Asthma is characterized by chronic inflammation and respiratory tract remodeling. Peroxisome proliferator-activated receptors (PPARs) play important roles in the pathogenesis and regulation of chronic inflammatory processes in asthma. The role of PPARγ has been studied using synthetic PPARγ agonists in patients with asthma. However, involvement of PPARα/δ has not been studied in asthma. In the present study, we investigated if elafibranor, a PPARα/δ dual agonist, can modulate ovalbumin (OVA)-induced allergic asthma, which is a potential drug candidate for non-alcoholic fatty liver in obese patients. Elafibranor suppresses antigeninduced degranulation in RBL-2H3 mast cells without inducing cytotoxicity in vitro. In mice with OVA-induced allergic asthma, the administration of elafibranor suppressed OVA-induced airway hyper-responsiveness at a dose of 10 mg/kg. Elafibranor also suppressed the OVA-induced increase in immune cells and pro-inflammatory cytokine production in the bronchoalveolar lavage fluid (BALF). Histological studies suggested that elafibranor suppressed OVA-induced lung inflammation and mucin hyper-production in the bronchial airways. In addition, elafibranor suppressed OVA-induced increases in serum immunoglobulin E and IL-13 levels in BALF. Conversely, the present study suggests that elafibranor has the potential for use in patients with allergic asthma.

Purpose: This study evaluated thyroid cancer risk in a lung cancer screening population according to the presence of an incidental thyroid nodule (ITN) detected on low-dose chest computed tomography (LDCT). Methods: Of 47,837 subjects who underwent LDCT, a lung cancer screening population according to the National Lung Screening Trial results was retrospectively enrolled. The prevalence of ITN on LDCT was calculated, and the ultrasonography (US)/fine-needle aspiration (FNA)–based risk of thyroid cancer according to the presence of ITN on LDCT was compared using the Fisher exact or Student t-test as appropriate. Results: Of the 2,329 subjects (female:male=44:2,285; mean age, 60.9±4.9 years), the prevalence of ITN on LDCT was 4.8% (111/2,329). The incidence of thyroid cancer was 0.8% (18/2,329, papillary thyroid microcarcinomas [PTMCs]) and was higher in the ITN-positive group than in the ITN-negative group (3.6% [4/111] vs. 0.6% [14/2,218], P=0.009). Among the 2,011 subjects who underwent both LDCT and thyroid US, all risks were higher (P<0.001) in the ITNpositive group than in the ITN-negative group: presence of thyroid nodule on US, 94.1% (95/101) vs. 48.6% (928/1,910); recommendation of FNA according to the American Thyroid Association guideline and Korean Thyroid Imaging Reporting and Data System guideline, 41.2% (42/101) vs. 2.4% (46/1,910) and 39.6% (40/101) vs. 1.9% (37/1,910), respectively. Conclusion Despite a higher risk of thyroid cancer in the LDCT ITN-positive group than in the ITN-negative group in a lung cancer screening population, all cancers were PTMCs. A heavy smoking history may not necessitate thorough screening US for thyroid incidentalomas.

Objective: This study aimed to validate the risk stratification system (RSS) and biopsy criteria for cervical lymph nodes (LNs) proposed by the Korean Society of Thyroid Radiology (KSThR). Materials and Methods: This retrospective study included a consecutive series of preoperative patients with thyroid cancer who underwent LN biopsy, ultrasound (US), and computed tomography (CT) between December 2006 and June 2015. LNs were categorized as probably benign, indeterminate, or suspicious according to the current US- and CT-based RSS and the size thresholds for cervical LN biopsy as suggested by the KSThR. The diagnostic performance and unnecessary biopsy rates were calculated. Results: A total of 277 LNs (53.1% metastatic) in 228 patients (mean age ± standard deviation, 47.4 years ± 14) were analyzed. In US, the malignancy risks were significantly different among the three categories (all P < 0.001); however, CTdetected probably benign and indeterminate LNs showed similarly low malignancy risks (P = 0.468). The combined US + CT criteria stratified the malignancy risks among the three categories (all P < 0.001) and reduced the proportion of indeterminate LNs (from 20.6% to 14.4%) and the malignancy risk in the indeterminate LNs (from 31.6% to 12.5%) compared with US alone. In all image-based classifications, nodal size did not affect the malignancy risks (short diameter [SD] ≤ 5 mm LNs vs. SD > 5 mm LNs, P ≥ 0.177). The criteria covering only suspicious LNs showed higher specificity and lower unnecessary biopsy rates than the current criteria, while maintaining sensitivity in all imaging modalities. Conclusion Integrative evaluation of US and CT helps in reducing the proportion of indeterminate LNs and the malignancy risk among them. Nodal size did not affect the malignancy risk of LNs, and the addition of indeterminate LNs to biopsy candidates did not have an advantage in detecting LN metastases in all imaging modalities.

