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.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Background: A nationwide Rehabilitation at Home Care Pilot Program for patients undergoing lower extremity orthopedic surgeries has been ongoing since 2020. The program was designed to improve clinical outcomes through early mobilization and rehabilitation after discharge. This study aimed to analyze the interim data to assess its effectiveness and suggest improvements, particularly for older patients who are more vulnerable compared to younger patients. Methods: We analyzed the data of 872 patients from seven hospitals. Patients were divided into an older-age group (OG; ≥60 years) and younger-age group (YG; <60 years). The Berg Balance Scale (BBS) and Numeric Rating Scale (NRS) scores for pain were the main outcomes. Results: Participants were categorized into OG (n=801) and YG (n=71). The most common surgeries were knee joint replacement (63.7%) in OG and hip joint replacement in YG (77.5%). It took more days to enroll in the pilot program in OG (4.4 days) than YG (3.2 days). OG showed less improvement in BBS than YG for all surgeries (23.3 vs. 31.9) and hip joint surgery (19.8 vs. 33.5). In patients with hip joint replacement in OG, those with a higher number of comorbidities (≥3) showed less BBS improvement than those with fewer comorbidities (<3). In the pain domain, NRS scores decreased in both groups. Conclusion The postoperative rehabilitation education program appeared to be effective in improving physical function and reducing pain severity, though the improvement was less obvious in older patients who may require a more comprehensive approach compared to younger patients.

Objective: To compare coronary artery dimension-adjusted subtended myocardial mass between patients with hypertrophic cardiomyopathy (HCM) and a normal population without detectable atherosclerosis, and between HCM patients with and without chest pain. Materials and Methods: Twenty-five patients with HCM but no detectable atherosclerosis on coronary computed tomography angiography (CCTA) were included in the study. This group comprised 14 patients with chest pain and 11 patients without chest pain. They were matched with 25 healthy participants based on sex, age, coronary dominance pattern, and body surface area. The minimal lumen area (MLA) and subtended myocardial volume (V sub) were assessed in the left main (LM), proximal left anterior descending (pLAD), proximal left circumflex (pLCx), and proximal right coronary (pRCA) arteries. Additionally, an index of the subtended myocardial mass adjusted for the MLA, calculated as V sub/MLA 2 , was determined. Results: MLA was significantly larger in patients with HCM compared to the control group in LM (20.93 ± 6.31 mm 2 vs.15.24 ± 3.90 mm 2 , P< 0.001), pLAD (14.28 ± 3.55 mm 2 vs. 11.36 ± 2.07 mm 2, P = 0.001), pLCx (10.94 ± 3.60 mm 2 vs. 9.15 ± 2.93 mm 2 , P = 0.045), and pRCA (13.41 ± 4.85 mm 2 vs. 11.22 ± 3.20 mm 2 , P = 0.018). Despite an increase in coronary luminal area, patients with HCM exhibited significantly higher V sub/MLA 2 compared to the control group in both the pLAD (403.56 ± 200.35 mm -1 vs. 241.70 ± 85.87 mm -1 , P < 0.001) and the pRCA (186.06 ± 95.07 mm -1 vs. 125.07 ± 70.18 mm -1 , P= 0.007). V sub/MLA 2 was significantly elevated in patients with chest pain compared to those without in the pLAD (473.75 ± 227.38 mm -1 vs. 314.24 ± 110.74 mm -1 , P = 0.018) and the pLCx (417.04 ± 182.65 mm -1 vs. 275.29 ± 112.97 mm -1 , P = 0.044). Conclusion CCTA-derived V sub/MLA 2 may more accurately reflect the balance between myocardial blood supply and demand, offering insights into the occurrence of demand angina in patients with HCM without obstructive coronary artery disease.

Objective: To compare coronary artery dimension-adjusted subtended myocardial mass between patients with hypertrophic cardiomyopathy (HCM) and a normal population without detectable atherosclerosis, and between HCM patients with and without chest pain. Materials and Methods: Twenty-five patients with HCM but no detectable atherosclerosis on coronary computed tomography angiography (CCTA) were included in the study. This group comprised 14 patients with chest pain and 11 patients without chest pain. They were matched with 25 healthy participants based on sex, age, coronary dominance pattern, and body surface area. The minimal lumen area (MLA) and subtended myocardial volume (V sub) were assessed in the left main (LM), proximal left anterior descending (pLAD), proximal left circumflex (pLCx), and proximal right coronary (pRCA) arteries. Additionally, an index of the subtended myocardial mass adjusted for the MLA, calculated as V sub/MLA 2 , was determined. Results: MLA was significantly larger in patients with HCM compared to the control group in LM (20.93 ± 6.31 mm 2 vs.15.24 ± 3.90 mm 2 , P< 0.001), pLAD (14.28 ± 3.55 mm 2 vs. 11.36 ± 2.07 mm 2, P = 0.001), pLCx (10.94 ± 3.60 mm 2 vs. 9.15 ± 2.93 mm 2 , P = 0.045), and pRCA (13.41 ± 4.85 mm 2 vs. 11.22 ± 3.20 mm 2 , P = 0.018). Despite an increase in coronary luminal area, patients with HCM exhibited significantly higher V sub/MLA 2 compared to the control group in both the pLAD (403.56 ± 200.35 mm -1 vs. 241.70 ± 85.87 mm -1 , P < 0.001) and the pRCA (186.06 ± 95.07 mm -1 vs. 125.07 ± 70.18 mm -1 , P= 0.007). V sub/MLA 2 was significantly elevated in patients with chest pain compared to those without in the pLAD (473.75 ± 227.38 mm -1 vs. 314.24 ± 110.74 mm -1 , P = 0.018) and the pLCx (417.04 ± 182.65 mm -1 vs. 275.29 ± 112.97 mm -1 , P = 0.044). Conclusion CCTA-derived V sub/MLA 2 may more accurately reflect the balance between myocardial blood supply and demand, offering insights into the occurrence of demand angina in patients with HCM without obstructive coronary artery disease.

