Background: Lung ultrasound (LUS) has proven valuable in the initial assessment of coronavirus disease 2019 (COVID-19), but its role in detecting pulmonary fibrosis following intensive care remains unclear. This study aims to assess the presence of pulmonary sequelae and fibrosis-like changes using LUS in survivors of severe COVID-19 pneumonia one month after discharge. Methods: We prospectively enrolled patients with severe COVID-19 who required mechanical ventilation in the intensive care unit (ICU) and conducted LUS assessments from admission to the outpatient visit after discharge. We tracked changes in key LUS findings and applied our proprietary LUS scoring system. To evaluate LUS accuracy, we correlated measured LUS values with computed tomography scores. Results: We evaluated B-line presence, pleural thickness, and consolidation in 14 eligible patients. The LUS scores exhibited minimal changes, with values of 19.1, 19.2, and 17.5 at admission, discharge, and the outpatient visit, respectively. Notably, the number of B-lines decreased significantly, from 1.92 at admission to 0.56 at the outpatient visit (p<0.05), while pleural thickness increased significantly, from 2.05 at admission to 2.48 at the outpatient visit (p≤0.05). Conclusion This study demonstrates that LUS can track changes in lung abnormalities in severe COVID-19 patients from ICU admission through to outpatient follow-up. While pleural thickening and B-line patterns showed significant changes, no correlation was found between LUS and high-resolution computed tomography fibrosis scores. These findings suggest that LUS may serve as a supplementary tool for assessing pulmonary recovery in severe COVID-19 cases.

Purpose: Pediatric papillary thyroid cancer (PTC) is recommended to perform aggressive surgery to reduce the risk of recurrence.This study was designed to evaluate the concurrent association between multifocality, bilaterality, and the risk of recurrence in pediatric PTC. Materials and Methods: This retrospective cohort study included pediatric patients (age <19 years) who underwent total thyroidectomy for PTC between 1996 and 2014 in a single tertiary center. Clinicopathological parameters were analyzed to evaluate the prevalence of multifocality, bilaterality, recurrence, and their association. Results: We analyzed 58 pediatric patients with PTC. There was no factor related to the presence of multifocality or bilaterality in multivariate analysis. Also, in univariate analysis, multifocality and bilaterality were not independent risk factors of each other’s presentation (p=0.061 and p=0.061, respectively). Recurrence was observed in 19 (32.8%) patients. In multivariate analysis of recurrence, clear cell subtype, multifocality, and gross extrathyroidal extension (ETE) were independent risk factors (p=0.027, p=0.035, and p=0.038, respectively). Most recurrences (68.4%) happened during the first 4 years of follow-up after the initial thyroidectomy. Conclusion Multifocality and bilaterality were not independent risk factors of each other’s presentation; however, multifocality was the risk factor for recurrence in pediatric PTC. For pediatric PTC, close monitoring for recurrence within the initial 4 years is recommended, particularly in patients with clear cell subtype, multifocality, and gross ETE.

Objective: To test the performance of an artificial intelligence-based computer-aided diagnosis (AI-CAD) designed for fullfield digital mammography (FFDM) when applied to synthetic mammography (SM). Materials and Methods: We analyzed 501 women (mean age, 57 ± 11 years) who underwent preoperative mammography and breast cancer surgery. This cohort consisted of 1002 breasts, comprising 517 with cancer and 485 without. All patients underwent digital breast tomosynthesis (DBT) and FFDM during the preoperative workup. The SM is routinely reconstructed using DBT. Commercial AI-CAD (Lunit Insight MMG, version 1.1.7.2) was retrospectively applied to SM and FFDM to calculate the abnormality scores for each breast. The median abnormality scores were compared for the 517 breasts with cancer using the Wilcoxon signed-rank test. Calibration curves of abnormality scores were evaluated. The discrimination performance was analyzed using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity using a 10% preset threshold. Sensitivity and specificity were further analyzed according to the mammographic and pathological characteristics.The results of SM and FFDM were compared. Results: AI-CAD demonstrated a significantly lower median abnormality score (71% vs. 96%, P < 0.001) and poorer calibration performance for SM than for FFDM. SM exhibited lower sensitivity (76.2% vs. 82.8%, P < 0.001), higher specificity (95.5% vs.91.8%, P < 0.001), and comparable AUC (0.86 vs. 0.87, P = 0.127) than FFDM. SM showed lower sensitivity than FFDM in asymptomatic breasts, dense breasts, ductal carcinoma in situ, T1, N0, and hormone receptor-positive/human epidermal growth factor receptor 2-negative cancers but showed higher specificity in non-cancerous dense breasts. Conclusion AI-CAD showed lower abnormality scores and reduced calibration performance for SM than for FFDM.Furthermore, the 10% preset threshold resulted in different discrimination performances for the SM. Given these limitations, off-label application of the current AI-CAD to SM should be avoided.

