Clinical utility of repeated rebiopsy for EGFR T790M mutation detection in non-small cell lung cancer.

Purpose: In cases where rebiopsy fails to find the epidermal growth factor receptor (EGFR) T790M mutation, the criteria for selecting patients for repeated rebiopsy remains unclear. This study aimed to assess the impact of repeated rebiopsy on T790M mutation detection in non-small cell lung cancer (NSCLC) patients. Methods: Patients with advanced EGFR-mutated NSCLC between January 2018 and December 2021 at three-referral hospitals in South Korea underwent retrospective review. Of 682 patients who had rebiopsy after disease progression, T790M mutation status was assessed in plasma circulating tumor DNA (ctDNA) and/or tumor tissues. Results: The overall T790M positivity rate increased from 40.8% after the first rebiopsy to 52.9% following multiple rebiopsies in the entire study population. Longer duration of initial EGFR TKI use (OR 1.792, ≥8 months vs. <8 months, p=0.004), better EGFR TKI responses (OR 1.611, complete or partial response vs. stable disease, p=0.006), presence of bone metastasis (OR 2.286, p<0.001) were correlated with higher T790M positivity. Longer EGFR TKI use and better responses increased T790M positivity in repeated tissue rebiopsy, while bone metastasis favored liquid rebiopsy. Additionally, T790M status has been shown to be positive over time through repeated rebiopsies ranging from several months to years, suggesting its dynamic nature. Conclusion: In this study, among patients who initially tested negative for T790M in rebiopsy, repeated rebiopsies uncovered an additional 23.5% T790M positivity. Particularly, it is suggested that repeated rebiopsies may be valuable for patients with prolonged EGFR TKI usage, better responses to treatment, and bone metastasis.

Impact of AI-assisted CXR analysis in detecting incidental lung nodules and lung cancers in non-respiratory outpatient clinics.

Purpose: The use of artificial intelligence (AI) for chest X-ray (CXR) analysis is becoming increasingly prevalent in medical environments. This study aimed to determine whether AI in CXR can unexpectedly detect lung nodule detection and influence patient diagnosis and management in non-respiratory outpatient clinics. Methods: In this retrospective study, patients over 18 years of age, who underwent CXR at Yongin Severance Hospital outpatient clinics between March 2021 and January 2023 and were identified to have lung nodules through AI software, were included. Commercially available AI-based lesion detection software (Lunit INSIGHT CXR) was used to detect lung nodules. Results: Out Of 56,802 radiographic procedures, 40,191 were from non-respiratory departments, with AI detecting lung nodules in 1,754 cases (4.4%). Excluding 139 patients with known lung lesions, 1,615 patients were included in the final analysis. Out of these, 30.7% (495/1,615) underwent respiratory consultation and 31.7% underwent chest CT scans (512/1,615). As a result of the CT scans, 71.5% (366 cases) were found to have true nodules. Among these, the final diagnoses included 36 lung cancers (7.0%, 36/512), 141 lung nodules requiring follow-up (27.5%, 141/512), 114 active pulmonary infections (22.3%, 114/512), and 75 old inflammatory sequelae (14.6%, 75/512). The mean AI nodule score for lung cancer was significantly higher than that for other nodules (56.72 vs. 33.44, p < 0.001). Additionally, active pulmonary infection had a higher consolidation score, and old inflammatory sequelae had the highest fibrosis score, demonstrating differences in the AI analysis among the final diagnosis groups. Conclusion: This study indicates that AI-detected incidental nodule abnormalities on CXR in non-respiratory outpatient clinics result in a substantial number of clinically significant diagnoses, emphasizing AI's role in detecting lung nodules and need for further evaluation and specialist consultation for proper diagnosis and management.

Implementation rate and related factors of confirmatory tests following an abnormal Pap smear: a nationwide study from the National Health Insurance.

