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: 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: 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: 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: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Background/Aims: Palliative chemotherapy (PC) is not standardized for patients with advanced ampulla of Vater adenocarcinoma (AA). This multicenter, retrospective study evaluated first-line PC outcomes in patients with AA. Methods: Patients diagnosed with AA between January 2010 and December 2020 who underwent PC were enrolled from 10 institutions. Overall survival (OS) and progression-free survival (PFS) according to the chemotherapy regimen were analyzed. Results: Of 255 patients (mean age, 64.0±10.0 years; male, 57.6%), 14 (5.5%) had locally advanced AA and 241 (94.5%) had metastatic AA. Gemcitabine plus cisplatin (GP) was administered as first-line chemotherapy to 192 patients (75.3%), whereas capecitabine plus oxaliplatin (CAPOX) was administered to 39 patients (15.3%). The median OS of all patients was 19.8 months (95% confidence interval [CI], 17.3 to 22.3), and that of patients who received GP and CAPOX was 20.4 months (95% CI, 17.2 to 23.6) and 16.0 months (95% CI, 11.2 to 20.7), respectively. The median PFS of GP and CAPOX patients were 8.4 months (95% CI, 7.1 to 9.7) and 5.1 months (95% CI, 2.5 to 7.8), respectively. PC for AA demonstrated improved median outcomes in both OS and PFS compared to conventional bile duct cancers that included AA. Conclusions While previous studies have shown mixed prognostic outcomes when AA was analyzed together with other biliary tract cancers, our study unveils a distinct clinical prognosis specific to AA on a large scale with systemic anticancer therapy. These findings suggest that AA is a distinct type of tumor, different from other biliary tract cancers, and AA itself could be expected to have a favorable response to PC.

Prime editing (PE) is a recently developed genome-editing technique that enables versatile editing. Despite its flexibility and potential, applying PE in human induced pluripotent stem cells (hiPSCs) has not been extensively addressed. Genetic disease models using patient-derived hiPSCs have been used to study mechanisms and drug efficacy. However, genetic differences between patient and control cells have been attributed to the inaccuracy of the disease model, highlighting the significance of isogenic hiPSC models. Hereditary hemorrhagic telangiectasia 1 (HHT1) is a genetic disorder caused by an autosomal dominant mutation in endoglin (ENG). Although previous HHT models using mice and HUVEC have been used, these models did not sufficiently elucidate the relationship between the genotype and disease phenotype in HHT, demanding more clinically relevant models that reflect human genetics. Therefore, in this study, we used PE to propose a method for establishing an isogenic hiPSC line. Clinically reported target mutation in ENG was selected, and a strategy for PE was designed. After cloning the engineered PE guide RNA, hiPSCs were nucleofected along with PEmax and hMLH1dn plasmids. As a result, hiPSC clones with the intended mutation were obtained, which showed no changes in pluripotency or genetic integrity. Furthermore, introducing the ENG mutation increased the expression of proangiogenic markers during endothelial organoid differentiation. Consequently, our results suggest the potential of PE as a toolkit for establishing isogenic lines, enabling disease modeling based on hiPSC-derived disease-related cells or organoids.This approach is expected to stimulate mechanistic and therapeutic studies on genetic diseases.

