Publications by authors named "Myung Jin Chung"

144 Publications

Nogo-A Is Critical for Pro-Inflammatory Gene Regulation in Myocytes and Macrophages.

Cells 2021 Jan 31;10(2). Epub 2021 Jan 31.

Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea.

Nogo-A (Rtn 4A), a member of the reticulon 4 (Rtn4) protein family, is a neurite outgrowth inhibitor protein that is primarily expressed in the central nervous system (CNS). However, previous studies revealed that Nogo-A was upregulated in skeletal muscles of Amyotrophic lateral sclerosis (ALS) patients. Additionally, experiments showed that endoplasmic reticulum (ER) stress marker, C/EBP homologous protein (CHOP), was upregulated in gastrocnemius muscle of a murine model of ALS. We therefore hypothesized that Nogo-A might relate to skeletal muscle diseases. According to our knocking down and overexpression results in muscle cell line (C2C12), we have found that upregulation of Nogo-A resulted in upregulation of CHOP, pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, while downregulation of Nogo-A led to downregulation of CHOP, IL-6 and TNF-α. Immunofluorescence results showed that Nogo-A and CHOP were expressed by myofibers as well as tissue macrophages. Since resident macrophages share similar functions as bone marrow-derived macrophages (BMDM), we therefore, isolated macrophages from bone marrow to study the role of Nogo-A in activation of these cells. Lipopolysaccharide (LPS)-stimulated BMDM in Nogo-KO mice showed low mRNA expression of CHOP, IL-6 and TNF-α compared to BMDM in wild type (WT) mice. Interestingly, Nogo knockout (KO) BMDM exhibited lower migratory activity and phagocytic ability compared with WT BMDM after LPS treatment. In addition, mice experiments data revealed that upregulation of Nogo-A in notexin- and tunicamycin-treated muscles was associated with upregulation of CHOP, IL-6 and TNF-α in WT group, while in Nogo-KO group resulted in low expression level of CHOP, IL-6 and TNF-α. Furthermore, upregulation of Nogo-A in dystrophin-deficient (mdx) murine model, myopathy and Duchenne muscle dystrophy (DMD) clinical biopsies was associated with upregulation of CHOP, IL-6 and TNF-α. To the best of our knowledge, this is the first study to demonstrate Nogo-A as a regulator of inflammation in diseased muscle and bone marrow macrophages and that deletion of Nogo-A alleviates muscle inflammation and it can be utilized as a therapeutic target for improving muscle diseases.
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http://dx.doi.org/10.3390/cells10020282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912613PMC
January 2021

Nogo-A regulates myogenesis via interacting with Filamin-C.

Cell Death Discov 2021 Jan 6;7(1). Epub 2021 Jan 6.

Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, Republic of Korea.

Among the three isoforms encoded by Rtn4, Nogo-A has been intensely investigated as a central nervous system inhibitor. Although Nogo-A expression is increased in muscles of patients with amyotrophic lateral sclerosis, its role in muscle homeostasis and regeneration is not well elucidated. In this study, we discovered a significant increase in Nogo-A expression in various muscle-related pathological conditions. Nogo mice displayed dystrophic muscle structure, dysregulated muscle regeneration following injury, and altered gene expression involving lipid storage and muscle cell differentiation. We hypothesized that increased Nogo-A levels might regulate muscle regeneration. Differentiating myoblasts exhibited Nogo-A upregulation and silencing Nogo-A abrogated myoblast differentiation. Nogo-A interacted with filamin-C, suggesting a role for Nogo-A in cytoskeletal arrangement during myogenesis. In conclusion, Nogo-A maintains muscle homeostasis and integrity, and pathologically altered Nogo-A expression mediates muscle regeneration, suggesting Nogo-A as a novel target for the treatment of myopathies in clinical settings.
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http://dx.doi.org/10.1038/s41420-020-00384-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791112PMC
January 2021

Mesenchymal Stem Cell and MicroRNA Therapy of Musculoskeletal Diseases.

Int J Stem Cells 2020 Dec 31. Epub 2020 Dec 31.

Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, Korea.

The therapeutic effects of mesenchymal stem cells (MSCs) in musculoskeletal diseases (MSDs) have been verified in many human and animal studies. Although some tissues contain MSCs, the number of cells harvested from those tissues and rate of proliferation are not enough for continuous transplantation. In order to produce and maintain stable MSCs, many attempts are made to induce differentiation from pluripotent stem cells (iPSCs) into MSCs. In particular, it is also known that the paracrine action of stem cell-secreted factors could promote the regeneration and differentiation of target cells in damaged tissue. MicroRNAs (miRNAs), one of the secreted factors, are small non-coding RNAs that regulate the translation of a gene. It is known that miRNAs help communication between stem cells and their surrounding niches through exosomes to regulate the proliferation and differentiation of stem cells. While studies have so far been underway targeting therapeutic miRNAs of MSDs, studies on specific miRNAs secreted from MSCs are still minimal. Hence, our ultimate goal is to obtain sufficient amounts of exosomes from iPSC-MSCs and develop them into therapeutic agents, furthermore to select specific miRNAs and provide safe cell-free clinical setting as a cell-free status with purpose of delivering them to target cells. This review article focuses on stem cell therapy on MSDs, specific microRNAs regulating MSDs and updates on novel approaches.
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http://dx.doi.org/10.15283/ijsc20167DOI Listing
December 2020

Establishment of a Nationwide Korean Imaging Cohort of Coronavirus Disease 2019.

J Korean Med Sci 2020 Nov 30;35(46):e413. Epub 2020 Nov 30.

Department of Radiology, Pusan National University Hospital, Pusan National University School of Medicine and Biomedical Research Institute, Busan, Korea.

Background: The Korean Society of Thoracic Radiology (KSTR) recently constructed a nation-wide coronavirus disease 2019 (COVID-19) database and imaging repository, referred to the Korean imaging cohort of COVID-19 (KICC-19) based on the collaborative efforts of its members. The purpose of this study was to provide a summary of the clinico-epidemiological data and imaging data of the KICC-19.

Methods: The KSTR members at 17 COVID-19 referral centers retrospectively collected imaging data and clinical information of consecutive patients with reverse transcription polymerase chain reaction-proven COVID-19 in respiratory specimens from February 2020 through May 2020 who underwent diagnostic chest computed tomography (CT) or radiograph in each participating hospital.

