1.Adjuvant Pembrolizumab in Patients with Stage IIIA/N2 Non–Small Cell Lung Cancer Completely Resected after Neoadjuvant Concurrent Chemoradiation: A Prospective, Open-Label, Single-Arm, Phase 2 Trial
Junghoon SHIN ; Sehhoon PARK ; Kyung Hwan KIM ; Eui-Cheol SHIN ; Hyun Ae JUNG ; Jong Ho CHO ; Jong-Mu SUN ; Se-Hoon LEE ; Yong Soo CHOI ; Jin Seok AHN ; Jhingook KIM ; Keunchil PARK ; Young Mog SHIM ; Hong Kwan KIM ; Jae Myoung NOH ; Yong Chan AHN ; Hongryull PYO ; Myung-Ju AHN
Cancer Research and Treatment 2024;56(4):1084-1095
Purpose:
Optimal treatment for stage IIIA/N2 non–small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT).
Materials and Methods:
In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39+PD-1+CD8+ T cells using fold changes in the percentage of proliferating Ki-67+ cells from days 1 to 7 of cycle 1 (Ki-67D7/D1).
Results:
Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39+PD-1+CD8+ T cells than those without (p=0.036). No new safety signals were identified.
Conclusion
Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.
2.Anatomical study of the adductor canal: three-dimensional micro-computed tomography, histological, and immunofluorescence findings relevant to neural blockade
Shin Hyo LEE ; Hee Jung KIM ; Shin Hyung KIM ; Tae-Hyeon CHO ; Hyun-Jin KWON ; Jehoon O ; Ju Eun HONG ; Seung Hyun NAM ; Young-Il HWANG ; Hun-Mu YANG
Korean Journal of Anesthesiology 2023;76(3):252-260
Background:
A precise anatomical understanding of the adductor canal (AC) and its neural components is essential for discerning the action mechanism of the AC block. We therefore aimed to clarify the detailed anatomy of the AC using micro-computed tomography (micro-CT), histological evaluation, and immunofluorescence (IF) assays.
Methods:
Gross dissections of 39 thighs provided morphometric data relevant to injection landmarks. Serial sectional images of the AC were defined using micro-CT and ultrasonography. The fascial and neural structures of the AC proper were histologically evaluated using Masson’s trichrome and Verhoeff-Van Gieson staining, and double IF staining using choline acetyltransferase (ChAT) and neurofilament 200 antibodies.
Results:
The posteromedial branch insertion of the nerve to vastus medialis (NVM) into the lateral border of the AC proper was lower (14.5 ± 2.4 cm [mean ± SD] above the base of the patella) than the origin of the proximal AC. The AC consists of a thin subsartorial fascia in the proximal region and a thick aponeurosis-like vastoadductor membrane in the distal region. In the proximal AC, the posteromedial branch of the NVM (pmNVM) consistently contained both sensory and motor fibers, and more ChAT-positive fibers were observed than in the saphenous nerve (27.5 ± 11.2 / 104 vs. 4.2 ± 2.6 / 104 [counts/µm2], P < 0.001).
Conclusions
Anatomical differences in fascial structures between the proximal and distal AC and a mixed neural component of the neighboring pmNVM have been visualized using micro-CT images, histological evaluation, and IF assays.
3.Xenogeneic Humoral Immune Responses to Human Mesenchymal Stem Cells in Mice
Jun-Man HONG ; Jin-Hee KIM ; Gwang-Hoon KIM ; Hyun-Mu SHIN ; Young-il HWANG
International Journal of Stem Cells 2022;15(3):291-300
Background and Objectives:
Many preclinical studies have been conducted using animal disease models to determine the effectiveness of human mesenchymal stem cells (hMSCs) for treating immune and inflammatory diseases based on the belief that hMSCs are not immunogenic across species. However, several researchers have suggested xenogeneic immune responses to hMSCs in animals, still without detailed features. This study aimed to investigate a xenogeneic humoral immune response to hMSCs in mice in detail.