Purpose: Predicting improvements in voiding symptoms following deobstructive surgery for male lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) is challenging when detrusor contractility is impaired. This study aimed to develop an artificial intelligence model that predicts symptom improvement after holmium laser enucleation of the prostate (HoLEP), focusing on changes in maximum flow rate (MFR) and voiding efficiency (VE) 1-month postsurgery. Methods: We reviewed 1,933 patients who underwent HoLEP at Samsung Medical Center from July 2008 to January 2024. The study employed a deep neural network (DNN) for multiclass classification to predict changes in MFR and VE, each divided into 3 categories. For comparison, additional machine learning (ML) models such as extreme gradient boosting, random forest classification, and support vector machine were utilized. To address class imbalance, we applied the least squares method and multitask learning. Results: A total of 1,142 patients with complete data were included in the study, with 992 allocated for model training and 150 for external validation. In predicting MFR, the DNN achieved a microaverage area under the receiver operating characteristic curve (AUC) of 0.884±0.006, sensitivity of 0.783±0.020, and specificity of 0.891±0.010. For VE prediction, the microaverage AUC was 0.817±0.007, with sensitivity and specificity values of 0.660±0.014 and 0.830±0.007, respectively. These results indicate that the DNN's predictive performance was superior to that of other ML models. Conclusions The DNN model provides detailed and accurate predictions for recovery after HoLEP, providing valuable insights for clinicians managing patients with LUTS/BPH.

Background: Medullary thyroid carcinoma (MTC) has a poorer prognosis than differentiated thyroid cancers; however, comprehensive data on the long-term outcomes of MTC remain scarce. This study investigated the extended clinical outcomes of MTC and aimed to identify prognostic factors. Methods: Patients diagnosed with MTC between 1980 and 2020 were retrospectively reviewed. Their clinical characteristics, longterm clinical outcomes, and prognostic factors for recurrence and mortality were analyzed. Results: The study included 226 patients (144 women, 82 men). The disease-specific survival (DSS) rates for all MTC patients at 5-, 10-, 20-, and 30-year intervals were 92.7%, 89.4%, 74.3%, and 68.1%, respectively. The recurrence-free survival (RFS) rates were 71.1%, 56.1%, 40.2%, and 32.1% at these intervals. DSS was comparable between the groups from 1980–2009 and 2010–2020 (P=0.995); however, the 1980–2009 group had significantly lower RFS rates (P=0.031). The 2010–2020 group exhibited greater extents of surgical and lymph node dissection (P=0.003) and smaller tumors (P=0.003). Multivariate analysis identified extrathyroidal extension as the strongest prognostic factor for both RFS and DSS. Age >55 years and tumor size of ≥2 cm were also significant prognostic factors for DSS, while hereditary disease and lymph node metastasis were significant for RFS. Survival analysis after propensity-score matching of rearranged during transfection (RET)-negative and non-screened RET-positive groups showed comparable DSS but longer RFS in the RET-negative group. Conclusion Extrathyroidal extension was identified as the strongest prognostic factor for RFS and DSS. Older age and larger tumor size were associated with decreased DSS, while RET mutation and lymph node metastasis significantly impacted RFS.

Non-gonococcal sexually transmitted infections (STIs) include chlamydia, syphilis, and chancroids. Chlamydia is the most common STI caused by Chlamydia trachomatis and is mainly transmitted through sexual intercourse or vertical transmission at birth. Although symptoms are mostly absent or mild, untreated chlamydial infections in females can lead to pelvic inflammatory disease, chronic pelvic pain, and infertility due to the narrowing of fallopian tubes. Syphilis is caused by Treponema pallidum and is divided into phase I, phase II, latent syphilis, and phase III. The incidence of syphilis, including congenital syphilis, has significantly increased in the United States in recent years. The chronic status of this disease can significantly increase morbidity and potentially affect almost all body organs, which, in rare cases, can lead to death. Additionally, untreated maternal syphilis can lead to fetal death and fatal congenital infections in newborns. Chancroid is an STI caused by Haemophilus ducreyi, and its prevalence is gradually decreasing in Korea and worldwide. The symptoms include shallow genital ulcers with suppurative granulomatous inflammation and tender inguinal lymphadenopathy. Chancroids can be differentiated from syphilitic chancres based on their appearance. In contrast to painless chancres, chancroids are painful. Ureaplasma urealyticum, Ureaplasma parvum, and Mycoplasma hominis are considered symbiotic bacteria.Infections caused by these bacteria are usually not considered STIs and do not require treatment unless they are suspected of being associated with infertility. This article presents the 2023 Korean STI guidelines for non-gonococcal bacterial infections.