Purpose: Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

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: Recombinant human follicle-stimulating hormone (rhFSH) is commonly used to treat female infertility, but its short half-life necessitates multiple doses. Even corifollitropin alfa, with an extended half-life, requires supplementary injections of rhFSH after 7 days. This study aimed to develop and evaluate a long-acting follicle-stimulating hormone (FSH) formulation using anti-serum albumin Fab-associated (SAFA) technology to avoid additional injections and enhance ovarian function. Methods: SAFA-FSH was synthesized using a Chinese hamster ovary expression system. Its biological efficacy was confirmed through assays measuring its ability to stimulate cyclic adenosine monophosphate (cAMP) production, estradiol synthesis, and the expression of human cytochrome P450 family 19 subfamily A member 1 (hCYP19α1) and human steroidogenic acute regulatory protein (hSTAR) in human ovarian granulosa (KGN) cells. To evaluate the effects of SAFA-FSH, we compared its impact on serum estradiol levels and ovarian weight increase with that of rhFSH in Sprague-Dawley (SD) rats using the modified Steelman-Pohley test. Results: The results indicated that SAFA-FSH induces cAMP synthesis in KGN cells and upregulates the expression of hCYP19α1 and hSTAR in a dose-dependent manner. Female SD rats, aged 21 days, receiving daily subcutaneous human chorionic gonadotropin injections for 5 days exhibited a significant increase in serum estradiol levels and ovarian weight when administered SAFA-FSH on the first day or when given nine injections of rhFSH over 5 days. Notably, the group receiving SAFA-FSH on the first and third days demonstrated an even greater rise in serum estradiol levels and ovarian weight. Conclusion These findings suggest that SAFA-FSH presents a promising alternative to current rhFSH treatments for female infertility. However, further research is essential to thoroughly assess its safety and efficacy in clinical contexts.

Objective: To test the performance of an artificial intelligence-based computer-aided diagnosis (AI-CAD) designed for fullfield digital mammography (FFDM) when applied to synthetic mammography (SM). Materials and Methods: We analyzed 501 women (mean age, 57 ± 11 years) who underwent preoperative mammography and breast cancer surgery. This cohort consisted of 1002 breasts, comprising 517 with cancer and 485 without. All patients underwent digital breast tomosynthesis (DBT) and FFDM during the preoperative workup. The SM is routinely reconstructed using DBT. Commercial AI-CAD (Lunit Insight MMG, version 1.1.7.2) was retrospectively applied to SM and FFDM to calculate the abnormality scores for each breast. The median abnormality scores were compared for the 517 breasts with cancer using the Wilcoxon signed-rank test. Calibration curves of abnormality scores were evaluated. The discrimination performance was analyzed using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity using a 10% preset threshold. Sensitivity and specificity were further analyzed according to the mammographic and pathological characteristics.The results of SM and FFDM were compared. Results: AI-CAD demonstrated a significantly lower median abnormality score (71% vs. 96%, P < 0.001) and poorer calibration performance for SM than for FFDM. SM exhibited lower sensitivity (76.2% vs. 82.8%, P < 0.001), higher specificity (95.5% vs.91.8%, P < 0.001), and comparable AUC (0.86 vs. 0.87, P = 0.127) than FFDM. SM showed lower sensitivity than FFDM in asymptomatic breasts, dense breasts, ductal carcinoma in situ, T1, N0, and hormone receptor-positive/human epidermal growth factor receptor 2-negative cancers but showed higher specificity in non-cancerous dense breasts. Conclusion AI-CAD showed lower abnormality scores and reduced calibration performance for SM than for FFDM.Furthermore, the 10% preset threshold resulted in different discrimination performances for the SM. Given these limitations, off-label application of the current AI-CAD to SM should be avoided.