Methods:
and Results: Balb/c mice were intraperitoneally injected with adipose tissue-derived or Wharton’s jelly-derived hMSCs. Sera from these mice were titrated for each isotype. To confirm specificity of the antibodies, hMSCs were stained with the sera and subjected to a flow cytometic analysis. Spleens were immunostained for proliferating cell nuclear antigen to verify the germinal center formation. Additionally, splenocytes were subjected to a flow cytometric analysis for surface markers including GL-7, B220, CD4, CD8, CD44, and CD62L. Similar experiments were repeated in C57BL/6 mice. The results showed increased IgG 1 and IgG 2a titers in the sera from Balb/c mice injected with hMSCs, and the titers were much higher in the secondary sera than in the primary sera. These antibodies were specifically stained the hMSCs. Germinal centers were observed in the spleen, and flow cytometric analysis of the splenocytes showed higher frequencies of centroblasts (B220 + GL7 + ) and memory T cells (CD62L + CD44 + ) both in CD4 + and CD8 + subsets. Similar results were obtained for C57BL/6 mice.
Conclusions
hMSCs induced a humoral immune response in mice, with characters of T cell-dependent immunity
4.Evaluation of the clinical efficacy of a TW3-based fully automated bone age assessment system using deep neural networks
Nan-Young SHIN ; Byoung-Dai LEE ; Ju-Hee KANG ; Hye-Rin KIM ; Dong Hyo OH ; Byung Il LEE ; Sung Hyun KIM ; Mu Sook LEE ; Min-Suk HEO
Imaging Science in Dentistry 2020;50(3):237-243
Purpose:
The aim of this study was to evaluate the clinical efficacy of a Tanner-Whitehouse 3 (TW3)-based fully automated bone age assessment system on hand-wrist radiographs of Korean children and adolescents.
Materials and Methods:
Hand-wrist radiographs of 80 subjects (40 boys and 40 girls, 7-15 years of age) were collected. The clinical efficacy was evaluated by comparing the bone ages that were determined using the system with those from the reference standard produced by 2 oral and maxillofacial radiologists. Comparisons were conducted using the paired t-test and simple regression analysis.
Results:
The bone ages estimated with this bone age assessment system were not significantly different from those obtained with the reference standard (p>0.05) and satisfied the equivalence criterion of 0.6 years within the 95% confidence interval ( - 0.07 to 0.22), demonstrating excellent performance of the system. Similarly, in the comparisons of gender subgroups, no significant difference in bone age between the values produced by the system and the reference standard was observed (p>0.05 for both boys and girls). The determination coefficients obtained via regression analysis were 0.962, 0.945, and 0.952 for boys, girls, and overall, respectively (p=0.000); hence, the radiologist-determined bone ages and the system-determined bone ages were strongly correlated.
Conclusion
This TW3-based system can be effectively used for bone age assessment based on hand-wrist radiographs of Korean children and adolescents.
5.Development of Predictive Models in Patients with Epiphora Using Lacrimal Scintigraphy and Machine Learning
Yong Jin PARK ; Ji Hoon BAE ; Mu Heon SHIN ; Seung Hyup HYUN ; Young Seok CHO ; Yearn Seong CHOE ; Joon Young CHOI ; Kyung Han LEE ; Byung Tae KIM ; Seung Hwan MOON
Nuclear Medicine and Molecular Imaging 2019;53(2):125-135
PURPOSE: We developed predictive models using different programming languages and different computing platforms for machine learning (ML) and deep learning (DL) that classify clinical diagnoses in patients with epiphora. We evaluated the diagnostic performance of these models.METHODS: Between January 2016 and September 2017, 250 patients with epiphora who underwent dacryocystography (DCG) and lacrimal scintigraphy (LS) were included in the study. We developed five different predictive models using ML tools, Python-based TensorFlow, R, and Microsoft Azure Machine Learning Studio (MAMLS). A total of 27 clinical characteristics and parameters including variables related to epiphora (VE) and variables related to dacryocystography (VDCG) were used as input data. Apart from this, we developed two predictive convolutional neural network (CNN) models for diagnosing LS images. We conducted this study using supervised learning.RESULTS: Among 500 eyes of 250 patients, 59 eyes had anatomical obstruction, 338 eyes had functional obstruction, and the remaining 103 eyes were normal. For the data set that excluded VE and VDCG, the test accuracies in Python-based TensorFlow, R, multiclass logistic regression in MAMLS, multiclass neural network in MAMLS, and nuclear medicine physician were 81.70%, 80.60%, 81.70%, 73.10%, and 80.60%, respectively. The test accuracies of CNN models in three-class classification diagnosis and binary classification diagnosis were 72.00% and 77.42%, respectively.CONCLUSIONS: ML-based predictive models using different programming languages and different computing platforms were useful for classifying clinical diagnoses in patients with epiphora and were similar to a clinician's diagnostic ability.
