Dyhrmunck6591

This study sought to identify acute changes in human atrial electrophysiology during alcohol exposure.

The mechanism by which a discrete episode of atrial fibrillation (AF) occurs remains unknown. Alcohol appears to increase the risk for AF, providing an opportunity to study electrophysiologic effects that may render the heart prone to arrhythmia.

In this randomized, double-blinded, placebo-controlled trial, intravenous alcohol titrated to 0.08% blood alcohol concentration was compared with a volume and osmolarity-matched, masked, placebo in patients undergoing AF ablation procedures. Right, left, and pulmonary vein atrial effective refractory periods (AERPs) and conduction times were measured pre- and post-infusion. Isoproterenol infusions and burst atrial pacing were used to assess AF inducibility.

Of 100 participants (50 in each group), placebo recipients were more likely to be diabetic (22% vs. 4%; p=0.007) and to have undergone a prior AF ablation (36% vs. 22%; p=0.005). Pulmonary vein AERPs decrdiate proarrhythmic effects in human atria. (How Alcohol Induces Atrial Tachyarrhythmias Study [HOLIDAY]; NCT01996943).

A substantial proportion of patients with nonischemic dilated cardiomyopathy (NICM) and ventricular tachycardia (VT) do not have scar detectable by cardiac magnetic resonance late gadolinium enhancement (LGE) imaging. In these patients, the significance of diffuse fibrosis (DF) detected with T

mapping has not been previously investigated.

The goal of this study was to characterize the relationship between DF, the electroanatomic mapping (EAM) substrate, and outcomes of catheter ablation of VT in NICM.

This study included 51 patients with NICM and VT undergoing catheter ablation (median age 55 years; 77% male subjects) who had no evidence of LGE on pre-procedural cardiac magnetic resonance. Post-contrast T

relaxation time determined on the septum was assessed as a surrogate of DF burden. The extent of endocardial low-voltage areas (LVAs) at EAM was correlated with T

mapping data.

Bipolar LVAs were present in 22 (43%) patients (median extent 15 [8 to 29] cm

) and unipolar LVA in all patients (median extent 48 [26 to 120] cm

). A significant inverse correlation was found between T

values and both unipolar-LVA (R

=0.64; β=-0.85; p<0.01) and bipolar-LVA (R

=0.16; β=-1.63; p<0.01). After a median follow-up of 45 (22 to 57) months, 2 (4%) patients died, 3 (6%) underwent heart transplantation, and 8 (16%) experienced VT recurrence. Shorter post-contrast T

time was associated with an increased risk of VT recurrence (hazard ratio 1.16; 95% confidence interval 1.03 to 1.33 per 10ms decrease; p=0.02).

In patients with NICM and no evidence of LGE undergoing catheter ablation of VT, DF estimated by using post-contrast T

mapping correlates with the voltage abnormality at EAM and seems to affect post-ablation outcomes.

In patients with NICM and no evidence of LGE undergoing catheter ablation of VT, DF estimated by using post-contrast T1 mapping correlates with the voltage abnormality at EAM and seems to affect post-ablation outcomes.

The authors reviewed 3-dimensional electroanatomic maps of perimitral flutter to identify scar-related isthmuses and determine their effectiveness as ablation sites.

Perimitral flutter is usually treated by linear ablation between the left lower pulmonary vein and mitral annulus. Conduction block can be difficult to achieve, and recurrences are common.

Patients undergoing atrial tachycardia ablation using CARTO3 (Biosense Webster Inc., Irvine, California) were screened from 4 centers. Patients with confirmed perimitral flutter were reviewed for the presence of scar-related isthmuses by using CARTO3 with the ConfiDense and Ripple Mapping modules.

Confirmed perimitral flutter was identified in 28 patients (age 65.2 ± 8.1 years), of whom 26 patients had prior atrial fibrillation ablation. Scar-related isthmus ablation was performed in 12 of 28 patients. Perimitral flutter was terminated in all following correct identification of a scar-related isthmus using ripple mapping. The mean scar voltage thresholddia and avoiding anatomic ablation lines. This approach has a higher termination rate with less radiofrequency ablation required.

This study sought to systematically evaluate the ability of a high-resolution mapping system (Rhythmia, Boston Scientific, Marlborough, Massachusetts) to rapidly and accurately localize residual endocardial and epicardial conduction after mitral isthmus (MI) ablation, facilitating MI block.

Achieving conduction block across the mitral isthmus (MI) is challenging.

Fifty consecutive patients undergoing MI ablation after pulmonary vein isolation were enrolled. After initial endocardial radiofrequency (RF) ablation across the lateral MI, high-resolution activation mapping of the MI with simultaneous coronary sinus (CS) mapping was performed to verify block or localize residual conduction across the MI during left atrial (LA) appendage and CS pacing. Propagation maps were used to identify residual conduction across the MI as endocardial, via the CS or Marshall tract.

In all 50 patients, after the initial endocardial ablation across the MI, repeat high-resolution mapping of the LA and CS was obtained (medial endocardial and epicardial conduction across the MI. Focal ablation with short RF time at the identified gap(s) achieved complete block across MI in 98% of cases.

This study sought to estimate the temporal development in rates and incidences of appropriate and inappropriate implantable cardioverter-defibrillator (ICD) therapy and shocks by cardiac diagnosis in a real-world population of patients with secondary prevention ICDs.

