Pulmonary vein (PV) isolation has become the mainstay acute procedural end point for paroxysmal atrial fibrillation (AF) ablation.
To examine the incidence of conduction recovery in the PVs in ...patients without clinical recurrence of AF after paroxysmal AF ablation.
From August 2008 to March 2011, 392 patients with drug-refractory PAF underwent catheter ablation in our center, a wide area circumferential ablation approach guided with a circular mapping catheter was performed with the intended endpoint of entrance block in all PVs. 276 (70.4%) of them were free from recurrence at one year follow-up, and 32 of them were enrolled to assess the incidence of PV reconnection. Forty-three patients with clinical recurrence after ablation were analyzed for comparison. The regions of gap were mapped and characterized in all of the reconnected PVs.
Among patients without recurrence, recovery of PV conduction was observed in 29 of 32 (90.6%) patients: 10/32 (31.2%) reconnection in 4 veins, 7/32 (21.9%) in 3 veins, 10/32 (31.2%) in 2 veins, and 2/32 (6.2%) in 1 vein. No anatomic propensity was seen because reconnection was evenly distributed throughout all veins (left superior pulmonary vein 21, left inferior pulmonary vein 20, right superior pulmonary vein 19, and right inferior pulmonary vein 23). When compared to patients with recurrence, no significant differences were seen in the proportion of patients with reconnection (P = 1.0) or in left atrium-PV intervals (73.4 ± 43.3 ms vs 61.9 ± 31.8 ms; P > .05).
A high incidence of PV reconnection was similarly observed in patients with and without recurrence of AF, suggesting that sustained PV isolation may not be required for freedom from clinical recurrence of AF.
Glioma is the most common type of malignant neoplasm in the central nervous system, with high incidence and mortality rate. MicroRNAs, as a class of small non-coding RNAs, play an important role in ...carcinogenesis and correlate with glioma diagnosis and prognosis. In this study, we investigated the microRNA-204 (miR-204) concentration in glioma tissues and its relation to the expression of ezrin and bcl-2 mRNA, as well as its potential predictive and prognostic values in glioma. The concentrations of miR-204 were significantly lower in glioma tissues than in non-tumor brain tissues and also were lower in high-grade than in low-grade gliomas (World Health Organization WHO grades III and IV vs grades I and II). The miR-204 concentration was inversely correlated with the ezrin and bcl-2 concentrations. The miR-204 concentration was classified as high or low according to the median value, and low miR-204 correlated with higher WHO grade, larger tumor, and worse Karnofsky performance score (KPS). Kaplan-Meier survival analysis demonstrated that patients with low miR-204 expression had shorter progression-free survival (PFS) and overall survival (OS) than patients with high miR-204 expression. In addition, univariate and multivariate analyses showed that miR-204 expression was an independent prognostic feature of OS and PFS. In conclusion, our study indicates that miR-204 is downregulated in glioma and may be a biomarker of poor prognosis in patients with this cancer.
Abstract Background Pathogenesis and diagnostic biomarkers for diseases can be discovered by metabolomic profiling of human fluids. If the various types of coronary artery disease (CAD) can be ...accurately characterized by metabolomics, effective treatment may be targeted without using unnecessary therapies and resources. Objectives The authors studied disturbed metabolic pathways to assess the diagnostic value of metabolomics-based biomarkers in different types of CAD. Methods A cohort of 2,324 patients from 4 independent centers was studied. Patients underwent coronary angiography for suspected CAD. Groups were divided as follows: normal coronary artery (NCA), nonobstructive coronary atherosclerosis (NOCA), stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI). Plasma metabolomic profiles were determined by liquid chromatography–quadrupole time-of-flight mass spectrometry and were analyzed by multivariate statistics. Results We made 12 cross-comparisons to and within CAD to characterize metabolic disturbances. We focused on comparisons of NOCA versus NCA, SA versus NOCA, UA versus SA, and AMI versus UA. Other comparisons were made, including SA versus NCA, UA versus NCA, AMI versus NCA, UA versus NOCA, AMI versus NOCA, AMI versus SA, significant CAD (SA/UA/AMI) versus nonsignificant CAD (NCA/NOCA), and acute coronary syndrome (UA/AMI) versus SA. A total of 89 differential metabolites were identified. The altered metabolic pathways included reduced phospholipid catabolism, increased amino acid metabolism, increased short-chain acylcarnitines, decrease in tricarboxylic acid cycle, and less biosynthesis of primary bile acid. For differential diagnosis, 12 panels of specific metabolomics-based biomarkers provided areas under the curve of 0.938 to 0.996 in the discovery phase (n = 1,086), predictive values of 89.2% to 96.0% in the test phase (n = 933), and 85.3% to 96.4% in the 3-center external sets (n = 305). Conclusions Plasma metabolomics are powerful for characterizing metabolic disturbances. Differences in small-molecule metabolites may reflect underlying CAD and serve as biomarkers for CAD progression.
To evaluate the effects of combining the assessment of circulating high-sensitivity C-reactive protein (hs-CRP) with that of Epstein-Barr virus DNA (EBV DNA) in the pretherapy prognostication of ...nasopharyngeal carcinoma (NPC).
