Supplementary Table 1. Cancer classification by anatomic site.

Supplementary Table 2. Characteristics of pre-propensity score-matched MHT and non-MHT groups in women

BACKGROUND:Vocal cord dysfunction is a significant complication after thyroid surgery, typically evaluated with invasive laryngoscopy. This study assessed diagnostic accuracy and feasibility of lateral laryngeal ultrasound as a noninvasive alternative. METHODS:In a prospective, double-blind study at Gyeongsang National University Changwon Hospital (February 2016 to June 2023), 718 patients underwent preoperative and postoperative vocal cord assessment using laryngoscopy and lateral laryngeal ultrasound. Both patients and assessors were blinded to the counterpart modality. Sensitivity, specificity, and visualization rates were analyzed. RESULTS:Lateral laryngeal ultrasound visualized vocal cords in 99.6% of cases (715/718), with 100% sensitivity and 99.5% specificity for detecting vocal cord paralysis compared with laryngoscopy. No adverse effects were reported. CONCLUSIONS:Lateral laryngeal ultrasound is a reliable, noninvasive tool for perioperative vocal cord evaluation, offering a patient-friendly alternative that may reduce the need for laryngoscopy in thyroid surgery.

PURPOSE:To evaluate the effectiveness of deep learning (DL)-based reconstruction for improving image quality and reducing scan time in multi-shot diffusion-weighted imaging (DWI) of the breast, compared with standard readout-segmented echo-planar imaging (rs-EPI). MATERIALS AND METHODS:This retrospective study included 146 women (mean age: 55.8 years) with newly diagnosed breast cancer who underwent preoperative breast MRI with both rs-EPI and prototype DL-reconstructed (DLR) multi-shot DWI. Quantitative metrics-signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), lesion contrast, and apparent diffusion coefficient (ADC)-were compared between sequences. Two radiologists independently assessed overall image quality, artifact suppression, lesion conspicuity, and fibroglandular tissue suppression using a 5-point Likert scale. An independent validation cohort of 39 consecutive patients was analyzed using the same methodology. RESULTS:Compared with rs-EPI, DLR multi-shot DWI demonstrated significantly higher SNR, CNR, and lesion contrast at both b = 800 and synthetic b = 1500 s/mm2 (all p < 0.05). Tumor ADC values were slightly lower and fibroglandular tissue ADC values slightly higher with DLR (both p < 0.05). Qualitative assessments demonstrated higher scores for overall image quality and lesion conspicuity with DLR, with improved artifact suppression at b = 800 s/mm2. Interobserver agreement was substantial to almost perfect (weighted κ = 0.753-0.981). DL reconstruction reduced acquisition time by 29% compared with rs-EPI. In the validation cohort, improvements in SNR, CNR, and overall image quality were also observed, whereas ADC values did not differ significantly between techniques. CONCLUSION:DL-based reconstruction improves quantitative and qualitative image quality in multi-shot breast DWI while reducing scan time. These findings support its potential integration into clinical breast MRI.

Background Transoral thyroidectomy is an established remote-access alternative to open thyroidectomy, performed mainly as the transoral endoscopic thyroidectomy vestibular approach or transoral robotic thyroidectomy. Their comparative safety and oncologic performance remain under investigation. Methods This retrospective multicenter study included 2,144 patients who underwent transoral thyroidectomy at 4 high-volume centers between January 2017 and May 2024 (546 transoral endoscopic thyroidectomy vestibular approach, 1,598 transoral robotic thyroidectomy). Patient, operative, complication, and oncologic outcomes were compared. Results Total thyroidectomy was performed in 205 patients (9.6%), unilateral lobectomy or isthmectomy was performed in 1,774 (82.8%) patients, and subtotal/completion thyroidectomy was performed in the remaining patients. The mean operative time was longer for transoral robotic thyroidectomy than for transoral endoscopic thyroidectomy vestibular approach (167.5 ± 42.5 vs 121.3 ± 37.2 minutes; P < .001), whereas the postoperative hospital stay was shorter (2.5 ± 0.8 vs 3.5 ± 1.7 days; P < .001). Transient hypoparathyroidism occurred in 12 of 546 patients (2.2%) in the transoral endoscopic thyroidectomy vestibular approach group and 2 of 1,598 (0.1%) in the transoral robotic thyroidectomy group (P = .002). Transient recurrent laryngeal nerve palsy occurred in 24 transoral endoscopic thyroidectomy vestibular approach patients (4.4%) and 5 transoral robotic thyroidectomy patients (0.3%; P < .001). Mental nerve injury was more frequent after transoral endoscopic thyroidectomy vestibular approach (1.1% vs 0.2%; P = .005). No conversions or perioperative deaths occurred. At a mean 40-month follow-up, locoregional recurrence was observed in 9 patients (0.4%) with no disease-specific mortality. Conclusion Both transoral endoscopic thyroidectomy vestibular approach and transoral robotic thyroidectomy are safe, feasible, and oncologically sound in appropriately selected patients. Transoral robotic thyroidectomy offers lower rates of nerve injury and hypoparathyroidism and may be preferred for more complex cases, whereas the transoral endoscopic thyroidectomy vestibular approach remains an effective scarless option for benign and low-risk malignancies.

