1.Roles of Inflammatory Biomarkers in Exhaled Breath Condensates in Respiratory Clinical Fields
Yong Jun CHOI ; Min Jae LEE ; Min Kwang BYUN ; Sangho PARK ; Jimyung PARK ; Dongil PARK ; Sang-Hoon KIM ; Youngsam KIM ; Seong Yong LIM ; Kwang Ha YOO ; Ki Suck JUNG ; Hye Jung PARK
Tuberculosis and Respiratory Diseases 2024;87(1):65-79
Background:
Exhaled condensates contain inflammatory biomarkers; however, their roles in the clinical field have been under-investigated.
Methods:
We prospectively enrolled subjects admitted to pulmonology clinics. We collected exhaled breath condensates (EBC) and analysed the levels of six and 12 biomarkers using conventional and multiplex enzyme-linked immunosorbent assay, respectively.
Results:
Among the 123 subjects, healthy controls constituted the largest group (81 participants; 65.9%), followed by the preserved ratio impaired spirometry group (21 patients; 17.1%) and the chronic obstructive pulmonary disease (COPD) group (21 patients; 17.1%). In COPD patients, platelet derived growth factor-AA exhibited strong positive correlations with COPD assessment test (ρ=0.5926, p=0.0423) and COPD-specific version of St. George’s Respiratory Questionnaire (SGRQ-C) score (total, ρ=0.6725, p=0.0166; activity, ρ=0.7176, p=0.0086; and impacts, ρ=0.6151, p=0.0333). Granzyme B showed strong positive correlations with SGRQ-C score (symptoms, ρ=0.6078, p=0.0360; and impacts, ρ=0.6007, p=0.0389). Interleukin 6 exhibited a strong positive correlation with SGRQ-C score (activity, ρ=0.4671, p=0.0378). The absolute serum eosinophil and basophil counts showed positive correlations with pro-collagen I alpha 1 (ρ=0.6735, p=0.0164 and ρ=0.6295, p=0.0283, respectively). In healthy subjects, forced expiratory volume in 1 second (FEV1)/forced vital capacity demonstrated significant correlation with CC chemokine ligand 3 (CCL3)/macrophage inflammatory protein 1 alpha (ρ=0.3897 and p=0.0068). FEV1 exhibited significant correlation with CCL11/eotaxin (ρ=0.4445 and p=0.0017).
Conclusion
Inflammatory biomarkers in EBC might be useful to predict quality of life concerning respiratory symptoms and serologic markers. Further studies are needed.
2.Efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for hepatitis C in Korea: a Phase 3b study
Jeong HEO ; Yoon Jun KIM ; Sung Wook LEE ; Youn-Jae LEE ; Ki Tae YOON ; Kwan Soo BYUN ; Yong Jin JUNG ; Won Young TAK ; Sook-Hyang JEONG ; Kyung Min KWON ; Vithika SURI ; Peiwen WU ; Byoung Kuk JANG ; Byung Seok LEE ; Ju-Yeon CHO ; Jeong Won JANG ; Soo Hyun YANG ; Seung Woon PAIK ; Hyung Joon KIM ; Jung Hyun KWON ; Neung Hwa PARK ; Ju Hyun KIM ; In Hee KIM ; Sang Hoon AHN ; Young-Suk LIM
The Korean Journal of Internal Medicine 2023;38(4):504-513
Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.
3.Performance of a Novel CT-Derived Fractional Flow Reserve Measurement to Detect Hemodynamically Significant Coronary Stenosis
Si-Hyuck KANG ; Soo-Hyun KIM ; Sun-Hwa KIM ; Eun Ju CHUN ; Woo-Young CHUNG ; Chang-Hwan YOON ; Sang-Don PARK ; Chang-Wook NAM ; Ki-Hwan KWON ; Joon-Hyung DOH ; Young-Sup BYUN ; Jang-Whan BAE ; Tae-Jin YOUN ; In-Ho CHAE
Journal of Korean Medical Science 2023;38(32):e254-
Background:
Fractional flow reserve (FFR) based on computed tomography (CT) has been shown to better identify ischemia-causing coronary stenosis. However, this current technology requires high computational power, which inhibits its widespread implementation in clinical practice. This prospective, multicenter study aimed at validating the diagnostic performance of a novel simple CT based fractional flow reserve (CT-FFR) calculation method in patients with coronary artery disease.