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.

Objective: To compare coronary artery dimension-adjusted subtended myocardial mass between patients with hypertrophic cardiomyopathy (HCM) and a normal population without detectable atherosclerosis, and between HCM patients with and without chest pain. Materials and Methods: Twenty-five patients with HCM but no detectable atherosclerosis on coronary computed tomography angiography (CCTA) were included in the study. This group comprised 14 patients with chest pain and 11 patients without chest pain. They were matched with 25 healthy participants based on sex, age, coronary dominance pattern, and body surface area. The minimal lumen area (MLA) and subtended myocardial volume (V sub) were assessed in the left main (LM), proximal left anterior descending (pLAD), proximal left circumflex (pLCx), and proximal right coronary (pRCA) arteries. Additionally, an index of the subtended myocardial mass adjusted for the MLA, calculated as V sub/MLA 2 , was determined. Results: MLA was significantly larger in patients with HCM compared to the control group in LM (20.93 ± 6.31 mm 2 vs.15.24 ± 3.90 mm 2 , P< 0.001), pLAD (14.28 ± 3.55 mm 2 vs. 11.36 ± 2.07 mm 2, P = 0.001), pLCx (10.94 ± 3.60 mm 2 vs. 9.15 ± 2.93 mm 2 , P = 0.045), and pRCA (13.41 ± 4.85 mm 2 vs. 11.22 ± 3.20 mm 2 , P = 0.018). Despite an increase in coronary luminal area, patients with HCM exhibited significantly higher V sub/MLA 2 compared to the control group in both the pLAD (403.56 ± 200.35 mm -1 vs. 241.70 ± 85.87 mm -1 , P < 0.001) and the pRCA (186.06 ± 95.07 mm -1 vs. 125.07 ± 70.18 mm -1 , P= 0.007). V sub/MLA 2 was significantly elevated in patients with chest pain compared to those without in the pLAD (473.75 ± 227.38 mm -1 vs. 314.24 ± 110.74 mm -1 , P = 0.018) and the pLCx (417.04 ± 182.65 mm -1 vs. 275.29 ± 112.97 mm -1 , P = 0.044). Conclusion CCTA-derived V sub/MLA 2 may more accurately reflect the balance between myocardial blood supply and demand, offering insights into the occurrence of demand angina in patients with HCM without obstructive coronary artery disease.

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.

While advances in cancer treatment have led to improved survival rates, cancer survivors are at a significant risk of developing atherosclerotic cardiovascular disease (ASCVD).This review examines the risk, diagnosis, and prevention of ASCVD in this population.Cancer survivors, especially those diagnosed with certain types, face a significantly higher risk of developing ASCVD than the general population. We introduce the “triad model” to explain this increased risk of ASCVD among cancer patients. This model includes three interconnected components: common catalysts, cancer influence, and treatment impact.The factors contributing to this model are the shared risk factors between cancer and ASCVD, such as smoking, obesity, and systemic inflammation; the direct effects of cancer on cardiovascular health through chronic systemic inflammation and endothelial damage;and the significant effects of anticancer treatments, including chemotherapy and radiation, which can worsen cardiovascular complications and hasten the progression of ASCVD.Furthermore, cancer survivors are at a higher risk of developing and dying from ASCVD, highlighting the necessity for tailored guidelines and strategies for ASCVD prevention and management in this population. The review explores the utility of diagnostic tools, such as coronary artery calcium scoring, in predicting and managing ASCVD risk. It also emphasizes the importance of prevention strategies that include regular cardiovascular monitoring and lifestyle modifications. Finally, the relationship between cancer survival and cardiovascular health highlights the importance of integrated and comprehensive care approaches.Continued research, the development of prediction models, and specific preventative strategies are essential to improve cancer survivors’ overall health outcomes.