1.Neutralization Testing–based Immunogenicity Analysis of Recent Prevalent Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Sublineages
Eun Ju LEE ; Hyeokjin LEE ; Sang Won O ; Jee Eun RHEE ; Jeong-Min KIM ; Dong Ju KIM ; Il-Hwan KIM ; Jin Sun NO ; Ae Kyung PARK ; Jeong-Ah KIM ; Chae Young LEE ; Young-Ki CHOI ; Eun-Jin KIM
Annals of Laboratory Medicine 2024;44(3):289-293
Although WHO declared the end of the public health emergency for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), XBB lineages continue to evolve and emerge globally. In particular, XBB.1.5 and XBB.1.16 are raising concerns because of their high immune evasion, leading to apprehensions regarding vaccine efficacy reduction and potential reinfection. We aimed to investigate the COVID-19 outbreak in Korea and predict the likelihood of reinfection by testing neutralizing activity against live viruses from the S clade and 19 Omicron sublineages.We found a significant risk of infection with the currently prevalent XBB lineage for individuals who were either vaccinated early or infected during the initial Omicron outbreak. Vaccinated individuals were better equipped than unvaccinated individuals to produce neutralizing antibodies for other SARS-CoV-2 variants upon infection. Therefore, unvaccinated individuals do not easily develop neutralizing activity against other variants and face the highest risk of reinfection by the XBB lineage. Our study provides important information to facilitate the development of strategies for monitoring populations that would be the most susceptible to new COVID-19 outbreaks.
2.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Overview and Summary 2024
Young Joo PARK ; Eun Kyung LEE ; Young Shin SONG ; Bon Seok KOO ; Hyungju KWON ; Keunyoung KIM ; Mijin KIM ; Bo Hyun KIM ; Won Gu KIM ; Won Bae KIM ; Won Woong KIM ; Jung-Han KIM ; Hee Kyung KIM ; Hee Young NA ; Shin Je MOON ; Jung-Eun MOON ; Sohyun PARK ; Jun-Ook PARK ; Ji-In BANG ; Kyorim BACK ; Youngduk SEO ; Dong Yeob SHIN ; Su-Jin SHIN ; Hwa Young AHN ; So Won OH ; Seung Hoon WOO ; Ho-Ryun WON ; Chang Hwan RYU ; Jee Hee YOON ; Ka Hee YI ; Min Kyoung LEE ; Sang-Woo LEE ; Seung Eun LEE ; Sihoon LEE ; Young Ah LEE ; Joon-Hyop LEE ; Ji Ye LEE ; Jieun LEE ; Cho Rok LEE ; Dong-Jun LIM ; Jae-Yol LIM ; Yun Kyung JEON ; Kyong Yeun JUNG ; Ari CHONG ; Yun Jae CHUNG ; Chan Kwon JUNG ; Kwanhoon JO ; Yoon Young CHO ; A Ram HONG ; Chae Moon HONG ; Ho-Cheol KANG ; Sun Wook KIM ; Woong Youn CHUNG ; Do Joon PARK ; Dong Gyu NA ;
International Journal of Thyroidology 2024;17(1):1-20
Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.
3.Automated Detection and Segmentation of Bone Metastases on Spine MRI Using U-Net:A Multicenter Study
Dong Hyun KIM ; Jiwoon SEO ; Ji Hyun LEE ; Eun-Tae JEON ; DongYoung JEONG ; Hee Dong CHAE ; Eugene LEE ; Ji Hee KANG ; Yoon-Hee CHOI ; Hyo Jin KIM ; Jee Won CHAI
Korean Journal of Radiology 2024;25(4):363-373
Objective:
To develop and evaluate a deep learning model for automated segmentation and detection of bone metastasis on spinal MRI.