OBJECTIVE: This study aims to investigate the implementation rate and influencing factors of confirmatory tests for women with abnormal cervical cytology results in the Korean nationwide cervical cancer screening program. METHODS: The National Health Insurance Service (NHIS) database was utilized to identify all Korean women who have participated in the Korean nationwide cervical cancer screening program from January 2011 and December 2021 using the NHIS database. Multiple logistic regression analysis was performed to estimate the multivariate odds ratio and evaluate the patients' characteristics. RESULTS: The rate of abnormal Papanicolaou (Pap) smears showed an initial increase from 2011 to 2015 and subsequently reached a plateau after 2016. When examining specific subcategories, cases of atypical squamous cells of undetermined significance (ASC-US) increased from 28,546 cases (1.1%) in 2011 to 62,850 cases (1.7%) in 2021. In contrast, cases of HSIL and SCC declined from 3,535 cases (0.14%) to 2,763 cases (0.07%) and from 383 cases (0.01%) to 179 cases (0.005%), respectively. Furthermore, the implementation rate of confirmatory tests for women with abnormal cytology increased from 8,865 cases (21.0%) in 2011 to 39,045 cases (51.2%) in 2021. Regarding the specific subcategory of ASC-US, the number of confirmatory tests exhibited a substantial increase from 4,101 cases (14.4%) in 2011 to 30,482 cases (48.5%) in 2021. For SCC, there was no significant change, with 216 cases (56.4%) in 2011 and 102 cases (57.0%) in 2021. The implementation rate of confirmatory tests was found to be significantly associated with results of abnormal Pap smear, age, and residence. Notably, economic status did not emerge as a significant factor affecting the likelihood of undergoing confirmatory tests. CONCLUSIONS: The severity of abnormal Pap smear results is a reliable indicator of the probability of undergoing a confirmatory test. Additional endeavors are required to improve the implementation rate among women who have received abnormal Pap smear results.

Optimization of Plant Growth Regulators for In Vitro Mass Propagation of a Disease-Free 'Shine Muscat' Grapevine Cultivar.

This study addresses the propagation challenges faced by 'Shine Muscat', a newly introduced premium grapevine cultivar in South Korea, where multiple viral infections pose considerable economic loss. The primary objective was to establish a robust in vitro propagation method for producing disease-free grapes and to identify effective plant growth regulators to facilitate large-scale mass cultivation. After experimentation, 2.0 µM 6-benzyladenine (BA) exhibited superior shoot formation in the Murashige and Skoog medium compared with kinetin and thidiazuron. Conversely, α-naphthaleneacetic acid (NAA) hindered shoot growth and induced callus formation, while indole-3-butyric acid (IBA) and indole-3-acetic acid (IAA) demonstrated favorable root formation, with IBA showing better results overall. Furthermore, inter simple sequence repeat analysis confirmed the genetic stability of in vitro-cultivated seedlings using 2.0 µM BA and 1.0 µM IBA, validating the suitability of the developed propagation method for generating disease-free 'Shine Muscat' grapes. These findings offer promising prospects for commercial grape cultivation, ensuring a consistent supply of healthy grapes in the market.

Association between morbidity of non-communicable disease and employment status: a comparison between Korea and the United States.

BACKGROUND: Globally, the prevalence of chronic disease continues to rise and is likely to grow further over the coming decades due to population ageing. Since older age is associated closely with development of chronic disease, it stands to reason that demographic changes will increase the proportion of older workers with chronic disease. The aim of the present study was to determine how chronic diseases affect employment status in Korea and the USA. METHODS: The study was based on National Health and Nutrition Survey data (2007-2014) obtained by the Korean and American Centers for Disease Control and Prevention. A total of 44,693 subjects were categorized into two geographical groups: Korea (29,260 subjects) and the USA (15,433 subjects). A chi-square test was used to compare the groups in terms of socio-demographic factors, health-related factors, and chronic disease. Multivariate logistic regression analysis was conducted to determine the effect of five chronic diseases (hypertension, diabetes, dyslipidemia, cardiovascular disease, and cancer) on employment status. RESULTS: There were 29,260 Korean and 15,433 American respondents. Chronic disease increased the risk of unemployment in Korea markedly (Odds ratio [OR] range, 1.17-2.47). Cardiovascular disease and cancer had the most profound negative effect on Korean unemployment (OR = 2.47 and 2.03, respectively). The risk of unemployment was generally 2-3-fold lower in the USA (OR range, 0.5-1.04). CONCLUSIONS: Chronic disease had a significant impact on economic activity in Korea, but a smaller impact in the USA. This difference may be related to different health insurance schemes and cultural approaches to people with diseases in the two countries. It is important to explore factors that limit economic participation by people with chronic diseases, and to identify social policies that will overcome these factors. Further between-country studies are needed to identify social solutions to the socio-economic burden of chronic illness.