Results: The cohort consisted of 239 men and 283 women (mean age, 52.3 years; age range, 11-97 years). Of the 522 subjects, 201 (38.5%) had an underlying disease. The most common symptoms were fever (n = 292) and cough (n = 245). The 151 patients (28.9%) had lymphocytopenia, 86 had (16.5%) thrombocytopenia, and 227 patients (43.5%) had an elevated CRP at admission. The 121 (23.4%) needed nasal oxygen therapy or mechanical ventilation (n = 38; 7.3%), and 49 patients (9.4%) were admitted to an intensive care unit. Although most patients had cured, 21 patients (4.0%) died. The 465 (89.1%) subjects underwent a low to standard-dose chest CT scan at least once during hospitalization, resulting in a total of 658 CT scans. The 497 subjects (95.2%) underwent chest radiography at least once during hospitalization, which resulted in a total of 1,475 chest radiographs.

Conclusion: The KICC-19 was successfully established and comprised of 658 CT scans and 1,475 chest radiographs of 522 hospitalized Korean COVID-19 patients. The KICC-19 will provide a more comprehensive understanding of the clinical, epidemiological, and radiologic characteristics of patients with COVID-19.
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http://dx.doi.org/10.3346/jkms.2020.35.e413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707929PMC
November 2020

Automatic stenosis recognition from coronary angiography using convolutional neural networks.

Comput Methods Programs Biomed 2021 Jan 2;198:105819. Epub 2020 Nov 2.

Department of Medical Device Management and Research, SAIHST, Sungkyunkwan University, Seoul 06351, South Korea; Department of Emergency Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea. Electronic address:

Background And Objective: Coronary artery disease, which is mostly caused by atherosclerotic narrowing of the coronary artery lumen, is a leading cause of death. Coronary angiography is the standard method to estimate the severity of coronary artery stenosis, but is frequently limited by intra- and inter-observer variations. We propose a deep-learning algorithm that automatically recognizes stenosis in coronary angiographic images.

Methods: The proposed method consists of key frame detection, deep learning model training for classification of stenosis on each key frame, and visualization of the possible location of the stenosis. Firstly, we propose an algorithm that automatically extracts key frames essential for diagnosis from 452 right coronary artery angiography movie clips. Our deep learning model is then trained with image-level annotations to classify the areas narrowed by over 50 %. To make the model focus on the salient features, we apply a self-attention mechanism. The stenotic locations are visualized using the activated area of feature maps with gradient-weighted class activation mapping.

Results: The automatically detected key frame was very close to the manually selected key frame (average distance (1.70 ± 0.12) frame per clip). The model was trained with key frames on internal datasets, and validated with internal and external datasets. Our training method achieved high frame-wise area-under-the-curve of 0.971, frame-wise accuracy of 0.934, and clip-wise accuracy of 0.965 in the average values of cross-validation evaluations. The external validation results showed high performances with the mean frame-wise area-under-the-curve of (0.925 and 0.956) in the single and ensemble model, respectively. Heat map visualization shows the location for different types of stenosis in both internal and external data sets. With the self-attention mechanism, the stenosis could be precisely localized, which helps to accurately classify the stenosis by type.

Conclusions: Our automated classification algorithm could recognize and localize coronary artery stenosis highly accurately. Our approach might provide the basis for a screening and assistant tool for the interpretation of coronary angiography.
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http://dx.doi.org/10.1016/j.cmpb.2020.105819DOI Listing
January 2021

Computer-aided recognition of myopic tilted optic disc using deep learning algorithms in fundus photography.

BMC Ophthalmol 2020 Oct 9;20(1):407. Epub 2020 Oct 9.

Medical AI Research Center, Institute of Smart Healthcare, Samsung Medical Center, Seoul, Korea.

Background: It is necessary to consider myopic optic disc tilt as it seriously impacts normal ocular parameters. However, ophthalmologic measurements are within inter-observer variability and time-consuming to get. This study aimed to develop and evaluate deep learning models that automatically recognize a myopic tilted optic disc in fundus photography.

Methods: This study used 937 fundus photographs of patients with normal or myopic tilted disc, collected from Samsung Medical Center between April 2016 and December 2018. We developed an automated computer-aided recognition system for optic disc tilt on color fundus photographs via a deep learning algorithm. We preprocessed all images with two image resizing techniques. GoogleNet Inception-v3 architecture was implemented. The performances of the models were compared with the human examiner's results. Activation map visualization was qualitatively analyzed using the generalized visualization technique based on gradient-weighted class activation mapping (Grad-CAM++).

Results: Nine hundred thirty-seven fundus images were collected and annotated from 509 subjects. In total, 397 images from eyes with tilted optic discs and 540 images from eyes with non-tilted optic discs were analyzed. We included both eye data of most included patients and analyzed them separately in this study. For comparison, we conducted training using two aspect ratios: the simple resized dataset and the original aspect ratio (AR) preserving dataset, and the impacts of the augmentations for both datasets were evaluated. The constructed deep learning models for myopic optic disc tilt achieved the best results when simple image-resizing and augmentation were used. The results were associated with an area under the receiver operating characteristic curve (AUC) of 0.978 ± 0.008, an accuracy of 0.960 ± 0.010, sensitivity of 0.937 ± 0.023, and specificity of 0.963 ± 0.015. The heatmaps revealed that the model could effectively identify the locations of the optic discs, the superior retinal vascular arcades, and the retinal maculae.

Conclusions: We developed an automated deep learning-based system to detect optic disc tilt. The model demonstrated excellent agreement with the previous clinical criteria, and the results are promising for developing future programs to adjust and identify the effect of optic disc tilt on ophthalmic measurements.
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http://dx.doi.org/10.1186/s12886-020-01657-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547463PMC
October 2020

Risk prediction platform for pancreatic fistula after pancreatoduodenectomy using artificial intelligence.

World J Gastroenterol 2020 Aug;26(30):4453-4464

Medical Artificial Intelligence Research Center, Department of Medical Device Management and Research, SAIHST, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, South Korea.

Background: Despite advancements in operative technique and improvements in postoperative managements, postoperative pancreatic fistula (POPF) is a life-threatening complication following pancreatoduodenectomy (PD). There are some reports to predict POPF preoperatively or intraoperatively, but the accuracy of those is questionable. Artificial intelligence (AI) technology is being actively used in the medical field, but few studies have reported applying it to outcomes after PD.

Aim: To develop a risk prediction platform for POPF using an AI model.

Methods: Medical records were reviewed from 1769 patients at Samsung Medical Center who underwent PD from 2007 to 2016. A total of 38 variables were inserted into AI-driven algorithms. The algorithms tested to make the risk prediction platform were random forest (RF) and a neural network (NN) with or without recursive feature elimination (RFE). The median imputation method was used for missing values. The area under the curve (AUC) was calculated to examine the discriminative power of algorithm for POPF prediction.

