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Kyun-Ho Shin, Jae-Joong Kim, Sei-Wook Son, Kyo-Sun Hwang, Seung-Beom Han Department of Orthopaedic Surgery, Anam Hospital, Korea University College of Medicine, Seoul, South KoreaCorrespondence: Seung-Beom HanKorea University College of Medicine, 73 Inchon-Ro, Sungbuk-gu, Seoul 02841, South KoreaTel +82-2-920-5924Fax +82-2-924-2471Email oshan@korea.ac.krPurpose: Postoperative pneumonia is a common and devastating complication of hip fracture surgery in older individuals. This study aimed to determine the relationship between early postoperative hypoalbuminaemia and pneumonia after hip fracture surgery.Patients and Methods: In this retrospective cohort study conducted at one centre, we reviewed the medical records of 1155 consecutive patients (> 60 years) who underwent hip fracture surgery. Multivariate logistic regression analysis was performed to identify the independent risk factors for postoperative pneumonia. After determining the cut-off value for postoperative serum albumin, the patients were divided into two groups according to the minimum serum albumin level recorded during the first two postoperative days: group A included patients with a minimum serum album level less than 3.0 g/dL and group B included patients with a minimum serum album level of at least 3.0 g/dL. The prevalence of postoperative pneumonia was analysed using inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) analyses.Results: The incidence of postoperative pneumonia following hip fracture surgery was 5.1% (n=59). Age, cardiovascular disease, and early postoperative hypoalbuminaemia during the first two postoperative days were independent risk factors for postoperative pneumonia. Early postoperative hypoalbuminaemia was associated with postoperative pneumonia development in the PSM and IPTW analyses (P = 0.016 and < 0.001, respectively).Conclusion: This study demonstrated that early postoperative hypoalbuminaemia is an independent risk factor for the development of postoperative pneumonia in patients undergoing hip fracture surgery.Keywords: osteoporosis, osteoporotic fracture, albumin, complication

Kwang-Hee Shin,1 Ji-Young Jeon,2 Kyungho Jang,2 Tae-Eun Kim,3 Min-Gul Kim2,4 1College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea; 2Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea; 3Department of Clinical Pharmacology, Konkuk University Medical Center, Seoul, Republic of Korea; 4Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju, Republic of Korea Purpose: The aim of this study was to evaluate the dose-proportional pharmacokinetic characteristics of pregabalin following the administration of GLA5PR GLARS-NF1 tablets (150, 300, 450, and 600 mg) in the fed state.Subjects and methods: An open-label, randomized, single-dose, parallel study was conducted in 40 eligible subjects who were randomly assigned to receive a single 150, 300, 450, or 600 mg dose of GLA5PR GLARS-NF1. Serial blood samples were collected before and after dosing for 36 hours, and plasma concentrations were determined using liquid chromatography-tandem mass spectrometry. Safety profiles were evaluated throughout the study (trial registration number: NCT02327000).Results: Thirty-seven subjects completed the studies. The area under the plasma concentration-time curve up to the last measurable concentration of pregabalin exhibited dose proportionality following administration of GLA5PR GLARS-NF1 tablets from 150 to 600 mg while its maximum plasma concentration showed dose proportionality at a dose range of 150–450 mg. The safety evaluations showed no clinically significant finding after administration of GLA5PR GLARS-NF1 tablets (150, 300, 450, and 600 mg) in the fed state.Conclusions: The dose-proportional properties of GLA5PR GLARS-NF1 150–450 mg tablets were determined. Keywords: gamma-aminobutyric acid analog, GABA analog, maximum concentration, safety evaluation, Korean

Tae-Eun Kim,1 Kwang-Hee Shin,2 Jeong-Eun Park,2 Min-Gul Kim,3 Yeo-Min Yun,4 Dong-Hee Choi,5 Kyoung Ja Kwon,5 Jongmin Lee6 1Department of Clinical Pharmacology, Konkuk University Medical Center, Seoul, Republic of Korea; 2Department of Pharmacotherapy & Translational Research, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea; 3Department of Pharmacology, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea; 4Department of Laboratory Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea; 5Department of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea; 6Department of Rehabilitation Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea Background: Previous in vitro studies have reported the inhibitory effect of green tea on p-glycoprotein (p-gp) encoded by ABCB1. This study aimed to investigate the effect of green tea on the pharmacokinetics of digoxin, a typical probe drug of p-gp. Methods: Sixteen healthy volunteers participated in this study. At Day 1, 0.5 mg of digoxin was administered via oral route. After a 14-day washout period, 630 mg of green tea catechins (GTC) was administered via oral route, followed by 0.5 mg of digoxin 1 hour later. From Day 16 through Day 28, 630 mg of GTC was administered alone. At Day 29, 630 mg of GTC and 0.5 mg of digoxin were administered in the same way as Day 15. Blood samples for the pharmacokinetic assessments of digoxin were collected up to 8 hours after each dose. Pharmacokinetic parameters were estimated by noncompartmental analysis. Area under the curve (AUC) and peak plasma concentration (Cmax) were compared using mixed effect model between digoxin alone and digoxin with GTC. ABCB1 was genotyped to determine whether its polymorphism affects digoxin–GTC interaction. Results: Fifteen subjects completed the study. Compared to digoxin alone, the concomitant administration of digoxin and GTC significantly reduced the systemic exposure of digoxin: geometric mean ratios (GMR) and 90% confidence intervals (CI) of area under the concentration–time curve from time 0 to the last measurable time (AUClast) and Cmax were 0.69 (0.62–0.75) and 0.72 (0.61–0.85), respectively. The concomitant administration of digoxin and GTC following pretreatment of GTC (Day 29) similarly reduced the AUClast (GMR [90% CI]: 0.67 [0.61–0.74]) and Cmax (GMR [90% CI]: 0.74 [0.63–0.87]). In the comparison of the percentage changes from Day 1 (digoxin single administration) of AUClast between genotypes, C1236T variant type showed a significant difference to wild-type on Day 15 (concomitant administration of digoxin and GTC) (P=0.005). Conclusion: This study demonstrates that the coadministration of GTC reduces the systemic exposure of digoxin regardless of pretreatment of GTC. Keywords: digoxin, green tea, catechin, p-glycoprotein, pharmacokinetics, drug interaction

