Background: This study compared the costs associated with transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) in Korea by utilizing the National Health Insurance Service database. Methods: Between June 2015 and May 2019, 1,468 patients underwent primary isolated transfemoral TAVI, while 2,835 patients received primary isolated SAVR with a bioprosthesis. We assessed the costs of index hospitalization and subsequent healthcare utilization, categorizing the cohort into 6 age subgroups: <70, 70–74, 75–79, 80–84, 85–89, and ≥90 years. The median follow-up periods were 2.5 and 3.0 years in the TAVI and SAVR groups, respectively. Results: The index hospitalization costs were 41.0 million Korean won (KRW) (interquartile range [IQR], 39.1–44.7) for the TAVI group and 24.6 million KRW (IQR, 21.3–30.2) for the SAVR group (p<0.001). The TAVI group exhibited relatively constant index hospitalization costs across different age subgroups. In contrast, the SAVR group showed increasing index hospitalization costs with advancing age. The healthcare utilization costs were 5.7 million KRW per year (IQR, 3.3–14.2) for the TAVI group and 4.0 million KRW per year (IQR, 2.2–9.0) for the SAVR group (p<0.001). Healthcare utilization costs were higher in the TAVI group than in the SAVR group for the age subgroups of <70, 70–74, and 75–79 years, and were comparable in the age subgroups of 80–84, 85–89, and ≥90 years. Conclusion TAVI had much higher index hospitalization costs than SAVR. Additionally, the overall healthcare utilization costs post-discharge for TAVI were also marginally higher than those for SAVR in younger age subgroups.

Background: This study compared the costs associated with transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) in Korea by utilizing the National Health Insurance Service database. Methods: Between June 2015 and May 2019, 1,468 patients underwent primary isolated transfemoral TAVI, while 2,835 patients received primary isolated SAVR with a bioprosthesis. We assessed the costs of index hospitalization and subsequent healthcare utilization, categorizing the cohort into 6 age subgroups: <70, 70–74, 75–79, 80–84, 85–89, and ≥90 years. The median follow-up periods were 2.5 and 3.0 years in the TAVI and SAVR groups, respectively. Results: The index hospitalization costs were 41.0 million Korean won (KRW) (interquartile range [IQR], 39.1–44.7) for the TAVI group and 24.6 million KRW (IQR, 21.3–30.2) for the SAVR group (p<0.001). The TAVI group exhibited relatively constant index hospitalization costs across different age subgroups. In contrast, the SAVR group showed increasing index hospitalization costs with advancing age. The healthcare utilization costs were 5.7 million KRW per year (IQR, 3.3–14.2) for the TAVI group and 4.0 million KRW per year (IQR, 2.2–9.0) for the SAVR group (p<0.001). Healthcare utilization costs were higher in the TAVI group than in the SAVR group for the age subgroups of <70, 70–74, and 75–79 years, and were comparable in the age subgroups of 80–84, 85–89, and ≥90 years. Conclusion TAVI had much higher index hospitalization costs than SAVR. Additionally, the overall healthcare utilization costs post-discharge for TAVI were also marginally higher than those for SAVR in younger age subgroups.

Background: This study compared the costs associated with transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) in Korea by utilizing the National Health Insurance Service database. Methods: Between June 2015 and May 2019, 1,468 patients underwent primary isolated transfemoral TAVI, while 2,835 patients received primary isolated SAVR with a bioprosthesis. We assessed the costs of index hospitalization and subsequent healthcare utilization, categorizing the cohort into 6 age subgroups: <70, 70–74, 75–79, 80–84, 85–89, and ≥90 years. The median follow-up periods were 2.5 and 3.0 years in the TAVI and SAVR groups, respectively. Results: The index hospitalization costs were 41.0 million Korean won (KRW) (interquartile range [IQR], 39.1–44.7) for the TAVI group and 24.6 million KRW (IQR, 21.3–30.2) for the SAVR group (p<0.001). The TAVI group exhibited relatively constant index hospitalization costs across different age subgroups. In contrast, the SAVR group showed increasing index hospitalization costs with advancing age. The healthcare utilization costs were 5.7 million KRW per year (IQR, 3.3–14.2) for the TAVI group and 4.0 million KRW per year (IQR, 2.2–9.0) for the SAVR group (p<0.001). Healthcare utilization costs were higher in the TAVI group than in the SAVR group for the age subgroups of <70, 70–74, and 75–79 years, and were comparable in the age subgroups of 80–84, 85–89, and ≥90 years. Conclusion TAVI had much higher index hospitalization costs than SAVR. Additionally, the overall healthcare utilization costs post-discharge for TAVI were also marginally higher than those for SAVR in younger age subgroups.