Results: The number of POPFs was 221 (12.5%) according to the International Study Group of Pancreatic Fistula definition 2016. After median imputation, AUCs using 38 variables were 0.68 ± 0.02 with RF and 0.71 ± 0.02 with NN. The maximal AUC using NN with RFE was 0.74. Sixteen risk factors for POPF were identified by AI algorithm: Pancreatic duct diameter, body mass index, preoperative serum albumin, lipase level, amount of intraoperative fluid infusion, age, platelet count, extrapancreatic location of tumor, combined venous resection, co-existing pancreatitis, neoadjuvant radiotherapy, American Society of Anesthesiologists' score, sex, soft texture of the pancreas, underlying heart disease, and preoperative endoscopic biliary decompression. We developed a web-based POPF prediction platform, and this application is freely available at http://popfrisk.smchbp.org.

Conclusion: This study is the first to predict POPF with multiple risk factors using AI. This platform is reliable (AUC 0.74), so it could be used to select patients who need especially intense therapy and to preoperatively establish an effective treatment strategy.
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http://dx.doi.org/10.3748/wjg.v26.i30.4453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438201PMC
August 2020

Imaging findings in coronavirus infections: SARS-CoV, MERS-CoV, and SARS-CoV-2.

Br J Radiol 2020 Aug 6;93(1112):20200515. Epub 2020 Jul 6.

Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine (SKKU-SOM), Seoul, Korea.

During the first two decades of the 21st century, there have been three coronavirus infection outbreaks raising global health concerns by severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the SARS-CoV-2. Although the reported imaging findings of coronavirus infection are variable and non-specific, the most common initial chest radiograph (CXR) and CT findings are ground-glass opacities and consolidation with peripheral predominance and eventually spread to involve both lungs as the disease progresses. These findings can be explained by the immune pathogenesis of coronavirus infection causing diffuse alveolar damage. Although it is insensitive in mild or early coronavirus infection, the CXR remains as the first-line and the most commonly used imaging modality. That is because it is rapid and easily accessible and helpful for monitoring patient progress during treatment. CT is more sensitive to detect early parenchymal lung abnormalities and disease progression, and can provide an alternative diagnosis. In this pictorial review, various coronavirus infection cases are presented to provide imaging spectrums of coronavirus infection and present differences in imaging among them or from other viral infections, and to discuss the role of imaging in viral infection outbreaks.
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http://dx.doi.org/10.1259/bjr.20200515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446008PMC
August 2020

Five transcriptional factors reprogram fibroblast into myogenic lineage cells via paraxial mesoderm stage.

Cell Cycle 2020 07 17;19(14):1804-1816. Epub 2020 Jun 17.

Department of Pathology, College of Veterinary Medicine, Kyungpook National University , Daegu, Republic of Korea.

It is hard to supply satellite cells as a cell source for therapy of muscle degenerative disease since the sampling of muscle tissue is very invasive to a patient with muscular disease. Direct conversion allows us to get specific cell types by transduction of defined transcriptional factors. To induce myogenic direct conversion, we transduced five transcriptional factors including Pax3, Sox2, Klf4, c-Myc, and Esrrb into mouse embryonic fibroblasts. We found that the transduction of the five transcriptional factors induced myogenic direct conversion of fibroblast. We revealed that the transduced cells with the five transcriptional factors were converted to myogenic lineage cells through a paraxial mesoderm-like stage. The expression level of myogenic-related genes of the transduced cells gradually increased as the passage increased. The induced myogenic lineage cells differentiated into muscle fibers and . The current study revealed that the five transcription factors generated myogenic lineage cells from fibroblast via a paraxial mesoderm stage. The induced myogenic lineage cells may have a potential being applied as cell source for degenerative muscle disease.
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http://dx.doi.org/10.1080/15384101.2020.1780384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469637PMC
July 2020

Automated measurement of hydrops ratio from MRI in patients with Ménière's disease using CNN-based segmentation.

Sci Rep 2020 04 24;10(1):7003. Epub 2020 Apr 24.

Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Ménière's Disease (MD) is difficult to diagnose and evaluate objectively over the course of treatment. Recently, several studies have reported MD diagnoses by MRI-based endolymphatic hydrops (EH) analysis. However, this method is time-consuming and complicated. Therefore, a fast, objective, and accurate evaluation tool is necessary. The purpose of this study was to develop an algorithm that can accurately analyze EH on intravenous (IV) gadolinium (Gd)-enhanced inner-ear MRI using artificial intelligence (AI) with deep learning. In this study, we developed a convolutional neural network (CNN)-based deep-learning model named INHEARIT (INner ear Hydrops Estimation via ARtificial InTelligence) for the automatic segmentation of the cochlea and vestibule, and calculation of the EH ratio in the segmented region. Measurement of the EH ratio was performed manually by a neuro-otologist and neuro-radiologist and by estimation with the INHEARIT model and were highly consistent (intraclass correlation coefficient = 0.971). This is the first study to demonstrate that automated EH ratio measurements are possible, which is important in the current clinical context where the usefulness of IV-Gd inner-ear MRI for MD diagnosis is increasing.
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http://dx.doi.org/10.1038/s41598-020-63887-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181627PMC
April 2020

Surgically Resected Esophageal Squamous Cell Carcinoma: Patient Survival and Clinicopathological Prognostic Factors.

Sci Rep 2020 03 19;10(1):5077. Epub 2020 Mar 19.

Division of Hemato-oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine (SKKU-SOM), Seoul, South Korea.

We aimed to report patients' survival after surgical resection of eSCC and to ascertain the clinical, imaging, and pathological factors related to patient prognosis. This retrospective study included 435 patients with eSCC of
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http://dx.doi.org/10.1038/s41598-020-62028-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081270PMC
March 2020

Management of incidental pulmonary nodules: current strategies and future perspectives.

Expert Rev Respir Med 2020 02 3;14(2):173-194. Epub 2019 Dec 3.

Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine (SKKU-SOM), Seoul, South Korea.

: Detection and characterization of pulmonary nodules is an important issue, because the process is the first step in the management of lung cancers.: Literature review was performed on May 15 2019 by using the PubMed, US National Library of Medicine National Institutes of Health, and the National Center for Biotechnology information. CT features helping identify the druggable mutations and predict the prognosis of malignant nodules were presented. Technical advancements in MRI and PET/CT were introduced for providing functional information about malignant nodules. Advances in various tissue biopsy techniques enabling molecular analysis and histologic diagnosis of indeterminate nodules were also presented. New techniques such as radiomics, deep learning (DL) technology, and artificial intelligence showing promise in differentiating between malignant and benign nodules were summarized. Recently, updated management guidelines for solid and subsolid nodules incidentally detected on CT were described. Risk stratification and prediction models for indeterminate nodules under active investigation were briefly summarized.: Advancement in CT knowledge has led to a better correlation between CT features and genomic alterations or tumor histology. Recent advances like PET/CT, MRI, radiomics, and DL-based approach have shown promising results in the characterization and prognostication of pulmonary nodules.
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http://dx.doi.org/10.1080/17476348.2020.1697853DOI Listing
February 2020

Deep Convolutional Neural Network-based Software Improves Radiologist Detection of Malignant Lung Nodules on Chest Radiographs.

