Publications by authors named "Kyung Min Shin"

131 Publications

Clinical relevance of emphysema in patients hospitalized with community-acquired pneumonia: clinical features and prognosis.

Clin Respir J 2021 Apr 7. Epub 2021 Apr 7.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.

Introduction: Few studies have investigated the influence of emphysema on clinical features of patients presenting with community-acquired pneumonia (CAP).

Objectives: The aim of this study was to examine the clinical and microbiological features of patients with both CAP and emphysema.

Methods: This retrospective study included patients with CAP who underwent computed tomography (CT) scan at the time of presentation. Patients were allocated into emphysema and control groups, and clinical variables were compared between the 2 groups. The emphysema group was further divided into 3 subgroups (mild, moderate, and severe) according to the extent of emphysema on CT scan. The clinical variables of each subgroup were compared with the control group.

Results: Of 1676 patients, 431 patients (25.7%) were classified into the emphysema group. CAP patients with emphysema were more likely to have a high CURB-65 score and pneumonia severity index and a lower incidence of complicated parapneumonic effusion or empyema. The emphysema group exhibited longer hospital stay. In addition, 30-day mortality in the severe emphysema group was significantly higher compared with the control group. As etiological agents, Streptococcus pneumoniae, Pseudomonas aeruginosa, Enterobacteriaceae, and multi-drug resistant pathogens were significantly more common in the emphysema group compared with the control group.

Conclusions: The presence of emphysema in CAP patients was associated with a more severe form of CAP, a longer hospital stay, and a lower incidence of complicated parapneumonic effusion or empyema. Moreover, CAP patients with severe emphysema exhibited higher 30-day mortality than those without emphysema.
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http://dx.doi.org/10.1111/crj.13370DOI Listing
April 2021

Quantitative CT imaging and advanced visualization methods: potential application in novel coronavirus disease 2019 (COVID-19) pneumonia.

BJR Open 2021 22;3(1):20200043. Epub 2021 Jan 22.

VIDA Diagnostics, Coralville, IA, USA.

Increasingly, quantitative lung computed tomography (qCT)-derived metrics are providing novel insights into chronic inflammatory lung diseases, including chronic obstructive pulmonary disease, asthma, interstitial lung disease, and more. Metrics related to parenchymal, airway, and vascular anatomy together with various measures associated with lung function including regional parenchymal mechanics, air trapping associated with functional small airways disease, and dual-energy derived measures of perfused blood volume are offering the ability to characterize disease phenotypes associated with the chronic inflammatory pulmonary diseases. With the emergence of COVID-19, together with its widely varying degrees of severity, its rapid progression in some cases, and the potential for lengthy post-COVID-19 morbidity, there is a new role in applying well-established qCT-based metrics. Based on the utility of qCT tools in other lung diseases, previously validated supervised classical machine learning methods, and emerging unsupervised machine learning and deep-learning approaches, we are now able to provide desperately needed insight into the acute and the chronic phases of this inflammatory lung disease. The potential areas in which qCT imaging can be beneficial include improved accuracy of diagnosis, identification of clinically distinct phenotypes, improvement of disease prognosis, stratification of care, and early objective evaluation of intervention response. There is also a potential role for qCT in evaluating an increasing population of post-COVID-19 lung parenchymal changes such as fibrosis. In this work, we discuss the basis of various lung qCT methods, using case-examples to highlight their potential application as a tool for the exploration and characterization of COVID-19, and offer scanning protocols to serve as templates for imaging the lung such that these established qCT analyses have the best chance at yielding the much needed new insights.
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http://dx.doi.org/10.1259/bjro.20200043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931412PMC
January 2021

Genetic Polymorphisms in Activating Transcription Factor 3 Binding Site and the Prognosis of Early-Stage Non-Small Cell Lung Cancer.

Oncology 2021 Feb 24:1-9. Epub 2021 Feb 24.

Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: Activating transcription factor 3 (ATF3) plays a significant role in cancer development and progression. We investigated the association between variants in expression quantitative trait loci (eQTLs) within ATF3 binding regions and the prognosis of non-small cell lung cancer (NSCLC) after surgery.

Methods: A total of 772 patients with NSCLC who underwent curative surgery were enrolled. Using a public database (http://galaxyproject.org), we selected 104 single nucleotide polymorphisms (SNPs) in eQTLs in the ATF3 binding regions. The association of those SNPs with disease-free survival (DFS) was evaluated.

