Thoracoscopic Left Atrial Appendage Excision Plus Ablation for Atrial Fibrillation to Prevent Stroke

Atrial fibrillation (AF) patients with a previous stroke are often at a high risk of recurrent stroke and bleeding. Anticoagulation therapy in such patients is a challenging dilemma. Thoracoscopic left atrial appendage excision (LAAE) plus AF ablation is an interventional approach offered to some AF patients. We hypothesized that this approach may be suitable as a secondary stroke prevention strategy for these high-risk patients. Between January 2013 and December 2016, a total of 44 patients (26 male; mean age 65.0 ± 9.1 years) with nonvalvular AF and a previous stroke or systemic thromboembolic event were enrolled. The patients underwent thoracoscopic LAAE plus AF ablation by experienced operators and were followed up for 2 years (at 1, 3, 6, 9, and 12 months postoperatively and every 6 months thereafter). Thromboembolic and major bleeding events were recorded. Cerebral computed tomography or magnetic resonance imaging and 7-day Holter monitoring were performed annually. Mean CHA2DS2-VASc and HAS-BLED scores were 4.2 ± 1.2 and 3.3 ± 0.7, respectively. All patients discontinued oral anticoagulation therapy after the surgical intervention. One patient suffered a periprocedural transient ischemic attack, and another was diagnosed with a new ischemic stroke at 491 days after surgery. The annual rate of total thromboembolism was 2.05%. No deaths or major bleeding events were observed postoperatively. The rate of successful AF ablation with no AF recurrence was 76.3%. Transthoracoscopic LAAE plus AF ablation may be a promising approach for this high-risk population. Thromboembolism event in this secondary prevention cohort was low, even without oral anticoagulation treatment

Family-based whole-exome sequencing identifies novel loss-of-function mutations of FBN1 for Marfan syndrome

Background Marfan syndrome (MFS) is an inherited connective tissue disorder affecting the ocular, skeletal and cardiovascular systems. Previous studies of MFS have demonstrated the association between genetic defects and clinical manifestations. Our purpose was to investigate the role of novel genetic variants in determining MFS clinical phenotypes. Methods We sequenced the whole exome of 19 individuals derived from three Han Chinese families. The sequencing data were analyzed by a standard pipeline. Variants were further filtered against the public database and an in-house database. Then, we performed pedigree analysis under different inheritance patterns according to American College of Medical Genetics guidelines. Results were confirmed by Sanger sequencing. Results Two novel loss-of-function indels (c.5027_5028insTGTCCTCC, p.D1677Vfs*8; c.5856delG, p.S1953Lfs*27) and one nonsense variant (c.8034C>A, p.Y2678*) of FBN1 were identified in Family 1, Family 2 and Family 3, respectively. All affected members carried pathogenic mutations, whereas other unaffected family members or control individuals did not. These different kinds of loss of function (LOF) variants of FBN1 were located in the cbEGF region and a conserved domain across species and were not reported previously. Conclusions Our study extended and strengthened the vital role of FBN1 LOF mutations in the pathogenesis of MFS with an autosomal dominant inheritance pattern. We confirm that genetic testing by next-generation sequencing of blood DNA can be fundamental in helping clinicians conduct mutation-based pre- and postnatal screening, genetic diagnosis and clinical management for MFS

Human kinematic responses to walking and riding camels and horses.

Hippotherapy is a novel and promising therapeutic method. The prevailing rationale for hippotherapy is that the motion of a horse can provide movement patterns that mimic those of walking. The purpose of this study is to measure and compare human pelvic kinematics during natural walking, horse riding, and camel riding. Motion capture of three human subjects walking, riding on three horses, and riding on two camels was recorded. Pelvic trajectories exhibit many similar features between walking, horse-riding, and camel-riding, including distorted infinity-shape patterns in the transverse and frontal planes. In the sagittal plane, pelvic trajectories display an oval pattern during walking and camel-riding and a more diagonal pattern during horse riding. This study shows that many features of human pelvic kinematics during walking can be reproduced when riding on a horse or camel. To date, this is the first and only study that compared pelvic movement during camel-riding to walking

Comparative Transcriptome Analysis Reveals Substantial Tissue Specificity in Human Aortic Valve