Yu Kyong Kim,1 Kwang-Hee Shin,2 Jeffrey Alderman,3 Kyung-Sang Yu,1 In-Jin Jang,1 SeungHwan Lee1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; 2College of Pharmacy, Kyungpook National University, Daegu, Republic of Korea; 3Pfizer, Inc., New York, NY, USA Background: Migraine is one of the most common headache disorders that greatly affect the quality of life. Selective serotonin (5-HT) receptor agonists such as triptamine-based drugs called triptans are used for treatment of migraine. Purpose: This study aimed to evaluate the pharmacokinetic (PK) and tolerability profiles of eletriptan hydrobromide (eletriptan HBr), a selective 5-hydroxytryptamine (also known as serotonin) 1B/1D receptor agonist, in Koreans and compare the results to those observed in non-Koreans in a previously published study. Patients and methods: A randomized, open-label, single, and repeated-dose study was conducted in 16 healthy Korean male subjects using a four-treatment, four-period, and four-sequence crossover design (NCT01139515). The subjects received one of the following four treatments in each period: a single dose of 20, 40, 80 mg eletriptan HBr or a repeated oral dose of 40 mg 2 h apart. Blood samples were collected before and up to 26 h after dosing for quantification of plasma eletriptan concentration by high-performance liquid chromatography tandem–mass spectrometry. The PK parameters were estimated using noncompartmental methods. Ethnicity differences between Korean and non-Korean subjects were identified using geometric mean ratios and 90% confidence intervals (CIs) of dose-normalized maximum plasma concentration (Cmax) and dose-normalized area under the plasma concentration versus time curve from 0 h to the last measurable concentration (AUC0–t). Results: After single-dose administration of eletriptan HBr to Korean subjects, the mean Cmax and AUC0–t increased linearly with dose. Comparable total systemic exposures were observed in the 2 h apart 40 mg repeated and single 80 mg dose. The geometric mean ratios (90% CIs) of the dose-normalized Cmax and AUC0–t of Korean subjects were similar to those of non-Korean subjects reported in the literature. The adverse events observed were transient and mild in severity. Conclusion: Eletriptan HBr showed linear PK and was well tolerated in Korean subjects. The PK and tolerability of eletriptan HBr did not differ between Korean and non-Korean subjects. Keywords: pharmacokinetics, migraine, eletriptan hydrobromide, Korean subjects

Kwang-Hee Shin,1 Hyeon Cheol Jeong,1 Dong-Hee Choi,2 Sung Nyun Kim,3 Tae-Eun Kim4 1College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 2Department of Medical Science, Konkuk University School of Medicine, 3Department of Psychiatry, Seoul Medical Center, 4Department of Clinical Pharmacology, Konkuk University Medical Center, Seoul, Republic of Korea Background: Although many studies have investigated the association of a single nucleotide polymorphism in TNF-α G-308A gene with depression, their association is still controversial. To clarify this, we performed a meta-analysis.Method: Studies related to TNF-α G-308A and depression were retrieved from PubMed, Medline, Embase, and Scopus (up to April 18, 2017). The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in the models of allele comparison (G vs A), homozygote comparison (GG vs AA), dominant (GG vs GA + AA), and recessive (GG + GA vs AA) to estimate the strength of the associations.Results: A total of 10 case–control studies were included in this meta-analysis. Overall, no significant association between TNF-α G-308A and depression was found (G vs A: OR [95% CI] =1.09 [0.92, 1.29]; GG vs AA: 1.24 [0.71, 2.15]; GG vs GA + AA: 1.01 [0.76, 1.35]; GG + GA vs AA: 1.22 [0.70, 2.13]). In subgroup analyses by ethnicity or age group, no statistically significant association between TNF-α G-308A polymorphisms and depression was shown.Conclusion: This meta-analysis revealed that TNF-α G-308A polymorphism is not associated with susceptibility to depression. Keywords: TNF-α G-308A, rs1800629, genetic polymorphism, depressive disorder

Namyi Gu,1,2 Joo-Youn Cho,3 Kwang-Hee Shin,4 In-Jin Jang,3 Moo-Yong Rhee2,5 1Department of Clinical Pharmacology and Therapeutics, 2Clinical Trial Center, Dongguk University College of Medicine and Ilsan Hospital, Goyang, 3Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 4Pharmacotherapy & Translational Research Lab., College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 5Cardiovascular Center, Dongguk University College of Medicine and Ilsan Hospital, Goyang, Republic of Korea Abstract: A low sodium diet enhances the hemodynamic effect of renin–angiotensin system blockers. It was suggested that the substrates of P-glycoprotein or cytochrome P450 3A4 were reduced on a high sodium diet. This study aimed to investigate the influence of high sodium diet on the pharmacokinetics and pharmacodynamics of fimasartan, which is a substrate of cytochrome P450 3A4 but not P-glycoprotein. The study design was a two-diet, two-period, two-sequence, randomized, open-label, and crossover with 1-week washout for diet. Eligible subjects were fed with either low sodium (50 mEq/day) diet or high sodium diet (300 mEq/day) for 7 days in the first hospitalization period and the other diet in the second period. On the seventh morning of each period, subjects received a single dose of fimasartan 60 mg in a fasted state. The serial plasma concentrations of fimasartan, serum aldosterone concentration (SAC), and plasma renin activity (PRA) were measured for pharmacokinetic–pharmacodynamic analysis. Sixteen subjects completed the study satisfying the compliance test for diets. Although the mean systemic exposure of fimasartan is slightly (≈10%) decreased on a high sodium diet, the difference was not statistically or clinically significant (P>0.05). The SAC and PRA after fimasartan administration were highly dependent on their baseline levels. The dietary sodium content influenced the baseline of SAC and PRA, but did not influence the ratio change of SAC and PRA after fimasartan treatment. The ratio change of SAC after fimasartan treatment was correlated to the systemic exposure of fimasartan (P0.05). In conclusion, the pharmacokinetics of fimasartan and ratio changes of SAC and PRA after fimasartan treatment were not significantly influenced by dietary sodium content. Keywords: aldosterone, renin activity, angiotensin receptor blocker, aldosterone, renin, cytochrome P450 3A4, P-glycoprotein, healthy, sodium diet