Results: Among those SNPs, HAX1 rs11265425T>G was associated with significantly worse DFS (aHR = 1.30, 95% CI = 1.00-1.69, p = 0.05), and ME3 rs10400291C>A was associated with significantly better DFS (aHR = 0.66, 95% CI = 0.46-0.95, p = 0.03). Regarding HAX1 rs11265425T>G, the significant association remained only in adenocarcinoma, and the association was significant only in squamous cell carcinoma regarding ME3 rs10400291C>A. ChIP-qPCR assays showed that the two variants reside in active enhancers where H3K27Ac and ATF3 binding occurs. Promoter assays showed that rs11265425 G allele had significantly higher HAX1 promoter activity than T allele. HAX1 RNA expression was significantly higher in tumor than in normal lung, and higher in rs11265425 TG+GG genotypes than in TT genotype. Conversely, ME3 expression was significantly lower in tumor than in normal lung, and higher in rs10400291 AA genotype than in CC+CA genotypes.

Conclusions: In conclusion, this study shows that the functional polymorphisms in ATF3 binding sites, HAX1 rs11265425T>G and ME3 rs10400291C>A are associated with the clinical outcomes of patients in surgically resected NSCLC.
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http://dx.doi.org/10.1159/000514131DOI Listing
February 2021

Prognostic significance of genetic variants in GLUT1 in stage III non-small cell lung cancer treated with radiotherapy.

Thorac Cancer 2021 03 31;12(6):874-879. Epub 2021 Jan 31.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.

Background: To examine the impact of polymorphisms of glucose transporter 1 (GLUT1) gene on the prognosis of patients with stage III non-small cell lung cancer (NSCLC) who received radiotherapy.

Methods: Five single nucleotide polymorphisms (SNPs) (rs4658C>G, rs1385129G>A, rs3820589A>T, rs3806401A>C and rs3806400C>T) in GLUT1 gene were evaluated in 90 patients with pathologically confirmed stage III NSCLC. A total of 21 patients were treated with radiotherapy alone, 25 with sequential chemoradiotherapy, and 44 with concurrent chemoradiotherapy. The association of the genetic variations of five SNPs with overall survival (OS) and progression-free survival (PFS) was analyzed.

Results: Two SNPs (rs1385129 and rs3806401) were significant risk factors for OS. Three SNPs (rs1385129, rs3820589 and rs3806401) were in linkage disequilibrium. In Cox proportional hazard models, GAA haplotype was a good prognostic factor for OS (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.39-0.81, p = 0.002) and PFS (HR = 0.68, 95% CI: 0.47-0.99, p = 0.043), compared to variant haplotypes. The GAA/GAA diplotype was observed in 46.7% of patients; these patients showed significantly better OS (HR = 0.38, 95% CI: 0.22-0.65, p < 0.001) and PFS (HR = 0.51, 95% CI: 0.31-0.85, p = 0.009) compared to those with other diplotypes.

Conclusions: These results suggest that polymorphisms of GLUT1 gene could be used as a prognostic marker for patients with stage III NSCLC treated with radiotherapy.
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http://dx.doi.org/10.1111/1759-7714.13851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952810PMC
March 2021

Multicentre randomised controlled clinical trial of electroacupuncture with usual care for patients with non-acute pain after back surgery.

Br J Anaesth 2021 Mar 16;126(3):692-699. Epub 2020 Dec 16.

Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon, South Korea. Electronic address:

Background: The purpose of this study was to investigate the effectiveness and safety between electroacupuncture (EA) combined with usual care (UC) and UC alone for pain reduction and functional improvement in patients with non-acute low back pain (LBP) after back surgery.

Methods: In this multicentre, randomised, assessor-blinded active-controlled trial, 108 participants were equally randomised to either the EA with UC or the UC alone. Participants in the EA with UC group received EA treatment and UC treatment twice a week for 4 weeks; those allocated to the UC group received only UC. The primary outcome was the VAS pain intensity score. The secondary outcomes were functional improvement (Oswestry Disability Index [ODI]) and the quality of life (EuroQol-5-dimension questionnaire [EQ-5D]). The outcomes were measured at Week 5.