Classification
;
Dataset
;
Diagnosis
;
Humans
;
Lacrimal Apparatus Diseases
;
Learning
;
Logistic Models
;
Machine Learning
;
Nuclear Medicine
;
Programming Languages
;
Radionuclide Imaging
6.Development of Predictive Models in Patients with Epiphora Using Lacrimal Scintigraphy and Machine Learning
Yong Jin PARK ; Ji Hoon BAE ; Mu Heon SHIN ; Seung Hyup HYUN ; Young Seok CHO ; Yearn Seong CHOE ; Joon Young CHOI ; Kyung Han LEE ; Byung Tae KIM ; Seung Hwan MOON
Nuclear Medicine and Molecular Imaging 2019;53(2):125-135
PURPOSE:
We developed predictive models using different programming languages and different computing platforms for machine learning (ML) and deep learning (DL) that classify clinical diagnoses in patients with epiphora. We evaluated the diagnostic performance of these models.
METHODS:
Between January 2016 and September 2017, 250 patients with epiphora who underwent dacryocystography (DCG) and lacrimal scintigraphy (LS) were included in the study. We developed five different predictive models using ML tools, Python-based TensorFlow, R, and Microsoft Azure Machine Learning Studio (MAMLS). A total of 27 clinical characteristics and parameters including variables related to epiphora (VE) and variables related to dacryocystography (VDCG) were used as input data. Apart from this, we developed two predictive convolutional neural network (CNN) models for diagnosing LS images. We conducted this study using supervised learning.
RESULTS:
Among 500 eyes of 250 patients, 59 eyes had anatomical obstruction, 338 eyes had functional obstruction, and the remaining 103 eyes were normal. For the data set that excluded VE and VDCG, the test accuracies in Python-based TensorFlow, R, multiclass logistic regression in MAMLS, multiclass neural network in MAMLS, and nuclear medicine physician were 81.70%, 80.60%, 81.70%, 73.10%, and 80.60%, respectively. The test accuracies of CNN models in three-class classification diagnosis and binary classification diagnosis were 72.00% and 77.42%, respectively.
CONCLUSIONS
ML-based predictive models using different programming languages and different computing platforms were useful for classifying clinical diagnoses in patients with epiphora and were similar to a clinician's diagnostic ability.
7.Clinical Factors Influencing Outcomes of 1064 nm Neodymium-Doped Yttrium Aluminum Garnet (Nd:YAG) Laser Treatment for Onychomycosis.
Hyun Joo KIM ; Hyung jin PARK ; Dong Hye SUH ; Sang Jun LEE ; Ki Heon JEONG ; Mu Hyoung LEE ; Min Kyung SHIN
Annals of Dermatology 2018;30(4):493-495
No abstract available.
Aluminum*
;
Onychomycosis*
;
Yttrium*
8.Sonographic Growth Charts for Kidney Length in Normal Korean Children: a Prospective Observational Study.
Min Su OH ; Geol HWANG ; Sanghoon HAN ; Hyun Sik KANG ; Seung Hyo KIM ; Young Don KIM ; Ki Soo KANG ; Kyung Sue SHIN ; Mu Sook LEE ; Guk Myung CHOI ; Kyoung Hee HAN
Journal of Korean Medical Science 2016;31(7):1089-1093
Kidney length is the most useful parameter for clinical measurement of kidney size, and is useful to distinguish acute kidney injury from chronic kidney disease. In this prospective observational study of 437 normal children aged between 0 and < 13 years, kidney length was measured using sonography. There were good correlations between kidney length and somatic values, including age, weight, height, and body surface area. The rapid growth of height during the first 2 years of life was intimately associated with a similar increase in kidney length, suggesting that height should be considered an important factor correlating with kidney length. Based on our findings, the following regression equation for the reference values of bilateral kidney length for Korean children was obtained: kidney length of the right kidney (cm) = 0.051 × height (cm) + 2.102; kidney length of the left kidney (cm) = 0.051 × height (cm) + 2.280. This equation may aid in the diagnosis of various kidney disorders.