Supplementary Table 3. Characteristics of women who use menopausal hormone therapy.

BACKGROUND:The treatment strategy for intestinal non-Hodgkin lymphoma (NHL) and the role of surgery warrant reevaluation. METHODS:This study analyzed clinical data from a cohort of 12,047 patients diagnosed with intestinal NHL, extracted from the Korean National Health Insurance System database between 2002 and 2021. RESULTS:Among these patients, 3,566 (29.6%) were categorized into the surgery group, while 8,481 (70.4%) were included in the nonsurgery group. Surgery was independently associated with both prolonged overall survival (OS) and a favorable prognosis in multivariate analysis (Hazard Ratio [HR] = 0.645, 95% Confidence Interval [CI] = 0.598-0.695, p <.001). The median OS was longer in patients who underwent lymph node dissection during surgery than in patients who did not undergo lymph node dissection (10-year OS with lymph node dissection 63.17% vs. surgery without lymph node dissection 54.78%, p < .001). CONCLUSIONS:To our knowledge, this is the first Korean population-based nationwide study to describe the clinical impact of surgery on the OS of patients with intestinal NHL. A prospective randomized study evaluating strategies to improve the survival of intestinal NHL patients is needed.

Supplementary Table 9. Hazard ratios of cancer risk associated with MHT use by duration

BACKGROUND:The relationship between sex differences and clinical outcomes following coronary artery bypass grafting (CABG) has been highlighted in several studies. However, these studies were mostly based on single- or multi-center data, and only a few meta-analyses examined long-term outcomes. To address this limitation, we conducted a nationwide population-based cohort study in Korea. METHODS:A total of 48,206 adult patients who underwent first-time isolated CABG between January 2005 and December 2021 were enrolled. To address potential confounding, propensity score (PS) matching was conducted. The primary outcome was overall mortality. RESULTS:Among the enrolled patients, 12,270 (25.5%) were female. The median age of the overall cohort was 66.0 years (interquartile range [IQR], 59.0-72.0), with female patients (median, 69.0; IQR, 63.0-75.0) being significantly older than male patients (P < 0.001). In the PS-matched cohort, in-hospital mortality did not differ significantly between female and male groups (odds ratio, 1.13; 95% confidence interval [CI], 0.78-1.64). However, the female group was a significant predictor of better overall survival (hazard ratio [HR], 0.83; 95% CI, 0.77-0.90) compared to the male group. Cardiac-related mortality was comparable between the two groups (HR, 0.89; 95% CI, 0.65-1.22). The median duration of the follow-up period was 7.8 (IQR, 4.0-12.6) years. CONCLUSION:In this nationwide population-based PS-matched cohort study, female patients who underwent isolated CABG exhibited significantly lower overall mortality compared to male patients during long-term follow-up, whereas no significant difference was observed in cardiac-related mortality.