Oral mucosa provides the first line of defense against a diverse array of environmental and microbial irritants by forming the barrier of epithelial cells interconnected by multiprotein tight junctions (TJ), adherens junctions, desmosomes, and gap junction complexes. Grainyhead-like 2 (GRHL2), an epithelial-specific transcription factor, may play a role in the formation of the mucosal epithelial barrier, as it regulates the expression of the junction proteins. The current study investigated the role of GRHL2 in the Porphyromonas gingivalis (Pg)-induced impairment of epithelial barrier functions. Exposure of human oral keratinocytes (HOK-16B and OKF6 cells) to Pg or Pg-derived lipopolysaccharides (Pg LPSs) led to rapid loss of endogenous GRHL2 and the junction proteins (e.g., zonula occludens, E-cadherin, claudins, and occludin). GRHL2 directly regulated the expression levels of the junction proteins and the epithelial permeability for small molecules (e.g., dextrans and Pg bacteria). To explore the functional role of GRHL2 in oral mucosal barrier, we used a Grhl2 conditional knockout (KO) mouse model, which allows for epithelial tissue-specific Grhl2 KO in an inducible manner. Grhl2 KO impaired the expression of the junction proteins at the junctional epithelium and increased the alveolar bone loss in the ligature-induced periodontitis model. Fluorescence in situ hybridization revealed increased epithelial penetration of oral bacteria in Grhl2 KO mice compared with the wild-type mice. Also, blood loadings of oral bacteria (e.g., Bacteroides, Bacillus, Firmicutes, β-proteobacteria, and Spirochetes) were significantly elevated in Grhl2 KO mice compared to the wild-type littermates. These data indicate that Pg bacteria may enhance paracellular penetration through oral mucosa in part by targeting the expression of GRHL2 in the oral epithelial cells, which then impairs the epithelial barrier by inhibition of junction protein expression, resulting in increased alveolar tissue destruction and systemic bacteremia.

High-risk human papillomavirus (HPV) is a major risk factor for oral and pharyngeal cancers (OPCs), yet the detailed mechanisms by which HPV promotes OPCs are not understood. Forkhead box M1B (FoxM1B) is an oncogene essential for cell cycle progression and tumorigenesis, and it is aberrantly overexpressed in many tumors. We previously showed that FoxM1B was the putative target of an epithelial-specific transcription factor, Grainyhead-like 2 (GRHL2). In the current study, we demonstrate that HPV type 16 (HPV-16) E6 induces FoxM1B in human oral keratinocytes (HOKs) and tonsillar epithelial cells (TECs) in part through GRHL2. FoxM1B was barely detectable in cultured normal human oral keratinocytes (NHOKs) and progressively increased in immortalized HOKs harboring HPV-16 genome (HOK-16B) and tumorigenic HOK-16B/BaP-T cells. Retroviral expression of HPV-16 E6 and/or E7 in NHOKs, TECs, and hypopharyngeal carcinoma cells (FaDu) revealed induction of FoxM1B and GRHL2 by the E6 protein but not E7. Both GRHL2 and FoxM1B were strongly induced in the epidermis of HPV-16 E6 transgenic mice and HPV+ oral squamous cell carcinomas. Ectopic expression of FoxM1B led to acquisition of transformed phenotype in HOK-16B cells. Loss of FoxM1B by lentiviral short hairpin RNA vector or chemical inhibitor led to elimination of tumorigenic characteristics of HOK-16B/BaP-T cells. Luciferase reporter assay revealed that GRHL2 directly bound and regulated the FoxM1B gene promoter activity. Using epithelial-specific Grhl2 conditional knockout mice, we exposed wild-type (WT) and Grhl2 KO mice to 4-nitroquinolin 1-oxide (4-NQO), which led to induction of FoxM1B in the tongue tissues and rampant oral tumor development in the WT mice. However, 4-NQO exposure failed to induce tongue tumors or induction of FoxM1B expression in Grhl2 KO mice. Collectively, these results indicate that HPV-16 induces FoxM1B in part through GRHL2 transcriptional activity and that elevated FoxM1B level is required for oropharyngeal cancer development.

To explore potential biomarkers for amoxicillin/clavulanate-induced liver injury (AC-DILI), we conducted a clinical trial in 32 healthy subjects based on multi-omics approaches. Every subject was administered amoxicillin/clavulanate for 14 days. The liver-specific microRNA-122 (miR-122) level increased prior to and correlated well with the observed alanine aminotransferase (ALT) level increase. This result indicates its potential as a sensitive early marker for AC-DILI. We also identified urinary metabolites, such as azelaic acid and 7-methylxanthine, with levels that significantly differed among the groups classified by ALT elevation level on day 8 after drug administration ( P < 0.05). Lymphocyte proliferation in response to the drug was also observed. These findings demonstrate sequential changes in the process of AC-DILI, including metabolic changes, increased miR-122 level, increased liver enzyme activity, and enhanced lymphocyte proliferation after drug administration. In conclusion, this study provides potential biomarkers for AC-DILI based on currently known mechanisms using comprehensive multi-omics approaches. [ABSTRACT FROM AUTHOR]

Background: Social support may influence the impact of stressful life events on breast cancer patients' psychological state. However, the precise status of depressive mood in breast cancer during the first year after diagnosis is not yet known.Methods: Perceived social support, health-related quality of life, and depressive mood were assessed at enrollment and 1 year after breast cancer diagnosis in 286 women newly diagnosed with stages I-III breast cancer. Breast cancer patients' social support and depressive mood at diagnosis and 1 year after diagnosis were compared with the general female population (GFP), and predictors of worsened depressive mood were identified.Results: All subscales of social support and depressive mood among breast cancer patients were significantly lower at one after diagnosis than at diagnosis (all p<0.001). At diagnosis, breast cancer patients reported better emotional (p=0.004), informational (p=0.006), and affectionate support (p=0.002), and poorer depressive mood (p<0.001) than the GFP. After 1 year, however, perceived social support in breast cancer patients was significantly decreased and depressive mood was significantly improved, becoming similar to scores of the GFP. Only tangible support was significantly lower than the GFP at 1 year after diagnosis (p=0.028). Hierarchical multiple logistic regression analysis for best fitting the model statistically and clinically indicated that decreased emotional support, transition to post-menopausal status, impaired role functioning, and financial difficulties predicted deteriorated depressive mood.Conclusion: Breast cancer patients might have greater control over tangible support than any other type of social support. Together with the transition to post-menopausal status, decreased perceived emotional social support was the best predictor of depressive mood among breast cancer patients during the first year after diagnosis. [ABSTRACT FROM AUTHOR]