Purpose: To explore cerebrovascular reservoir (CVR) and arterial transit time (ATT) changes using acetazolamide-challenged multi-phase arterial spin labeling (MP-ASL) perfusion-weighted MRI in chronic cerebrovascular steno-occlusive disease. Materials and Methods: This retrospective study enrolled patients with chronic steno-occlusion who underwent acetazolamide-challenged MP-ASL between June 2019 and October 2020.Cerebral blood flow, CVR, basal ATT, and ATT changes associated with severe stenosis, total occlusion, and chronic infarction lesions were compared. Results: There were 32 patients (5 with bilateral steno-occlusion) in our study sample. The CVR was significantly reduced during total occlusion compared with severe stenosis (26.2% ± 28.8% vs. 41.4% ± 34.1%, respectively, p = 0.004). The ATT changes were not significantly different (p = 0.717). The CVR was marginally lower in patients with chronic infarction (29.6% ± 39.1% vs. 38.9% ± 28.7%, respectively, p = 0.076). However, the ATT was less shortened in pa-tients with chronic infarction (-54 ± 135 vs. -117 ± 128 ms, respectively, p = 0.013). Conclusion Acetazolamide-challenged MP-ASL provides an MRI-based CVR evaluation tool for chronic steno-occlusive disease.

Purpose: To explore cerebrovascular reservoir (CVR) and arterial transit time (ATT) changes using acetazolamide-challenged multi-phase arterial spin labeling (MP-ASL) perfusion-weighted MRI in chronic cerebrovascular steno-occlusive disease. Materials and Methods: This retrospective study enrolled patients with chronic steno-occlusion who underwent acetazolamide-challenged MP-ASL between June 2019 and October 2020.Cerebral blood flow, CVR, basal ATT, and ATT changes associated with severe stenosis, total occlusion, and chronic infarction lesions were compared. Results: There were 32 patients (5 with bilateral steno-occlusion) in our study sample. The CVR was significantly reduced during total occlusion compared with severe stenosis (26.2% ± 28.8% vs. 41.4% ± 34.1%, respectively, p = 0.004). The ATT changes were not significantly different (p = 0.717). The CVR was marginally lower in patients with chronic infarction (29.6% ± 39.1% vs. 38.9% ± 28.7%, respectively, p = 0.076). However, the ATT was less shortened in pa-tients with chronic infarction (-54 ± 135 vs. -117 ± 128 ms, respectively, p = 0.013). Conclusion Acetazolamide-challenged MP-ASL provides an MRI-based CVR evaluation tool for chronic steno-occlusive disease.

