Objectives: This study investigated changes in toothbrushing in adolescents in response to public health policy changes during coronavirus disease 2019 (COVID-19) focusing on behavioral trends before, during, and after policy enforcement according to socio-demographic subgroups. Methods: Data from the Korean Youth Risk Behavior Survey (2018–2024) were divided into 3 periods: before (2018–2019), during (2020–2022), and after (2023–2024) the implementation of COVID-19 school restrictions. A total of 354 943 middle and high school students were included. The primary outcome variable was self-reported toothbrushing after lunch at school. Multivariable logistic regression was conducted, adjusting for confounders such as sex, academic performance, school level, school type, handwashing, and oral health status (toothache and gum bleeding). Results: The compliance rate for toothbrushing declined significantly during the restriction period across all groups. It varied by sex, school type, school level, health-related behaviors (drinking, smoking, handwashing), and oral health status. Female students, middle schoolers, students in single-sex schools, non-smokers, and those practicing hand hygiene showed higher compliance. After restrictions were lifted, toothbrushing rates improved but remained lower than pre-pandemic levels. Recovery of the toothbrushing rate was observed in most groups, particularly among female students, high schoolers, and those with positive health-related behaviors. However, academic performance and oral health status were not significantly associated with recovery rate in adjusted analyses. Conclusions This study highlights that adolescents’ health behaviors are highly sensitive to environmental and policy changes. Variations in compliance and recovery rates underscore the need for adolescent-centered policies that account for both compliance and recovery, especially during crises such as pandemics.

Purpose: This study aimed to report the real-world outcomes of intravesical gemcitabine for bacillus Calmette–Guérin (BCG)–unresponsive, high-risk, non–muscle-invasive bladder cancer (HR-NMIBC) in Korean patients who were unable or unwilling to undergo radical cystectomy (RC). Materials and Methods: This retrospective study included 131 patients (median age, 69 years; 88.5% men) treated with intravesical gemcitabine for BCG-unresponsive HR-NMIBC at nine centers between May 2019 and April 2022. The primary endpoint was 1-year recurrence-free survival (RFS). The secondary endpoints included factors influencing RFS, progression-free survival (PFS), cystectomy- free survival, cancer-specific survival (CSS), overall survival (OS), and safety. Survival analysis was performed using the Kaplan-Meier method, and risk factors for recurrence were assessed using Cox regression models. Results: Patients were followed up for a median duration of 25 months, with carcinoma in situ (CIS) in 41.9% of the patients. The 1-year and 2-year RFS rates were 68% and 42%, while the 1-year and 2-year PFS rates were 87% and 77%, respectively. No significant factors influencing RFS were identified. Seventeen patients underwent RC during a median follow-up of 16 months, with the condition in three patients progressing to muscle-invasive disease on final pathological analysis. The 2-year CSS and OS rates were 98% and 97%, respectively. Intravesical gemcitabine was well-tolerated, with only seven patients (5.3%) unable to complete the full induction course. Conclusion Our research highlights the potential of intravesical gemcitabine as a viable bladder-sparing treatment option for BCG-unresponsive HR-NMIBC, providing real-world evidence on its safety, efficacy, and tolerability.

Purpose: Radiotherapy (RT) remains a cornerstone of curative treatment for localized and locally advanced prostate cancer. However, dose escalation to improve tumor control is often constrained by the proximity of the rectum, which increases the risk of gastrointestinal (GI) and genitourinary toxicities. Biodegradable rectal spacers inserted between the prostate and rectum have emerged as an effective approach to reduce rectal radiation exposure. This guideline provides evidence-based recommendations on indications, contraindications, procedural standards, and clinical management for biodegradable rectal spacer insertion during prostate cancer RT. Materials and Methods: This guideline was developed by a multidisciplinary expert panel through a systematic review of the literature, analysis of international guidelines (National Comprehensive Cancer Network, European Association of Urology, American Society for Radiation Oncology), and expert consensus among radiation oncologists, radiologists, and urologists with clinical experience in spacer insertion. The strength of each recommendation and the level of evidence were classified according to the modified GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system. Results: Spacer insertion is conditionally recommended (Grade C, Level I) for patients receiving definitive external-beam RT without rectal invasion. It reduces the high-dose rectal irradiation volume (V70–75) by >50%, decreases acute GI toxicity, and helps maintain bowel-related quality of life. However, the benefit for late severe toxicity (grade 2 or higher) remains debated in recent meta-analyses. Contraindications include rectal invasion, anatomical inaccessibility, infection, and material hypersensitivity. Procedures should be performed under local anesthesia in a sterile environment by trained physicians. Short-course antibiotics and simulator-based training, including completion of multiple supervised cases, are advised. Conclusion Biodegradable rectal spacer insertion is clinically validated and effective in reducing acute rectal toxicity. Although pivotal trials demonstrated a favorable procedural safety profile, real-world postmarket data include reports of rare but severe procedural complications. This guideline provides standardized recommendations tailored to Korean clinical practice while remaining consistent with international standards, emphasizing the importance of operator training and careful patient selection.