BackgroundNutritional and exercise interventions have shown beneficial effects after gastrectomy for gastric cancer. While digital health tools show promise in cancer care, their long-term effectiveness in patients with gastric cancer remains unclear. In addition, large-scale studies of personalized interventions initiated in the immediate postoperative period are lacking. ObjectiveThis study aimed to determine whether a personalized mobile health intervention incorporating exercise and nutrition confers additional benefits in weight change, body composition, nutritional status, physical fitness, and quality of life compared with standard care when applied continuously for 12 months after gastrectomy. MethodsThis multicenter, randomized controlled trial enrolled 257 patients who had undergone curative resection for stage I-III gastric cancer. Participants were randomly assigned (2:1) to either a 12-month personalized mobile health intervention group or a standard rehabilitation control group. The digital intervention incorporated a smartphone app and wearable device, offering exercise and dietary plans tailored to clinical parameters such as BMI, surgery type, and recovery stage. Standard care, including nutritional education, was provided to all patients. The primary outcome was a change in body weight over 12 months. Secondary outcomes included quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Stomach 22), nutritional status (Mini Nutritional Assessment Score), physical fitness (grip strength, 30-second chair stand test, and 2-minute walk test), physical activity (International Physical Activity Questionnaire-Short Form), pain intensity (average Numeric Rating Scale), body composition (skeletal muscle mass, lean body mass, and fat mass), BMI, hemoglobin, vitamin B12, and albumin. Assessments were conducted at baseline and at 1, 3, 6, and 12 months postoperatively. ResultsNo significant group-by-time effects were observed for weight change. Secondary outcomes showed no between-group differences, except for 1 subscale of the EORTC QLQ-C30, which lacked clinical significance. The intervention group reported high satisfaction and adherence to the mobile app, and no adverse events or incidents were observed during the 12-month study period. ConclusionsThe digital health program integrating exercise and nutrition was safe and feasible, with high satisfaction and adherence among patients with gastric cancer. However, it was not superior to standard education in modifying the postoperative trajectory in patients with gastric cancer after surgery, including body weight change and related functional or nutritional outcomes. These findings suggest that future digital health programs should be precisely targeted and tailored to specific patient populations and recovery phases. Trial RegistrationClinicalTrials.gov NCT04907591; https://clinicaltrials.gov/ct2/show/NCT04907591

Supplementary Table 7. Hazard ratios of cancer risk associated with combined estrogen/progestogen.

Supplementary Table 6. Hazard ratios of cancer risk associated with tibolone.

Supplementary Table 4. Total cancer incidence per 100,000 person-years by use of menopausal hormone therapy.

Supplementary Table 8. Hazard ratios of cancer risk associated with estrogen alone.

Breast cancer is a highly heterogeneous disease; hence, it is crucial to understand its biology and identify new targets for the development of effective treatments. Galectin-1 is known to play an oncogenic role in breast cancer progression. It is known that oncogenic factors can influence cancer progression through interactions with miRNAs. The purpose of this study is to identify the clinical significance and biological role of galectin-1 and miR-22-3p in cancer progression according to the molecular subtype of breast cancer. We analyzed the expression of galectin-1 and miR-22-3p using cancer tissues and the correlation with clinical pathological characteristics. In addition, we investigated the regulation of the cell cycle and EMT processes of cancer progression through the galectin-1/miR-22-3p axis using cell lines of different breast cancer subtypes. miR-22-3p negatively regulates galectin-1 expression and the two molecules have opposite patterns of oncogenic and tumor-suppressive functions, respectively; furthermore, these two molecules are associated with metastasis-free survival. Cell experiments showed that miR-22-3p overexpression and galectin-1 knockdown inhibited the proliferation and invasion of breast cancer cells. Galectin-1 regulates different cancer progression pathways depending on the molecular subtype. In hormone receptor-positive breast cancer cells, galectin-1 knockdown mainly inhibited cell cycle-related substances and induced G0/G1 arrest, whereas in triple-negative breast cancer cells, it suppressed molecules related to the epithelial-mesenchymal transition pathway. In conclusion, the miR-22-3p/galectin-1 axis regulates different cancer metastasis mechanisms depending on the specific molecular subtype of breast cancer, and miR-22-3p/galectin-1 axis modulation may be a novel target for molecular subtype-specific personalized treatment.

Coronary artery bypass grafting (CABG) remains a key revascularization strategy for ischemic heart disease; however, nationwide trends in the Republic of Korea have not been thoroughly investigated. Using data from the Korean National Health Insurance Service, we analyzed adult patients who underwent isolated CABG between 2005 and 2022. We evaluated surgical volume, patient demographics, procedural strategies (off-pump vs. on-pump), and outcomes. International comparisons were conducted using national cardiac surgery registry data. A total of 51,923 CABG cases were identified. Annual surgical volume declined until 2013 but gradually increased thereafter, reaching 3,717 cases in 2022. Despite this recovery, Korea's per capita CABG rate remains among the lowest worldwide. In contrast, more than 60% of procedures were performed off-pump-the highest rate worldwide. Over time, the average patient age and prevalence of diabetes increased, whereas in-hospital mortality showed a modest decline. Compared with other countries, the Republic of Korea demonstrated a uniquely low procedural volume and a strong preference for off-pump CABG. This nationwide analysis highlights Korea's distinctive CABG practice patterns and provides valuable insights for optimizing future clinical and policy decisions in cardiac surgical care.

