Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Background: The ionic mechanism underlying Brugada syndrome (BrS) arises from an imbalance in transient outward current flow between the epicardium and endocardium.Previous studies report that artemisinin, originally derived from a Chinese herb for antimalarial use, inhibits the Ito current in canines. In a prior study, we showed the antiarrhythmic effects of artemisinin in BrS wedge preparation models. However, quinidine remains a well-established antiarrhythmic agent for treating BrS. Therefore, this study aims to investigate the efficacy of combining artemisinin with low-dose quinidine in suppressing ventricular tachyarrhythmia (VTA) in experimental canine BrS models. Methods: Transmural pseudo-electrocardiogram and epicardial/endocardial action potential (AP) were recorded from coronary-perfused canine right ventricular wedge preparation. To mimic the BrS model, acetylcholine (3 μM), calcium channel blocker verapamil (1 μM), and Ito agonist NS5806 (6–10 μM) were administered until VTA was induced. Subsequently, lowdose quinidine (1–2 μM) combined with artemisinin (100 μM) was perfused to mitigate VTA.Key parameters, including AP duration, J wave area, notch index, and T wave dispersion, were measured. Results: After administering the provocation agents, all sample models exhibited prominent J waves and VTA. Artemisinin alone (100–150 μM) suppressed VTA and restored the AP dome in all three preparations. Its infusion resulted in reductions in the J wave area and epicardial notch index. Consequently, low-dose quinidine (1–2 μM) did not fully restore the AP dome in all six sample models. However, when combined with additional artemisinin (100 μM), lowdose quinidine effectively suppressed VTA in all six models and restored the AP dome while also decreasing the J wave area and epicardial notch index. Conclusion Low-dose quinidine alone fails to fully alleviate VTA in the BrS wedge model.However, its combination with artemisinin effectively suppresses VTA. Artemisinin may reduce the therapeutic dose of quinidine, potentially minimizing its associated adverse effects.

Objective: It has been 1 year since the start of the worldwide coronavirus disease-19 (COVID-19) pandemic. This study analyzed the indirect effects of COVID-19 on treating patients with non-infectious diseases by comparing the incidence of complicated appendicitis before and after the pandemic. Methods: The target group included patients aged at least 16 years diagnosed with acute appendicitis between February 23 and July 31, 2020. Patients diagnosed during the same period in 2019 were selected as the control group. The differences in the incidence of complicated appendicitis before and after COVID-19 were investigated, and the association with various variables was analyzed using the odds ratios and 95% confidence intervals (CIs). Results: The study included 120 subjects in 2019 (pre-COVID group) and 119 cases in 2020 (post-COVID group). The pre-COVID group included 25 cases (20.8%) of complicated appendicitis, while the post-COVID group included 48 cases (40.3%). The median time from symptom onset to visit (pre-hospital time) increased from 15 to 22 hours, and the median time from the visit to surgery (in-hospital time) increased from 7 to 11 hours. Multivariate regression analysis of the three variables revealed odds ratios (95% CIs) of pre-hospital time, erythrocyte sedimentation rate, and inclusion in the post-COVID group of 1.02 (1.01-1.02), 2.07 (1.11-3.86), and 2.15 (1.12-4.11), respectively. Conclusion The incidence of complicated appendicitis increased after the COVID-19 pandemic. Therefore, a healthcare system that can minimize the delay in treating non-infectious emergency patients is needed.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Ketone bodies produced by sodium-glucose cotransporter 2 (SGLT2) inhibitors can be advantageous, providing an efficient and stable energy source for the brain and muscles. However, in patients with diabetes, ketogenesis induced by SGLT2 inhibitors may be harmful, potentially resulting in severe diabetic ketoacidosis (DKA). During fasting, ketone body production serves as an alternative and efficient energy source for the brain by utilizing stored fat, promoting mental clarity, and reducing dependence on glucose. The concurrent use of SGLT2 inhibitors during perioperative fasting may further elevate the risk of euglycemic DKA. We describe a case of DKA that occurred during perioperative fasting in a patient receiving empagliflozin, an SGLT2 inhibitor. This case underscores the importance of recognizing the potential risk of DKA in patients with diabetes using SGLT2 inhibitors during perioperative fasting.