Radiology 2020 01 12;294(1):199-209. Epub 2019 Nov 12.

From the Department of Radiology, Research Institute of Radiological Science, Center for Clinical Imaging Data Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea (Y.S., K.H., B.W.C.); Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (M.J.C.); Department of Radiology, University Medical Center Freiburg, Freiburg, Germany (E.K.); Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Mass (S. Yune, M.K., S.D.); and Samsung Electronics, Suwon, Republic of Korea (H.K., S. Yang, D.J.L.).

Background Multicenter studies are required to validate the added benefit of using deep convolutional neural network (DCNN) software for detecting malignant pulmonary nodules on chest radiographs. Purpose To compare the performance of radiologists in detecting malignant pulmonary nodules on chest radiographs when assisted by deep learning-based DCNN software with that of radiologists or DCNN software alone in a multicenter setting. Materials and Methods Investigators at four medical centers retrospectively identified 600 lung cancer-containing chest radiographs and 200 normal chest radiographs. Each radiograph with a lung cancer had at least one malignant nodule confirmed by CT and pathologic examination. Twelve radiologists from the four centers independently analyzed the chest radiographs and marked regions of interest. Commercially available deep learning-based computer-aided detection software separately trained, tested, and validated with 19 330 radiographs was used to find suspicious nodules. The radiologists then reviewed the images with the assistance of DCNN software. The sensitivity and number of false-positive findings per image of DCNN software, radiologists alone, and radiologists with the use of DCNN software were analyzed by using logistic regression and Poisson regression. Results The average sensitivity of radiologists improved (from 65.1% [1375 of 2112; 95% confidence interval {CI}: 62.0%, 68.1%] to 70.3% [1484 of 2112; 95% CI: 67.2%, 73.1%], < .001) and the number of false-positive findings per radiograph declined (from 0.2 [488 of 2400; 95% CI: 0.18, 0.22] to 0.18 [422 of 2400; 95% CI: 0.16, 0.2], < .001) when the radiologists re-reviewed radiographs with the DCNN software. For the 12 radiologists in this study, 104 of 2400 radiographs were positively changed (from false-negative to true-positive or from false-positive to true-negative) using the DCNN, while 56 of 2400 radiographs were changed negatively. Conclusion Radiologists had better performance with deep convolutional network software for the detection of malignant pulmonary nodules on chest radiographs than without. © RSNA, 2019 See also the editorial by Jacobson in this issue.
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http://dx.doi.org/10.1148/radiol.2019182465DOI Listing
January 2020

Sertoli Cell Tumor (SCT) in a Captive Black Bear ().

Vet Sci 2019 Sep 26;6(4). Epub 2019 Sep 26.

Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Korea.

A black bear of 29-year-old () died unexpectedly in captivity without any gross lesions or clinical signs. We identified a firm, lobulated, yellowish tan, and well-circumscribed mass embedded inside the testicular tissue at the time of necropsy. The tumor sections exhibited soft necrotic and hemorrhagic areas beneath its capsule. Histologically, the tumor comprised Sertoli cells arranged in tubules and solid sheets supported by prominent fibrous connective tissues. The Sertoli cells were positive for vimentin and ER-β expression, whereas it showed negative staining for inhibin-α, cytokeratin 19, and S-100. To the best of our knowledge, this is the rare case report of testicular Sertoli cell tumor in black bear.
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http://dx.doi.org/10.3390/vetsci6040077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958315PMC
September 2019

Differentiation of equine induced pluripotent stem cells into mesenchymal lineage for therapeutic use.

Cell Cycle 2019 Nov 11;18(21):2954-2971. Epub 2019 Sep 11.

College of Veterinary Medicine, Kyungpook National University , Daegu , Republic of Korea.

In previous work, we established an equine induced pluripotent stem cell line (E-iPSCs) from equine adipose-derived stem cells (ASCs) using a lentiviral vector encoding four transcription factors: Oct4, Sox2, Klf4, and c-Myc. In the current study, we attempted to differentiate these established E-iPSCs into mesenchymal stem cells (MSCs) by serial passaging using MSC-defined media for stem cell expansion. Differentiation of the MSCs was confirmed by analyzing expression levels of the MSC surface markers CD44 and CD29, and the pluripotency markers Nanog and Oct4. Results indicated that the E-iPSC-derived MSCs (E-iPSC-MSCs) retained the characteristics of MSCs, including the ability to differentiate into chondrogenic, osteogenic, or myogenic lineages. E-iPSC-MSCs were rendered suitable for therapeutic use by inhibiting immune rejection through exposure to transforming growth factor beta 2 (TGF-β2) in culture, which down-regulated the expression of major histocompatibility complex class I (MHC class I) proteins that cause immune rejection if they are incompatible with the MHC antigen of the recipient. We reported 16 cases of E-iPSC-MSC transplantations into injured horses with generally positive effects, such as reduced lameness and fraction lines. Our findings indicate that E-iPSC-MSCs can demonstrate MSC characteristics and be safely and practically used in the treatment of musculoskeletal injuries in horses.
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http://dx.doi.org/10.1080/15384101.2019.1664224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791704PMC
November 2019

Computed tomographic findings of macrolide-resistant Mycobacterium massiliense pulmonary disease and changes after antibiotic treatment.

Medicine (Baltimore) 2019 Sep;98(36):e16826

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.

The purpose of this study was to present the computed tomographic (CT) findings of lung abnormalities in macrolide-resistant Mycobacterium massiliense pulmonary disease and its changes in follow-up CT after antibiotic treatment.Chest CT scans of patients with macrolide-resistant M massiliense pulmonary disease (n = 19) were retrospectively reviewed. Patients were treated with multidrug therapy, and sputum examinations were performed. Follow-up CT scans obtained during antibiotic treatment after detection of macrolide resistance were also reviewed, if available (n = 13). The CT scores at detection of macrolide resistance and at the last follow-up periods were also compared.Of all patients with macrolide-resistant M massiliense pulmonary disease, 2 (11%) patients achieved sputum culture conversion during the follow-up period. The most common CT findings of M massiliense pulmonary disease at detection of macrolide resistance were bronchiectasis and bronchiolitis (n = 19, 100%), followed by consolidation (n = 16, 84%), cavities (n = 11, 58%), and nodules (n = 6, 32%). On the last follow-up CT, overall CT scores were increased in 8 (62%) of 13 patients, and total mean CT score was significantly increased (P = .021). For each CT pattern, the cavity showed the greatest increase in CT score (P = .027), followed by bronchiectasis (P = .038).Common CT findings of macrolide-resistant M massiliense pulmonary disease were similar to those of pulmonary disease caused by other species of nontuberculous mycobacteria at presentation. However, in macrolide-resistant M massiliense pulmonary disease, serial CT scans showed deterioration with cavitary and bronchiectatic change in most patients despite multidrug antibiotic therapy.
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http://dx.doi.org/10.1097/MD.0000000000016826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738990PMC
September 2019

Risk factors and clinical characteristics of lung cancer in idiopathic pulmonary fibrosis: a retrospective cohort study.

