Real-World Bleeding Risk of Anticoagulant and Nonsteroidal Anti-inflammatory Drugs Combotherapy versus Anticoagulant Monotherapy.

Background/Aims: The incidence of acute gastrointestinal bleeding (GIB) increases with the utilization of anticoagulant and nonsteroidal anti-inflammatory drugs (NSAIDs). This study aimed to compare the risk of GIB between anticoagulant and NSAIDs combotherapy and anticoagulant monotherapy in real-world practice. Methods: We investigated the relative risk of GIB in individuals newly prescribed anticoagulant and NSAIDs combination therapy and that in individuals newly prescribed anticoagulant monotherapy at three hospitals using "common data model." Cox proportional hazard models and Kaplan-Meier estimation were employed for risk comparison after propensity score matching. Results: A comprehensive analysis of 2,951 matched pairs showed that patients who received anticoagulant and NSAIDs combousers exhibited a significantly higher risk of GIB than those who received anticoagulant monousers (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.30 to 2.12; p<0.001). The risk of GIB associated with anticoagulant and NSAIDs combination therapy was also significantly higher than that associated with anticoagulant monotherapy in patients aged >65 years (HR, 1.53; 95% CI, 1.15 to 2.03; p=0.003) and >75 years (HR, 1.89; 95% CI, 1.23 to 2.90; p=0.003). We also found that the risk of GIB was significantly higher in the patients who received anticoagulant and NSAIDs combousers than that in patients who received anticoagulant monousers in both male (p=0.016) and female cohorts (p=0.010). Conclusions: The risk of GIB is significantly higher in patients who receive anticoagulant and NSAIDs combotherapy than that in patients who receive anticoagulant monotherapy. In addition, the risk of GIB associated with anticoagulant and NSAIDs combotherapy was much higher in individuals aged >75 years. Therefore, physicians should be more aware of pay more attention to the risk of GIB when they prescribe anticoagulant and NSAIDs.

Efficacy of Transarterial Chemoembolization (TACE) for Early-Stage Hepatocellular Carcinoma.

Backgound and Objectives: The treatments of choice for patients with early-stage hepatocellular carcinoma (HCC) are surgical resection, local ablation therapy, and liver transplantation; however, transarterial chemoembolization (TACE) is commonly performed due to variations among patients and liver diseases. This study aimed to assess the efficacy of TACE in patients with early-stage HCC. Materials and Methods: A retrospective analysis was performed of all TACE procedures performed at Kyung Hee University Hospital at Gangdong over a 15-year period (July 2006 to November 2021). The study included a total of 97 eligible patients with early-stage HCC ≤ 5 cm initially treated with TACE. The mean participant age was 63.47 ± 11.02 years; 69 were men (71.1%). The number of Child-Pugh class A patients was the highest (74 patients [76.3%]), followed by Child-Pugh class B (19 patients [19.6%]) and Child-Pugh class C (4 patients [4.12%]). Results: A complete response was achieved in 84 (86.6%) patients after the first TACE procedure, with 1-, 2-, and 3-year survival rates of 91.8%, 87.3%, and 75.4%, respectively. In the multivariate analysis, the patients with a low initial alpha-fetoprotein (AFP) ≤ 20 ng/mL (p = 0.02) and a complete response after the first TACE (p = 0.03) were associated with favorable overall survival. Conclusions: TACE can be used to treat patients with early-stage HCC who are unsuitable for ablation or surgery. If patients are well selected, TACE may be an alternative treatment for patients with low AFP levels who respond well to the initial TACE procedure.

Impact of COVID-19 Pandemic on Performance of Gastrointestinal Endoscopy.

Background/Aims: Non-time-sensitive gastrointestinal endoscopy was deferred because of the risk of exposure to coronavirus disease 2019 (COVID-19), but no population-based studies have quantified the adverse impact on gastrointestinal procedures. This study examined the impact of the COVID-19 pandemic on the performance of esophagogastroduodenoscopy (EGD), colonoscopy, ERCP, and abdominal ultrasonography (US) in South Korea. Methods: This nationwide, population-based study compared the claim data of EGD, colonoscopy, ERCP, and abdominal US in 2020 and 2021 (COVID-19 era) with those in 2019 (before the COVID-19 era). Results: During the first year (2020) of the COVID-19 pandemic, the annual claim data of EGD and colonoscopy were reduced by 6.3% and 6.9%, respectively, but those of ERCP and abdominal US were increased by 1.0% and 2.9%, compared to those in 2019. During the first surge (March and April 2020) of COVID-19, the monthly claim data of EGD, colonoscopy, ERCP, and abdominal US were reduced by 28.8%, 43.8%, 5.1%, and 21.6%, respectively, in March 2020, and also reduced by 17.2%, 32.8%, 4.4%, and 9.5%, respectively, in April 2020, compared to those in March and April 2019. During March and April 2020, the monthly claims of ERCP, compared with those in 2019, declined less significantly than those of EGD and colonoscopy (both p<0.001). Conclusions: The claims of EGD and colonoscopy were reduced more significantly than those of ERCP and abdominal US during the COVID-19 pandemic because ERCPs are time-sensitive procedures and abdominal USs are non-aerosolized procedures.

