Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a lethal threat.Increasing Severe fever with thrombocytopenia syndrome (SFTS) risk in Asia and the United States stems from the spread of natural host, Haemaphysalis longicornis. Rapid and accurate SFTSV molecular diagnosis is crucial for treatment decisions, reducing fatality risk. Methods: Blood samples from 17 suspected SFTS patients at Chuncheon Sacred Heart Hospital (September-December 2022) were collected. SFTSV was diagnosed using two reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays from Gangwon Institute of Health and Environment (RT-qPCR/GIHE) and Asan Medical Center (RT-qPCR/AMC). To address RT-qPCR disparities, amplicon-based MinION sequencing traced SFTSV genomic sequences in clinical samples. Results: In two samples (N39 and N50), SFTSV was detected in both RT-qPCR/GIHE and RTqPCR/AMC. Among 11 samples, RT-qPCR/AMC exclusively detected SFTSV. In four samples, both assays yielded negative results. Amplicon-based MinION sequencing enabled nearly whole-genome sequencing of SFTSV in samples N39 and N50. Among 11 discordant samples, five contained significant SFTSV reads, aligning with the RT-qPCR/AMC findings. However, another six samples showed insufficient viral reads in accordance with the negativity observed in RT-qPCR/GIHE. The phylogenetic pattern of SFTSV demonstrated N39 formed a genetic lineage with genotype A in all segments. SFTSV N50 grouped with the B-1 sub-genotype for L segment and B-2 sub-genotype for the M and S segments, indicating genetic reassortment. Conclusion The study demonstrates the robust sensitivity of amplicon-based MinION sequencing for the direct detection of SFTSV in clinical samples containing ultralow copies of viral genomes. Next-generation sequencing holds potential in resolving SFTSV diagnosis discrepancies, enhancing understanding of diagnostic capacity, and risk assessment for emerging SFTSV.

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a lethal threat.Increasing Severe fever with thrombocytopenia syndrome (SFTS) risk in Asia and the United States stems from the spread of natural host, Haemaphysalis longicornis. Rapid and accurate SFTSV molecular diagnosis is crucial for treatment decisions, reducing fatality risk. Methods: Blood samples from 17 suspected SFTS patients at Chuncheon Sacred Heart Hospital (September-December 2022) were collected. SFTSV was diagnosed using two reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays from Gangwon Institute of Health and Environment (RT-qPCR/GIHE) and Asan Medical Center (RT-qPCR/AMC). To address RT-qPCR disparities, amplicon-based MinION sequencing traced SFTSV genomic sequences in clinical samples. Results: In two samples (N39 and N50), SFTSV was detected in both RT-qPCR/GIHE and RTqPCR/AMC. Among 11 samples, RT-qPCR/AMC exclusively detected SFTSV. In four samples, both assays yielded negative results. Amplicon-based MinION sequencing enabled nearly whole-genome sequencing of SFTSV in samples N39 and N50. Among 11 discordant samples, five contained significant SFTSV reads, aligning with the RT-qPCR/AMC findings. However, another six samples showed insufficient viral reads in accordance with the negativity observed in RT-qPCR/GIHE. The phylogenetic pattern of SFTSV demonstrated N39 formed a genetic lineage with genotype A in all segments. SFTSV N50 grouped with the B-1 sub-genotype for L segment and B-2 sub-genotype for the M and S segments, indicating genetic reassortment. Conclusion The study demonstrates the robust sensitivity of amplicon-based MinION sequencing for the direct detection of SFTSV in clinical samples containing ultralow copies of viral genomes. Next-generation sequencing holds potential in resolving SFTSV diagnosis discrepancies, enhancing understanding of diagnostic capacity, and risk assessment for emerging SFTSV.

Purpose: Thrombosis and bleeding significantly affect morbidity and mortality in myeloproliferative neoplasms (MPNs). The efficacy and safety of direct oral anticoagulants (DOACs) in MPN patients remain uncertain. Materials and Methods: We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service database from 2010 to 2021. Results: Out of the 368 MPN patients included in the final analysis, 62.8% were treated with DOACs for atrial fibrillation (AF), and 37.2% for venous thromboembolism (VTE). The AF group was statistically older with higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category [female]) scores compared to the VTE group. Antiplatelet agents were used in 51.1% of cases, and cytoreductive drugs in 79.3%, with hydroxyurea being the most common (64.9%). The median follow-up was 22.3 months, with 1-year cumulative incidence rates of thrombosis and bleeding at 11.1% and 3.7%, respectively. Multivariate analysis identified CHA2DS2-VASc scores ≥ 3 (hazard ratio [HR], 3.48), concomitant antiplatelet use (HR, 2.57), and cytoreduction (HR, 2.20) as significant thrombosis risk factors but found no significant predictors for major bleeding. Conclusion Despite the limitations of retrospective data, DOAC treatment in MPN patients seems effective and has an acceptable bleeding risk.