BACKGROUND:The association between preoperative diabetes mellitus (DM) duration and outcomes of coronary artery bypass grafting (CABG) remains unclear. This study aimed to investigate the relationship between DM duration at the time of CABG and long-term outcomes, particularly in patients with acute myocardial infarction. METHODS:Using data from South Korea's National Health Insurance Service database, the study included adult patients who underwent first-time isolated CABG with an acute myocardial infarction diagnosis between 2005 and 2021. Patients with DM were categorized based on whether their diagnosis occurred within 5 years before CABG. Patients with impaired fasting glucose were also classified. The primary outcome was all-cause overall mortality. The secondary outcome was repeat revascularization. RESULTS:A total of 21,957 patients (median age, 65.0 years) were categorized into 4 groups: without DM, impaired fasting glucose, DM diagnosed within 5 years, and DM diagnosed more than 5 years before CABG. Patients with DM <5 years had a higher overall mortality rate (hazard ratio, 1.16; 95% CI, 1.08-1.24), and those with DM >5 years had an even higher rate (hazard ratio, 1.36; 95% CI, 1.27-1.46) compared with those without DM. The incidence rate of repeat revascularization was significantly higher in those with DM >5 years (hazard ratio, 2.07; 95% CI, 1.89-2.28). CONCLUSIONS:The duration of DM before CABG is correlated with worse clinical outcomes. A prolonged period of DM before CABG may be a significant risk factor for poorer long-term outcomes in patients with acute myocardial infarction.

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) has the potential to improve neurological outcomes in patients with refractory out-of-hospital cardiac arrest (OHCA), offering an alternative to conventional cardiopulmonary resuscitation (CCPR). However, its effectiveness in OHCA remains controversial despite advancements in resuscitation techniques. Methods: This retrospective single-center study compared neurological outcomes and 30-day survival between ECPR and CCPR patients from January 2014 to January 2022. Patients aged 18–75 with witnessed OHCA, minimal no flow and low flow times, and cardiac arrests occurring at home or in public places were included. All patients were transported directly to our institution, a tertiary medical center serving the southeastern region of Seoul, where extracorporeal membrane oxygenation implantation was consistently performed in the emergency department. Neurological outcomes were assessed using Cerebral Performance Category scores, with good outcomes defined as scores of 1–2. Statistical analyses included logistic regression models and Kaplan–Meier survival curves, adjusted for confounders using inverse probability of treatment weighting. Results: ECPR was associated with significantly better neurological outcomes than CCPR (p < 0.001). Factors predicting poor outcomes included older age and longer low flow times, while male sex and shockable rhythms were protective. No significant difference was found in 30-day survival between the ECPR and CCPR groups, although a trend toward better survival was noted with ECPR. Conclusions: ECPR may improve neurological outcomes in patients with refractory OHCA compared to CCPR, although it does not significantly affect 30-day survival. Further studies are necessary to validate these findings and explore the long-term impacts of ECPR.

Blood transfusions are frequently administered to extracorporeal membrane oxygenation (ECMO) patients. However, the relationship between blood transfusion and outcomes in ECMO patients remains unclear. This study investigated the association between blood transfusion and 90-day mortality in ECMO patients. Using a large administrative database (National Health Insurance Service, NHIS) from the Republic of Korea during 2014–2020, ECMO cases were identified. Patients younger than 19 years and those with ECMO durations of less than 1 day were excluded. Transfusion variables included the total volumes of red blood cells (RBC), fresh frozen plasma (FFP), and platelet concentrates (PC), normalized by hospital stays. The primary outcome was 90-day mortality. Variable importance calculation using Random Forest and XGBoost models identified RBC, FFP, and PC transfusions among the top 10 predictors of mortality. Variable importance was calculated to identify the most influential variables in predicting the outcome among 51 variables. A total of 11,874 patients were included. The median age was 62 years (IQR 51–71), and 32.7% were female. 90-day mortality occurred in 6980 patients (58.8%). The proportion of patients who received at least one transfusion during hospitalization was 96.2% for RBC, 68.8% for FFP, and 74.4% for PC. Higher transfusion volumes (50–100%) were consistently associated with an increased risk of death compared to lower volumes (0–49%). Odds ratios for mortality were 6.764 (95% confidence interval (CI), 6.227–7.347) for RBC/hospital day, 3.702 (95% CI 3.426–4.000) for FFP/hospital day, and 5.082 (95% CI 4.691–5.506) for PC/hospital day in the higher transfusion group. In a multivariable logistic regression model, RBC, FFP, and PC transfusions normalized by hospital stay were significantly associated with mortality (p < 0.001). Variable importance calculation using Random Forest and XGBoost models identified RBC, FFP, and PC transfusions among the top 10 predictors of mortality. Blood transfusion normalized by hospital stay emerged as a critical predictor of 90-day mortality in ECMO patients. Thus, optimizing blood transfusion practices is essential to improve patient outcomes and safety.