BACKGROUND/AIMS: The aim of this study was to identify the profile of rare variants associated with Crohn's disease (CD) using whole exome sequencing (WES) analysis of Korean children with CD and to evaluate whether genetic profiles could provide information during medical decision making. METHODS: DNA samples from 18 control individuals and 22 patients with infantile, very-early and early onset CD of severe phenotype were used for WES. Genes were filtered using panels of inflammatory bowel disease (IBD)-associated genes and genes of primary immunodeficiency (PID) and monogenic IBD. RESULTS: Eighty-one IBD-associated variants and 35 variants in PID genes were revealed by WES. The most frequently occurring variants were carried by nine (41%) and four (18.2%) CD probands and were ATG16L2 (rs11235604) and IL17REL (rs142430606), respectively. Twenty-four IBD-associated variants and 10 PID variants were predicted to be deleterious and were identified in the heterozygous state. However, their functions were unknown with the exception of a novel p.Q111X variant in XIAP (X chromosome) of a male proband. CONCLUSIONS: The presence of many rare variants of unknown significance limits the clinical applicability of WES for individual CD patients. However, WES in children may be beneficial for distinguishing CD secondary to PID.
Asian Continental Ancestry Group/genetics ; Carrier Proteins/genetics ; Child ; Child, Preschool ; Crohn Disease/*genetics ; *Exome ; Female ; Genetic Predisposition to Disease ; *Genetic Variation ; Humans ; Immunologic Deficiency Syndromes/genetics ; Infant ; Male ; Phenotype ; Receptors, Interleukin-17/genetics ; Republic of Korea ; Sequence Analysis, DNA/*methods ; X-Linked Inhibitor of Apoptosis Protein/genetics

Objective: To evaluate the diagnostic performance of the modified Korean Thyroid Imaging Reporting and Data System (K-TIRADS), and compare it with the 2016 version of K-TIRADS using the Thyroid Imaging Network of Korea. Materials and Methods: Between June and September 2015, 5708 thyroid nodules (≥ 1.0 cm) from 5081 consecutive patients who had undergone thyroid ultrasonography at 26 institutions were retrospectively evaluated. We used a biopsy size threshold of 2 cm for K-TIRADS 3 and 1 cm for K-TIRADS 4 (modified K-TIRADS 1) or 1.5 cm for K-TIRADS 4 (modified K-TIRADS 3). The modified K-TIRADS 2 subcategorized the K-TIRADS 4 into 4A and 4B, and the cutoff sizes for the biopsies were defined as 1 cm for K-TIRADS 4B and 1.5 cm for K-TIRADS 4A. The diagnostic performance and the rate of unnecessary biopsies of the modified K-TIRADS for detecting malignancy were compared with those of the 2016 K-TIRAD, which were stratified by nodule size (with a threshold of 2 cm). Results: A total of 1111 malignant nodules and 4597 benign nodules were included. The sensitivity, specificity, and unnecessary biopsy rate of the benign nodules were 94.9%, 24.4%, and 60.9% for the 2016 K-TIRADS; 91.0%, 39.7%, and 48.6% for the modified K-TIRADS 1; 84.9%, 45.9%, and 43.5% for the modified K-TIRADS 2; and 76.1%, 50.2%, and 40.1% for the modified K-TIRADS 3. For small nodules (1–2 cm), the diagnostic sensitivity of the modified K-TIRADS decreased by 5.2–25.6% and the rate of unnecessary biopsies reduced by 19.2–32.8% compared with those of the 2016 K-TIRADS (p < 0.001). For large nodules (> 2 cm), the modified K-TIRADSs maintained a very high sensitivity for detecting malignancy (98%). Conclusion The modified K-TIRADSs significantly reduced the rate of unnecessary biopsies for small (1–2 cm) nodules while maintaining a very high sensitivity for malignancy for large (> 2 cm) nodules.

Purpose: Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease (AD). Brain atrophy in this disease spectrum begins in the medial temporal lobe structure, which can be recognized by magnetic resonance imaging. To overcome the unsatisfactory inter-observer reliability of visual evaluation, quantitative brain volumetry has been developed and widely investigated for the diagnosis of MCI and AD. The aim of this study was to assess the prediction accuracy of quantitative brain volumetry using a fully automated segmentation software package, NeuroQuant®, for the diagnosis of MCI. Materials and Methods: A total of 418 subjects from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease cohort were included in our study. Each participant was allocated to either a cognitively normal old group (n = 285) or an MCI group (n = 133). Brain volumetric data were obtained from T1-weighted images using the NeuroQuant software package. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to investigate relevant brain regions and their prediction accuracies. Results: Multivariate logistic regression analysis revealed that normative percentiles of the hippocampus (P < 0.001), amygdala (P = 0.003), frontal lobe (P = 0.049), medial parietal lobe (P = 0.023), and third ventricle (P = 0.012) were independent predictive factors for MCI. In ROC analysis, normative percentiles of the hippocampus and amygdala showed fair accuracies in the diagnosis of MCI (area under the curve: 0.739 and 0.727, respectively). Conclusion Normative percentiles of the hippocampus and amygdala provided by the fully automated segmentation software could be used for screening MCI with a reasonable post-processing time. This information might help us interpret structural MRI in patients with cognitive impairment.

