Objective: To improve our understanding of EPEC, this study focused on analyzing and comparing the genomic characteristics of EPEC isolates from humans and companion animals in Korea. Methods: The whole genome of 26 EPEC isolates from patients with diarrhea and 20 EPEC isolates from companion animals in Korea were sequenced using the Illumina HiSeq X (Illumina, USA) and Oxford Nanopore MinION (Oxford Nanopore Technologies, UK) platforms. Results: Most isolates were atypical EPEC, and did not harbor the bfpA gene. The most prevalent virulence genes were found to be ompT (humans: 61.5%; companion animals:60.0%) followed by lpfA (humans: 46.2%; companion animals: 60.0%). Although pangenome analyses showed no apparent correlation among the origin of the strains, virulence profiles, and antimicrobial resistance profiles, isolates included in clade A obtained from both humans and companion animals exhibited high similarity. Additionally, all the isolates included in clade A encoded the ompT gene and did not encode the hlyE gene. The two isolates from companion animals harbored an incomplete bundle-forming pilus region encoding bfpA and bfpB. Moreover, the type IV secretion system-associated genes tra and trb were found in the bfpA-encoding isolates from humans. Conclusions and Relevance: Whole-genome sequencing enabled a more accurate analysis of the phylogenetic structure of EPEC and provided better insights into the understanding of EPEC epidemiology and pathogenicity.

Background: Complete revascularization has demonstrated better outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, in the case of left main (LM) culprit lesion AMI with multivessel disease, there is limited evidence to suggest that complete revascularization is better. Methods: We reviewed 16,831 patients in the Korea Acute Myocardial Infarction Registry who were treated from July 2016 to June 2020, and 399 patients were enrolled with LM culprit lesion AMI treated with percutaneous coronary intervention. We categorized the patients as those treated with complete revascularization (n=295) or incomplete revascularization (n=104). The study endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, ischemia-driven revascularization, stent thrombosis, and stroke. We performed propensity score matching (PSM) and analyzed the incidence of MACCE at 1 year. Results: After PSM, the two groups were well balanced. There was no significant difference between the two groups in MACCE at 1 year (12.1% vs. 15.2%; hazard ratio, 1.28; 95% confidence interval, 0.60–2.74; p=0.524) after PSM. The components of MACCE and major bleeding were also not significantly different. Conclusion There was no significant difference in clinical outcomes between the groups treated with complete or incomplete revascularization for LM culprit lesion AMI with multivessel disease.

Background and Objectives: Cigarette smoking is a major risk factor for atherosclerosis.Nicotine, a crucial constituent of tobacco, contributes to atherosclerosis development and progression. However, evidence of the association between nicotine and neointima formation is limited. We aimed to evaluate whether nicotine enhances neointimal hyperplasia in the native epicardial coronary arteries of pigs after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). Methods: After coronary angiography (CAG) and quantitative coronary angiography (QCA), we implanted 20 DES into 20 pigs allocated to 2 groups: no-nicotine (n=10) and nicotine (n=10) groups. Post-PCI CAG and QCA were performed immediately. Follow-up CAG, QCA, optical coherence tomography (OCT), and histopathological analyses were performed 2 months post-PCI. Results: Despite intergroup similarities in the baseline QCA findings, OCT analysis showed that the nicotine group had a smaller mean stent and lumen areas, a larger mean neointimal area, greater percent area stenosis, and higher peri-strut fibrin and inflammation scores than the no-nicotine group. In immunofluorescence analysis, the nicotine group displayed higher expression of CD68 and α-smooth muscle actin but lower CD31 expression than the no-nicotine group. Conclusions Nicotine inhibited re-endothelialization and promoted inflammation and NIH after PCI with DES in a porcine model.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Background and Objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

Background: Remimazolam is a novel ultra-short-acting benzodiazepine known for its hemodynamic stability over propofol. However, its hemodynamic effects compared to those of etomidate are not well established. This study aimed to determine whether the use of remimazolam is non-inferior to etomidate with regard to the occurrence of post-induction hypotension in patients undergoing coronary artery bypass grafting. Methods: Patients were randomly assigned to either the remimazolam group (6 mg/kg/h) or the etomidate group (0.3 mg/kg) for induction of anesthesia. Anesthetic depth was adjusted based on the bispectral index. Primary outcome was the incidence of post-induction hypotension, defined as a mean arterial pressure less than 65 mmHg within 15 min after endotracheal intubation, with a non-inferiority margin of 12%. Results: A total of 144 patients were finally analyzed. Incidence of post-induction hypotension was 36/71 (50.7%) in the remimazolam group and 25/73 (34.2%) in the etomidate group, with a rate difference of 16.5% (95% CI [3.0–32.6]) between the two groups that was beyond the prespecified non-inferiority margin of 12.0%. The number of patients who needed vasopressors was similar in the two groups. Conclusions In this non-inferiority trial, remimazolam failed to show non-inferiority to etomidate in terms of post-induction hypotension when used as an induction drug for general anesthesia in patients undergoing coronary artery bypass grafting. However, different doses or infusion techniques of remimazolam should be compared with etomidate in various patient groups to fully assess its hemodynamic non-inferiority during induction of anesthesia.