RNA sequencing (RNA-seq) has revolutionary roles in transcriptome identification and quantification of different types of tissues and cells in many organisms. Although numerous RNA-seq data derived from many types of human tissues and cell lines, little is known on the transcriptome repertoire of human aortic valve. In this study, we sequenced the total RNA prepared from two calcified human aortic valves and reported the whole transcriptome of human aortic valve. Integrating RNA-seq data of 13 human tissues from Human Body Map 2 Project, we constructed a transcriptome repertoire of human tissues, including 19,505 protein-coding genes and 4,948 long intergenic noncoding RNAs (lincRNAs). Among them, 263 lincRNAs were identified as novel noncoding transcripts in our data. By comparing transcriptome data among different human tissues, we observed substantial tissue specificity of RNA transcripts, both protein-coding genes and lincRNAs, in human aortic valve. Further analysis revealed that aortic valve-specific lincRNAs were more likely to be recently derived from repetitive elements in the primate lineage, but were less likely to be conserved at the nucleotide level. Expression profiling analysis showed significant lower expression levels of aortic valve-specific protein-coding genes and lincRNA genes, when compared with genes that were universally expressed in various tissues. Isoform-level expression analysis also showed that a majority of mRNA genes had a major isoform expressed in the human aortic valve. To our knowledge, this is the first comparative transcriptome analysis between human aortic valve and other human tissues. Our results are helpful to understand the transcriptome diversity of human tissues and the underlying mechanisms that drive tissue specificity of protein-coding genes and lincRNAs in human aortic valve

Frequency of prothrombin time-international normalized ratio monitoring and the long-term prognosis in patients with mechanical valve replacement

Abstract Background The study aimed to assess the correlation between the monitoring frequency of PT-INR and the long-term prognosis in patients with mechanical heart valve (MHV) replacement after discharge. Methods This single-center, observational study enrolled patients who underwent MHV replacement and discharged from June 2015 to May 2018. Patients or their corresponding family members were followed with a telephone questionnaire survey in July-October 2020. Based on monitoring intervals, patients were divided into frequent monitoring (FM) group (≤ 1 month) and less frequent monitoring (LFM) group (> 1 month). The primary endpoint was the composite of thromboembolic event, major bleeding or all-cause death. The secondary endpoints were thromboembolic event, major bleeding or all-cause death, respectively. Results A total of 188 patients were included in the final analysis. The median follow-up duration was 3.6 years (Interquartile range: 2.6 to 4.4 years). 104 (55.3%) patients and 84 (44.7%) patients were classified into the FM group and the LFM group, respectively. The FM group had a significantly lower incidence of the primary endpoint than the LFM group (3.74 vs. 1.16 per 100 patient-years, adjusted HR: 3.31 [95% CI 1.05–10.42, P = 0.041]). Secondary analysis revealed that the risk of thromboembolic events and all-cause death were also reduced in the FM group. Conclusions The management of warfarin treatment in patients after MHV replacement remains challenging. Patients with less frequent monitoring of PT-INR might have worse clinical prognosis than those with frequent PT-INR monitoring

Palmitic Acid Promotes Lung Metastasis of Melanomas via the TLR4/TRIF-Peli1-pNF-κB Pathway

A high-fat diet plays an important role in aggravating cancers. Palmitic acid (PA) is one of the components of saturated fatty acids; it has been reported to promote tumor proliferation in melanomas, but the signal transduction pathway mediated by palmitic acid remains unclear. This study showed that palmitic acid can promote the lung metastasis of melanomas. Moreover, the interaction between palmitic acid and toll-like receptor 4 (TLR4) was predicted by molecular docking. The experimental results proved that palmitic acid could promote the TLR4 and Toll/IL-1 receptor domain-containing adaptor-inducing IFN-β (TRIF) expression. The expression of Pellino1 (Peli1) and the phosphorylation of NF-kappa B (pNF-κB) were downregulated after the suppression of TLR4 and the silencing of Peli1 also inhibited the phosphorylation of NF-κB. Therefore, we concluded that palmitic acid promoted the lung metastasis of melanomas through the TLR4/TRIF-Peli1-pNF-κB pathway