Materials and Methods:
We included whole spine MRI scans of adult patients with bone metastasis: 662 MRI series from 302 patients (63.5 ± 11.5 years; male:female, 151:151) from three study centers obtained between January 2015 and August 2021 for training and internal testing (random split into 536 and 126 series, respectively) and 49 MRI series from 20 patients (65.9 ± 11.5 years; male:female, 11:9) from another center obtained between January 2018 and August 2020 for external testing. Three sagittal MRI sequences, including non-contrast T1-weighted image (T1), contrast-enhanced T1-weighted Dixon fat-only image (FO), and contrast-enhanced fat-suppressed T1-weighted image (CE), were used. Seven models trained using the 2D and 3D U-Nets were developed with different combinations (T1, FO, CE, T1 + FO, T1 + CE, FO + CE, and T1 + FO + CE). The segmentation performance was evaluated using Dice coefficient, pixel-wise recall, and pixel-wise precision. The detection performance was analyzed using per-lesion sensitivity and a free-response receiver operating characteristic curve. The performance of the model was compared with that of five radiologists using the external test set.
Results:
The 2D U-Net T1 + CE model exhibited superior segmentation performance in the external test compared to the other models, with a Dice coefficient of 0.699 and pixel-wise recall of 0.653. The T1 + CE model achieved per-lesion sensitivities of 0.828 (497/600) and 0.857 (150/175) for metastases in the internal and external tests, respectively. The radiologists demonstrated a mean per-lesion sensitivity of 0.746 and a mean per-lesion positive predictive value of 0.701 in the external test.
Conclusion
The deep learning models proposed for automated segmentation and detection of bone metastases on spinal MRI demonstrated high diagnostic performance.
4.The Profile of Early Sedation Depth and Clinical Outcomes of Mechanically Ventilated Patients in Korea
Dong-gon HYUN ; Jee Hwan AHN ; Ha-Yeong GIL ; Chung Mo NAM ; Choa YUN ; Jae-Myeong LEE ; Jae Hun KIM ; Dong-Hyun LEE ; Ki Hoon KIM ; Dong Jung KIM ; Sang-Min LEE ; Ho-Geol RYU ; Suk-Kyung HONG ; Jae-Bum KIM ; Eun Young CHOI ; JongHyun BAEK ; Jeoungmin KIM ; Eun Jin KIM ; Tae Yun PARK ; Je Hyeong KIM ; Sunghoon PARK ; Chi-Min PARK ; Won Jai JUNG ; Nak-Jun CHOI ; Hang-Jea JANG ; Su Hwan LEE ; Young Seok LEE ; Gee Young SUH ; Woo-Sung CHOI ; Keu Sung LEE ; Hyung Won KIM ; Young-Gi MIN ; Seok Jeong LEE ; Chae-Man LIM
Journal of Korean Medical Science 2023;38(19):e141-
Background:
Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known.
Methods:
From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups.
Results:
Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582).
Conclusion
In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.
5.Response Evaluation to Neoadjuvant Chemotherapy in Breast Cancer Patients: Sequential Dynamic Contrast-Enhanced MRI Using Computer-Aided Detection
In Hye CHAE ; Eun-Suk CHA ; Jee Eun LEE ; Jin CHUNG ; Jeoung Hyun KIM ; Sun Hee SUNG ; Mira HAN
Investigative Magnetic Resonance Imaging 2023;27(1):21-31
Purpose:
We evaluated whether there is an association between sequential changes in kinetic profiles by computer-aided detection (CAD) during neoadjuvant chemotherapy (NAC) and pathologic complete response (pCR) and residual cancer burden (RCB) in dynamic contrast-enhanced MRI (DCE-MRI) of patients with invasive breast cancer.
Materials and Methods:
This retrospective study involved 51 patients (median age, 48 years; range, 33–60 years) who underwent pre-, interim-, and post-NAC DCE-MRIs at 3 T. The tumor size and CAD-generated kinetic profiles (peak enhancement and delayed enhancement [persistent, plateau, and washout] components) were measured. Percentage changes in pre- and interim-NAC (ΔMRI value1) and pre- and post-NAC (ΔMRI value2) were compared between pCR and non-pCR cases, and according to RCB. Receiver operating characteristic curve analysis was performed to evaluate the association between pCR and MRI parameters (including CAD-generated kinetic profiles).