Methods:
Patients who underwent coronary CT angiography (CCTA) within 90 days and invasive coronary angiography (ICA) were prospectively enrolled. A hemodynamically significant lesion was defined as an FFR ≤ 0.80, and the area under the receiver operating characteristic curve (AUC) was the primary measure. After the planned analysis for the initial algorithm A, we performed another set of exploratory analyses for an improved algorithm B.
Results:
Of 184 patients who agreed to participate in the study, 151 were finally analyzed.Hemodynamically significant lesions were observed in 79 patients (52.3%). The AUC was 0.71 (95% confidence interval [CI], 0.63–0.80) for CCTA, 0.65 (95% CI, 0.56–0.74) for CT-FFR algorithm A (P = 0.866), and 0.78 (95% CI, 0.70–0.86) for algorithm B (P = 0.112). Diagnostic accuracy was 0.63 (0.55–0.71) for CCTA alone, 0.66 (0.58–0.74) for algorithm A, and 0.76 (0.68–0.82) for algorithm B.
Conclusion
This study suggests the feasibility of automated CT-FFR, which can be performed on-site within several hours. However, the diagnostic performance of the current algorithm does not meet the a priori criteria for superiority. Future research is required to improve the accuracy.
4.Extraventricular Neurocytoma: Clinical Investigation of Heterogenous Prognosis
Joonho BYUN ; Moinay KIM ; Sang Woo SONG ; Young-Hoon KIM ; Chang Ki HONG ; Jeong Hoon KIM
Brain Tumor Research and Treatment 2022;10(1):22-28
Background:
Extraventricular neurocytoma (EVN) is an extremely rare neuronal neoplasm that arises outside the ventricle. The clinical implication of the heterogenous prognosis of this rare tumor has not yet been clarified. Herein, we analyzed our institutional series of EVN.
Methods:
A total of eight consecutive cases were enrolled and investigated. The prognosis of EVN was analyzed and compared to that of central neurocytoma (CN).
Results:
There were two male and six female patients, and the median age was 36.5 years. The median tumor size was 38 mm, and the most common location of the tumor was the frontal lobe (3, 37.5%), followed by the parietal and temporal lobes. In brain imaging, four (50%) tumors showed peritumoral edema and three (37.5%) tumors showed calcification. All patients underwent gross total resection, and two (25%) underwent adjuvant radiotherapy. The 5-year overall survival (OS) was 55.6%, and the 2-year progression-free survival (PFS) was 42.9%. The OS and PFS of EVN were poor compared to those of CN. Although EVN is a single disease entity, individual patients showed varying prognosis. One patient showed no recurrence during the 7-year follow-up period; however, another patient had a recurrence 4 months after surgery and died 2 years later.
Conclusion
EVN may be a heterogenous disease entity. Additional cases with long-term followup are needed to develop optimal management protocols.
5.The Prediction of HER2-Targeted Treatment Response Using 64CuTetra- Azacyclododecanetetra-Acetic Acid (DOTA)-Trastuzumab PET/CT in Metastatic Breast Cancer: A Case Report
Inki LEE ; Ilhan LIM ; Byung Hyun BYUN ; Byung Il KIM ; Chang Woon CHOI ; Kyo Chul LEE ; Choong Mo KANG ; Min-Ki SEONG ; Hyun-Ah KIM ; Woo Chul NOH ; Sang Moo LIM
Journal of Breast Cancer 2022;25(1):69-73
A 45-year-old woman diagnosed with breast cancer reported disease progression in the form of metastatic lung and recurrent breast lesions following chemotherapy and human epidermal growth factor receptor 2 (HER2)-targeted therapy. The patient underwent 64 Cu-tetra-azacyclododecanetetra-acetic acid (DOTA)-trastuzumab positron emission tomography/computed tomography (PET/CT) to evaluate the HER2 expression status.64 Cu-DOTA-trastuzumab accumulated in the left breast and lymph nodes but not in the lung lesions. Following trastuzumab emtansine treatment, there was a significant improvement in the lesions with 64 Cu-DOTA-trastuzumab accumulation. However, the lesions that did not accumulate 64 Cu-DOTA-trastuzumab aggravated. Therefore, it was concluded that 64 CuDOTA-trastuzumab PET/CT can be used to predict the outcome of HER2-targeted treatment by evaluating HER2 expression in breast cancer patients.