The chloroform and the ethyl acetate fractions from the roots of Acanthopanax chiisanensis exhibited the significant inhibition of TPA-induced prostaglandin E(2) (PGE(2)) production in rat peritoneal macrophages. Five lignans were isolated from the chloroform fraction and their structures were elucidated as l-sesamin, helioxanthin, savinin, taiwanin C, and 3-(3,4-dimethoxybenzyl)-2-(3,4-methylenedioxybenzyl)butyrola Among the lignans tested, taiwanin C showed the most potent inhibitory activity (IC(50) = 0.12 microM) on PGE(2) production with the relative order of potency, taiwanin C >> 3-(3,4-dimethoxybenzyl)-2-(3,4-methylenedioxybenzyl)butyrola > savinin = helioxanthin. l-Sesamin showed no inhibitory activity at 30 microM. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the treatment outcome and efficacy of regional lymph node irradiation after neoadjuvant chemotherapy (NCT) and surgery in positron emission tomography (PET)-positive clinical N3 (cN3) breast cancer patients. Methods and Materials: A total of 55 patients with ipsilateral infraclavicular (ICL), internal mammary (IMN), or supraclavicular (SCL) lymph node involvement in the absence of distant metastases, as revealed by an initial PET scan, were retrospectively analyzed. The clinical nodal stage at diagnosis (2002 AJCC) was cN3a in 14 patients (26%), cN3b in 12 patients (22%), and cN3c in 29 patients (53%). All patients were treated with NCT, followed by mastectomy or breast-conserving surgery and subsequent radiotherapy (RT) with curative intent. Results: At the median follow-up of 38 months (range, 9-80 months), 20 patients (36%) had developed treatment failures, including distant metastases either alone or combined with locoregional recurrences that included one ipsilateral breast recurrence (IBR), six regional failures (RF), and one case of combined IBR and RF. Only 3 patients (5.5%) exhibited treatment failure at the initial PET-positive clinical N3 lymph node. The 5-year locoregional relapse-free survival, disease-free survival (DFS), and overall survival rates were 80%, 60%, and 79%, respectively. RT delivered to PET-positive IMN regions in cN3b patients and at higher doses (≥55 Gy) to SCL regions in cN3c patients was not associated with improved 5-year IMN/SCL relapse-free survival or DFS. Conclusion: NCT followed by surgery and RT, including the regional lymph nodes, resulted in excellent locoregional control for patients with PET-positive cN3 breast cancer. The primary treatment failure in this group was due to distant metastasis rather than RF. Neither higher-dose RT directed at PET-positive SCL nodes nor coverage of PET-positive IMN nodes was associated with additional gains in locoregional control or DFS. [ABSTRACT FROM AUTHOR]

Background: In clinical laboratories, the precision and sensitivity of autoverification technologies are crucial for ensuring reliable diagnostics. Conventional methods have limited sensitivity and applicability, making error detection challenging and reducing laboratory efficiency. This study introduces a machine learning (ML)-based autoverification technology to enhance tumor marker test error detection., Methods: The effectiveness of various ML models was evaluated by analyzing a large data set of 397 751 for model training and internal validation and 215 339 for external validation. Sample misidentification was simulated by random shuffling error-free test results with a 1% error rate to achieve a real-world approximation. The ML models were developed with Bayesian optimization for tuning. Model validation was performed internally at the primary institution and externally at other institutions, comparing the ML models' performance with conventional delta check methods., Results: Deep neural networks and extreme gradient boosting achieved an area under the receiver operating characteristic curve of 0.834 to 0.903, outperforming that of conventional methods (0.705 to 0.816). External validation by 3 independent laboratories showed that the balanced accuracy of the ML model ranged from 0.760 to 0.836, outperforming the balanced accuracy of 0.670 to 0.773 of the conventional models., Conclusions: This study addresses limitations regarding the sensitivity of current delta check methods for detection of sample misidentification errors and provides versatile models that mitigate the operational challenges faced by smaller laboratories. Our findings offer a pathway toward more efficient and reliable clinical laboratory testing., (© Association for Diagnostics & Laboratory Medicine 2024.)

This paper proposes a heuristic association algorithm between access points (APs) and user equipment (UE) in user-centric cell-free massive multiple-input-multiple-output (MIMO) systems, specifically targeting scenarios where UEs share the same frequency and time resources. The proposed algorithm prevents overserving APs and ensures the connectivity of all UEs, even when the number of UEs is significantly greater than the number of APs. Additionally, we assume the use of low-resolution analog-to-digital converters (ADCs) to reduce fronthaul capacity. While realistic massive access scenarios, such as those in Internet-of-Things (IoT) environments, often involve hundreds or thousands of UEs per AP using multiple access techniques to allocate different frequency and time resources, our study focuses on scenarios where UEs within each AP cluster share the same frequency and time resources to highlight the impact of pilot contamination in dense network environments. The proposed algorithm is validated through simulations, confirming that it guarantees the connection of all UEs and prevents overserving APs. Furthermore, we analyze the required fronthaul capacity based on quantization bits and confirm that the proposed algorithm outperforms existing algorithms in terms of SE and average SE performance for UEs.