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Purpose: Thrombosis and bleeding significantly affect morbidity and mortality in myeloproliferative neoplasms (MPNs). The efficacy and safety of direct oral anticoagulants (DOACs) in MPN patients remain uncertain. Materials and Methods: We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service database from 2010 to 2021. Results: Out of the 368 MPN patients included in the final analysis, 62.8% were treated with DOACs for atrial fibrillation (AF), and 37.2% for venous thromboembolism (VTE). The AF group was statistically older with higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category [female]) scores compared to the VTE group. Antiplatelet agents were used in 51.1% of cases, and cytoreductive drugs in 79.3%, with hydroxyurea being the most common (64.9%). The median follow-up was 22.3 months, with 1-year cumulative incidence rates of thrombosis and bleeding at 11.1% and 3.7%, respectively. Multivariate analysis identified CHA2DS2-VASc scores ≥ 3 (hazard ratio [HR], 3.48), concomitant antiplatelet use (HR, 2.57), and cytoreduction (HR, 2.20) as significant thrombosis risk factors but found no significant predictors for major bleeding. Conclusion Despite the limitations of retrospective data, DOAC treatment in MPN patients seems effective and has an acceptable bleeding risk.

Purpose: Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC. Materials and Methods: Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed. Results: In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT. Conclusion Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

Background/Aims: Proprotein-converting enzyme subtilisin-kexin type 9 (PCSK9) inhibitors act more promptly and efficiently than statins and reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS). This study aimed to assess the short-term effects of perioperative administration of a single-dose PCSK9 inhibitor in patients with ACS. Methods: This study included 789 consecutive patients undergoing percutaneous coronary intervention (PCI) for ACS. The primary clinical endpoint was the occurrence of major adverse cardiovascular events (MACEs) within one month, including cardiac death, non-fatal myocardial infarction, unanticipated revascularization, stroke, stent thrombosis, and rehospitalization for ischemic causes or heart failure. Results: PCSK9 inhibitors were administered to 201 of 789 patients. MACEs occurred in eight patients (4.0%) in the treated group and 60 patients (10.2%) in the non-treated group for one month (hazard ratio 0.38, 95% confidence interval 0.18 to 0.80, p = 0.010). The benefit of PCSK9 inhibitors in terms of MACEs was greater in the subgroup of patients treated more than 1 hour before PCI than in the subgroup treated less than 1 hour before PCI or treated after PCI and in the non-treated group. Conclusions In patients undergoing PCI for ACS, the risk of MACEs was lower in those treated with perioperative single-dose PCSK9 inhibitors than in those in the untreated group. This benefit was especially noticeable in the subgroups treated > 1 hour before PCI than in those treated less than 1 hour before PCI or after PCI, regardless of the clinical presentation of ACS.

Background/Aims: Proprotein-converting enzyme subtilisin-kexin type 9 (PCSK9) inhibitors act more promptly and efficiently than statins and reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS). This study aimed to assess the short-term effects of perioperative administration of a single-dose PCSK9 inhibitor in patients with ACS. Methods: This study included 789 consecutive patients undergoing percutaneous coronary intervention (PCI) for ACS. The primary clinical endpoint was the occurrence of major adverse cardiovascular events (MACEs) within one month, including cardiac death, non-fatal myocardial infarction, unanticipated revascularization, stroke, stent thrombosis, and rehospitalization for ischemic causes or heart failure. Results: PCSK9 inhibitors were administered to 201 of 789 patients. MACEs occurred in eight patients (4.0%) in the treated group and 60 patients (10.2%) in the non-treated group for one month (hazard ratio 0.38, 95% confidence interval 0.18 to 0.80, p = 0.010). The benefit of PCSK9 inhibitors in terms of MACEs was greater in the subgroup of patients treated more than 1 hour before PCI than in the subgroup treated less than 1 hour before PCI or treated after PCI and in the non-treated group. Conclusions In patients undergoing PCI for ACS, the risk of MACEs was lower in those treated with perioperative single-dose PCSK9 inhibitors than in those in the untreated group. This benefit was especially noticeable in the subgroups treated > 1 hour before PCI than in those treated less than 1 hour before PCI or after PCI, regardless of the clinical presentation of ACS.

Background and Objectives: Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15–49 mL/min). Methods: XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints. Results: XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30–49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15–29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m 2 . The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA 2 DS 2 -VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m 2 per year. Conclusions XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice.

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.