6.A Rare Case of Metastatic Brain Tumor From Classic Biphasic Pulmonary Blastoma Presented as Intracerebral Hemorrhage
Sanghyeok PARK ; Joonho BYUN ; Sang Woo SONG ; Young-Hoon KIM ; Chang-Ki HONG ; Jeong Hoon KIM
Brain Tumor Research and Treatment 2021;9(2):81-86
Pulmonary blastoma is a rare type of primary lung cancer that accounts for only 0.25%-0.5% of all lung malignancies. Pulmonary blastoma consists of three subgroups: classic biphasic pulmonary blastoma (CBPB), pleuropulmonary blastoma, and well-differentiated fetal adenocarcinoma. Due to the rarity of the tumor, metastatic brain tumor from CBPB is extremely rare, and only 13 cases, including our case, have been reported. A 60-year-old woman who underwent left upper lobectomy of the lung because of pathologically diagnosed as CBPB 5 months ago, suddenly lost consciousness and presented with stupor mental status. The emergent CT scan showed a large, 51 mL, intracerebral hemorrhage on left parieto-occipital lobe with midline shifting. The patient underwent emergent craniotomy, and a hypervascular tumor was identified during the operation. Histopathologic examination reported metastatic pulmonary blastoma, CBPB. The patient has been in a vegetative state, but there has been no evidence of recurrence over a 6-month follow-up period. We report a rare case of brain metastasis from CBPB presenting with altered mentality due to massive tumor bleeding. This is the only reported case of brain metastasis from CBPB presenting with acute intracerebral hemorrhage.
7.The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 1. Definition, Methodology and First-line Management
Woo-Jung SONG ; Mira CHOI ; Dong Hun LEE ; Jae-Woo KWON ; Gun-Woo KIM ; Myung Hwa KIM ; Mi-Ae KIM ; Min-Hye KIM ; Byung-Keun KIM ; Sujeong KIM ; Joung Soo KIM ; Jung Eun KIM ; Ju-Young KIM ; Joo-Hee KIM ; Hyun Jung KIM ; Hye One KIM ; Hyo-Bin KIM ; Joo Young ROH ; Kyung Hee PARK ; Kui Young PARK ; Han-Ki PARK ; Hyunsun PARK ; Jung Min BAE ; Ji Yeon BYUN ; Dae Jin SONG ; Young Min AHN ; Seung Eun LEE ; Young Bok LEE ; Joong Sun LEE ; Ji Hyun LEE ; Kyung-Hwan LIM ; Young-Min YE ; Yoon-Seok CHANG ; You Hoon JEON ; Jiehyun JEON ; Mihn-Sook JUE ; Sun Hee CHOI ; Jeong-Hee CHOI ; Gyu-Young HUR ; Young Min PARK ; Dae Hyun LIM ; Sang Woong YOUN
Allergy, Asthma & Immunology Research 2020;12(4):563-578
Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.
8.The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 1. Definition, Methodology and First-line Management
Woo-Jung SONG ; Mira CHOI ; Dong Hun LEE ; Jae-Woo KWON ; Gun-Woo KIM ; Myung Hwa KIM ; Mi-Ae KIM ; Min-Hye KIM ; Byung-Keun KIM ; Sujeong KIM ; Joung Soo KIM ; Jung Eun KIM ; Ju-Young KIM ; Joo-Hee KIM ; Hyun Jung KIM ; Hye One KIM ; Hyo-Bin KIM ; Joo Young ROH ; Kyung Hee PARK ; Kui Young PARK ; Han-Ki PARK ; Hyunsun PARK ; Jung Min BAE ; Ji Yeon BYUN ; Dae Jin SONG ; Young Min AHN ; Seung Eun LEE ; Young Bok LEE ; Joong Sun LEE ; Ji Hyun LEE ; Kyung-Hwan LIM ; Young-Min YE ; Yoon-Seok CHANG ; You Hoon JEON ; Jiehyun JEON ; Mihn-Sook JUE ; Sun Hee CHOI ; Jeong-Hee CHOI ; Gyu-Young HUR ; Young Min PARK ; Dae Hyun LIM ; Sang Woong YOUN
Allergy, Asthma & Immunology Research 2020;12(4):563-578
Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.
