Background: Atrial fibrillation (AF) is associated with increased risks of adverse events including stroke and all-cause death. Understanding the pattern of causes of death (COD) with the relative risks in patients with AF compared to the non-AF population is essential in planning optimal care for patients with AF. We aimed to analyze the COD and its relative risks in patients with AF, using a nationwide population-based cohort. Methods: Using the Korean nationwide claims database, people aged 40 or older who received health examinations in 2009 were included if they had no missing values (n = 6,877,929).In total the study included 40,585 people with AF and 6,837,344 without AF. COD was defined by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes. Comparison between the AF and non-AF groups was performed with Multivariate Cox proportional regression model. Results: In the AF group, cardiovascular diseases were the most common COD, causing 39.8% of all deaths, compared with 19.0% for non-AF subjects. The AF group was associated with a higher risk of death from cardiovascular and cerebrovascular diseases by almost 3-fold than the matched non-AF group (hazard ratios [HR], 3.082; 95% confidence intervals [CIs], 2.963–3.205 for cardiovascular diseases; HR, 2.981; 95% CI, 2.799–3.175 for cerebrovascular diseases, all P < 0.001). Among patients with AF, the risks of all-cause, cardiovascular, and cerebrovascular death were well-stratified by CHA2DS2 -VASc scores. The risk of cerebrovascular death was 11 times higher among patients with a CHA2DS2 -VASc score ≥ 7. Conclusion Compared to non-AF individuals, patients with AF had a higher risk of death from cardiovascular and cerebrovascular diseases, and the mortality risks were wellstratified by the CHA2DS2 -VASc score. Integrated care management of cardiovascular and cerebrovascular diseases for patients with AF might help mitigate mortality.

Background: Atrial fibrillation (AF) is associated with increased risks of adverse events including stroke and all-cause death. Understanding the pattern of causes of death (COD) with the relative risks in patients with AF compared to the non-AF population is essential in planning optimal care for patients with AF. We aimed to analyze the COD and its relative risks in patients with AF, using a nationwide population-based cohort. Methods: Using the Korean nationwide claims database, people aged 40 or older who received health examinations in 2009 were included if they had no missing values (n = 6,877,929).In total the study included 40,585 people with AF and 6,837,344 without AF. COD was defined by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes. Comparison between the AF and non-AF groups was performed with Multivariate Cox proportional regression model. Results: In the AF group, cardiovascular diseases were the most common COD, causing 39.8% of all deaths, compared with 19.0% for non-AF subjects. The AF group was associated with a higher risk of death from cardiovascular and cerebrovascular diseases by almost 3-fold than the matched non-AF group (hazard ratios [HR], 3.082; 95% confidence intervals [CIs], 2.963–3.205 for cardiovascular diseases; HR, 2.981; 95% CI, 2.799–3.175 for cerebrovascular diseases, all P < 0.001). Among patients with AF, the risks of all-cause, cardiovascular, and cerebrovascular death were well-stratified by CHA2DS2 -VASc scores. The risk of cerebrovascular death was 11 times higher among patients with a CHA2DS2 -VASc score ≥ 7. Conclusion Compared to non-AF individuals, patients with AF had a higher risk of death from cardiovascular and cerebrovascular diseases, and the mortality risks were wellstratified by the CHA2DS2 -VASc score. Integrated care management of cardiovascular and cerebrovascular diseases for patients with AF might help mitigate mortality.

Background: Atrial fibrillation (AF) is associated with increased risks of adverse events including stroke and all-cause death. Understanding the pattern of causes of death (COD) with the relative risks in patients with AF compared to the non-AF population is essential in planning optimal care for patients with AF. We aimed to analyze the COD and its relative risks in patients with AF, using a nationwide population-based cohort. Methods: Using the Korean nationwide claims database, people aged 40 or older who received health examinations in 2009 were included if they had no missing values (n = 6,877,929).In total the study included 40,585 people with AF and 6,837,344 without AF. COD was defined by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes. Comparison between the AF and non-AF groups was performed with Multivariate Cox proportional regression model. Results: In the AF group, cardiovascular diseases were the most common COD, causing 39.8% of all deaths, compared with 19.0% for non-AF subjects. The AF group was associated with a higher risk of death from cardiovascular and cerebrovascular diseases by almost 3-fold than the matched non-AF group (hazard ratios [HR], 3.082; 95% confidence intervals [CIs], 2.963–3.205 for cardiovascular diseases; HR, 2.981; 95% CI, 2.799–3.175 for cerebrovascular diseases, all P < 0.001). Among patients with AF, the risks of all-cause, cardiovascular, and cerebrovascular death were well-stratified by CHA2DS2 -VASc scores. The risk of cerebrovascular death was 11 times higher among patients with a CHA2DS2 -VASc score ≥ 7. Conclusion Compared to non-AF individuals, patients with AF had a higher risk of death from cardiovascular and cerebrovascular diseases, and the mortality risks were wellstratified by the CHA2DS2 -VASc score. Integrated care management of cardiovascular and cerebrovascular diseases for patients with AF might help mitigate mortality.