Results: Significant reductions were observed in the VAS (mean difference [MD] -8.15; P=0.0311) and ODI scores (MD -3.98; P=0.0460) between two groups after 4 weeks of treatment. No meaningful differences were found in the EQ-5D scores and incidence of adverse events (AEs) between the groups. The reported AEs did not have a causal relationship with EA treatment.

Conclusions: The results showed that EA with UC treatment was more effective than UC alone and relatively safe in patients with non-acute LBP after back surgery. EA with UC treatment may be considered as an effective, integrated, conservative treatment for patients with non-acute LBP after back surgery.

Clinical Trial Registration: KCT0001939.
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http://dx.doi.org/10.1016/j.bja.2020.10.038DOI Listing
March 2021

Clinical implication of minimal presence of solid or micropapillary subtype in early-stage lung adenocarcinoma.

Thorac Cancer 2021 01 24;12(2):235-244. Epub 2020 Nov 24.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea.

Background: We investigated the clinical features and surgical outcomes of lung adenocarcinoma with minimal solid or micropapillary (S/MP) components, with a focus on stage IA.

Methods: We enrolled 506 patients with lung adenocarcinoma who underwent curative resection in this study. Clinical features and surgical outcomes were compared between the groups with and without the S/MP subtype (S/MP+ and S/MP-, respectively), and between the group with an S/MP proportion of ≤5% (S/MP5) and the S/MP-.

Results: The S/MP subtype was present in 247 patients (48.8%); 129 (25.5%) were grouped as the S/MP5 group. The S/MP+ and S/MP5 groups had larger tumors, higher frequency of lymph node metastasis, and more advanced stages of disease than the S/MP- group (P < 0.001, all comparisons). Pleural, lymphatic, and vascular invasions occurred more frequently in the S/MP+ and S/MP5 groups (P < 0.001, all comparisons for S/MP+ vs. S/MP-; P ≤ 0.01, all comparisons for S/MP5 vs. S/MP-). The S/MP+ and S/MP5 groups showed a shorter time to recurrence and cancer-related death than the S/MP- group(P < 0.001, both comparisons). For stage I, the presence or absence of the S/MP subtype defined prognostic subgroups better than the stage IA/IB classification. Notably, in the multivariate analysis, the minimal S/MP component was a significant predictor of recurrence, even in stage IA.

Conclusions: The presence of the minimal S/MP component was a significant predictor of poor prognosis after surgery, even in stage IA patients. Clinical trials to evaluate the advantages of adjuvant chemotherapy for this subset of patients and further investigations to understand underlying biological mechanisms of poor prognosis are needed.

Key Points: Significant findings of the study: We demonstrated that only minimal presence of solid or micropapillary component was profoundly associated with aggressive clinicopathological features and poor prognosis after complete resection even in stage IA lung adenocarcinoma.

What This Study Adds: Our results suggest that minimal presence of these subtypes is a strong prognostic factor which should be taken into account in the risk assessment for adjuvant chemotherapy in lung adenocarcinoma.
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http://dx.doi.org/10.1111/1759-7714.13754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812076PMC
January 2021

Spondylodiscitis initially presenting as exudative pleural effusion: A case report and review of the literature.

Eur J Radiol Open 2020 15;7:100279. Epub 2020 Oct 15.

Department of Radiology, Seoul National University Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul 03080, South Korea.

Pleural effusions are associated with a variety of disease states, rendering the differential diagnosis challenging. Spondylodiscitis is an uncommon disease, and its prompt diagnosis can reduce morbidity and mortality. However, an atypical manifestation of the disease, such as pleural effusion, can result in delayed diagnosis. A 76-year-old woman presented with back pain and right pleural effusion. Magnetic resonance imaging revealed paravertebral soft tissue infiltration, with enhancement of bone marrow and intervertebral disk at the T8 and T9 levels, suggesting spondylodiscitis. In patients with exudative pleural effusion, spondylodiscitis may be the cause, so careful analysis of imaging is necessary.
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http://dx.doi.org/10.1016/j.ejro.2020.100279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569184PMC
October 2020

Ultrasound-guided Percutaneous Needle Biopsy for Small Pleural Lesions: Diagnostic Yield and Impact of CT and Ultrasound Characteristics.