9.Nucleotide-Binding Oligomerization Domain-Like Receptor 3 Inflammasome Inhibition by MCC950 Reduces the Lipopolysaccharide-Induced Interleukin-1β in Cultured Dispersed Nasal Polyp Cells
Soo Kyoung PARK ; Rui-Ning HAN ; Jun XU ; Sun Hee YEON ; Sung Bok LEE ; Kunho SONG ; Jenny BYUN ; Ki Sang RHA ; Yong Min KIM
Korean Journal of Otolaryngology - Head and Neck Surgery 2020;63(5):206-215
Background and Objectives:
The nucleotide-binding oligomerization domain-like receptor (NLRP) 3 is known as a member of the NLR family, and it has been confirmed that the NLRP3 inflammasome is associated with various diseases such as asthma, inflammatory bowel disease, metabolic disorders and multiple sclerosis, as well as other auto-immune and auto-inflammatory diseases. However, the role of NLRP3 in chronic rhinosinusitis with nasal polyps (CRSwNP) has not yet been explored.Subjects and Method Forty-four specimens of nasal polyps and 25 specimens of uncinate processes were collected from patients with chronic rhinosinusitis with nasal polyps, and 25 specimens of uncinate tissues were collected from patients who underwent other rhino-surgeries. The western blot assay was employed to analyze the expression of NLRP3; interleukin (IL)-1β and IL-17A were detected using immunohistochemistry and real-time polymerase chain reaction. The production of lipopolysaccharide (LPS) induced IL-1β and IL-17A with or without the NLRP3 inflammasome inhibitor (MCC950) was measured using an enzyme linked immunosorbent assay in cultured dispersed nasal polyp cells.
Results:
NLRP3 showed a high level of expression in nasal polyps than in the control group (p<0.01). The expression of IL-1β and IL-17A was significantly higher in nasal polyps in the CRSwNP group than in the control group (p<0.05). LPS-induced production of IL-1β was significantly suppressed by treatment with the NLRP3 inflammasome inhibitor (p<0.05).
Conclusion
The NLRP3 inflammasome plays an essential role in the pathogenesis of CRSwNP, and thus MCC950 can be considered a prospective therapeutic for NLRP3 inflammasome-mediated inflammation in nasal polyps. Our data provide new evidence that IL-17A is involved in inflammasome-associated inflammation in nasal polyps.
10.Comorbid Depression Is Associated with a Negative Treatment Response in Idiopathic REM Sleep Behavior Disorder
Jun-Sang SUNWOO ; Young Ji KIM ; Jung-Ick BYUN ; Tae-Joon KIM ; Jin-Sun JUN ; Soon-Tae LEE ; Keun-Hwa JUNG ; Kyung-Il PARK ; Kon CHU ; Manho KIM ; Sang Kun LEE ; Han-Joon KIM ; Carlos H. SCHENCK ; Ki-Young JUNG
Journal of Clinical Neurology 2020;16(2):261-269
Background:
and PurposeThe first-line medications for the symptomatic treatment of rapid eye movement sleep behavior disorder (RBD) are clonazepam and melatonin taken at bedtime. We aimed to identify the association between depression and treatment response in patients with idiopathic RBD (iRBD).
Methods:
We reviewed the medical records of 123 consecutive patients (76 males; age, 66.0±7.7 years; and symptom duration, 4.1±4.0 years) with iRBD who were treated with clonazepam and/or melatonin. Clonazepam and melatonin were initially administered at 0.25–0.50 and 2 mg/day, respectively, at bedtime, and the doses were subsequently titrated according to the response of individual patients. Treatment response was defined according to the presence or absence of any improvement in dream-enacting behaviors or unpleasant dreams after treatment.
Results:
Forty (32.5%) patients were treated with clonazepam, 56 (45.5%) with melatonin, and 27 (22.0%) with combination therapy. The doses of clonazepam and melatonin at followup were 0.5±0.3 and 2.3±0.7 mg, respectively. Ninety-six (78.0%) patients reported improvement in their RBD symptoms during a mean follow-up period of 17.7 months. After adjusting for potential confounders, depression was significantly associated with a negative treatment response (odds ratio=3.76, 95% confidence interval=1.15–12.32, p=0.029).
Conclusions
We found that comorbid depression is significantly associated with a negative response to clonazepam and/or melatonin in patients with iRBD. Further research with larger numbers of patients is needed to verify our observations and to determine the clinical implications of comorbid depression in the pathophysiology of iRBD.

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