Background: Atrial fibrillation (AF) is associated with increased risks of adverse events including stroke and all-cause death. Understanding the pattern of causes of death (COD) with the relative risks in patients with AF compared to the non-AF population is essential in planning optimal care for patients with AF. We aimed to analyze the COD and its relative risks in patients with AF, using a nationwide population-based cohort. Methods: Using the Korean nationwide claims database, people aged 40 or older who received health examinations in 2009 were included if they had no missing values (n = 6,877,929).In total the study included 40,585 people with AF and 6,837,344 without AF. COD was defined by International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes. Comparison between the AF and non-AF groups was performed with Multivariate Cox proportional regression model. Results: In the AF group, cardiovascular diseases were the most common COD, causing 39.8% of all deaths, compared with 19.0% for non-AF subjects. The AF group was associated with a higher risk of death from cardiovascular and cerebrovascular diseases by almost 3-fold than the matched non-AF group (hazard ratios [HR], 3.082; 95% confidence intervals [CIs], 2.963–3.205 for cardiovascular diseases; HR, 2.981; 95% CI, 2.799–3.175 for cerebrovascular diseases, all P < 0.001). Among patients with AF, the risks of all-cause, cardiovascular, and cerebrovascular death were well-stratified by CHA2DS2 -VASc scores. The risk of cerebrovascular death was 11 times higher among patients with a CHA2DS2 -VASc score ≥ 7. Conclusion Compared to non-AF individuals, patients with AF had a higher risk of death from cardiovascular and cerebrovascular diseases, and the mortality risks were wellstratified by the CHA2DS2 -VASc score. Integrated care management of cardiovascular and cerebrovascular diseases for patients with AF might help mitigate mortality.

Background: Factors related to the development and severity of polycystic liver disease (PLD) have not been well established. We aimed to evaluate the genetic and epidemiologic risk factors of PLD in patients with autosomal dominant polycystic kidney disease (ADPKD). Methods: Adult patients with inherited cystic kidney disease were enrolled from May 2019 to May 2021. Demographic, clinical, and laboratory data were collected at the initial study visit. The severity of PLD was graded based on the height-adjusted total liver volume: < 1,000 mL/m (Gr1), 1,000–1,800 mL/m (Gr2), and > 1,800 mL/m (Gr3). Targeted exome sequencing was done by a gene panel including 89 ciliopathy-related genes. We searched out the relative factors to the presence and the severity of PLD using logistic regression analysis. Results: Of 602 patients with typical ADPKD, 461 (76.6%) patients had PLD. The patients with PLD showed female predominance and a higher frequency of other ADPKD-related complications. The genetic variants with truncating mutation of PKD1 (PKD1-proteintruncating [PT]) or PKD2 commonly affected the development and severity of PLD. An older age, female sex, and higher kidney volume with Mayo classification 1C-1E was significantly associated with the development of PLD, but not with the severity of PLD. On the other hand, higher body mass index, lower hemoglobin, and higher alkaline phosphatase (ALP) were the significant risk factors of severe PLD (≥ Gr2). Conclusion Hepatic involvement in ADPKD could be related to kidney manifestations and genetic variants including PKD1-PT or PKD2. Monitoring hemoglobin and ALP and evaluating the genetic variants might help predict severe PLD.