AJR Am J Roentgenol 2020 Oct 7. Epub 2020 Oct 7.

Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu, 41944, South Korea.

Ultrasound (US)-guided percutaneous pleural needle biopsy (PCPNB) is widely used to evaluate pleural lesions, though has variable diagnostic accuracy. To assess the diagnostic yield of US-guided PCPNB for small (≤ 2 cm) pleural lesions and the impact of CT and US morphologic and technical factors. 103 patients (73 men, 30 women; age, 60.8±13.3 years) who underwent US-guided PCPNB of a small pleural lesion by a single experienced operator from July 2013 to December 2019 were retrospectively analyzed. Final diagnosis was established via histopathological results, including from repeat US-guided and CT-guided biopsies, as well as imaging and clinical follow-up. Pleural morphology and thickness were assessed on CT and US, and needle pathway length throughout the pleura was measured on US. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. The association between diagnostic yield with imaging and technical factors was evaluated. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal CT pleural thickness cutoff value. Multivariable logistic regression was performed to identify independent predictors of diagnostic yield. Diagnostic accuracy, sensitivity, specificity, PPV, and NPV of US-guided PCPNB were 85.4%, 84.8%, 100%, 100%, and 21.1%, respectively. Diagnostic, compared with non-diagnostic, procedures more commonly (p≤0.002) exhibited nodular morphology on CT (96.4% vs. 3.6%) and US (97.3% vs. 2.7%,), greater pleural thickness on CT (7.5 mm vs. 3.2 mm) and US (7.4 mm vs. 3.0 mm), and greater needle pathway length (11.0 mm vs. 6.1 mm). Optimal CT pleural thickness cut-off value was 4.5 mm. Diagnostic yield was 96.4% for nodular CT lesions, 95.0% for diffuse CT lesions with thickness ≥4.5 mm, 55.6% for diffuse CT lesions with thickness <4.5 mm, and 100.0% for diffuse CT lesions with nodular US morphology. Nodular US morphology (p=0.002) and needle pathway length (p=0.035) were independent predictors of diagnostic yield. US-guided PCPNB has excellent diagnostic accuracy for small pleural lesions; imaging characteristics influence this accuracy. US-guided PCPNB is highly likely to be diagnostic for small pleural lesions with nodular morphology on CT or US, or with pleural thickness ≥4.5 mm.
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http://dx.doi.org/10.2214/AJR.20.24120DOI Listing
October 2020

Quantitative CT-based image registration metrics provide different ventilation and lung motion patterns in prone and supine positions in healthy subjects.

Respir Res 2020 Oct 2;21(1):254. Epub 2020 Oct 2.

Department of Radiology, University of Iowa, Iowa City, USA.

Background: Previous studies suggested that the prone position (PP) improves oxygenation and reduces mortality among patients with acute respiratory distress syndrome (ARDS). However, the mechanism of this clinical benefit of PP is not completely understood. The aim of the present study was to quantitatively compare regional characteristics of lung functions in the PP with those in the supine position (SP) using inspiratory and expiratory computed tomography (CT) scans.

Methods: Ninety subjects with normal pulmonary function and inspiration and expiration CT images were included in the study. Thirty-four subjects were scanned in PP, and 56 subjects were scanned in SP. Non-rigid image registration-based inspiratory-expiratory image matching assessment was used for regional lung function analysis. Tissue fractions (TF) were computed based on the CT density and compared on a lobar basis. Three registration-derived functional variables, relative regional air volume change (RRAVC), volumetric expansion ratio (J), and three-dimensional relative regional displacement (s*) were used to evaluate regional ventilation and deformation characteristics.

Results: J was greater in PP than in SP in the right middle lobe (P = 0 .025), and RRAVC was increased in the upper and right middle lobes (P < 0.001). The ratio of the TF on inspiratory and expiratory scans, J, and RRAVC at the upper lobes to those at the middle and lower lobes and that ratio at the upper and middle lobes to those at the lower lobes of were all near unity in PP, and significantly higher than those in SP (0.98-1.06 vs 0.61-0.94, P < 0.001).

Conclusion: We visually and quantitatively observed that PP not only induced more uniform contributions of regional lung ventilation along the ventral-dorsal axis but also minimized the lobar differences of lung functions in comparison with SP. This may help in the clinician's search for an understanding of the benefits of the application of PP to the patients with ARDS or other gravitationally dependent pathologic lung diseases.