Although microalgae typically serve as prey for jellyfish ephyrae in marine food webs, this study investigated the potential of harmful microalgae to produce detrimental effects on the moon jellyfish Aurelia aurita. Understanding the biological interactions between Aurelia and microalgal species is crucial, particularly considering their common co-occurrence in coastal waters worldwide. We examined the effects of 11 protist strains, comprising seven species of harmful microalgae and two non-toxic microalgae, on A. aurita ephyrae. The rhythmic pulsation behavior of A. aurita was significantly suppressed when exposed to the raphidophytes Heterosigma akashiwo and Chattonella marina var. ovata and the dinoflagellates Amphidinium carterae, Coolia canariensis, and Pfiesteria piscicida. Notably, the media filtrates of all H. akashiwo strains and C. marina var. ovata killed ephyrae, implying a possible extracellular release of chemicals. This study discovered novel interactions between microalgae and jellyfish ephyrae, implying that harmful algal blooms may suppress mass occurrences of Aurelia medusae., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To investigate the potential relationship between trastuzumab emtansine (T-DM1) treatment and radionecrosis induced by brain stereotactic radiosurgery (SRS) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer., Materials and Methods: Patients with HER2-positive breast cancer who were diagnosed with brain metastasis and received both SRS and HER2-targeted agents between 2012 and 2022 were retrospectively analyzed. Patients who received T-DM1 within 1 year (either before or after) of SRS were considered as 'T-DM1 exposure (+)'. T-DM1 exposure (-) group had other HER2-targeted agents or received T-DM1 more than 1 year before or after SRS. Symptomatic radionecrosis was defined as Common Terminology Criteria for Adverse Events grade 2 or greater., Results: A total of 103 patients with 535 treatment sessions were included from seven tertiary medical centers in Korea and Italy. The median follow-up duration was 15.5 months (range 1.1-101.9). By per-patient analysis, T-DM1 exposure (+) group had an increased risk of overall radionecrosis after multivariate analysis (HR 2.71, p = 0.020). Additionally, T-DM1 exposure (+) group was associated with a higher risk of symptomatic radionecrosis compared to T-DM1 exposure (-) patients (HR 4.34, p = 0.030). In per-treatment analysis, T-DM1 exposure (+) was linked to higher incidences of overall (HR 3.13, p = 0.036) and symptomatic radionecrosis (HR 10.4, p = 0.013) after multivariate analysis. A higher prevalence of radionecrosis was observed with T-DM1 exposure (+) and a previous history of whole brain radiotherapy., Conclusion: An increased risk of radionecrosis was observed in patients receiving T-DM1 with brain SRS. Further research is needed to better understand the optimal sequence and interval for administering T-DM1 and SRS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sufentanil is frequently used as an anesthetic agent in cardiac surgery owing to its cardiovascular safety and favorable pharmacokinetics. However, the pharmacokinetics profiles of sufentanil in patients undergoing cardiopulmonary bypass (CPB) surgery remain less understood, which is crucial for achieving the desired level of anesthesia and mitigating surgical complications. Therefore, this study aimed to develop a population pharmacokinetic model of sufentanil in patients undergoing CPB surgery and elucidate the clinical factors affecting its pharmacokinetic profile. Adult patients who underwent cardiac surgery with CPB and were administered sufentanil for anesthesia were enrolled. Arterial blood samples were collected to quantify plasma concentrations of sufentanil and clinical laboratory parameters, including inflammatory cytokines. A population pharmacokinetic model was established using nonlinear mixed-effects modeling. Simulations were performed using the pharmacokinetic parameters of the final model. Overall, 20 patients were included in the final analysis. Sufentanil pharmacokinetics were modeled using a two-compartment model, accounting for CPB effects. Sufentanil clearance increased 2.80-fold during CPB and warming phases, while the central compartment volume increased 2.74-fold during CPB. CPB was a significant covariate affecting drug clearance and distribution volume. No other significant covariates were identified despite increased levels of the inflammatory cytokines, including IL-6, IL-8, and TNF-α during CPB. The simulation indicated a 30 μg loading dose and 40 μg/h maintenance infusion for target-controlled infusion. Additionally, a bolus dose of 60 μg was added at CPB initiation to adjust for exposure changes during this phase. Considering the target sufentanil concentrations, a uniform dosing regimen was acceptable for effective analgesia., (© 2024 The Author(s). CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: This study aimed to determine practical delta check limits (DCLs) for thyroid function tests (TFTs) to detect sample misidentifications across various clinical settings., Methods: Between 2020 and 2022, 610,437 paired TFT results were collected from six university hospitals. The absolute DCL (absDCL) was determined using the 95th percentile for each clinical setting from a random 60 % of the total data. These absDCLs were then tested within and across different settings using the remaining 40 % of the data, alongside mix-up datasets for result and sample comparisons. The sensitivities of absDCL were calculated within and across groups in the mix-up datasets., Results: Health screening absDCLs were notably lower than in other settings (2.58 vs. 5.93-7.08 for thyroid-stimulating hormone; 4.12 vs. 8.24-10.04 for free thyroxine; 0.49 vs. 0.82-0.91 for total triiodothyronine). The proportion of results exceeding absDCL of health screening differed from those of other clinical settings. Furthermore, sensitivity between health screening and other clinical settings was significantly different in both the result mix-up and sample mix-up datasets., Conclusions: This study determined practical DCLs for TFTs and highlighted differences in absDCLs between health screening and other settings. These findings emphasize the importance of tailored DCLs in improving the accurate reporting of TFTs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: This study aims to evaluate the treatment approaches and locoregional patterns for Adenoid cystic carcinoma (ACC) in the breast, which is an uncommon malignant tumor with limited clinical data., Materials and Methods: A total of 93 patients diagnosed with primary ACC in the breast between 1992 and 2022 were collected from multi-institutions. All patients underwent surgical resection, including breast-conserving surgery (BCS) or total mastectomy (TM). The recurrence patterns and locoregional recurrence-free survival (LRFS) were assessed., Results: Seventy-five patients (80.7%) underwent BCS, and 71 of them (94.7%) received post-operative radiation therapy (PORT). Eighteen patients (19.3%) underwent TM, with 5 of them (27.8%) also receiving PORT. With a median follow-up of 50 months, the LRFS rate was 84.2% at 5 years. Local recurrence (LR) was observed in 5 patients (5.4%) and 4 cases (80%) of the LR occurred in the tumor bed. Three of LR (3/75, 4.0%) had a history of BCS and PORT, meanwhile, two of LR (2/18, 11.1%) had a history of mastectomy. Regional recurrence occurred in 2 patients (2.2%), and both cases had a history of PORT with (n=1) and without (n=1) irradiation of the regional lymph nodes. Partial breast irradiation (p=0.35), BCS (p=0.96) and PORT in BCS group (p=0.33) had no significant association with LRFS., Conclusion: BCS followed by PORT was the predominant treatment approach for ACC of the breast and local recurrence mostly occurred in the tumor bed. The findings of this study suggest that partial breast irradiation might be considered for PORT in primary breast ACC.

Considering the rising prevalence of breast reconstruction followed by radiotherapy (RT), evaluating the cosmetic impact of RT is crucial. Currently, there are limited tools for objectively assessing cosmetic outcomes in patients who have undergone reconstruction. Therefore, we validated the cosmetic outcome using a previously developed anomaly Generative Adversarial Network (GAN)-based model and evaluated its utility. Between January 2016 and December 2020, we collected computed tomography (CT) images from 82 breast cancer patients who underwent immediate reconstruction surgery followed by radiotherapy. Among these patients, 38 received immediate implant insertion, while 44 underwent autologous breast reconstruction. Anomaly scores (AS) were estimated using an anomaly GAN model at pre-RT, 1st follow-up, 1-year (Post-1Y) and 2-year (Post-2Y) after RT. Subsequently, the scores were analyzed in a time-series manner, considering reconstruction types (implant versus autologous), RT techniques, and the incidence of major complications. The median age of the patients was 46 years (range 29-62). The AS between Post-1Y and Post-2Y demonstrated a positive relationship (coefficient 0.515, P < 0.001). The AS was significantly associated with objective cosmetic indices, namely Breast Contour Difference (P = 0.009) and Breast Area Difference (P = 0.004), at both Post-1Y and Post-2Y. Subgroup analysis stratified by type of breast reconstruction revealed significantly higher AS values in patients who underwent prosthetic implant insertion compared to those with autologous reconstruction at all follow-up time points (1st follow-up, P = 0.001; Post-1Y, P < 0.001; and Post-2Y, P < 0.001). A threshold AS of ≥ 1.9 was associated with a 10% predicted risk of developing major complications. The feasibility of an AS generated by a GAN model for predicting both cosmetic outcomes and the likelihood of complications following RT has been successfully validated. Further investigation involving a larger patient cohort is warranted., (© 2024. The Author(s).)