Identifying genetic mutations in individuals with inherited cystic kidney disease is necessary for precise treatment. We aimed to elucidate the genetic characteristics of cystic kidney disease in the Korean population. Methods: We conducted a 3-year prospective, multicenter cohort study at eight hospitals from May 2019 to May 2022. Patients with more than three renal cysts were enrolled and classified into two categories, typical autosomal dominant polycystic kidney disease (ADPKD) and atypical PKD. We identified the clinical characteristics and performed a genetic analysis using a targeted gene panel. Results: A total of 725 adult patients were included in the study, of which 560 (77.2%) were diagnosed with typical ADPKD and 165 (22.8%) had atypical PKD. Among the typical ADPKD cases, the Mayo imaging classification was as follows: 1A (55, 9.9%), 1B (149, 26.6%), 1C (198, 35.8%), 1D (90, 16.3%), and 1E (61, 11.0%). The atypical PKD cases were classified as bilateral cystic with bilateral atrophic (31, 37.3%), lopsided (27, 32.5%), unilateral (nine, 10.8%), segmental (eight, 9.6%), bilateral cystic with unilateral atrophic (seven, 8.4%), and asymmetric (one, 1.2%). Pathogenic variants were found in 64.3% of the patients using the ciliopathy-related targeted gene panel. The typical ADPKD group demonstrated a higher discovery rate (62.3%) than the atypical PKD group (41.8%). Conclusion: We present a nationwide genetic cohort’s baseline clinical and genetic characteristics for Korean cystic kidney disease.

Background/Aims: Patients with liver cirrhosis (LC) have low levels of branchedchain amino acids (BCAAs). There is accumulating evidence that BCAAs have anti- fibrotic effects in cirrhosis. This study is aimed to evaluate the effect of BCAAs on the function and phenotype of activated hepatic stellate cells (HSCs). Methods: LX-2, an immortalized human stellate cell line, was used in in vitro experiments. LX-2 cells were exposed to transforming growth factor β1 (TGF-β1) and BCAAs or to valine, leucine, and isoleucine, which are components of BCAAs. Activation of the TGF-β signaling pathway in LX-2 cells was observed using real- time quantitative polymerase chain reaction and Western blotting. Results: The increased expression of snail family transcriptional repressor 1 (SNAI1) was observed in LX-2 cells activated by TGF-β1. After BCAA treatment, its expression was significantly decreased at the mRNA level. The increased expression of Col1α1 and TIMP2 at the mRNA level and alpha smooth muscle actin at the protein level in activated LX-2 cells decreased after BCAA treatment. Among the BCAA components, leucine and valine significantly abrogated TGF-β-induced activation of LX-2 cells. BCAA treatment led to the decreased phosphorylation of Smad2 and p38 proteins, which are markers for Smad and Smad-independent p38 mitogen-activated protein kinase signaling pathways, respectively. Conclusions BCAA treatment can improve hepatic fibrosis by directly affecting the activated state of hepatic stellate cells through inhibition of the TGF-β signaling pathway. Among BCAA components, leucine and valine mainly abrogated TGF-β-induced activation of HSCs. Our results suggest that BCAA may be used to attenuate the progression of liver fibrosis.

Novel coronavirus (SARS-CoV-2) has caused more than 100 million confirmed cases of human infectious disease (COVID-19) since December 2019 to paralyze our global community. However, only limited access has been allowed to COVID-19 vaccines and antiviral treatment options. Here, we report the efficacy of the anticancer drug pralatrexate against SARS-CoV-2. In Vero and human lung epithelial Calu-3 cells, pralatrexate reduced viral RNA copies of SARS-CoV-2 without detectable cytotoxicity, and viral replication was successfully inhibited in a dose-dependent manner. In a time-to-addition assay, pralatrexate treatment at almost half a day after infection also exhibited inhibitory effects on the replication of SARS-CoV-2 in Calu-3 cells. Taken together, these results suggest the potential of pralatrexate as a drug repurposing COVID-19 remedy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission among non-close contacts is not infrequent. We evaluated the proportion and circumstances of individuals to whom SARS-CoV-2 was transmitted without close contact with the index patient in a nosocomial outbreak in a tertiary care hospital in Korea. From March 2020 to March 2021, there were 36 secondary cases from 14 SARS-CoV-2 infected individuals. Of the 36 secondary cases, 26 (72%) had been classified as close contact and the remaining 10 (28%) were classified as non-close contact. Of the 10 non-close contact, 4 had short conversations with both individuals masked, 4 shared a space without any conversation with both masked, and the remaining 2 entered the space after the index had left. At least one quarter of SARSCoV-2 transmissions occurred among non-close contacts. The definition of close contact for SARS-CoV-2 exposure based on the mode of droplet transmission should be revised to reflect the airborne nature of SARS-CoV-2 transmission.