Purpose: Due to chronic toxicity, tacrolimus-sparing is an important issue in kidney transplant recipients (KTRs). Several studies have shown that bisphosphonate use is associated with favorable graft outcomes in KTRs. We investigated whether the association between tacrolimus trough levels (TTLs) and graft outcomes differed according to bisphosphonate use in KTRs. Materials and Methods: We conducted a retrospective study encompassing 1441 KTRs who were administered tacrolimus-based immunosuppressants. The primary exposure was a time-dependent cross-product of TTLs (low TTLs vs. normal-high TTLs with a reference of 6 ng/mL) and bisphosphonate use. Two primary outcomes were evaluated: overall graft loss (death or conversion to kidney replacement) and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 . Results: During the median follow-up of 6.1 (3.4–9.7) years, overall graft loss occurred in 157 (10.9%) patients. Cox regression revealed that normal-high TTLs without bisphosphonate use were associated with a reduced risk of overall graft loss [adjusted hazard ratio (aHR), 0.65; 95% confidence interval (CI), 0.45–0.95] compared to low TTLs without bisphosphonate use. The use of bisphosphonate in conjunction with normal-high TTLs correlated with an even lower risk of overall graft loss (aHR, 0.25; 95% CI, 0.08–0.80) compared with low TTLs without bisphosphonate use. In patients with low TTLs, bisphosphonate use was associated with a reduced risk of overall graft loss compared with non-use (aHR, 0.20; 95% CI, 0.09–0.43). Similar trends were observed in the eGFR outcome. Conclusion The use of bisphosphonate was associated with favorable graft outcomes, even with low TTLs. Incorporating bisphosphonate into a conventional immunosuppressant regimen may potentially reduce tacrolimus requirement.

Purpose: In this study, we investigated the effect of bisphenol-A (BPA) and its major analogs, bisphenol-F (BPF), and bisphenol-S (BPS), on spermatogonial stem cells (SSCs) populations using in vitro SSC culture and in vivo transplantation models. Materials and Methods: SSCs enriched from 6- to 8-day-old C57BL/6-eGFP+ male mice testes were treated with varying concentrations of bisphenols for 7 days to examine bisphenol-derived cytotoxicity and changes in SSC characteristics. We utilized flow cytometry, immunocytochemistry, real-time quantitative reverse transcription-PCR, and western blot analysis. The functional alteration of SSCs was further investigated by examining donor SSC-derived spermatogenesis evaluation through in vivo transplantation and subsequent testis analysis. Results: BPF exhibited a similar inhibitory effect on SSCs as BPA, demonstrating a significant decrease in SSC survival, inhibition of proliferation, and induction of apoptosis. On the other hand, while BPS was comparatively weaker than BPA and BPF, it still showed significant SSC cytotoxicity. Importantly, SSCs exposed to BPA, BPF, and BPS exhibited a significant reduction in donor SSC-derived germ cell colonies per total number of cultured cells, indicating that, like BPA, BPF, and BPS can induce a comparable reduction in functional SSCs in the recipient animals. However, the progress of spermatogenesis, as evidenced by histochemistry and the expressions of PCNA and SSC specific markers, collectively indicates that BPA, BPF, and BPS may not adversely affect the spermatogenesis. Conclusions Our findings indicate that the major BPA substitutes, BPF and BPS, have significant cytotoxic effects on SSCs, similar to BPA. These effects may lead to a reduction in the functional self-renewal stem cell population and potential impacts on male fertility.

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/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Background: The advantages of using an acellular dermal matrix (ADM) for implantbased breast reconstruction in breast cancer patients are well-documented across multiple studies. However, there have been no previous instances of using multilayered ADM for reconstruction following breast-conserving surgery (BCS). This study evaluated the outcomes of breast reconstruction employing multilayered ADM for volume replacement using a local glandular flap post-BCS, and aims to underscore the advantages of this surgical approach. Methods: Breast cancer patients who underwent BCS using several layers of ADM from August 2016 to December 2019 were retrospectively reviewed. Only patients with at least 3 years of follow-up were included in this study. The anticipated postoperative complications were breast deformity, seroma, hematoma, and infection. Results: Seventy-four patients were included in this study. Most patients experienced symptoms of hard palpation at the reconstruction site, which indicated the surface of the ADM inserted into the breast. Ten patients developed breast deformities, accounting for 13.5% of the cases, and required surgical correction. Other complications were less frequent: four patients (5.3%) had a confirmed seroma for 6 months or longer, two patients (2.6%) experienced fat necrosis, and one patient (1.3%) underwent re-operation to remove the ADM. Conclusions Reconstruction with a glandular flap and ADM following BCS is generally simpler and requires less surgical time compared to using a latissimus dorsi flap or other local flaps. Additionally, it avoids complications at the donor site, presenting a feasible surgical alternative for BCS in breasts with small defects.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Materials and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.