Background: We examined the patterns of breast reconstruction postmastectomy in breast cancer patients undergoing postmastectomy radiotherapy (PMRT) and compared complications based on radiotherapy fractionation and reconstruction procedures., Methods: Using National Health Insurance Service (NHIS) data (2015-2020), we analysed 4669 breast cancer patients with PMRT and reconstruction. Using propensity matching, cohorts for hypofractionated fractionation (HF) and conventional fractionation (CF) were created, adjusting for relevant factors and identifying grade ≥3 complications., Result: Of 4,669 patients, 30.6% underwent HF and 69.4% CF. The use of HF has increased from 19.4% in 2015 to 41.0% in 2020. Immediate autologous (32.9%) and delayed two-stage implant reconstruction (33.9%) were common. Complication rates for immediate (N = 1286) and delayed two-stage (N = 784) reconstruction were similar between HF and CF groups (5.1% vs. 5.4%, P = 0.803, and 10.5% vs. 10.7%, P = 0.856, respectively) with median follow-ups of 2.5 and 2.6 years. HF showed no increased risk of complications across reconstruction methods., Conclusion: A nationwide cohort study revealed no significant difference in complication rates between the HF and CF groups, indicating HF for reconstructed breasts is comparable to CF. However, consultation regarding the fractionation for reconstructed breast cancer patients may still be necessary., (© 2024. The Author(s).)

The lattice oxygen mechanism (LOM) offers an efficient reaction pathway for oxygen evolution reactions (OERs) in energy storage and conversion systems. Owing to the involvement of active lattice oxygen enhancing electrochemical activity, addressing the structural and electrochemical stabilities of LOM materials is crucial. Herein, a heterostructure (Bi/BiCeO 1.8 H) containing abundant under-coordinated oxygen atoms having oxygen nonbonding states is synthesized by a simple electrochemical deposition method. Given the difference in reduction potentials between Bi and Ce, partially reduced Bi nanoparticles and surrounding under-coordinated oxygen atoms are generated in BiCeO 1.8 H. It is found that the lattice oxygen can be activated as a reactant of the OER when the valence state of Bi increases to Bi 5+ , leading to increased metal-oxygen covalency and that the oxophilic Ce 3+ / 4+ redox couple can maintain the Bi nanoparticles and surrounding under-coordinated oxygen atoms by preventing over-oxidation of Bi. The anion exchange membrane water electrolyzer with Bi/BiCeO 1.8 H exhibits a low cell voltage of 1.79 V even at a high practical current density of 1.0 A cm -2 . Furthermore, the cell performance remains significantly stable over 100 h with only a 2.2% increase in the initial cell voltage, demonstrating sustainable lattice oxygen redox., (© 2024 Wiley‐VCH GmbH.)

Forkhead box O1 (FOXO1) regulates muscle growth, but the metabolic role of FOXO1 in skeletal muscle and its mechanisms remain unclear. To explore the metabolic role of FOXO1 in skeletal muscle, we generated skeletal muscle-specific Foxo1 inducible knockout (mFOXO1 iKO) mice and fed them a high-fat diet to induce obesity. We measured insulin sensitivity, fatty acid oxidation, mitochondrial function, and exercise capacity in obese mFOXO1 iKO mice and assessed the correlation between FOXO1 and mitochondria-related protein in the skeletal muscle of patients with diabetes. Obese mFOXO1 iKO mice exhibited improved mitochondrial respiratory capacity, which was followed by attenuated insulin resistance, enhanced fatty acid oxidation, and improved skeletal muscle exercise capacity. Transcriptional inhibition of FOXO1 in peroxisome proliferator-activated receptor δ (PPARδ) expression was confirmed in skeletal muscle, and deletion of PPARδ abolished the beneficial effects of FOXO1 deficiency. FOXO1 protein levels were higher in the skeletal muscle of patients with diabetes and negatively correlated with PPARδ and electron transport chain protein levels. These findings highlight FOXO1 as a new repressor in PPARδ gene expression in skeletal muscle and suggest that FOXO1 links insulin resistance and mitochondrial dysfunction in skeletal muscle via PPARδ., (© 2024 by the American Diabetes Association.)

The chemical stability and energy density of redox couples are crucial factors in enhancing the durability and cost competitiveness of aqueous flow batteries. This study proposed integrating functional groups to viologen anolyte to increase its solubility and, consequently, energy density and stability for prolonged performance. Specifically, sulfonate and ester groups were selectively incorporated at the nitrogen sites of viologen to enhance solubility, leveraging their asymmetry and double hydrophilicity. Furthermore, an alpha-methyl group was introduced between the bipyridine and ester groups to enhance the chemical stability by preventing stacking and dimerization that can lead to irreversible degradation. The modified viologen demonstrated a remarkable solubility of 3.0 M in deionized water, corresponding to a volumetric capacity of 80.404 Ah L -1 . Additionally, the designed viologen exhibits outstanding retention of 92.4% after 200 cycles with a minimal capacity fading rate of 0.055% per cycle in a 0.1 M flow cell test.

Objectives: Although the clinical role of protein convertase subtilisin kexin type 9 (PCSK9) inhibitors for cholesterol management is increasing, the post-marketing period of use is short compared to other lipid-lowering drugs, so there is still insufficient evidence for their efficacy and safety. In this meta-analysis, we evaluated preventive effects of stroke and cardiovascular (CV) events using evolocumab and alirocumab., Materials and Methods: We assessed the relative risk of stroke and CV events after alirocumab or evolocumab treatment in individuals with or without clinical CV diseases compared with that in controls. In addition, we evaluated the relative risk of hemorrhagic stroke., Results: A total of 25 articles were included (median of study duration = 52 weeks). The risk of stroke was significantly decreased after treatment with alirocumab or evolocumab (primary prevention in patients without CV diseases: RR = 0.733; 95% CI, 0.618 - 0.870; secondary prevention in patients with CV diseases: RR = 0.703; 95% CI, 0.562 - 0.880). The risk of CV events also significantly decreased in patients treated with alirocumab or evolocumab (primary prevention: RR = 0.818; 95% CI, 0.777 - 0.861; secondary prevention: RR = 0.725; 95% CI, 0.578 - 0.910). The relative risk of hemorrhagic stroke was not significantly different between PCSK9 inhibitor-treated patients and controls (RR = 1.041; 95% CI, 0.690 - 1.573)., Conclusion: Our findings indicate that evolocumab and alirocumab are significantly effective without increasing the risk of hemorrhagic stroke. Based on this, the PCSK9 inhibitors can be highly recommended for cholesterol management.