Data on cardiac diagnoses and temporal development of ICD therapies in patients with secondary prevention ICDs are limited.

Patients (N=4,587) with a secondary prevention ICD were identified from the Danish Pacemaker and ICD Register (January 1, 2007, to December 31, 2016) and linked to nationwide administrative registers. The outcome of appropriate and inappropriate ICD therapy and all-cause mortality were analyzed by annual event rates, cumulative incidence plots, and Cox regression models.

During a mean follow-up of 3.6 ± 2.4 years, 1,362 patients (30%) experienced appropriate ICD therapy (16.8% shocks), and 350 patients (7.6%) experienced inappropriate ICD therapy (4.6% shocks). From 2007 to 2016, there was a significant temporal reduith secondary prevention ICDs, we observed a significant temporal decline in delivered appropriate and inappropriate shocks and ICD therapies in the last decade. A large proportion of patients still experienced ICD therapy but with significant differences by cardiac diagnosis.

Chest radiography (CXR) often is performed in the acute setting to help understand the extent of respiratory disease in patients with coronavirus disease 2019 (COVID-19), but a clearly defined role for negative chest radiograph results in assessing patients has not been described.

Is portable CXR an effective exclusionary test for future adverse clinical outcomes in patients suspected of having COVID-19?

Charts of consecutive patients suspected of having COVID-19 at five EDs in New York City between March 19, 2020, and April 23, 2020, were reviewed. Patients were categorized based on absence of findings on initial CXR. The primary outcomes were hospital admission, mechanical ventilation, ARDS, and mortality.

Three thousand two hundred forty-five adult patients, 474 (14.6%) with negative initial CXR results, were reviewed. Among all patients, negative initial CXR results were associated with a low probability of future adverse clinical outcomes, with negative likelihood ratios of 0.27 (95%CI, 0.23-0.31t for adverse clinical outcomes is highest among young adults, patients with few comorbidities, and those with a prolonged duration of symptoms.

To establish a microsatellite instability (MSI) predictive model in pan-cancer and compare the multi-omics characterization of MSI-related molecular features.

We established a 15-gene signature for predicting MSI status and performed a systematic assessment of MSI-related molecular features including gene and miRNA expression, DNA methylation, and somatic mutation, in approximately 10,000 patients across 30 cancer types from The Cancer Genome Atlas, Gene Expression Omnibus database, and our institution. Then we identified common MSI-associated dysregulated molecular features across six cancers and explored their mutual interfering relationships and the drug sensitivity.

we demonstrated the model's high prediction performance and found the samples with high-MSI were mainly distributed in six cancers BRCA, COAD, LUAD, LIHC, STAD, and UCEC. We found RPL22L1 was up-regulated in the high-MSI group of 5/6 cancer types. CYP27A1 and RAI2 were down-regulated in 4/6 cancer types. More than 20 miRNAs and 39 DMGs were found up-regulated in MSI-H at least three cancers. We discovered some drugs, including OSI-027 and AZD8055 had a higher sensitivity in the high MSI-score group. Functional enrichment analysis revealed the correlation between MSI score and APM score, HLA score, or glycolysis score. The complicated regulatory mechanism of tumor MSI status in multiple dimensions was explored by an integrated analysis of the correlations among MSI-related genes, miRNAs, methylation, and drug response data.

Our pan-cancer study provides a valuable predictive model and a comprehensive atlas of tumor MSI, which may guide more precise and personalized therapeutic strategies for tumor patients.

Our pan-cancer study provides a valuable predictive model and a comprehensive atlas of tumor MSI, which may guide more precise and personalized therapeutic strategies for tumor patients.

Prolyl endopeptidase (PREP) is a serine endopeptidase widely distributed in the body, and accumulated evidence suggests that PREP participates in inflammation and oxidative stress. Here, we explored the effect of PREP gene disruption on hepatic inflammation and oxidative stress status in a methionine-choline-deficient (MCD)-induced nonalcoholic steatohepatitis (NASH) model.

PREP gene disruption (PREP

) mice and wild-type (WT) littermates were placed on a control or an MCD diet for 4weeks, respectively. The liver histopathological analysis and the number of inflammatory cells were determined by hematoxylin-eosin (HE) and immunohistochemical staining. Inflammation-associated genes and cytokine levels in liver tissue were evaluated by quantitative PCR and ELISA. check details The levels of P53, Sesn2, Nrf2, HO-1, and oxidative stress indicators in mice and the palmitic acid (PA)-treated human hepatocellular carcinoma cells (HepG2) were examined by immunoblotting and commercially available kits, respectively.

We found that PREP expression was upregulated in the MCD-induced NASH model. In addition, PREP disruption alleviated MCD-induced hepatic inflammation accompanied by diminished infiltration of inflammatory cells and secretion of inflammatory mediators. More importantly, the results of this study indicate that targeting PREP can improve oxidative stress status in the liver of MCD-diet mice and PA-exposed HepG2 cells. The effect is most likely mediated by the activation of P53 and its downstream signaling pathways (Sesn2/Nrf2/HO-1).

Our results showed that PREP disruption (or inhibition) could decrease oxidative stress and inflammation and improve liver function, indicating that targeting PREP might be a new potential therapeutic option for NAFLD/NASH.

Our results showed that PREP disruption (or inhibition) could decrease oxidative stress and inflammation and improve liver function, indicating that targeting PREP might be a new potential therapeutic option for NAFLD/NASH.