Background: Severe acute respiratory syndrome coronavirus 2, an RNA virus, exhibits variations in transmission power, severity rate, and vaccine effectiveness due to its mutable nature. We investigated the field epidemiological characteristics of the delta and omicron variants of coronavirus disease 2019 (COVID-19) clusters in a long-term care hospital. Materials and Methods: This study aimed to investigate the incidence, fatality, and vaccination effectiveness of confirmed COVID-19 cases caused by delta and omicron variants. The investigation focused on patients admitted to two long-term care hospitals in a Seoul autonomous district, comparing and analyzing relevant factors. Results: Among the COVID-19 cases, 101 (34.3%) exhibited delta variants, while 193 (65.4%) showcased omicron variants. The incidence rate of omicron variants, compared to delta variants, was 2.24 times higher (95% confidence interval [CI], 1.68–3.00). This elevation was particularly notable in women across all age groups, patients, workers, and individuals with a history of three or more vaccinations. Deaths were reported in 13 cases (52.0%) with the delta variant and 12 cases (48.0%) with the omicron variant. The fatality rate of the omicron variant, in comparison to the delta variant, was 0.09 times (95% CI, 0.44–2.26), indicating no significant difference. No discernible variations in variables were observed. Conclusion The noteworthy surge in outbreaks among female patients, workers engaged in outdoor activities, and the apparent ineffectiveness of vaccination against omicron mutations underscore the need for careful consideration in formulating quarantine measures.

Natural killer (NK) cells are gaining growing attention due to their promise for immunotherapy. A fast and accurate system is needed to test NK cell biology and their therapeutic application. Here, we report a lung cancer organoid-based system to evaluate NK cells’ cytotoxicity. We first established the lung cancer organoids on top of Matrigel, which allows the co-culture with NK cells. When co-cultured, NK cells moved close to and inside the lung cancer organoids. When we analyzed by flow cytometry, co-culture of NK cells induced a significantly higher ratio of cell death of lung cancer organoids, suggesting that lung cancer organoids can be employed to test the cytotoxicity of NK cells. Finally, the pre-treatment of NK cells with A83-01, a TGFβ inhibitor, significantly enhanced the cell death of lung cancer organoids by NK cells, indicating that lung cancer organoid-based system faithfully recapitulates cell line-based system in evaluating the in vitro cytotoxicity of NK cells. These data represent that cancer organoid-based NK cell co-culture system is a reliable platform for studying NK cell biology and evaluating their cytotoxicity for screening for NK cell immunotherapy.

Purpose: This study investigated urinary incontinence (UI) following holmium laser enucleation of the prostate (HoLEP), based on the postoperative period, type of UI, and severity according to prostate volume. Methods: We analyzed prospectively collected data from patients who underwent HoLEP for benign prostatic hyperplasia at Seoul National University Hospital between January 2010 and June 2022. Patients were followed-up at 2 weeks, 3 months, and 6 months postoperatively. The patients were divided into 3 prostate volume groups: A (30–80 mL), B (81–120 mL), and C (>120 mL). We compared clinical outcomes and UI rates between the groups. Results: In total, 1,675 patients were included. The preoperative urgency UI (UUI) rate was 16.1%, with no significant difference between the groups (P=0.81). Two weeks postoperatively, the UUI rate was 6.0% (including a de novo UUI rate of 4.2%), with no significant differences between the groups. The stress UI (SUI) rate at 2 weeks postoperatively was 6.3%, and increased with larger prostate volume (P=0.04). The UUI and SUI rates decreased to 0.9% and 1.2%, respectively, 6 months postoperatively. Six months postoperatively, the SUI rate was significantly lower in group A (P=0.02), whereas the UUI rate did not differ between the groups (P=0.69). Conclusions Our results demonstrated that the preoperative UUI rate was high at baseline. Both the UUI and SUI rates continuously decreased up to 6 months postoperatively. Although the SUI rates significantly differed according to prostate volume, there was no significant difference in the UUI rate.