Compound-specific isotope analysis stands as a promising tool for unveiling the behavior of pesticides in agricultural environments. Using the commercial formulations of persistent fungicide procymidone (PRO) and less persistent insecticide diazinon (DIA), respectively, we analyzed the concentration and carbon isotope composition (δ 13 C) of the residual pesticides through soil incubation experiments in a greenhouse (for 150 days) and lab conditions (for 50-70 days). Our results showed that the magnitude of δ 13 C variation depends on pesticide specificity, in which PRO in the soil exhibited little variation in δ 13 C values over the entire incubation times, while DIA demonstrated an increased δ 13 C value, with the extent of δ 13 C variability affected by different spiking concentrations, plant presence, and light conditions. Moreover, the pesticides extracted from soils were isotopically overlapped with those from crop lettuce. Ultimately, the isotope composition of pesticides could infer the degradation and translocation processes and might contribute to identifying the source(s) of pesticide formulation in agricultural fields.

The European Society for Radiotherapy and Oncology-Advisory Committee in Radiation Oncology Practice (ESTRO-ACROP) updated a new target volume delineation guideline for postmastectomy radiotherapy (PMRT) after implant-based reconstruction. This study aimed to evaluate the impact on breast complications with the new guideline compared to the conventional guidelines. In total, 308 patients who underwent PMRT after tissue expander or permanent implant insertion from 2016 to 2021 were included; 184 received PMRT by the new ESTRO-ACROP target delineation (ESTRO-T), and 124 by conventional target delineation (CONV-T). The endpoints were major breast complications (infection, necrosis, dehiscence, capsular contracture, animation deformity, and rupture) requiring re-operation or re-hospitalization and any grade ≥2 breast complications. With a median follow-up of 36.4 months, the cumulative incidence rates of major breast complications at 1, 2, and 3 years were 6.6%, 10.3%, and 12.6% in the ESTRO-T group, and 9.7%, 15.4%, and 16.3% in the CONV-T group; it did not show a significant difference between the groups (p = 0.56). In multivariable analyses, target delineation is not associated with the major complications (sHR = 0.87; p = 0.77). There was no significant difference in any breast complications (3-year incidence, 18.9% vs. 23.3%, respectively; p = 0.56). Symptomatic RT-induced pneumonitis was developed in six (3.2%) and three (2.4%) patients, respectively. One local recurrence occurred in the ESTRO-T group, which was within the ESTRO-target volume. The new ESTRO-ACROP target volume guideline did not demonstrate significant differences in major or any breast complications, although it showed a tendency of reduced complication risks. As the dosimetric benefits of normal organs and comparable oncologic outcomes have been reported, further analyses with long-term follow-up are necessary to evaluate whether it could be connected to better clinical outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Park, Jang, Chang, Kim, Choi, Hong, Jin, Chang, Myung, Jeong, Heo, Kim and Shin.)

Background/Objectives: Periprosthetic joint infection (PJI) is a severe complication in total knee arthroplasty (TKA) with catastrophic outcomes. The relationship between prolonged operative times and PJI remains debated. This meta-analysis investigated the link between prolonged operative times and the risk of PJI in primary TKA. Methods: A comprehensive search of the MEDLINE/PubMed, Cochrane Library, and EMBASE databases was conducted to identify studies comparing the incidence of PJI in TKAs with prolonged versus short operative times, as well as those comparing operative times in TKAs with and without PJI. Pooled standardized mean differences (SMD) in operative times between groups with and without PJI or surgical site infections (SSI), including superficial SSIs and PJIs, were analyzed. Additionally, the pooled odds ratios (OR) for PJI in TKAs with operative times exceeding 90 or 120 min were examined. Results: Seventeen studies involving 427,361 patients were included. Significant differences in pooled mean operative times between the infected and non-infected TKA groups were observed (PJI, pooled SMD = 0.38, p < 0.01; SSI, pooled SMD = 0.72, p < 0.01). A higher risk of PJI was noted in surgeries lasting over 90 or 120 min compared to those of shorter duration (90 min, pooled OR = 1.50, p < 0.01; 120 min, pooled OR = 1.56, p < 0.01). Conclusions: An association between prolonged operative time and increased risk of PJI in primary TKA has been established. Strategies for infection prevention should encompass thorough preoperative planning aimed at minimizing factors that contribute to prolonged operative times.

In this study, we estimated the contributions of carbonate mineral weathering to dissolved inorganic carbon (DIC) and carbonate-derived DIC to autochthonous particulate organic carbon (POC) in two temperate Korean rivers. We combined stoichiometric and stable carbon isotopic approaches to calculate the contribution of autochthonous POC, considering diverse riverine DIC sources. We collected surface water samples from May 2016 to May 2018 and analyzed the major ion composition of rivers along with the concentrations and stable carbon isotopes of DIC. Our estimates showed that the relative abundances of carbonate mineral weathering (0.41 ± 0.11 in the Geum River and 0.43 ± 0.07 in the Seomjin River) were only slightly lower than those of silicate mineral weathering (0.59 ± 0.1 in the Geum River and 0.57 ± 0.07 in the Seomjin River). The resulting percentage contributions of DIC derived from the carbonate mineral weathering to riverine autochthonous POC, if we consider the additional DIC sources of atmospheric and soil-derived CO 2 , were 10 ± 3 % in the Geum River and 2 ± 1 % in the Seomjin River. The calculated annual fluxes of carbonate-derived DIC for 2016-2018 were 23.2 ± 0.3 Gg C yr -1 in the Geum River and 1.1 ± 0.4 Gg C yr -1 in the Seomjin River. Moreover, the calculated annual fluxes of carbonate-derived POC were 3.6 ± 0.5 Gg C yr -1 in the Geum River and 0.1 ± 0.7 Gg C yr -1 in the Seomjin River. Accordingly, our study provides the first insight into the contribution of carbonate-derived DIC to riverine autochthonous POC in small temperate Korean river systems, dominated by silicate rocks., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

