The effect of off-label use of reduced-dose direct oral anticoagulants therapy in the treatment of pulmonary embolism comparable to standard-dose therapy.

Direct oral anticoagulants (DOACs) have been shown to be effective and safe in preventing pulmonary embolism recurrence. In this single-center retrospective observational study, we aimed to evaluate the efficacy and safety of reduced-dose DOACs in 86 consecutive patients with acute pulmonary embolism. Patients were divided into standard-dose and reduced-dose DOACs groups. Initial clot volume did not significantly differ between the two groups (standard-dose DOACs vs. reduced-dose DOACs, 18.8 [Q1-Q3 7.3-30.8] mL vs. 10.0 [Q1-Q3 3.2-27.9] mL, p = 0.1). Follow-up computed tomography (CT) within 30 days showed a higher rate of clot volume reduction or disappearance in the standard-dose group compared to the reduced-dose group (standard-dose DOACs vs. reduced-dose DOACs, 81.6% vs. 53.9%, p = 0.02). However, at the final follow-up CT, there was no significant difference in clot volume change between the two groups (standard-dose DOACs vs. reduced-dose DOACs, 91.5% vs. 82.0%, p = 0.19). Major bleeding occurred in two patients in the standard-dose group (4.3%) and three patients in the reduced-dose DOACs group (7.7%) (p = 0.5). In conclusion, while standard-dose DOACs demonstrated superior efficacy in early clot reduction, reduced doses of apixaban and edoxaban showed comparable efficacy and safety profiles in long-term treatment of acute pulmonary embolism in certain patients.

Proteomic analysis of fatty liver induced by starvation of medaka fish larvae.

When medaka fish (Oryzias latipes) larvae are grown in the absence of exogenous nutrition, the liver becomes dark and positive to Oil Red O staining from 7 days post-hatch (dph). We determined the mechanism of this starvation-induced development of fatty liver by proteomic analysis using livers obtained from larvae grown in the presence or absence of 2% glucose at 5 dph. Results showed that changes in the expression levels of enzymes involved in glycolysis or the tricarboxylic acid cycle were modest, whereas the expression levels of enzymes involved in amino acid catabolism or ß-oxidation of fatty acids were significantly elevated, suggesting that they become major energy sources under starvation conditions. Expression levels of enzymes for the uptake and ß-oxidation of fatty acids as well as synthesis of triacylglycerol were elevated, whereas those for the synthesis of cholesterol as well as export of cholesterol and triacylglycerol were decreased under starvation conditions, which explains the accumulation of triacylglycerol in the liver. Our results provide the basis for future research to understand how gene malfunction(s) affects the development of fatty liver, which can lead to nonalcoholic steatohepatitis and then to liver cirrhosis.Key words: amino acid catabolism, ß-oxidation, triacylglycerol, cholesterol, export.

Histopathological characteristics of the arrhythmogenic right ventricular cardiomyopathy presenting the electrocardiographic characteristics with Brugada syndrome.

INTRODUCTION: The histopathological characteristics of the overlapping disease states of Brugada syndrome (BrS) and arrhythmogenic right ventricular cardiomyopathy (ARVC) have not been fully elucidated. METHODS: A 71-year-old man showed coved-type ST-segment elevation with the right precordial leads, and the echocardiography demonstrated right ventricular (RV) dilatation. After 11 months, he died of a polymorphic VT storm. RESULTS: The pathological tissue demonstrated fibrofatty degeneration in the free wall of the RV outflow tract based on the heart autopsy. CONCLUSION: The overlapping disease states of BrS and ARVC showed histopathological characteristics consistent with ARVC.

Radiofrequency Ablation of Re-entrant Atrial Tachycardia Originating from the Superior Vena Cava with a High-resolution, 3-dimensional Mapping System.

An 80-year-old man with no previous history of catheter ablation or cardiac surgery underwent catheter ablation for atrial tachycardia (AT). We suspected that the mechanism causing AT was re-entry indicated by the entrainment phenomenon during AT and through activation mapping with a 3-dimensional mapping system (EnSite™ X EP system; Abbott, Chicago, IL, USA). We used a multipolar catheter (Advisor™ HD Grid Mapping Catheter; Abbott) inserted into the superior vena cava (SVC) to accomplish activation mapping. The AT circuit was localized inside the SVC with a fractionated potential recorded on its right lateral wall. A similar fractionated potential was observed in the surrounding area. These areas functioned as the critical isthmus of the AT. Radiofrequency (RF) catheter ablation at these sites eliminated the tachycardia. After RF delivery, no tachycardia was induced by programmed stimulation, even during isoproterenol infusion. Consequently, there was no recurrence of tachycardia even after catheter ablation.

Commitment toward cell death by activation of autophagy with survivin inhibitor YM155 in two canine squamous cell carcinoma cell lines with high expression of survivin.

Canine squamous cell carcinoma (SCC) is difficult to treat if local therapy is not feasible. Recently, survivin inhibitor YM155 was shown to have growth inhibitory activity on high-survivin-expressing canine SCC cell lines HAPPY and SQ4. Here, the mechanisms underlying the effect of YM155 on these cell lines were investigated. YM155 induced cleavage of poly(ADP-ribose) polymerase (PARP) in HAPPY, but not in SQ4 cells. Analyzing two autophagy markers, the level of microtubule-associated protein 1 light chain 3 (LC3)-II and the LC3-II/LC3-I ratio, indicated that YM155 activates autophagy in both cell lines, and this activation occurs prior to PARP cleavage in HAPPY cells. Moreover, inhibition of autophagic flux by chloroquine almost completely prevented the toxic effect of YM155 in both cell lines. Although there are differences in their eventual cell death type, both cell lines may be committed to cell death by activation of autophagy with YM155. Activation of autophagy is likely to be a key mechanism in the growth-inhibitory effects of YM155 in these lines. These data provide new insights into the cytotoxic mechanism of YM155 in canine SCC cells.

Usefulness of P-wave duration in patients with sick sinus syndrome as a predictor of atrial fibrillation.

BACKGROUND: This study aimed to clarify P-wave duration (PWD) ability before pacemaker implantation to predict worsening atrial fibrillation (AF) burden after the procedure. METHODS: We retrospectively investigated 75 patients who underwent permanent pacemaker implantation due to sick sinus syndrome (SSS) at Komaki City Hospital between January 2006 and May 2019. Worsening AF burden was defined as an increase in the number of AF episodes, each lasting ≥5.5 hours a day. RESULTS: In the study population, 17 patients (23%) had worsening AF burden during the follow-up period. These patients had significantly longer PWD in lead Ⅱ (117.9 ± 19.9 ms vs 101.3 ± 20.0 ms, P = .002) than the patients without worsening AF burden. The best discriminative cutoff value for PWD in lead Ⅱ was 108 ms (sensitivity, 77%; specificity, 67%). In multivariate analysis, PWD in lead II ≥108 ms (hazard ratio, 5.395; 95% confidence interval, 1.352-21.523; P = .017) was an independent predictor of worsening AF burden. Patients with PWD in lead II <108 ms showed a significantly higher event-free rate against worsening AF burden than those with PWD in lead II ≥108 ms (81% vs 9%, P = .005). CONCLUSIONS: Prolonged PWD before pacemaker implantation was the most important independent predictor of worsening AF burden after the procedure. In patients with SSS, prolonged PWD can be a useful marker for predicting worsening of AF burden after pacemaker implantation.