Cancer immunotherapy is widely used to treat various cancers to augment the weakened host immune response against tumors. Dendritic cells (DCs) are specialized antigen-presenting cells that play dual roles in inducing innate and adaptive immunity. Toxoplasma gondii is a protozoan parasite that exhibits anti-tumor activity against certain types of cancers. However, little is known about the anti-tumor effects of T. gondii or tumor/parasite antigen-pulsed DCs (DC vaccines, DCV) in breast cancer. In this study, C57BL/6 mice were administered E0771 mouse breast cancer cells (Cancer-injected) subcutaneously, T. gondii Me49 cysts orally (TG-injected), or DCs pulsed with breast cancer cell lysate antigen and T. gondii lysate antigens (DCV-injected) intraperitoneally. Tumor size and immunological characteristics were subsequently evaluated. We also evaluated matrix metalloproteinase (MMP)-2 and MMP-9 levels in E0771 mouse breast cancer cells co-cultured with T. gondii or DCs by RT-PCR. The tumor volumes of mice injected with breast cancer cells and antigen-pulsed DCs (Cancer/DCV-injected mice) were similar to those of Cancer-injected mice; however, they were significantly reduced in T. gondii-infected tumor-bearing (TG/Cancer-injected) mice. Moreover, tumor volumes were significantly reduced by adding antigen-pulsed DCs (TG/Cancer/DCV-injected mice) compared to TG/Cancer-injected mice. The levels of IFN-γ, serum IgG2a levels, and CD8+ T cell populations were significantly higher in DCV- and TG-injected mice than in control mice, while no significant differences between Cancer- and Cancer/DCV-injected mice were observed. The levels of IFN-γ, the IgG2a levels, and the percentage of CD8+ T cells were significantly increased in TG/Cancer- and TG/Cancer/DCV-injected mice than in Cancer-injected mice. IFN-γ levels and serum IgG2a levels were further increased in TG/Cancer/DCV-injected mice than in TG/Cancer-injected mice. The MMP-2 and MMP-9 mRNA expressions were significantly decreased in mouse breast cancer cells co-cultured with live T. gondii, T. gondii lysate antigen, or antigen-pulsed DCs (DCV) but not in inactivated DCs. These results indicate that T. gondii induces anti-tumor effects in breast cancer-bearing mice through the induction of strong Th1 immune responses, but not in antigen-pulsed DCs alone. The addition of antigen-pulsed DCs further augments the anti-tumor effects of T. gondii.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Ketone bodies produced by sodium-glucose cotransporter 2 (SGLT2) inhibitors can be advantageous, providing an efficient and stable energy source for the brain and muscles. However, in patients with diabetes, ketogenesis induced by SGLT2 inhibitors may be harmful, potentially resulting in severe diabetic ketoacidosis (DKA). During fasting, ketone body production serves as an alternative and efficient energy source for the brain by utilizing stored fat, promoting mental clarity, and reducing dependence on glucose. The concurrent use of SGLT2 inhibitors during perioperative fasting may further elevate the risk of euglycemic DKA. We describe a case of DKA that occurred during perioperative fasting in a patient receiving empagliflozin, an SGLT2 inhibitor. This case underscores the importance of recognizing the potential risk of DKA in patients with diabetes using SGLT2 inhibitors during perioperative fasting.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Cancer immunotherapy is widely used to treat various cancers to augment the weakened host immune response against tumors. Dendritic cells (DCs) are specialized antigen-presenting cells that play dual roles in inducing innate and adaptive immunity. Toxoplasma gondii is a protozoan parasite that exhibits anti-tumor activity against certain types of cancers. However, little is known about the anti-tumor effects of T. gondii or tumor/parasite antigen-pulsed DCs (DC vaccines, DCV) in breast cancer. In this study, C57BL/6 mice were administered E0771 mouse breast cancer cells (Cancer-injected) subcutaneously, T. gondii Me49 cysts orally (TG-injected), or DCs pulsed with breast cancer cell lysate antigen and T. gondii lysate antigens (DCV-injected) intraperitoneally. Tumor size and immunological characteristics were subsequently evaluated. We also evaluated matrix metalloproteinase (MMP)-2 and MMP-9 levels in E0771 mouse breast cancer cells co-cultured with T. gondii or DCs by RT-PCR. The tumor volumes of mice injected with breast cancer cells and antigen-pulsed DCs (Cancer/DCV-injected mice) were similar to those of Cancer-injected mice; however, they were significantly reduced in T. gondii-infected tumor-bearing (TG/Cancer-injected) mice. Moreover, tumor volumes were significantly reduced by adding antigen-pulsed DCs (TG/Cancer/DCV-injected mice) compared to TG/Cancer-injected mice. The levels of IFN-γ, serum IgG2a levels, and CD8+ T cell populations were significantly higher in DCV- and TG-injected mice than in control mice, while no significant differences between Cancer- and Cancer/DCV-injected mice were observed. The levels of IFN-γ, the IgG2a levels, and the percentage of CD8+ T cells were significantly increased in TG/Cancer- and TG/Cancer/DCV-injected mice than in Cancer-injected mice. IFN-γ levels and serum IgG2a levels were further increased in TG/Cancer/DCV-injected mice than in TG/Cancer-injected mice. The MMP-2 and MMP-9 mRNA expressions were significantly decreased in mouse breast cancer cells co-cultured with live T. gondii, T. gondii lysate antigen, or antigen-pulsed DCs (DCV) but not in inactivated DCs. These results indicate that T. gondii induces anti-tumor effects in breast cancer-bearing mice through the induction of strong Th1 immune responses, but not in antigen-pulsed DCs alone. The addition of antigen-pulsed DCs further augments the anti-tumor effects of T. gondii.