Age Factors
;
Asian Continental Ancestry Group
;
Body Height
;
Body Surface Area
;
Body Weight
;
Child
;
Child, Preschool
;
Female
;
Growth Charts
;
Humans
;
Infant
;
Infant, Newborn
;
Kidney/*diagnostic imaging
;
Kidney Diseases/diagnosis
;
Male
;
Prospective Studies
;
Reference Values
;
Republic of Korea
;
Ultrasonography
9.Prevalence of Vitiligo and Associated Comorbidities in Korea.
Hemin LEE ; Mu Hyoung LEE ; Dong Youn LEE ; Hee Young KANG ; Ki Ho KIM ; Gwang Seong CHOI ; Jeonghyun SHIN ; Hee Jung LEE ; Dong Hyun KIM ; Tae Heung KIM ; Ai Young LEE ; Seung Chul LEE ; Sanghoon LEE ; Kyoung Wan KIM ; Seung Kyung HANN ; Chul Jong PARK ; Sang Ho OH
Yonsei Medical Journal 2015;56(3):719-725
PURPOSE: Vitiligo prevalence and its associated comorbidities rate have been reported variably among different populations. We aimed to determine the prevalence of vitiligo in Korea along with the baseline rate of comorbidities and compared the risks to the general population using hospital visit information of the total population in Korea. MATERIALS AND METHODS: We assessed demographic characteristics of vitiligo patients in Korean population from 2009 to 2011 in a nationwide data from Health Insurance Review Assessment Service. Patients who had at least one visit to Korea's primary, secondary, or tertiary referral hospitals with International Classification of Diseases, 10th Revision, Clinical Modification diagnosis code for vitiligo were identified. As a supplementary study, comorbidities associated with vitiligo were selected for further review to calculate relative risks compared to the general population. RESULTS: The annual prevalence of vitiligo determined by hospital-visiting rate in Korea was 0.12% to 0.13% over a three year period. In sync with other previous epidemiological studies, there was bimodal distribution among the age groups and no difference between genders. Also, vitiligo in Korean population was associated with various autoimmune/non-autoimmune diseases such as thyroiditis, atopic dermatitis, and psoriasis. CONCLUSION: This study was by far the most comprehensive review on prevalence of vitiligo using a data of total population in Korea. The prevalence is within a range of those reported in previous literatures, and increased risk of comorbidities such as thyroid diseases and psoriasis in vitiligo might aid clinicians in the initial work up of vitiligo patients and concurrent follow ups.
Adult
;
Aged
;
Autoimmune Diseases/*epidemiology/immunology
;
Comorbidity
;
Diabetes Mellitus, Type 1/epidemiology
;
Female
;
Humans
;
Male
;
Middle Aged
;
Population Surveillance
;
Prevalence
;
Republic of Korea/epidemiology
;
Socioeconomic Factors
;
Thyroid Diseases/epidemiology
;
Vitiligo/*epidemiology
10.Role of Th17 and Treg during the Chronic Infection of Hepatitis C Virus.
Hyun Mu SHIN ; Jae Won LEE ; Nam Hyuk CHO
Journal of Bacteriology and Virology 2015;45(4):389-393
Hepatitis C virus (HCV) is one of the main causes of liver disease. 1~2% of the Korean people has been reported to be infected by HCV. Although HCV is less infectious than hepatitis B virus (HBV), it is more prone to develop chronic infection (~ 80%) which may link to cirrhosis and hepatocellular carcinogenesis. In addition, prevalence of hepatitis caused by HCV infection is gradually increased every year in Korea. Recently, a large number of clinical trials using direct-acting antiviral (DAA) drugs have been shown efficient therapeutic results for chronic HCV infections and some of them are on the market. However, there is still a concern on viral evasion to the DAAs and the effective mechanisms of immunological clearance of HCV remains to be elucidated. Here, we introduce the recent findings on the role of Th17-Treg axis which may play a critical role of the viral pathogenesis and/or immunological defense against HCV infection. The underlying regulatory mechanisms of Th17-Treg axis might be a potential candidate for the better control of HCV chronic infections.
Axis, Cervical Vertebra
;
Carcinogenesis
;
Fibrosis
;
Hepacivirus*
;
Hepatitis B virus
;
Hepatitis C*
;
Hepatitis*
;
Interleukin-17
;
Korea
;
Liver Diseases
;
Prevalence

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