In situ procedure for high-efficiency computational modeling of atrial fibrillation reflecting personal anatomy, fiber orientation, fibrosis, and electrophysiology.

We previously reported the feasibility and efficacy of a simulation-guided clinical catheter ablation of atrial fibrillation (AF) in an in-silico AF model. We developed a highly efficient realistic AF model reflecting the patient endocardial voltage and local conduction and tested its clinical feasibility. We acquired > 500 endocardial bipolar electrograms during right atrial pacing at the beginning of the AF ablation procedures. Based on the clinical bipolar electrograms, we generated simulated voltage maps by applying fibrosis and local activation maps adjusted for the fiber orientation. The software's accuracy (CUVIA2.5) was retrospectively tested in 17 patients and feasibility prospectively in 10 during clinical AF ablation. Results: We found excellent correlations between the clinical and simulated voltage maps (R = 0.933, p < 0.001) and clinical and virtual local conduction (R = 0.958, p < 0.001). The proportion of virtual local fibrosis was 15.4, 22.2, and 36.9% in the paroxysmal AF, persistent AF, and post-pulmonary vein isolation (PVI) states, respectively. The reconstructed virtual bipolar electrogram exhibited a relatively good similarities of morphology to the local clinical bipolar electrogram (R = 0.60 ± 0.08, p < 0.001). Feasibility testing revealed an in situ procedural computing time from the clinical data acquisition to wave-dynamics analyses of 48.2 ± 4.9 min. All virtual analyses were successfully achieved during clinical PVI procedures. We developed a highly efficient, realistic, in situ procedural simulation model reflective of individual anatomy, fiber orientation, fibrosis, and electrophysiology that can be applied during AF ablation.

Clinical characteristics and rhythm outcome of catheter ablation of hemodynamically corrected valvular atrial fibrillation.

BACKGROUND: Although the hemodynamic burden and structural substrate contribute to valvular atrial fibrillation (VAF) mechanisms, the role of catheter ablation has rarely been reported. We investigated the clinical characteristics, mapping findings, and long-term rhythm outcomes after catheter ablation of hemodynamically corrected VAF. METHODS: We compared 77 patients with VAF (46.8% male, 52.7±8.8 years old, 46.8% paroxysmal AF, 24.7% with maze procedures) and 2244 patients with non-VAF (NVAF) who underwent catheter ablation. Among the VAF patients, 44 (57.1%) had mechanical valve AF (MV-AF) and 33 (42.9%) underwent a prior mitral valvuloplasty (MVP-AF). We analyzed the catheter ablation rhythm outcomes for MV-AF and MVP-AF. RESULTS: The left atrial (LA) diameter was greater (p<0.001), LA voltage lower (p<0.001), and procedure-related complication rate higher (mainly sinus node dysfunction, p=0.004) for VAF than NVAF. During 70.2±1.8 months of follow-up, the rhythm outcome of VAF did not significantly differ from that of NVAF after catheter ablation (log rank p=0.399), even after excluding patients with maze procedures (log rank p=0.629). The clinical recurrence rates did not differ between the MV-AF and MVP-AF groups (log rank p=0.244), or between patients with prior maze procedures and those without (log rank p=0.651). The main conduction recovery sites of previous maze procedures were the perimitral (84.2%) and cavotricuspid isthmus (84.2%) areas, and recurrence mechanisms were macroreentry (63.2%) and focal/microreentry (26.3%) at scar border zones. CONCLUSIONS: Although hemodynamically corrected VAF was associated with advanced LA remodeling, the rhythm outcome did not significantly differ from that of NVAF after catheter ablation.

The effects of kinase modulation on in vitro maturation according to different cumulus-oocyte complex morphologies.

