Taipei Veterans General Hospital

About: Taipei Veterans General Hospital is a healthcare organization based out in Taipei, Taiwan. It is known for research contribution in the topics: Population & Cancer. The organization has 11878 authors who have published 16478 publications receiving 363424 citations. The organization is also known as: Táiběi Róngmín Zǒngyī Yuàn.

Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block

Abstract: Somatic reprogramming by reexpression of the embryonic transcription factor T-box 18 (TBX18) converts cardiomyocytes into pacemaker cells. We hypothesized that this could be a viable therapeutic avenue for pacemaker-dependent patients afflicted with device-related complications, and therefore tested whether adenoviral TBX18 gene transfer could create biological pacemaker activity in vivo in a large-animal model of complete heart block. Biological pacemaker activity, originating from the intramyocardial injection site, was evident in TBX18-transduced animals starting at day 2 and persisted for the duration of the study (14 days) with minimal backup electronic pacemaker use. Relative to controls transduced with a reporter gene, TBX18-transduced animals exhibited enhanced autonomic responses and physiologically superior chronotropic support of physical activity. Induced sinoatrial node cells could be identified by their distinctive morphology at the site of injection in TBX18-transduced animals, but not in controls. No local or systemic safety concerns arose. Thus, minimally invasive TBX18 gene transfer creates physiologically relevant pacemaker activity in complete heart block, providing evidence for therapeutic somatic reprogramming in a clinically relevant disease model.

Results of KEYNOTE-240: phase 3 study of pembrolizumab (Pembro) vs best supportive care (BSC) for second line therapy in advanced hepatocellular carcinoma (HCC).

Abstract: 4004Background: Pembro received accelerated approval based on results of KEYNOTE-224, a phase 2 trial in pts with advanced HCC in the second line setting. KEYNOTE-240 (NCT02702401) was a randomized...

Focal atrial tachycardia: new insight from noncontact mapping and catheter ablation.

Abstract: Background— This study investigated the electrophysiologic characteristics, atrial activation pattern, and effects of radiofrequency (RF) catheter ablation guided by noncontact mapping system in patients with focal atrial tachycardia (AT). Methods and Results— In 13 patients with 14 focal ATs, noncontact mapping system was used to map and guide ablation of AT. AT origins were in the crista terminalis (n=8), right atrial (RA) free wall (n=3), Koch triangle (n=1), anterior portion of RA–inferior vena cava junction (n=1), and superior portion of tricuspid annulus (n=1); breakout sites were in the crista terminalis (n=5), RA free wall (n=5), middle cavotricuspid isthmus (n=2), and RA–superior vena cava junction (n=2). ATs arose from the focal origins (11 ATs inside or at the border of low-voltage zone), with preferential conduction, breakout, and spread to the whole atrium. After applications of RF energy on the earliest activation site or the proximal portion of preferential conduction from AT origin, 13 ATs...

Propofol Inhibits Superoxide Production, Elastase Release, and Chemotaxis in Formyl Peptide–Activated Human Neutrophils by Blocking Formyl Peptide Receptor 1

Abstract: Neutrophils play a critical role in acute and chronic inflammatory processes, including myocardial ischemia/reperfusion injury, sepsis, and adult respiratory distress syndrome. Binding of formyl peptide receptor 1 (FPR1) by N -formyl peptides can activate neutrophils and may represent a new therapeutic target in either sterile or septic inflammation. Propofol, a widely used i.v. anesthetic, has been shown to modulate immunoinflammatory responses. However, the mechanism of propofol remains to be established. In this study, we showed that propofol significantly reduced superoxide generation, elastase release, and chemotaxis in human neutrophils activated by fMLF. Propofol did not alter superoxide generation or elastase release in a cell-free system. Neither inhibitors of γ-aminobutyric acid receptors nor an inhibitor of protein kinase A reversed the inhibitory effects of propofol. In addition, propofol showed less inhibitory effects in non-FPR1–induced cell responses. The signaling pathways downstream from FPR1, involving calcium, AKT, and ERK1/2, were also competitively inhibited by propofol. These results show that propofol selectively and competitively inhibits the FPR1-induced human neutrophil activation. Consistent with the hypothesis, propofol inhibited the binding of N -formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein, a fluorescent analog of fMLF, to FPR1 in human neutrophils, differentiated THP-1 cells, and FPR1-transfected human embryonic kidney-293 cells. To our knowledge, our results identify, for the first time, a novel anti-inflammatory mechanism of propofol by competitively blocking FPR1 in human neutrophils. Considering the importance of N -formyl peptides in inflammatory processes, our data indicate that propofol may have therapeutic potential to attenuate neutrophil-mediated inflammatory diseases by blocking FPR1.