Objective: Atomoxetine and fluoxetine are psychopharmacologic agents associated with loss of appetite and weight. Adenosine monophosphate-activated protein kinase (AMPK) is the cellular energy sensor that regulate metabolism and energy, being activated by fasting and inhibited by feeding in the hypothalamus. Methods: Human brain cell lines (SH-SY5Y and U-87 MG cells) were used to study the outcome of atomoxetine and fluoxetine treatment in the activity of AMPK-acetyl-CoA carboxylase (ACC)- carnitine palmitoyl transferase 1 (CPT1) pathway and upstream regulation by calcium/calmodulin-dependent kinase kinase β (CaMKKβ) using immunoblotting and CPT1 enzymatic activity measures. Results: Phosphorylation of AMPK and ACC increased significantly after atomoxetine and fluoxetine treatment in the first 30–60 minutes of treatment in the two cell lines. Activation of AMPK and inhibition of ACC was associated with an increase by 5-fold of mitochondrial CPT1 activity. Although the neuronal isoform CPT1C could be detected by immunoblotting, activity was not changed by the drug treatments. In addition, the increase in phospho-AMPK and phospho-ACC expression induced by atomoxetine was abolished by treatment with STO-609, a CaMKKβ inhibitor, indicating that AMPK-ACC-CPT1 pathway is activated through CaMKKβ phosphorylation. Conclusion These findings indicate that at the cellular level atomoxetine and fluoxetine treatments may activate AMPK-ACC-CPT1 pathways through CaMKKβ in human SH-SY5Y and U-87 MG cells.

Background/Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is categorized into three subtypes: overweight/obese (OW), leanormal weight with metabolic abnormalities, and diabetes mellitus (DM). We investigated whether fibrotic burden in liver differs across subtypes of MAFLD patients. Methods: This cross-sectional multicenter study was done in cohorts of subjects who underwent a comprehensive medical health checkup between January 2014 and December 2020. A total of 42,651 patients with ultrasound-diagnosed fatty liver were included. Patients were classified as no MAFLD, OW-MAFLD, lean-MAFLD, and DM-MAFLD. Advanced liver fibrosis was defined based on the nonalcoholic fatty liver disease fibrosis score (NFS) or fibrosis-4 (FIB-4) index. Results: The mean age of the patients was 50.0 years, and 74.1% were male. The proportion of patients with NFS-defined advanced liver fibrosis was the highest in DM-MAFLD (6.6%), followed by OW-MAFLD (2.0%), lean-MAFLD (1.3%), and no MAFLD (0.2%). The proportion of patients with FIB-4-defined advanced liver fibrosis was the highest in DM-MAFLD (8.6%), followed by lean-MAFLD (3.9%), OW-MAFLD (3.0%), and no MAFLD (2.0%). With the no MAFLD group as reference, the adjusted odds ratios (95% confidence intervals) for NFS-defined advanced liver fibrosis were 4.46 (2.09 to 9.51), 2.81 (1.12 to 6.39), and 9.52 (4.46 to 20.36) in OW-MAFLD, leanMAFLD, and DM-MAFLD, respectively, and the adjusted odds ratios for FIB-4-defined advanced liver fibrosis were 1.03 (0.78 to 1.36), 1.14 (0.82 to 1.57), and 1.97 (1.48 to 2.62) in OW-MAFLD, lean-MAFLD, and DM-MAFLD. Conclusions Fibrotic burden in the liver differs across MAFLD subtypes. Optimized surveillance strategies and therapeutic options might be needed for different MAFLD subtypes.