This study investigated the nitrate dual isotopic compositions (δ 15 N NO3 and δ 18 O NO3 ) of water samples to trace nitrate sources in Lake Sihwa, which encompasses various land-use types (e.g., urban, industry, wetland, and agriculture). The biogeochemical interactions of anthropogenic nitrogen sources (e.g., soil, road dust, and septic water) were also evaluated through multiple pathways from terrestrial boundaries to the water column. Based on increased concentrations of dissolved total nitrogen (DTN; 3.1 ± 1.6 mg/L) after typhoon, the variation of element stoichiometry (N:P:Si) in this system shifted to the relatively N-rich conditions (DIN/DIP; 14.1 ± 8.1, DIN/DSi; 1.4 ± 1.8), potentially triggering the occurrence of harmful algal blooms. Furthermore, discriminative isotopic compositions (δ 15 N NO3 ; 4.0 ± 2.1 ‰, δ 18 O NO3 ; 6.1 ± 4.3 ‰) after the typhoon suggested the increased DTN input of anthropogenic origins within Lake Sihwa would be mainly transported from urban sources (76 ± 9 %). Consequently, the isotopic-based approach may be useful for effective water quality management under increased anthropogenic activities near aquatic systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study was aimed to evaluate endogenous metabolic changes before and after cisplatin and radiation therapy in patients with cervical cancer via untargeted metabolomic analysis using plasma samples. A total of 13 cervical cancer patients were enrolled in this study. Plasma samples were collected from each patient on two occasions: approximately one week before therapy (P1) and after completion of cisplatin and radiation therapy (P2). Of the 13 patients, 12 patients received both cisplatin and radiation therapy, whereas one patient received radiation therapy alone. The samples were analyzed using the Ultimate 3000 coupled with Q Exactive TM Focus Hybrid Quadrupole-Orbitrap TM mass spectrometry (Thermo Fisher Scientific, Waltham, MA, USA). Chromatographic separation utilized a Kinetex C18 column 2.1×100 mm (2.6 μm) (Phenomenex, Torrance, CA, USA), and the temperature was maintained at 40°C. Following P2, there were statistically significant increases in the concentrations of indoxyl sulfate, phenylacetylglutamine, Lysophosphatidyethanolamine (LysoPE) (18:1), and indole-3-acetic acid compared with the concentrations observed at P1. Specifically, in the human papillomavirus (HPV) noninfection group, indoxyl sulfate, LysoPE (18:1), and phenylacetylglutamine showed statistically significant increases at P2 compared with P1. No significant changes in metabolite concentrations were observed in the HPV infection group. Indoxyl sulfate, LysoPE (18:1), phenylacetylglutamine, and indole-3-acetic acid were significantly increased following cisplatin and radiation therapy.

Background: Flow cytometric immunophenotyping of hematolymphoid neoplasms (FCI-HLN) is essential for diagnosis, classification, and minimal residual disease (MRD) monitoring. FCI-HLN is typically performed using in-house protocols, raising the need for standardization. Therefore, we surveyed the current status of FCI-HLN in Korea to obtain fundamental data for quality improvement and standardization., Methods: Eight university hospitals actively conducting FCI-HLN participated in our survey. We analyzed responses to a questionnaire that included inquiries regarding test items, reagent antibodies (RAs), fluorophores, sample amounts (SAs), reagent antibody amounts (RAAs), acquisition cell number (ACN), isotype control (IC) usage, positive/negative criteria, and reporting., Results: Most hospitals used acute HLN, chronic HLN, plasma cell neoplasm (PCN), and MRD panels. The numbers of RAs were heterogeneous, with a maximum of 32, 26, 12, 14, and 10 antibodies used for acute HLN, chronic HLN, PCN, ALL-MRD, and multiple myeloma-MRD, respectively. The number of fluorophores ranged from 4 to 10. RAs, SAs, RAAs, and ACN were diverse. Most hospitals used a positive criterion of 20%, whereas one used 10% for acute and chronic HLN panels. Five hospitals used ICs for the negative criterion. Positive/negative assignments, percentages, and general opinions were commonly reported. In MRD reporting, the limit of detection and lower limit of quantification were included., Conclusions: This is the first comprehensive study on the current status of FCI-HLN in Korea, confirming the high heterogeneity and complexity of FCI-HLN practices. Standardization of FCI-HLN is urgently needed. The findings provide a reference for establishing standard FCI-HLN guidelines.

Background: We aimed to construct an expert knowledge-based Bayesian network (BN) model for assessing the overall disease burden (ODB) in (y)pN1 breast cancer patients and compare ODB across arms of ongoing trials., Methods: Utilizing institutional data and expert surveys, we developed a BN model for (y)pN1 breast cancer. Expert-derived probabilities and disability weights for radiotherapy-related benefit (e.g., 7-year disease-free survival [DFS]) and toxicities were integrated into the model. ODB was defined as the sum of disability weights multiplied by probabilities. In silico predictions were conducted for Alliance A011202, PORT-N1, RAPCHEM, and RT-CHARM trials, comparing ODB, 7-year DFS, and side effects., Results: In the Alliance A011202 trial, 7-year DFS was 80.1% in both arms. Axillary lymph node dissection led to higher clinical lymphedema and ODB compared to sentinel lymph node biopsy with full regional nodal irradiation (RNI). In the PORT-N1 trial, the control arm (whole-breast irradiation [WBI] with RNI or post-mastectomy radiotherapy [PMRT]) had an ODB of 0.254, while the experimental arm (WBI alone or no PMRT) had an ODB of 0.255. In the RAPCHEM trial, the radiotherapy field did not impact the 7-year DFS in ypN1 patients. However, there was a mild ODB increase with a larger irradiation field. In the RT-CHARM trial, we identified factors associated with the major complication rate, which ranged from 18.3% to 22.1%., Conclusions: The expert knowledge-based BN model predicted ongoing trial outcomes, validating reported results and assumptions. In addition, the model demonstrated the ODB in different arms, with an emphasis on quality of life.

Purpose: We investigated the proportions of patients eligible for accelerated partial breast irradiation (APBI) among those with pT1-2N0 breast cancer, based on the criteria set by the American Society for Radiation Oncology (ASTRO), the Groupe Européen de Curiethérapie and the European Society for Radiotherapy and Oncology (GEC-ESTRO), the American Brachytherapy Society (ABS), and the American Society of Breast Surgeons (ASBS). Additionally, we analyzed the rate of APBI utilization among eligible patients., Materials and Methods: Patients diagnosed with pT1-2N0 breast cancer in 2019 were accrued in four tertiary medical centers in Korea. All patients had undergone breast conserving surgery followed by radiotherapy, either whole breast irradiation or APBI. To determine which guideline best predicts the use of APBI in Korea, the F1 score and Matthews Correlation Coefficient (MCC) were determined for each guideline., Results: A total of 1,251 patients were analyzed, of whom 196 (15.7%) underwent APBI. The percentages of eligible patients identified by the ASTRO, GEC-ESTRO, ABS, and ASBS criteria were 13.7%, 21.0%, 50.5%, and 63.5%, respectively. APBI was used to treat 54.4%, 37.2%, 27.1%, and 23.7% of patients eligible by the ASTRO, GEC-ESTRO, ABS, and ASBS criteria, respectively. The ASTRO guideline exhibited the highest F1 score (0.76) and MCC (0.67), thus showing the best prediction of APBI utilization in Korea., Conclusion: The proportion of Korean breast cancer patients who are candidates for APBI is substantial. The actual rate of APBI utilization among eligible patients may suggest there is a room for risk-stratified optimization in offering radiation therapy.