Detection of infectious hypodermal and hematopoietic necrosis virus and white spot syndrome virus in whiteleg shrimp (Penaeus vannamei) imported from Vietnam to South Korea.

In this study, whiteleg shrimp (Penaeus vannamei) imported from Vietnam were collected from South Korean markets, and examined for 2 viruses: infectious hypodermal and hematopoietic necrosis virus (IHHNV, recently classified as decapod penstyldensovirus-1), and white spot syndrome virus (WSSV). Among 58 samples, we detected IHHNV in 23 samples and WSSV in 2 samples, using polymerase chain reaction and sequencing analyses. This is the first report of IHHNV and WSSV detection in imported shrimp, suggesting that greater awareness and stricter quarantine policies regarding viruses infecting shrimp imported to South Korea are required.

Novel Associations between Related Proteins and Cellular Effects of High-Density Lipoprotein.

BACKGROUND AND OBJECTIVES: Recent studies have examined the structure-function relationship of high-density lipoprotein (HDL). This study aimed to identify and rank HDL-associated proteins involved in several biological function of HDL. METHODS: HDLs isolated from 48 participants were analyzed. Cholesterol efflux capacity, effect of HDL on nitric oxide production, and vascular cell adhesion molecule-1 expression were assessed. The relative abundance of identified proteins in the highest vs. lowest quartile was expressed using the normalized spectral abundance factor ratio. RESULTS: After adjustment by multiple testing, six proteins, thyroxine-binding globulin, alpha-1B-glycoprotein, plasma serine protease inhibitor, vitronectin, angiotensinogen, and serum amyloid A-4, were more abundant (relative abundance ratio ≥2) in HDLs with the highest cholesterol efflux capacity. In contrast, three proteins, complement C4-A, alpha-2-macroglobulin, and immunoglobulin mu chain C region, were less abundant (relative abundance ratio <0.5). In terms of nitric oxide production and vascular cell adhesion molecule-1 expression, no proteins showed abundance ratios ≥2 or <0.5 after adjustment. Proteins correlated with the functional parameters of HDL belonged to diverse biological categories. CONCLUSIONS: In summary, this study ranked proteins showing higher or lower abundance in HDLs with high functional capacities and newly identified multiple proteins linked to cholesterol efflux capacity.

The Effect of Special Medical Examination for Night Shift Workers and Follow-Up Management Against Hypertension.

BACKGROUND: Special health examination is a screening program introduced in 1973 in Korea to examine health problems of workers who are regularly exposed to 177 hazardous substances and physical environments specified by the Occupational Safety and Health Act. Shiftwork was added as a risk factor in 2013. The purpose of this study was to analyze changes of hypertension status after a special medical examination and subsequent follow-up management. METHODS: We used the data based on the special medical examination outcomes for night shift workers, performed at seven different health examination centers under the Korea Medical Institute (KMI) between 2014 and 2016. Workers who received special medical examinations for two consecutive years (2014⁻2015 and 2015⁻2016) were selected. A final study population of 2070 was evaluated. RESULTS: Compared with the first-year examination, 1503 subjects (72.6%) received hypertension medication or showed improvement in blood pressure in their second-year examination. Older age (≥40s), women, larger workplaces (≥300 full-time workers), long-term workers (≥12 years), improvement in smoking habits, improvements for diabetes or dyslipidemia, normal or reduced BMI, and normal waist circumference were associated with proper management of hypertension. CONCLUSIONS: An appropriate follow-up management program should be developed to provide health management for night shift workers that need to focus on the factors identified in this study.

