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.

Objective: Since coronavirus disease 2019 (COVID-19) vaccination began, abnormal uterine bleeding (AUB) has occurred at a high rate. This study assessed the association between COVID-19 vaccination and AUB. Methods: In this retrospective cohort study, we analyzed mobile application data on menstrual cycles to investigate differences in the prevalence, duration, and amount of intermenstrual bleeding (IMB) after COVID-19 vaccination. We also analyzed the duration of menstruation, menstrual cycle length, and associated symptoms after the COVID-19 vaccination. Additionally, we investigated the prevalence of IMB according to the vaccine type. Results: After vaccination, IMB prevalence increased to 3.35% (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.46-1.76; p<0.0001) and IMB duration increased by 0.43 days (95% CI, 0.25-0.60; p<0.0001). The proportion of respondents whose amount of IMB was heavier than regular menstruation increased (OR, 2.96; 95% CI, 1.47-5.93; p=0.002). Menstrual duration decreased by -0.01 days (95% CI, -0.023 to 0.003; p=0.114), and menstrual cycle length increased by 1.39 days (95% CI, 1.30-1.48; p<0.0001). The proportion of participants who answered that there was a difference in menstruation amount increased (OR, 1.52; 95% CI, 1.41-1.64; p<0.0001). The prevalence of IMB increased regardless of the vaccine type. Conclusion There were statistically significant differences in the prevalence, duration and amount of IMB, menstrual duration, menstrual cycle length, and menstrual amount after COVID-19 vaccination. However, these values were not clinically meaningful and could be regarded as within the normal menstruation range.

Objective: Phototherapy is a widely used treatment for neonatal hyperbilirubinemia, but the potential risks in early preterm infants are not well known. So it seems to be necessary to find out which parameters should be carefully observed during phototherapy. In this study, we analyzed blood pressure (BP), heart rate (HR), and body temperature (BT) in preterm infants under 32 weeks of gestational age before and after phototherapy. Methods: In this study, we analyzed the medical records of 103 early preterm infants with gestational age <32 weeks and birth weight >1,000 g admitted to the neonatal intensive care unit, treated with and without phototherapy, at Wonju Severance Christian Hospital, a tertiary center in Korea. Changes in BP, HR, and BT were analyzed before and after treatment. Results: A total of 91 patients taking phototherapy and 12 control subjects were enrolled. In the phototherapy group (PT group), PT was started on the second day after birth and lasted for 74 hours.In between-group analysis, HR was higher in the PT group after starting phototherapy (at 48 hours;median of differences 8 bpm, P=0.005, at 56 hours; median of differences 9 bpm, P=0.001), while there was no significant difference in BP. The rate of BP increase was lowered and HR was increased after phototherapy, in the PT group analysis. Conclusion After starting phototherapy in preterm infants less than 32 weeks of gestational age, the increasing trend in BP was ceased and the HR was increased.

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.

Objective: Since coronavirus disease 2019 (COVID-19) vaccination began, abnormal uterine bleeding (AUB) has occurred at a high rate. This study assessed the association between COVID-19 vaccination and AUB. Methods: In this retrospective cohort study, we analyzed mobile application data on menstrual cycles to investigate differences in the prevalence, duration, and amount of intermenstrual bleeding (IMB) after COVID-19 vaccination. We also analyzed the duration of menstruation, menstrual cycle length, and associated symptoms after the COVID-19 vaccination. Additionally, we investigated the prevalence of IMB according to the vaccine type. Results: After vaccination, IMB prevalence increased to 3.35% (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.46-1.76; p<0.0001) and IMB duration increased by 0.43 days (95% CI, 0.25-0.60; p<0.0001). The proportion of respondents whose amount of IMB was heavier than regular menstruation increased (OR, 2.96; 95% CI, 1.47-5.93; p=0.002). Menstrual duration decreased by -0.01 days (95% CI, -0.023 to 0.003; p=0.114), and menstrual cycle length increased by 1.39 days (95% CI, 1.30-1.48; p<0.0001). The proportion of participants who answered that there was a difference in menstruation amount increased (OR, 1.52; 95% CI, 1.41-1.64; p<0.0001). The prevalence of IMB increased regardless of the vaccine type. Conclusion There were statistically significant differences in the prevalence, duration and amount of IMB, menstrual duration, menstrual cycle length, and menstrual amount after COVID-19 vaccination. However, these values were not clinically meaningful and could be regarded as within the normal menstruation range.