Successful production of transgenic pigs requires oocytes with a high developmental competence. However, cumulus-oocyte complexes (COCs) obtained from antral follicles have a heterogeneous morphology. COCs can be classified into one of two classes: class I, with five or more layers of cumulus cells; and class II, with one or two layers of cumulus cells. Activator [e.g., epidermal growth factor (EGF)] or inhibitors (e.g., wortmannin and U0126) are added to modulate kinases in oocytes during meiosis. In the present study, we investigated the effects of kinase modulation on nuclear and cytoplasmic maturation in COCs. Class I COCs showed a significantly higher developmental competence than class II COCs. Moreover, the expression of two kinases, AKT and ERK, differed between class I and class II COCs during in vitro maturation (IVM). Initially, inhibition of the PI3K/AKT signaling pathway in class I COCs during early IVM (0-22 h) decreased developmental parameters, such as blastocyst formation rate, blastomere number, and cell survival. Conversely, EGF-mediated AKT activation in class II COCs enhanced developmental capacity. Regarding the MAPK signaling pathway, inhibition of ERK by U0126 in class II COCs during early IVM impaired developmental competence. However, transient treatment with U0126 in class II COCs increased oocyte maturation and AKT activity, improving embryonic development. Additionally, western blotting showed that inhibition of ERK activity negatively regulated the AKT signaling pathway, indicative of a relationship between AKT and MAPK signaling in the process underlying meiotic progression in pigs. These findings may help increase the developmental competence and utilization rate of pig COCs with regard to the production of transgenic pigs and improve our understanding of kinase-associated meiosis events.

Long-term changes in heart rate variability after radiofrequency catheter ablation for atrial fibrillation: 1-year follow-up study with irrigation tip catheter.

BACKGROUND: Radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) changes cardiac autonomic nerve activity. However, the long-term effect of RFCA has not yet been evaluated when an open irrigation tip catheter (OITC) was used. Therefore, we hypothesized that AF ablation changes heart rate variability (HRV) that would be maintained over 1 year after OITC ablation and be associated with clinical recurrence of AF. METHODS AND RESULTS: We analyzed pre-RFCA HRV (HRVpre ), HRV at 3 months (HRV3mo ) and 1 year (HRV1yr ) after RFCA using 24-hour Holter monitoring after excluding arrhythmic events in 144 patients (70% male, 57 ± 10 years old, 83% paroxysmal AF) who underwent RFCA with OITC. After RFCA with OITC, the increase in mean heart rate and the reduction in HF or LF/HF were significant at HRV3mo (P < 0.001) and were maintained at HRV1yr (P < 0.001). During 20 ± 8 months of follow-up, 33 of 144 patients (23%) showed clinical recurrence of AF. Patients in the nonrecurrence group showed significant reductions of rMSSD and HF at HRV3mo and HRV1yr , but patients with clinical recurrence did not. In Cox regression analysis, a reduction in LF/HF (ΔLF/HF) ≥0.26 at HRV3mo was significantly associated with clinical recurrence of AF (hazard ratio 2.52, 95% CI 1.19-5.32, P = 0.015). CONCLUSION: In contrast to previous reports about long-term HRV recovery after AF ablation with a conventional catheter, change in cardiac autonomic nervous activity was maintained for 1 year after RFCA when an OITC was used. A reduction in ΔLF/HF ≥0.26 at HRV3mo was independently associated with clinical recurrence of AF after RFCA.

Characteristics of complex fractionated atrial electrogram in the electroanatomically remodeled left atrium of patients with atrial fibrillation.

BACKGROUND: Complex fractionated atrial electrogram (CFAE) guided ablation is effective in some patients with persistent atrial fibrillation (PeAF), but the pattern of CFAE may be different in the remodeled left atrium (LA). METHODS AND RESULTS: In 100 AF patients (83 males, 55.0+/-10.6 years old) with AF (51 paroxysmal AF (PAF), 49 PeAF) who underwent catheter ablation, CFAE cycle length (CL) and distribution (NavX 3D map) were compared according to the LA volume (3D-CT) and endocardial voltage (during high right atrial pacing 500-ms (Vol(PACE)) and AF (Vol(AF); NavX). The mean CFAE-CL was longer (P=0.003) and the % area CFAE was smaller (P=0.006) in patients with LA >or=125 ml than those with <125 ml. The mean CFAE-CL was longer in patients with Vol(PACE) <1.7 mV than those with >or=1.7 mV (P=0.002) and in Vol(AF) <0.7 mV than >or=0.7 mV (P<0.001). The % area CFAE was smaller in patients with Vol(PACE) <1.7 mV than those with >or=1.7 mV (P=0.006). The incidence of septal CFAE was consistently high, regardless of the degree of LA remodeling. CONCLUSIONS: In the AF patients with an electroanatomically remodeled LA, the % area of CFAE was smaller and mean CFAE-CL was longer than in those with a less remodeled LA. However, the majority of CFAE are consistently positioned on the septum in the remodeled LA.