BACKGROUND/OBJECTIVES: This study aimed to use plasma metabolites to identify clusters of breast cancer survivors and to compare their dietary characteristics and health-related factors across the clusters using unsupervised machine learning. SUBJECTS/METHODS: A total of 419 breast cancer survivors were included in this crosssectional study. We considered 30 plasma metabolites, quantified by high-throughput nuclear magnetic resonance metabolomics. Clusters were obtained based on metabolites using 4 different unsupervised clustering methods: k-means (KM), partitioning around medoids (PAM), self-organizing maps (SOM), and hierarchical agglomerative clustering (HAC). The t-test, χ2 test, and Fisher’s exact test were used to compare sociodemographic, lifestyle, clinical, and dietary characteristics across the clusters. P-values were adjusted through a false discovery rate (FDR). RESULTS: Two clusters were identified using the 4 methods. Participants in cluster 2 had lower concentrations of apolipoprotein A1 and large high-density lipoprotein (HDL) particles and smaller HDL particle sizes, but higher concentrations of chylomicrons and extremely large very-low-density-lipoprotein (VLDL) particles and glycoprotein acetyls, a higher ratio of monounsaturated fatty acids to total fatty acids, and larger VLDL particle sizes compared with cluster 1. Body mass index was significantly higher in cluster 2 compared with cluster 1 (FDR adjusted-PKM < 0.001; PPAM = 0.001; PSOM < 0.001; and PHAC = 0.043). CONCLUSION The breast cancer survivors clustered on the basis of plasma metabolites had distinct characteristics. Further prospective studies are needed to investigate the associations between metabolites, obesity, dietary factors, and breast cancer prognosis.

BACKGROUND/OBJECTIVES: Isoflavones are estrogen-like compounds found in plants and their health effects remain equivocal. We investigated dietary isoflavone intake and its associated factors in Korean breast cancer survivors, with a comparison to cancer-free women. SUBJECTS/METHODS: The usual dietary intake of breast cancer survivors (n = 981, mean age 52 yrs) in 9 hospitals between 2012 and 2019 was assessed using 3-day food records or food frequency questionnaires (FFQs). They were age-matched to 2,943 cancer-free women who completed FFQs as part of a nationwide study conducted between 2012 and 2016. We used the flavonoid database of common Korean foods and the Phenol-Explorer database to estimate isoflavone intake. The contribution of each food or food group to the total isoflavone intake was calculated. The adjusted least-squares means of dietary isoflavone intake according to lifestyle and clinical factors were calculated using generalized linear models. RESULTS: Breast cancer survivors had a higher mean dietary isoflavone intake (23.59 mg/day) than cancer-free women (17.81 mg/day). Major food sources, including tofu, soybeans, and doenjang, contributed to over 70% of the isoflavone intake in both groups. When we estimated dietary isoflavone intake according to lifestyle characteristics, isoflavone intake increased with higher scores of adherence to the American Cancer Society dietary guidelines but decreased with increasing body mass index in both groups. Among cancer-free women, dietary isoflavone intake was higher among those who had never smoked and among dietary supplement users. Among breast cancer survivors, dietary isoflavone intakes did not vary with clinical characteristics, including time since surgery and estrogen receptor status. CONCLUSION Breast cancer survivors were more likely to consume isoflavones than agematched cancer-free women. Dietary isoflavone intake was associated with healthy lifestyle characteristics in women both with and without breast cancer. Further research is needed to understand the role of the higher isoflavone intake among breast cancer survivors compared to cancer-free women on their prognosis.

Background: Lung ultrasound (LUS) has proven valuable in the initial assessment of coronavirus disease 2019 (COVID-19), but its role in detecting pulmonary fibrosis following intensive care remains unclear. This study aims to assess the presence of pulmonary sequelae and fibrosis-like changes using LUS in survivors of severe COVID-19 pneumonia one month after discharge. Methods: We prospectively enrolled patients with severe COVID-19 who required mechanical ventilation in the intensive care unit (ICU) and conducted LUS assessments from admission to the outpatient visit after discharge. We tracked changes in key LUS findings and applied our proprietary LUS scoring system. To evaluate LUS accuracy, we correlated measured LUS values with computed tomography scores. Results: We evaluated B-line presence, pleural thickness, and consolidation in 14 eligible patients. The LUS scores exhibited minimal changes, with values of 19.1, 19.2, and 17.5 at admission, discharge, and the outpatient visit, respectively. Notably, the number of B-lines decreased significantly, from 1.92 at admission to 0.56 at the outpatient visit (p<0.05), while pleural thickness increased significantly, from 2.05 at admission to 2.48 at the outpatient visit (p≤0.05). Conclusion This study demonstrates that LUS can track changes in lung abnormalities in severe COVID-19 patients from ICU admission through to outpatient follow-up. While pleural thickening and B-line patterns showed significant changes, no correlation was found between LUS and high-resolution computed tomography fibrosis scores. These findings suggest that LUS may serve as a supplementary tool for assessing pulmonary recovery in severe COVID-19 cases.