Background/Aims: AT-rich interactive domain 1A (ARID1A) is frequently mutated in gastric cancer (GC), especially Epstein-Barr virus (EBV)-associated and microsatellite instability high GC.The loss of ARID1A expression has been reported as a poor prognostic marker in GC. However, the relationships between ARID1A alteration and EBV-associated and microsatellite instability high GC, which are known to have a favorable prognosis, has hampered proper evaluation of the prognostic significance of ARID1A expression in GC. We aimed to analyze the true prognostic significance of ARID1A expression by correcting confounding variables. Methods: We evaluated the ARID1A expression in a large series (n=1,032) of advanced GC and analyzed the relationships between expression pattern and variable parameters, including clinicopathologic factors, key molecular features such as EBV-positivity, mismatch repair protein deficiency, and expression of p53 and several receptor tyrosine kinases including human epidermal growth factor receptor 2, epidermal growth factor receptor, and mesenchymal-epithelial transition factor. Survival analysis of the molecular subtypes was done according to the ARID1A expression patterns. Results: Loss of ARID1A expression was found in 52.5% (53/101) of mutL homolog 1 (MLH1)-deficient and 35.8% (24/67) of EBV-positive GCs, compared with only 9.6% (82/864) of the MLH1-proficient and EBV-negative group (p<0.001). The loss of ARID1A expression was associated only with MLH1 deficiency and EBV positivity. On survival analysis, the loss of ARID1A expression was associated with worse prognosis only in MLH1-proficient and EBV-negative GC. Multivariate analysis revealed that both loss of ARID1A and decreased ARID1A expression were independent worse prognostic factors in patients with advanced GC. Conclusions Only in MLH1-proficient and EBV-negative GC, the loss of ARID1A expression is related to poorer prognosis.

Purpose: Gastric cancer (GC) is among the most prevalent and fatal cancers worldwide.National cancer screening programs in countries with high incidences of this disease provide medical aid beneficiaries with free-of-charge screening involving upper endoscopy to detect early-stage GC. However, the coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to routine healthcare access. Thus, this study aimed to assess the impact of COVID-19 on the diagnosis, overall incidence, and stage distribution of GC. Materials and Methods: We identified patients in our hospital cancer registry who were diagnosed with GC between January 2018 and December 2021 and compared the cancer stage at diagnosis before and during the COVID-19 pandemic. Subgroup analyses were conducted according to age and sex. The years 2018 and 2019 were defined as the “before COVID” period, and the years 2020 and 2021 as the “during COVID” period. Results: Overall, 10,875 patients were evaluated; 6,535 and 4,340 patients were diagnosed before and during the COVID-19 period, respectively. The number of diagnoses was lower during the COVID-19 pandemic (189 patients/month vs. 264 patients/month) than before it.Notably, the proportion of patients with stages 3 or 4 GC in 2021 was higher among men and patients aged ≥40 years. Conclusions During the COVID-19 pandemic, the overall number of GC diagnoses decreased significantly in a single institute. Moreover, GCs were in more advanced stages at the time of diagnosis. Further studies are required to elucidate the relationship between the COVID-19 pandemic and the delay in the detection of GC worldwide.

Background: In the era of transcatheter aortic valve implantation, this study was conducted to investigate the current trend of aortic valve procedures in Korea and to evaluate the early and mid-term outcomes of isolated surgical aortic valve replacement (SAVR) using bioprosthetic valves in contemporary Korea. Methods: Contemporary outcomes of isolated bioprosthetic SAVR in Korea were analyzed using the datasets on a multicenter basis. Patients who underwent isolated SAVR using bioprostheses from June 2015 to May 2019 were included, and those with concomitant cardiac procedures, SAVR with mechanical valve, or SAVR for infective endocarditis were excluded. A total of 456 patients from 4 large-volume centers were enrolled in this study.Median follow-up duration was 43.4 months. Early postoperative outcomes, mid-term clinical outcomes, and echocardiographic outcomes were evaluated. Results: Mean age of the patients was 73.1 ± 7.3 years, and EuroSCORE II was 2.23 ± 2.09. The cardiopulmonary bypass time and aortic cross-clamp times were median 106 and 76 minutes, respectively. SAVR was performed with full median sternotomy (81.8%), right thoracotomy (14.7%), or partial sternotomy (3.5%). Operative mortality was 1.8%. The incidences of stroke and permanent pacemaker implantation were 1.1% and 1.1%, respectively. Paravalvular regurgitation ≥ mild was detected in 2.6% of the patients. Cumulative incidence of all-cause mortality at 5 years was 13.0%. Cumulative incidences of cardiovascular mortality and bioprosthetic valve dysfunction at 5 years were 7.6% and 6.8%, respectively. Conclusion The most recent data for isolated SAVR using bioprostheses in Korea resulted in excellent early and mid-term outcomes in a multicenter study.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.