BMC Pulm Med 2019 Aug 14;19(1):149. Epub 2019 Aug 14.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnamgu, Seoul, Republic of Korea.

Background: Lung cancer is a common comorbidity of idiopathic pulmonary fibrosis (IPF) and has poor outcomes. The incidence and clinical factors related to development of lung cancer in idiopathic pulmonary fibrosis (IPF) are unclear. The aim of this study was to elucidate the cumulative incidence, risk factors, and clinical characteristics of lung cancer in IPF.

Methods: In this retrospective study, we analyzed clinical data for 938 patients who were diagnosed with IPF without lung cancer between 1998 and 2013. Demographic, physiologic, radiographic, and histologic characteristics were reviewed. Cumulative incidence of lung cancer and survival were estimated by the Kaplan-Meier method. Risk factors of lung cancer development were determined by Cox proportional hazard analysis.

Results: Among 938 IPF patients without lung cancer at initial diagnosis, lung cancer developed in 135 (14.5%) during the follow-up period. The cumulative incidences of lung cancer were 1.1% at 1 year, 8.7% at 3, 15.9% at 5, and 31.1% at 10 years. Risk factors of lung cancer were male gender, current smoking at IPF diagnosis, and rapid annual decline of 10% or more in forced vital capacity (FVC). Patients who developed lung cancer were mostly elderly men with smoking history. Squamous cell carcinoma followed by adenocarcinoma was the most common histologic type. Lung cancer was frequently located in areas abutting or within fibrosis. Survival was significantly worse in patients with lung cancer compared to patients with IPF alone.

Conclusion: Lung cancer frequently developed in patients with IPF and was common in current-smoking men with rapid decline of FVC.
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http://dx.doi.org/10.1186/s12890-019-0905-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693185PMC
August 2019

Long-term natural history of non-cavitary nodular bronchiectatic nontuberculous mycobacterial pulmonary disease.

Respir Med 2019 05 26;151:1-7. Epub 2019 Mar 26.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address:

Background: Information about the natural history of nontuberculous mycobacterial pulmonary disease (NTM-PD) is limited. The purpose of this study was to evaluate the long-term natural history of non-cavitary nodular bronchiectatic NTM-PD and the factors associated with treatment initiation and the frequency of spontaneous sputum culture conversion after diagnosis of NTM-PD.

Methods: We evaluated 1,021 patients with newly diagnosed non-cavitary nodular bronchiectatic NTM-PD caused by Mycobacterium avium complex or M. abscessus between 2003 and 2013.

Results: Of 1,021 patients, 562 (55%) initiated antibiotic treatment and 459 (45%) did not. Young age (adjusted hazard ratio [aHR] = 0.99; 95% confidence interval [CI] = 0.98-0.99), low body mass index (aHR = 0.96; 95% CI = 0.93-0.99), previous history of tuberculosis (aHR = 1.23; 95% CI = 1.01-1.50), respiratory complaints such as cough (aHR = 1.36; 95% CI = 1.05-1.75) and sputum production (aHR = 1.47; 95% CI = 1.13-1.91), and high number of involved lobes on high-resolution computed tomography (aHR = 1.22; 95% CI = 1.14-1.31) were associated with treatment initiation. Of 459 patients who did not initiate treatment, 157 (34%) showed spontaneous sputum culture conversion. None of the clinical factors was associated with spontaneous conversion. After spontaneous culture conversion, 26 of 157 (17%) showed redeveloped NTM-PD caused by a species different from the original species.

Conclusions: The natural history of non-cavitary nodular bronchiectatic NTM-PD is variable. After diagnosis, the decision to initiate antibiotic therapy should be individualized based on consideration of the risk factors for disease progression. However, for patients who do not start antibiotic therapy, continuous and lifetime follow-up is recommended to manage underlying bronchiectasis and the possibility of late progression of NTM-PD.
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http://dx.doi.org/10.1016/j.rmed.2019.03.014DOI Listing
May 2019

Performance of Deep Learning Model in Detecting Operable Lung Cancer With Chest Radiographs.

J Thorac Imaging 2019 Mar;34(2):86-91

Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: The aim of this study was to evaluate the diagnostic performance of a trained deep convolutional neural network (DCNN) model for detecting operable lung cancer with chest radiographs (CXRs).

Materials And Methods: The institutional review board approved this study. A deep learning model (DLM) based on DCNN was trained with 17,211 CXRs (5700 CT-confirmed lung nodules in 3500 CXRs and 13,711 normal CXRs), finally augmented to 600,000 images. For validation, a trained DLM was tested with 1483 CXRs with surgically resected lung cancer, marked and scored by 2 radiologists. Furthermore, diagnostic performances of DLM and 6 human observers were compared with 500 cases (200 visible T1 lung cancer on CXR and 300 normal CXRs) and analyzed using free-response receiver-operating characteristics curve (FROC) analysis.

Results: The overall detection rate of DLM for resected lung cancers (27.2±14.6 mm) was a sensitivity of 76.8% (1139/1483) with a false positive per image (FPPI) of 0.3 and area under the FROC curve (AUC) of 0.732. In the comparison with human readers, DLM demonstrated a sensitivity of 86.5% at 0.1 FPPI and a sensitivity of 92% at 0.3 FPPI with AUC of 0.899 at an FPPI range of 0.03 to 0.44 for detecting visible T1 lung cancers, which were superior to the average of 6 human readers [mean sensitivity; 78% (range, 71.6% to 82.6%) at an FPPI of 0.1% and 85% (range, 80.2% to 89.2%) at an FPPI of 0.3, AUC of 0.819 (range, 0.754 to 0.862) at an FPPI of 0.03 to 0.44).

Conclusions: A DLM has high diagnostic performance in detecting operable lung cancer with CXR, demonstrating a potential of playing a pivotal role for lung cancer screening.
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http://dx.doi.org/10.1097/RTI.0000000000000388DOI Listing
March 2019

Solitary Nodular Invasive Mucinous Adenocarcinoma of the Lung: Imaging Diagnosis Using the Morphologic-Metabolic Dissociation Sign.

