrobial resistance patterns of Acinetobacter baumanni in a university-affiliated hospital in China.

OBJECTIVES: To investigate the changes in resistance of Acinetobacter baumanni (A. baumannii) to different antimicrobial agents and the association of resistance rates with several independent factors: specimen origin, hospital wards, patients' gender and age, from 2008 to 2011. METHODS: Bacterial isolates were isolated from January 2008 to December 2011 in the First Affiliated Hospital of Nanjing Medical University. Antimicrobial susceptibility testing was determined by the Kirby-Bauer Disk Diffusion Agar method as recommended by CLSI. Data were managed by the software WHONET 5.4 and analyzed by SPSS 17.0 software. RESULTS: The proportion of A. baumannii in our hospital increased from 7.0% in 2008 to 18.8% in 2011, becoming the most frequent pathogen in gram-negative isolates. 79.9% of A. baumannii were cultured from respiratory tract and geriatrics showed the highest isolation rate of A. baumannii during 4 years. The resistance rates to 12 antibiotics significantly increased from 2008 to 2011, from 14.8% to 90.8% to imipenem, and from 23.3% to 91.1% to meropenem. Statistical analysis demonstrated that the specimen origin, hospital wards, patients' gender and age were associated with resistance rate in varying degrees. CONCLUSIONS: The 4-year surveillance of antimicrobial susceptibility demonstrated the rapid increase of drug-resistant strains of A. baumannii, and revealed several factors related with resistance rate. Knowing the antimicrobial resistance patterns will help guide the empirical therapy and strengthen interventional infection control measures in China.

GPU-assisted computation of centroidal Voronoi tessellation.

Centroidal Voronoi tessellations (CVT) are widely used in computational science and engineering. The most commonly used method is Lloyd's method, and recently the L-BFGS method is shown to be faster than Lloyd's method for computing the CVT. However, these methods run on the CPU and are still too slow for many practical applications. We present techniques to implement these methods on the GPU for computing the CVT on 2D planes and on surfaces, and demonstrate significant speedup of these GPU-based methods over their CPU counterparts. For CVT computation on a surface, we use a geometry image stored in the GPU to represent the surface for computing the Voronoi diagram on it. In our implementation a new technique is proposed for parallel regional reduction on the GPU for evaluating integrals over Voronoi cells.