Objective: Phototherapy is a widely used treatment for neonatal hyperbilirubinemia, but the potential risks in early preterm infants are not well known. So it seems to be necessary to find out which parameters should be carefully observed during phototherapy. In this study, we analyzed blood pressure (BP), heart rate (HR), and body temperature (BT) in preterm infants under 32 weeks of gestational age before and after phototherapy. Methods: In this study, we analyzed the medical records of 103 early preterm infants with gestational age <32 weeks and birth weight >1,000 g admitted to the neonatal intensive care unit, treated with and without phototherapy, at Wonju Severance Christian Hospital, a tertiary center in Korea. Changes in BP, HR, and BT were analyzed before and after treatment. Results: A total of 91 patients taking phototherapy and 12 control subjects were enrolled. In the phototherapy group (PT group), PT was started on the second day after birth and lasted for 74 hours.In between-group analysis, HR was higher in the PT group after starting phototherapy (at 48 hours;median of differences 8 bpm, P=0.005, at 56 hours; median of differences 9 bpm, P=0.001), while there was no significant difference in BP. The rate of BP increase was lowered and HR was increased after phototherapy, in the PT group analysis. Conclusion After starting phototherapy in preterm infants less than 32 weeks of gestational age, the increasing trend in BP was ceased and the HR was increased.

Background: The diagnosis of tuberculous pleural effusion (TPE) often relies on pleural fluid adenosine deaminase (ADA) levels. The diagnostic utility of ADA, however, is influenced by the prevalence of tuberculosis (TB) in local populations. Malignant pleural effusion (MPE) cases can exhibit moderately elevated ADA levels comparable to those seen in TPE. As population aging potentially impacts ADA levels, global TB incidence is decreasing whereas the burden of malignancy is on the rise. Consequently, epidemiological shifts and temporal changes in ADA distribution complicate the differential diagnosis between TPE and MPE when ADA levels are within the 40–70 IU/L range. Nonetheless, data specific to this subset are scarce. Methods: This retrospective study included consecutive patients aged > 18 years with confirmed TPE and MPE, spanning from 2012 to 2023. ADA levels in pleural fluid were categorized into three groups: < 40 IU/L, 40–70 IU/L, and > 70 IU/L. The study examined annual trends in the frequency of new cases and ADA level distributions over time and identified discriminating factors between TPE and MPE in cases with ADA levels of 40–70 IU/L. Results: In total, 297 TPE and 369 MPE cases were included in this study. Over the study period, the frequency of TPE progressively declined, while that of MPE increased. In the most recent four-year period, new TPE and MPE cases with ADA levels of 40–70 IU/L occurred at comparable numbers. Multivariable analysis identified pleural fluid carcinoembryonic antigen (CEA) levels and the number of focal pleural nodules as independent predictors for MPE. Specifically, the presence of either CEA levels > 15.7 ng/mL or more than eight pleural nodules yielded the highest diagnostic accuracy with a sensitivity of 88%, specificity of 100%, and an area under the curve of 0.95. Conclusion The differential diagnosis between TPE and MPE with pleural ADA levels of 40–70 IU/L has become increasingly critical due to evolving epidemiological patterns and ADA distribution changes over time. Pleural fluid CEA levels and the characteristics of pleural nodules may offer valuable guidance in distinguishing between TPE and MPE within this diagnostic gray zone.

Background: Graft failure (GF) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT). Secondary transplantation has been recognized as a potential curative intervention. Methods: This study aimed to investigate the characteristics and outcomes of salvage transplantation by analyzing the patients who underwent a second HCT for GF following the initial allo-HCT between 1998 and 2020. Results: Overall, 23 recipients were identified, including 14 and 9 individuals with primary and secondary GF, respectively. Nine recipients underwent a second transplant from the same donor. Familial mismatched donors predominated in the second HCT (86.9%), with reduced-intensity conditioning as the prevailing approach (60.9%). Neutrophil engraftment occurred in 17 patients (73.9%) following the second HCT at a median of 17 days (range: 9–58 days) post-transplantation. However, secondary GF subsequently occurred in 5 patients, and successful engraftment following salvage transplantation was achieved in 12 (52.2%) patients. In the entire study population, the estimated 5-year probability of overall survival (OS) and treatment-related mortality (TRM) were 30.4% and 58.5%, respectively. Among patients who achieved successful engraftment following a second transplantation, the OS and TRM rates were 41.7% and 33.3%, respectively, indicating a trend toward better OS and significantly lower TRM compared to those with GF. Notably, 17 patients died, with infection being the most common cause (n = 12), irrespective of the engraftment status. Conclusion A successful engraftment following a second allo-HCT reduced the TRM; however, the OS remained suboptimal. The effective control of infectious diseases remains crucial for patients with GF, regardless of the engraftment status following salvage transplantation.