Korean J Radiol 2019 03;20(3):513-521

Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.

Objective: To evaluate the efficacy of the morphologic-metabolic (M-M) dissociation sign based on computed tomography (CT) and fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/CT in discriminating invasive mucinous adenocarcinoma (IMA) from invasive non-mucinous adenocarcinomas (ADCs) of the lung.

Materials And Methods: The Institutional Review Board approved this retrospective study. Among surgically resected solitary pulmonary nodule (SPN)-type ADCs (< 3 cm in diameter), 35 patients with IMAs and 329 with invasive non-mucinous ADCs were included. Morphologic malignancy was established if the tumor with lobulated or spiculated margin on CT presented a tumor shadow disappearance rate of < 0.5. The M-M dissociation sign was determined when a malignant-morphologic nodule on CT showed maximum standardized uptake value (SUVmax) < 3.5 on PET/CT.

Results: Among 35 IMAs (size: 21 ± 7 mm, SUVmax: 1.8 ± 2.0) and 329 invasive non-mucinous ADCs (size: 21 ± 6 mm, SUVmax: 4.6 ± 4.2), the M-M dissociation sign was observed in 54% of IMAs (19/35) and 10% of invasive non-mucinous ADCs (34/329) ( < 0.001). The diagnostic performance of the sign in discriminating IMA from invasive non-mucinous ADCs showed a sensitivity of 54.3% (95% confidence interval [CI], 36.7-71.2), specificity 89.7% (95% CI, 85.9-92.7), positive predictive value 35.8% (95% CI, 26.5-46.5), and negative predictive value 94.9% (95% CI, 92.8-96.4). Multivariate analyses revealed metabolic benignity (odds ratio [OR] 2.99; 95% CI, 1.01-8.93; = 0.047) and M-M dissociation sign (OR 6.35; 95% CI, 2.76-14.62; < 0.001) to be significant predictors of SPN-type IMAs.

Conclusion: Identification of the absence of M-M dissociation sign is an accurate indicator for excluding IMA from SPN-type lung ADCs.
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http://dx.doi.org/10.3348/kjr.2018.0409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389819PMC
March 2019

Transthoracic Rebiopsy for Mutation Analysis in Lung Adenocarcinoma: Outcomes and Risk Factors for the Acquisition of Nondiagnostic Specimens in 199 Patients.

Clin Lung Cancer 2019 05 31;20(3):e309-e316. Epub 2018 Dec 31.

Department of Radiology, Samsung Medical Center, Seoul, Korea; Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: To determine the outcomes of transthoracic rebiopsy for epidermal growth factor receptor (EGFR) mutation in patients with lung adenocarcinoma and to explore the clinical and procedure-related risk factors for the acquisition of nondiagnostic rebiopsy specimens.

Patients And Methods: We retrospectively reviewed 367 patients with lung adenocarcinoma who underwent transthoracic core needle biopsy for mutation analysis from September 2011 to October 2016. Of these, 199 patients underwent rebiopsy. Patient characteristics, treatment history, target lesion characteristics, and procedure-related factors were evaluated. The adequacy rate of specimens for mutation analysis was evaluated. Univariable and multivariable analyses were performed to determine the independent predictors of nondiagnostic specimens.

Results: Ninety percent of specimens (179 of 199) were adequate for mutation analysis. The EGFR mutation (exon 18-21) was 65% (117 of 179) and the EGFR T790M mutation 33% (59 of 179) of specimens. In univariable analysis, an internal low-attenuation area in the target lesion (P = .001) and pleural contact (P = .004) on computed tomography were significant risk factors for nondiagnostic specimens. In multivariable analysis, an internal low-attenuation area in the target lesion (odds ratio = 7.333; 95% confidence interval, 1.755-30.633; P = .006) was an independent predictor for acquisition of nondiagnostic specimens.

Conclusion: Image-guided transthoracic rebiopsy to obtain specimens for mutation analysis in lung adenocarcinoma provides high diagnostic accuracy, with a low rate of nondiagnostic specimens. The presence of internal low-attenuation area in the target lesion on computed tomography was an independent predictor for acquiring nondiagnostic specimens.
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http://dx.doi.org/10.1016/j.cllc.2018.12.021DOI Listing
May 2019

Resected Pure Small Cell Lung Carcinomas and Combined Small Cell Lung Carcinomas: Histopathology Features, Imaging Features, and Prognoses.

AJR Am J Roentgenol 2019 04 23;212(4):773-781. Epub 2019 Jan 23.

3 Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Objective: The objective of our study was to investigate histopathology features, imaging features, and prognoses of surgically resected pure small cell lung carcinomas (SCLCs) and combined SCLCs.

Materials And Methods: Forty-one patients with a pure SCLC or a combined SCLC underwent preoperative chest CT and F-FDG PET/CT and subsequent surgical resection. The clinicopathologic findings were noted by reviewing the electronic medical records. The imaging features of individual tumors were analyzed on chest CT and PET/CT scans. Each tumor was classified as being located centrally (at or in the segmental bronchus or proximal to the segmental bronchus) or peripherally (distal to the segmental bronchus). The maximum standardized uptake value (SUV) of each tumor was measured at PET. The 7th edition of the TNM staging system was adopted for staging.

Results: The study group was composed of 34 men and seven women with a mean age of 62.0 ± 10.2 (SD) years. Sixteen of 41 (39%) patients had pure SCLC, and the remaining patients had combined SCLC. The most common combined SCLC histologic subgroup was combined SCLC and large cell neuroendocrine carcinoma in 17 (41%) patients. The mean SUV of pure SCLCs was 5.6 ± 2.2 and was significantly lower than that of combined SCLCs (p < 0.01). Thirty-one patients (76%) had a peripheral tumor, and 10 (24%) had a central tumor. The overall survival (OS) of the 10 patients with a central tumor was 44.6 months, significantly shorter than the OS of the 31 patients with a peripheral tumor (179.2 months) (p = 0.017). The OS of 21 patients with stage I disease was significantly longer than the OS of patients with higher-stage cancer (p = 0.004).

Conclusion: In our study group of patients with surgically resected SCLC, patients with a peripheral tumor (including a purely endobronchial tumor) or stage I disease showed a better prognosis than those with a central tumor or higher-stage disease.
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http://dx.doi.org/10.2214/AJR.18.20519DOI Listing
April 2019

F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Assessing Treatment Response of Pulmonary Multidrug-Resistant Tuberculosis.

J Clin Med 2018 Dec 17;7(12). Epub 2018 Dec 17.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnamgu, Seoul 06351, Korea.