Effect of two lipid-lowering strategies on high-density lipoprotein function and some HDL-related proteins: a randomized clinical trial.

BACKGROUND: The influence of lipid-lowering therapy on high-density lipoprotein (HDL) is incompletely understood. We compared the effect of two lipid-lowering strategies on HDL functions and identified some HDL-related proteins. METHODS: Thirty two patients were initially screened and HDLs of 21 patients were finally analyzed. Patients were randomized to receive atorvastatin 20 mg (n = 11) or atorvastatin 5 mg/ezetimibe 10 mg combination (n = 10) for 8 weeks. The cholesterol efflux capacity and other anti-inflammatory functions were assessed based on HDLs of the participants before and after treatment. Pre-specified HDL proteins of the same HDL samples were measured. RESULTS: The post-treatment increase in cholesterol efflux capacities was similar between the groups (35.6% and 34.6% for mono-therapy and combination, respectively, p = 0.60). Changes in nitric oxide (NO) production, vascular cell adhesion molecule-1 (VCAM-1) expression, and reactive oxygen species (ROS) production were similar between the groups. The baseline cholesterol efflux capacity correlated positively with apolipoprotein (apo)A1 and C3, whereas apoA1 and apoC1 showed inverse associations with VCAM-1 expression. The changes in the cholesterol efflux capacity were positively correlated with multiple HDL proteins, especially apoA2. CONCLUSIONS: Two regimens increased the cholesterol efflux capacity of HDL comparably. Multiple HDL proteins, not limited to apoA1, showed a correlation with HDL functions. These results indicate that conventional lipid therapy may have additional effects on HDL functions with changes in HDL proteins. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02942602 .

Paradoxical effects of elastase inhibitor guamerin on the tissue repair of two different wound models: sealed cutaneous and exposed tongue wounds.

Innate elastase inhibitors are known to be putatively involved in the regulation of tissue inflammation by inhibiting polymorphonuclear leukocyte (PMN) derived proteinases. The aim of this study was to evaluate affects of leukocyte elastase suppression and PMN infiltration on wound healing in mouse by administering the recombinant elastase inhibitor guamerin (rEIG) in two different wound models; 1) impaired pin-punctured dorsal mucosa of anterior tongue wound, 60 mice, treated with saline containing rEIG that were fed ad libitum and 2) stable linear excisional cutaneous wound, 40 mice, covered with fibrin sealant containing rEIG. The progress of healing was analyzed by histological methods. The tongue wounds treated with rEIG became edematous around the pin-punctured tongue wound, and influx of inflammatory cells and PMN into the underlying stromal tissue were seen rapidly after wounding and peaked between 2-4 days. Whereas the control mice showed almost no wheal formation in the pin-punctured wound, a far lesser levels of PMN infiltration, and almost complete wound closure in 4 days. In the other model, the liner excisional cutaneous wound treated with fibrin sealant containing rEIG showed early wound constriction, lesser degree of inflammatory cells influx, and complete reepithelialization in 4-5 days, whereas the wound of control mice with the fibrin sealant alone showed contrary delayed reepithelialization, greater degree of inflammatory cell infiltration, and consequencial formation of greater granulation tissue at wound site. Taken together, these data suggest paradoxical effects of rEIG on the wound healing where in the wound exposed to infiltrating milieu of microorganisms in the oral cavity, the rEIG aggravates the wound healing by interfering with other innate defensive factors and extended greater flux of PMNs to inflamed wound site, while in the wound enclosed by fibrin, the rEIG accelerated wound healing by inhibiting the inflammation-generated proteases and the acute inflammatory reaction.