Results:
The pCR rate was 19.6% (10/51). There were statistically significant differences in Δtumor size2 (p < 0.01), Δpeak enhancement2 (p = 0.01), Δpersistent2 (p = 0.01), Δplateau2 (p = 0.02), and Δwashout2 (p = 0.03) between pCR and non-pCR. ΔTumor size2 provided very good diagnostic accuracy for pCR (cut-off, -90%; area under the curve, 0.88). There were differences in Δtumor size2, Δpeak enhancement2, Δplateau2, and Δwashout2 between RCB classes (p < 0.01).
Conclusion
DCE-MRI using CAD has the potential for predicting pCR and RCB classes.
7.Indirect Method for Estimation of Reference Intervals of Inflammatory Markers
Taewon KANG ; Jeaeun YOO ; Dong Wook JEKARL ; Hyojin CHAE ; Myungshin KIM ; Yeon-Joon PARK ; Eun-Jee OH ; Yonggoo KIM
Annals of Laboratory Medicine 2023;43(1):55-63
Background:
The direct method for reference interval (RI) estimating is limited due to the requirement of resources, difficulties in defining a non-diseased population, or ethical problems in obtaining samples. We estimated the RI for inflammatory biomarkers using an indirect method (RII).
Methods:
C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and presepsin (PSEP) data of patients visiting a single hospital were retrieved from April 2009 to April 2021. Right-skewed data were transformed using the Box-Cox transformation method. A mixed population of non-diseased and diseased distributions was assumed, followed by latent profile analysis for the two classes. The intersection point of the distribution curve was estimated as the RI. The influence of measurement size was evaluated as the ratio of abnormal values and adjustment (n×bandwidth) of the distribution curve.
Results:
The RIs estimated by the proposed RII method (existing method) were as follows: CRP, 0–4.1 (0–4.7) mg/L; ESR, 0–10.2 (0–15) mm/hr and PSEP, 0–411 (0–300) pg/mL. Measurement sizes ≥2,500 showed stable results. An abnormal-to-normal value ratio of 0.5 showed the most accurate result for CRP. Adjustment values ≤5 or >5 were applicable for a measurement size <25,000 or ≥25,000, respectively.
Conclusions
The proposed RII method could provide additional information for RI verification or estimation with some limitations.
8.On-Field Evaluation of Exdia COVID-19 Antigen Point-of-Care Testing in the Emergency Department During the COVID-19 Pandemic
In Young YOO ; Gun Dong LEE ; Hyojin CHAE ; Chun Song YOUN ; Eun-Jee OH ; Yeon-Joon PARK
Annals of Clinical Microbiology 2022;25(3):79-85
Background:
We evaluated the diagnostic performance of the Exdia COVID-19 antigen test (Exdia Ag; Precision Biosensor Inc., Korea) as a point-of-care (POC) test performed in the emergency department (ED) for the rapid detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in comparison with the performance of the Real-Q 2019-nCoV Detection KIT (Real-Q; BioSewoom, Korea).
Methods:
Exdia Ag and Real-Q assays were performed simultaneously for all patients who were admitted to the ED with or without COVID-19 symptoms between December 2021 and March 2022.
Results:
Among the 2,523 samples analyzed by Real-Q assay, 149 samples (5.9%) showed positive results, and 2,374 samples showed negative results. The overall sensitivity and specificity of the Exdia Ag assay were 77.2% (95% confidence interval [CI], 69.6 – 83.7) and 99.8% (95% CI, 99.6 – 99.9), respectively. The positive and negative predictive values were 96.6% (95% CI, 91.5 – 98.7) and 98.6% (95% CI, 98.1 – 98.9), respectively. The cycle threshold value for 115 concordant Exdia Ag-positive/Real-Q-positive samples was significantly lower than that for 34 discordant Exdia Ag-negative/Real-Q-positive samples (P < 0.0001)
Conclusion
The Exdia Ag assay showed good diagnostic performance when the disease prevalence was high and may be useful for POC testing when the rapid detection of SARSCoV-2 is required for the isolation of patients in the ED.