Background: The purpose of this prospective study was to evaluate the role of F-Fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) for assessing treatment response in patients with pulmonary multidrug-resistant tuberculosis (MDR-TB).

Methods: The study subjects were four patients diagnosed with pulmonary MDR-TB who underwent MDR-TB treatment and serial F-FDG PET/CT at baseline and 6 and 12 months after treatment. The highest lung maximum standardized uptake value (SUV), average SUV (average of all hypermetabolic parenchymal lesions), total metabolic lung volume (TMLV, sum of metabolic volumes from the hypermetabolic parenchymal lesions), and total lung glycolysis (TLG, sum of lesion glycolysis from the hypermetabolic parenchymal lesions) were determined as representative quantitative PET parameters for each patient.

Results: All patients except one had negative sputum culture conversion after one month of treatment and achieved successful treatment outcomes. Baseline TMLV and TLG PET parameters were much higher in the single patient with treatment failure than in the remaining three patients with treatment success. No other PET parameters at baseline or follow-up were associated with the treatment results.

Conclusions: Pretreatment volume-based F-FDG PET/CT lung parameters were associated with the final therapeutic response in patients with pulmonary MDR-TB. Our preliminary results warrant a larger study.
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http://dx.doi.org/10.3390/jcm7120559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307081PMC
December 2018

CT findings in pulmonary alveolar proteinosis: serial changes and prognostic implications.

J Thorac Dis 2018 Oct;10(10):5774-5783

Department of Radiology, Samsung Medical Center, Seoul, Korea.

Background: Pulmonary alveolar proteinosis (PAP) is a rare disease of unknown origin, characterized by impaired surfactant metabolism. In some patients, residual disease is observed after treatment; notably, this may progress to end-stage pulmonary fibrosis. This study was performed to evaluate changes in lung abnormalities on serial CT scans performed on the lungs of patients diagnosed with PAP, as well as to identify factors that can be used to predict clinical improvement in PAP.

Methods: Twenty-five patients (16 men, nine women) were diagnosed with PAP at a single tertiary hospital. The extent and distribution of PAP were assessed on baseline and follow-up CT scans (median, 38 months; range, 2-96 months). Serial CT scans and clinical findings were analyzed to identify the predictive factors for clinical improvement in PAP.

Results: Baseline CT scans of patients diagnosed with PAP revealed that ground-glass opacity was the most common abnormality (100%); the second most common abnormality was interlobular/intralobular septal thickening (88%). Importantly, the final follow-up CT scans showed that the extent of lung abnormalities had decreased (n=13), including complete resolution (n=5), unchanged (n=9), and increased (n=3). Traction bronchiectasis and architectural distortion were detected in two patients (8%). On univariate and multivariate analyses, the change in the overall extent of lung abnormalities was a predictive factor for clinical improvement in PAP (odds ratio: 55.780; P=0.038).

Conclusions: Most patients with PAP exhibited residual disease; however, progression to pulmonary fibrosis was rare. Analyses of overall changes, with respect to lung abnormalities on serial CT scans, may be predictive of the extent of clinical improvement in given patient.
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http://dx.doi.org/10.21037/jtd.2018.09.86DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236152PMC
October 2018

Establishment of stably expandable induced myogenic stem cells by four transcription factors.

Cell Death Dis 2018 10 25;9(11):1092. Epub 2018 Oct 25.

Department of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu, 41566, Republic of Korea.

Life-long regeneration of healthy muscle by cell transplantation is an ideal therapy for patients with degenerative muscle diseases. Yet, obtaining muscle stem cells from patients is very limited due to their exhaustion in disease condition. Thus, development of a method to obtain healthy myogenic stem cells is required. Here, we showed that the four transcription factors, Six1, Eya1, Esrrb, and Pax3, converts fibroblasts into induced myogenic stem cells (iMSCs). The iMSCs showed effective differentiation into multinucleated myotubes and also higher proliferation capacity than muscle derived stem cells both in vitro and in vivo. The iMSCs do not lose their proliferation capacity though the passaging number is increased. We further isolated CD106-negative and α7-integrin-positive iMSCs (sort-iMSCs) showing higher myogenic differentiation capacity than iMSCs. Moreover, genome-wide transcriptomic analysis of iMSCs and sort-iMSCs, followed by network analysis, revealed the genes and signaling pathways associated with enhanced proliferation and differentiation capacity of iMSCs and sort-iMSCs, respectively. The stably expandable iMSCs provide a new source for drug screening and muscle regenerative therapy for muscle wasting disease.
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http://dx.doi.org/10.1038/s41419-018-1114-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202407PMC
October 2018

Clinical implication of radiographic scores in acute Middle East respiratory syndrome coronavirus pneumonia: Report from a single tertiary-referral center of South Korea.

Eur J Radiol 2018 Oct 11;107:196-202. Epub 2018 Sep 11.

Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.

The aim of this study is to determine the earliest cutoff of radiographic score as a potential prognostic indicator of fatal outcomes in patients with acute Middle East respiratory syndrome coronavirus (MERS-CoV) pneumonia. The institutional review board approved this retrospective study. Serial chest radiographies (CXRs) were obtained from viral exposure until death or discharge in 35 patients with laboratory confirmed MERS-CoV infection. Radiographic scores were calculated by multiplying a four-point scale of involved lung area and three-point scale of abnormal opacification, in each of the six lung zones. Receiver operating characteristics (ROC) analyses were performed to identify optimal day and radiographic score for the prediction of respiratory distress, and univariate and multivariate logistic regression analyses were performed to assess significant predictive factors for intubation or tracheostomy. Among 35 patients (22 men, 13 women; median age: 48 years), 25 demonstrated abnormal opacity on CXR (MERS pneumonia), whereas no abnormality was detected in 10 patients (MERS upper respiratory tract infection). Seven patients required ventilator support (intubation group) and three of them eventually expired. The average incubation period was 5.4 days (standard deviation, ±2.8; range, 2-11). Patients in the intubation group had a higher incidence of diffuse lung involvement, higher radiographic scores, and fibrosing sequela on follow up study compared with those in the non-intubation group. However, patients' age and comorbidity did not differ significantly between the two groups. The ROC analysis revealed an area under curve of 0.726 for the radiographic score on day 10 with an optimal cutoff score of 10 for prediction of intubation, with a sensitivity of 71% and specificity of 67%. Our study suggest that MERS patients with radiographic score > 10 on day 10 from viral exposure require aggressive therapy with careful surveillance and follow-up evaluation.
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http://dx.doi.org/10.1016/j.ejrad.2018.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127293PMC
October 2018

Lung Adenocarcinoma: CT Features Associated with Spread through Air Spaces.