Purpose: Mild cognitive impairment (MCI) is a prodromal stage of Alzheimer's disease (AD). Brain atrophy in this disease spectrum begins in the medial temporal lobe structure, which can be recognized by magnetic resonance imaging. To overcome the unsatisfactory inter-observer reliability of visual evaluation, quantitative brain volumetry has been developed and widely investigated for the diagnosis of MCI and AD. The aim of this study was to assess the prediction accuracy of quantitative brain volumetry using a fully automated segmentation software package, NeuroQuant®, for the diagnosis of MCI. Materials and Methods: A total of 418 subjects from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease cohort were included in our study. Each participant was allocated to either a cognitively normal old group (n = 285) or an MCI group (n = 133). Brain volumetric data were obtained from T1-weighted images using the NeuroQuant software package. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to investigate relevant brain regions and their prediction accuracies. Results: Multivariate logistic regression analysis revealed that normative percentiles of the hippocampus (P < 0.001), amygdala (P = 0.003), frontal lobe (P = 0.049), medial parietal lobe (P = 0.023), and third ventricle (P = 0.012) were independent predictive factors for MCI. In ROC analysis, normative percentiles of the hippocampus and amygdala showed fair accuracies in the diagnosis of MCI (area under the curve: 0.739 and 0.727, respectively). Conclusion Normative percentiles of the hippocampus and amygdala provided by the fully automated segmentation software could be used for screening MCI with a reasonable post-processing time. This information might help us interpret structural MRI in patients with cognitive impairment.

Objective: To evaluate the diagnostic performance of the modified Korean Thyroid Imaging Reporting and Data System (K-TIRADS), and compare it with the 2016 version of K-TIRADS using the Thyroid Imaging Network of Korea. Materials and Methods: Between June and September 2015, 5708 thyroid nodules (≥ 1.0 cm) from 5081 consecutive patients who had undergone thyroid ultrasonography at 26 institutions were retrospectively evaluated. We used a biopsy size threshold of 2 cm for K-TIRADS 3 and 1 cm for K-TIRADS 4 (modified K-TIRADS 1) or 1.5 cm for K-TIRADS 4 (modified K-TIRADS 3). The modified K-TIRADS 2 subcategorized the K-TIRADS 4 into 4A and 4B, and the cutoff sizes for the biopsies were defined as 1 cm for K-TIRADS 4B and 1.5 cm for K-TIRADS 4A. The diagnostic performance and the rate of unnecessary biopsies of the modified K-TIRADS for detecting malignancy were compared with those of the 2016 K-TIRAD, which were stratified by nodule size (with a threshold of 2 cm). Results: A total of 1111 malignant nodules and 4597 benign nodules were included. The sensitivity, specificity, and unnecessary biopsy rate of the benign nodules were 94.9%, 24.4%, and 60.9% for the 2016 K-TIRADS; 91.0%, 39.7%, and 48.6% for the modified K-TIRADS 1; 84.9%, 45.9%, and 43.5% for the modified K-TIRADS 2; and 76.1%, 50.2%, and 40.1% for the modified K-TIRADS 3. For small nodules (1–2 cm), the diagnostic sensitivity of the modified K-TIRADS decreased by 5.2–25.6% and the rate of unnecessary biopsies reduced by 19.2–32.8% compared with those of the 2016 K-TIRADS (p < 0.001). For large nodules (> 2 cm), the modified K-TIRADSs maintained a very high sensitivity for detecting malignancy (98%). Conclusion The modified K-TIRADSs significantly reduced the rate of unnecessary biopsies for small (1–2 cm) nodules while maintaining a very high sensitivity for malignancy for large (> 2 cm) nodules.