9.Protective efficacy of attenuated Salmonella Typhimurium strain expressing BLS, Omp19, PrpA, or SOD of Brucella abortus in goats
Mwense LEYA ; Won Kyong KIM ; Enkhsaikhan OCHIRKHUYAG ; Eun-Chae YU ; Young-Jee KIM ; Yoonhwan YEO ; Myeon-Sik YANG ; Sang-Seop HAN ; John Hwa LEE ; Dongseob TARK ; Jin HUR ; Bumseok KIM
Journal of Veterinary Science 2021;22(2):e15-
Background:
Attenuated Salmonella strain can be used as a vector to transport immunogens to the host antigen-binding sites.
Objectives:
The study aimed to determine the protective efficacy of attenuated Salmonellastrain expressing highly conserved Brucella immunogens in goats.
Methods:
Goats were vaccinated with Salmonella vector expressing individually lipoprotein outer-membrane protein 19 (Omp19), Brucella lumazine synthase (BLS), proline racemase subunit A (PrpA), Cu/Zn superoxide dismutase (SOD) at 5 × 10 9 CFU/mL and challenge of all groups was done at 6 weeks after vaccination.
Results:
Among these vaccines inoculated at 5 × 10 9 CFU/mL in 1 mL, Omp19 or SOD showed significantly higher serum immunoglobulin G titers at (2, 4, and 6) weeks post-vaccination, compared to the vector control. Interferon-γ production in response to individual antigens was significantly higher in SOD, Omp19, PrpA, and BLS individual groups, compared to that in the vector control (all p < 0.05). Brucella colonization rate at 8 weeks post-challenge showed that most vaccine-treated groups exhibited significantly increased protection by demonstrating reduced numbers of Brucella in tissues collected from vaccinated groups. Realtime polymerase chain reaction revealed that Brucella antigen expression levels were reduced in the spleen, kidney, and parotid lymph node of vaccinated goats, compared to the nonvaccinated goats. Besides, treatment with vaccine expressing individual antigens ameliorated brucellosis-related histopathological lesions.
Conclusions
These results delineated that BLS, Omp19, PrpA, and SOD proteins achieved a definite level of protection, indicating that Salmonella Typhimurium successfully delivered Brucella antigens, and that individual vaccines could differentially elicit an antigen-specific immune response.
10.Apixaban versus Warfarin in Patients with Chronic Kidney Disease; A Systematic Review and Meta-analysis
Jae Hyun NAM ; Chae Young KIM ; Yoo Kyung LEE ; Da Woom JUNG ; Hye Young GWAK ; Jee Eun CHUNG
Korean Journal of Clinical Pharmacy 2021;31(2):87-95
Background:
Patients with chronic kidney disease (CKD) are at a high risk of stroke-related morbidity, mortality, and bleeding. However, the overall risk/benefit of anticoagulant therapy among patients with CKD remains unclear.
Methods:
The MEDLINE, EMBASE, and CENTRAL databases were comprehensively searched until July 31, 2020, to investigate the safety and efficacy of apixaban in patients with stage 4 or 5 CKD, as compared with warfarin. The primary outcome was an incidence of major bleeding. Secondary outcomes included composite bleeding (major, clinically relevant, and minor bleeding), venous thromboembolism (VTE), stroke, and death.
Results:
In total, seven studies consisting of 10,816 patients were included. Compared with warfarin, apixaban was associated with a reduced risk of major bleeding (OR 0.49, 95% CI 0.41-0.58). In terms of composite bleeding, apixaban tended to pose a significantly lower risk than warfarin (OR 0.51, 95% CI 0.37-0.71). There was no difference between apixaban and warfarin with respect to the risk of stroke or death (stroke: OR 1.23, 95% CI 0.49-3.12; death: OR 0.73, 95% CI 0.45-1.18).
Conclusion
Among patients with stage 4 or 5 CKD, the use of apixaban was associated with a lower risk of bleeding compared to warfarin and was also found to pose no excess risk of thromboembolic events.

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