Radiology 2018 12 4;289(3):831-840. Epub 2018 Sep 4.

From the Departments of Radiology (S.K.K., T.J.K., M.J.C., T.S.K., K.S.L.) and Thoracic Surgery (J.I.Z., Y.M.S.), Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea.

Purpose To identify the features at CT that are predictive of spread through air spaces (STAS) in surgically resected lung adenocarcinomas. Materials and Methods For this retrospective study, presence of STAS was evaluated in 948 consecutive patients who underwent surgical resection for lung adenocarcinoma from April 2015 to December 2016. Patients who were positive for STAS and negative for STAS were matched at a ratio of 1:2 by using patient variables (age, sex, and smoking status). CT features (ie, percentage of solid component, maximum diameter of solid component, lesion density, location, margin, shape, pseudocavity, calcification, central low attenuation, ill-defined peripheral opacity, air bronchogram, satellite lesions, and pleural retraction) were analyzed by using multivariable logistic regression and receiver operating characteristic curves. Results The final study population consisted of 276 patients (mean age, 59 years; age range, 32-78 years) including 129 men (mean age, 60 years; age range, 36-78 years) and 147 women (mean age, 59 years; age range, 32-78 years). Ninety-two patients were positive for STAS and 184 patients were negative for STAS. STAS was more common in solid tumors (71 of 92; 77%) than in part-solid (21 of 92; 23%) or ground-glass lesions (0 of 92; 0%) (P < .001). STAS was also associated with central low attenuation, ill-defined opacity, air bronchogram, and percentage of solid component (all P < .001). Percentage of solid component was an independent predictor of STAS (odds ratio, 1.06; 95% confidence interval: 1.03, 1.08) and a cut-off value of 90% showed a discriminatory power with a sensitivity of 89.2% and a specificity of 60.3%. Conclusion Percentage of solid component was independently associated with spread through air spaces in lung adenocarcinomas. © RSNA, 2018 Online supplemental material is available for this article.
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http://dx.doi.org/10.1148/radiol.2018180431DOI Listing
December 2018

Surgically resected T1- and T2-stage esophageal squamous cell carcinoma: T and N staging performance of EUS and PET/CT.

Cancer Med 2018 08 22;7(8):3561-3570. Epub 2018 Jun 22.

Division of Hemato-oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

This study aimed to evaluate the frequency of nodal metastases and to disclose the diagnostic performance of endoscopic ultrasonography (EUS) and PET/CT in T and N staging in surgically resected early-stage esophageal squamous cell carcinomas (eSCCs). Institutional review board approved this retrospective study with waiver of informed consent for reviewing medical record. We included 435 patients with an early T-stage (Tis or T1a [≤T1a], T1b and T2) eSCC. The rates of metastatic lymphadenopathy were calculated. Then, the performance of EUS and PET/CT in subdividing T and N stages was assessed. 131 ≤ T1a, 234 T1b, and 70 T2 eSCCs were identified. In discriminating ≤T1a from other cancers, the sensitivity, specificity, and accuracy of EUS were 60.3% (79/131), 80.3% (244/304), and 74.3% (323/435) respectively. With ROC curve analysis, cut-off value of SUVmax 3.05 at PET provided sensitivity 74.8% (98/131), specificity 70.1% (213/304), and accuracy 71.5% (311/435) for differentiating ≤T1a eSCCs from others. Ten (7.6%) of 131 ≤ T1a cancers had nodal metastasis. In discriminating N0 from node-positive disease, sensitivity, specificity, and accuracy of EUS were 89.6% (267/298), 41.6% (57/137), and 74.5% (324/435), respectively, whereas those of PET/CT were 88.9% (265/298), 38.7% (53/137), and 73.1% (318/435) respectively. In >70% of patients with ≤T1a eSCCs, the tumor stage can be discriminated from higher stage cancers by using EUS or PET/CT. Substantial percentage (7.6%) of ≤T1a eSCC patients have nodal metastases, which are missed in more than half of the patients in clinical staging.
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http://dx.doi.org/10.1002/cam4.1617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089181PMC
August 2018

Radiological signs associated with pulmonary multi-drug resistant tuberculosis: an analysis of published evidences.

Quant Imaging Med Surg 2018 Mar;8(2):161-173

Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.

Background: Despite that confirmative diagnosis of pulmonary drug-sensitive tuberculosis (DS-TB) and multidrug resistant tuberculosis (MDR-TB) is determined by microbiological testing, early suspicions of MDR-TB by chest imaging are highly desirable in order to guide diagnostic process. We aim to perform an analysis of currently available literatures on radiological signs associated with pulmonary MDR-TB.

Methods: A literature search was performed using PubMed on January 29, 2018. The search words combination was "((extensive* drug resistant tuberculosis) OR (multidrug-resistant tuberculosis)) AND (CT or radiograph or imaging or X-ray or computed tomography)". We analyzed English language articles reported sufficient information of radiological signs of DS-TB MDR-TB.

Results: Seventeen articles were found to be sufficiently relevant and included for analysis. The reported pulmonary MDR-TB cases were grouped into four categories: (I) previously treated (or 'secondary', or 'acquired') MDR-TB in HIV negative (-) adults; (II) new (or 'primary') MDR-TB in HIV(-) adults; (III) MDR-TB in HIV positive (+) adults; and (IV) MDR-TB in child patients. The common radiological findings of pulmonary MDR-TB included centrilobular small nodules, branching linear and nodular opacities (tree-in-bud sign), patchy or lobular areas of consolidation, cavitation, and bronchiectasis. While overall MDR-TB cases tended to have more extensive disease, more likely to be bilateral, to have pleural involvement, to have bronchiectasis, and to have lung volume loss; these signs alone were not sufficient for differential diagnosis of MDR-TB. Current literatures suggest that the radiological sign which may offer good specificity for pulmonary MDR-TB diagnosis, though maybe at the cost of low sensitivity, would be thick-walled multiple cavities, particularly if the cavity number is ≥3. For adult HIV(-) patients, new MDR-TB appear to show similar prevalence of cavity lesion, which was estimated to be around 70%, compared with previously treated MDR-TB.

Conclusions: Thick-walled multiple cavity lesions present the most promising radiological sign for MDR-TB diagnosis. For future studies cavity lesion characteristics should be quantified in details.
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http://dx.doi.org/10.21037/qims.2018.03.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891679PMC
March 2018

Limitations of Detecting Small Solid Lung Nodules by Using Digital Chest Tomosynthesis.

Radiology 2018 06 3;287(3):1028-1029. Epub 2018 Apr 3.

From the Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.

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http://dx.doi.org/10.1148/radiol.2018180144DOI Listing
June 2018