Three independent cohorts of NPC patients (training set of n=3113, internal validation set of n=1556, and prospective validation set of n=1668) were studied. Determinants of disease-free survival, distant metastasis-free survival, and overall survival were assessed by multivariate analysis. Hazard ratios and survival probabilities of the patient groups, segregated by clinical stage (T1-2N0-1M0, T3-4N0-1M0, T1-2N2-3M0, and T3-4N2-3M0) and EBV DNA load (low or high) alone, and also according to hs-CRP level (low or high), were compared.
Elevated hs-CRP and EBV DNA levels were significantly correlated with poor disease-free survival, distant metastasis-free survival, and overall survival in both the training and validation sets. Associations were similar and remained significant after excluding patients with cardiovascular disease, diabetes, and chronic hepatitis B. Patients with advanced-stage disease were segregated by high EBV DNA levels and high hs-CRP level into a poorest-risk group, and participants with either high EBV DNA but low hs-CRP level or high hs-CRP but low EBV DNA values had poorer survival compared with the bottom values for both biomarkers. These findings demonstrate a significant improvement in the prognostic ability of conventional advanced NPC staging.
Baseline plasma EBV DNA and serum hs-CRP levels were significantly correlated with survival in NPC patients. The combined interpretation of EBV DNA with hs-CRP levels led to refinement of the risks for the patient subsets, with improved risk discrimination in patients with advanced-stage disease.
Background Intestinal ischemia/reperfusion (I/R) injury can cause a high rate of mortality in the perioperative period. Remifentanil has been reported to provide protection for organs against I/R ...injury. We hypothesized that remifentanil preconditioning would attenuate the small intestinal injury induced by intestinal I/R. Methods We used both an in vivo rat model of intestinal I/R injury and a cell culture model using IEC-6 cells (the rat intestinal epithelial cell line) subjected to oxygen and glucose deprivation (OGD). Remifentanil was administered before ischemia or OGD, and 3 specific opioid receptors antagonists, naltrindole (a δ-OR selective antagonist), nor-binaltorphimine (nor-BNI, a κ-OR selective antagonist), and CTOP (a μ-OR selective antagonist), were administered before preconditioning to determine the role of opioid receptors in the intestinal protection mediated by remifentanil. Results In the in vivo rat model, intestinal I/R induced obvious intestinal injury as evidenced by increases in the Chiu score, serum diamine oxidase activity, the apoptosis index, and the level of cleaved caspase-3 protein expression, whereas remifentanil preconditioning significantly improved these changes in vivo. In the in vitro cell culture exposed to OGD, cell viability (MTT, ie, (3-4,5-dimethylthiazol-2-yl-2,5 diphenyl tetrazolium bromide) assay and flow cytometric analysis showed that remifentanil preconditioning enhanced IEC-6 cell viability and decreased apoptosis. In both in vitro and in vivo models, the aforementioned protective effects of remifentanil preconditioning were abolished completely by previous administration of the δ- or μ-opioid markedly attentuated but not the κ-opioid receptor antagonist. Conclusion Remifentanil preconditioning appears to act via δ- and μ-opioid receptors to protect the small intestine from intestinal I/R injury by attenuating apoptosis of the intestinal mucosal epithelial cells.
Background Malfunction of the arteriovenous fistula (AVF) is an important cause of morbidity and hospitalization in hemodialysis (HD) patients. The aim of this study is to evaluate the effect of far ...infrared therapy on the maturation and patency of newly created AVFs in patients with chronic kidney disease stage 4 or 5. Study Design Randomized controlled study. Setting & Participants Patients with estimated glomerular filtration rate of 5-20 mL/min/1.73 m2. Intervention 40 minutes of far infrared therapy 3 times weekly for a year. Outcomes The primary outcome is the rate of AVF malfunction within 12 months, with malfunction defined as either: (1) thrombosis without thrill for AVFs not undergoing HD or (2) receiving any type of interventional procedure due to a lower Kt/V (<1.2) for patients undergoing HD. Secondary outcomes include: (1) cumulative primary unassisted AVF patency, defined as time from creation of the AVF to the first episode of AVF malfunction; (2) physiologic maturation of the AVF by the definition of AVF access blood flow (Qa) ≥500 mL/min and AVF diameter ≥4 mm at 3 months; and (3) clinical maturation of the AVF suitable for HD at 1 year. Measurements AVF Qa was measured by Doppler ultrasonography at 2 days and 1, 2, 3, and 12 months. Results We enrolled 122 patients who were randomly allocated to the intervention (n = 60) and control (n = 62) groups. In comparison to controls, patients in the intervention group had higher Qa values at 1, 2, 3, and 12 months; a higher rate of physiologic maturation (90% vs 76%; P = 0.04) at 3 months; and a lower rate of AVF malfunction (12% vs 29%; P = 0.02) but higher rates of AVF cumulative unassisted patency (87% vs 70%; P = 0.01) and clinical maturation (82% vs 60%; P = 0.008) within 12 months. Limitations This is a single-center nonblinded study. Conclusions Far infrared therapy improves the access flow, maturation, and patency of newly created AVFs in patients with chronic kidney disease stages 4 and 5.
A direct comparison of the efficacy and safety profiles of left atrial appendage occlusion (LAAO) devices and novel oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation is ...warranted but currently unavailable.
The aim of this study was to compare the >1-year efficacy and safety of LAAO devices and NOACs for stroke prevention in patients with atrial fibrillation.
We performed a systematic review on randomized controlled trials (RCTs) and observational studies. RCTs were analyzed by means of a network meta-analysis method using warfarin as a bridge to compare LAAO to individual NOAC or all NOACs as a whole. Observational studies were analyzed with the meta-proportion function where pooled event rates were compared.
A total of 6 RCTs and 27 observational studies were included. A network meta-analysis of RCTs indicated that LAAO was less effective than NOACs for stroke prevention (odds ratio 0.86), but had a lower rate of hemorrhagic events during follow-up. However, a meta-proportion analysis of observational studies revealed that LAAO devices were associated with a lower rate of both thromboembolic events (1.8 events per 100 patient-years vs 2.4 events per 100 patient-years) and major bleeding events during follow-up (2.2 events per 100 patient-years vs 2.5 events per 100 patient-years) as compared with NOACs. With prolonged follow-up duration after LAAO implantation, the rate of thromboembolic events decreased (2.1, 1.8, and 1.0 events per 100 person-years for 1, 1-2, and >2 years, respectively).
Although superiority of LAAO over NOACs was not demonstrated by RCTs in terms of stroke prevention, LAAO was found to be consistently associated with a lower rate of both thromboembolic and hemorrhagic events as compared with NOACs in observational studies.
Background
Microvascular invasion (MVI) plays an important role in tumor progression. The aim of this study is to establish and validate an effective hematological nomogram for MVI prediction in ...hepatocellular carcinoma (HCC).
Methods
A retrospective study was performed in a primary cohort that includes 1306 patients clinicopathologically diagnosed with HCC, and a validation cohort contained 563 continuous patients. Univariate logistic regression was used to assess the association between variables included both clinicopathologic factors and coagulation parameters (prothrombin time, activated partial thromboplastin time, fibrinogen, and thrombin time TT) and MVI. Multiple logistic regression was used to construct a prediction nomogram. We tested the accuracy of the nomogram by discrimination and calibration, and then plotted decision curves to assess the benefits of the nomogram-assisted decisions in a clinical context.
Results
In the two cohorts, patients without MVI had the longest overall survival (OS), compared the OS with MVI. The multivariate analysis indicated that age, sex, tumor node metastasis (TNM) stage, aspartate aminotransferase, alpha fetoprotein, C-reactive protein, and TT were identified as significant independent predictors of MVI of HCC patients. The Hosmer–Lemeshow test showed good point estimate associated P value between predicted risk and observed risk across the deciles. Moreover, the calibration performance of the nomogram risk scores in each decile of the primary cohort was within 5 percentage points of the mean predicted risk score, and in the validation cohort, the observed risk in 90% decile was within 5 percentage points of the mean predicted risk score.
Conclusions
A noninvasive and easy-to-use nomogram was established and may be used to predict preoperative MVI in HCC.
Background We demonstrated previously that ischemic postconditioning (IPo) attenuated intestinal injury induced by intestinal ischemia/reperfusion (I/R), and thereafter employed a proteomic method to ...identify aldose reductase (AR), a differentially expressed protein in intestinal mucosal tissue, which was downregulated by intestinal I/R and upregulated by IPo. This study aimed to further explore the possible role of AR in intestinal protection conferred by IPo. Methods Intestinal ischemia was induced by clamping the superior mesenteric artery (SMA) for 60 minutes in male adult rats. Then rats were allocated into 7 groups based on the random number table. The control group involved only sham operation; the control + AR inhibitor epalrestat group underwent sham operation and epalrestat administration; the I/R with and/or without epalrestat groups had SMA clamped for 60 minutes followed by 120 minutes of reperfusion with and/or without epalrestat given before index ischemia; the IPo group underwent 3 cycles of 30 seconds of reperfusion and 30 seconds of re-occlusion imposed immediately on reperfusion; and the epalrestat or vehicle control dimethylsulfoxide + IPo groups had the drugs administrated 10 minutes before ischemia. Results IPo resulted in significant intestinal protection evidenced as marked decreases in Chiu's score, reflecting changes intestinal histology, serum diamine oxidase activity, and intestinal mucosal levels of lactic acid, malondialdehyde, and myeloperoxidase, the apoptosis index, and downregulated cleaved caspase-3 protein expression; these changes were accompanied by an increase in superoxide dismutase activity and upregulation of AR protein levels. Epalrestat failed to protect against intestinal I/R insult, but abolished the protective effects of IPo. Conclusion These findings suggest that IPo attenuates intestinal I/R-induced intestinal injury via AR-mediated oxidative defense and apoptosis suppression; AR inhibition reverses the protective effects of IPo. AR seems to be an innate protective factor in this model of intestinal I/R.
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