Trial Registration: Retrospectively registered.
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http://dx.doi.org/10.1186/s12931-020-01519-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531138PMC
October 2020

Genetic Variants in One-Carbon Metabolism Pathway Predict Survival Outcomes of Early-Stage Non-Small Cell Lung Cancer.

Oncology 2020 13;98(12):897-904. Epub 2020 Aug 13.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: This study was conducted to investigate the association between genetic variants in one-carbon metabolism and survival outcomes of surgically resected non-small cell lung cancer (NSCLC).

Methods: We genotyped 41 potentially functional variants of 19 key genes in the one-carbon metabolism pathway among 750 NSCLC patients who underwent curative surgery. The association between genetic variants and overall survival (OS)/disease-free survival (DFS) were analyzed.

Results: Among the 41 single-nucleotide polymorphisms (SNPs) analyzed, 4 SNPs (MTHFD1L rs6919680T>G and rs3849794T>C, MTR rs2853523C>A, and MTHFR rs4846049G>T) were significantly associated with survival outcomes. MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (adjusted hazard ratio [aHR] = 0.73, 95% confidence interval [CI] = 0.54-0.99, p = 0.04) and worse OS (aHR = 2.14, 95% CI = 1.13-4.07, p = 0.02), respectively. MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.41, 95% CI = 1.08-1.83, p = 0.01; and aHR = 1.97, 95% CI = 1.10-3.53, p = 0.02, respectively). When the patients were divided according to histology, the associations were significant only in squamous cell carcinoma (SCC), but not in adenocarcinoma (AC). In SCC, MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (aHR = 0.64, 95% CI = 0.41-1.00, p = 0.05) and worse OS (aHR = 2.77, 95% CI = 1.11-6.91, p = 0.03), respectively, and MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.73, 95% CI = 1.17-2.56, p = 0.01; and aHR = 2.78, 95% CI = 1.12-6.88, p = 0.03, respectively).

Conclusions: Our results suggest that the genetic variants in the one-carbon metabolism pathway could be used as biomarkers for predicting the clinical outcomes of patients with early-stage NSCLC.
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http://dx.doi.org/10.1159/000509658DOI Listing
December 2020

Prognostic Implication of Volumetric Quantitative CT Analysis in Patients with COVID-19: A Multicenter Study in Daegu, Korea.

Korean J Radiol 2020 11 4;21(11):1256-1264. Epub 2020 Aug 4.

Department of Radiology, Yeungnam University Medical Center, Daegu, Korea.

Objective: Lung segmentation using volumetric quantitative computed tomography (CT) analysis may help predict outcomes of patients with coronavirus disease (COVID-19). The aim of this study was to investigate the relationship between CT volumetric quantitative analysis and prognosis in patients with COVID-19.

Materials And Methods: CT images from patients diagnosed with COVID-19 from February 18 to April 15, 2020 were retrospectively analyzed. CT with a negative finding, failure of quantitative analysis, or poor image quality was excluded. CT volumetric quantitative analysis was performed by automated volumetric methods. Patients were stratified into two risk groups according to CURB-65: mild (score of 0-1) and severe (2-5) pneumonia. Outcomes were evaluated according to the critical event-free survival (CEFS). The critical events were defined as mechanical ventilator care, ICU admission, or death. Multivariable Cox proportional hazards analyses were used to evaluate the relationship between the variables and prognosis.

Results: Eighty-two patients (mean age, 63.1 ± 14.5 years; 42 females) were included. In the total cohort, male sex (hazard ratio [HR], 9.264; 95% confidence interval [CI], 2.021-42.457; = 0.004), C-reactive protein (CRP) (HR, 1.080 per mg/dL; 95% CI, 1.010-1.156; = 0.025), and COVID-affected lung proportion (CALP) (HR, 1.067 per percentage; 95% CI, 1.033-1.101; < 0.001) were significantly associated with CEFS. CRP (HR, 1.164 per mg/dL; 95% CI, 1.006-1.347; = 0.041) was independently associated with CEFS in the mild pneumonia group (n = 54). Normally aerated lung proportion (NALP) (HR, 0.872 per percentage; 95% CI, 0.794-0.957; = 0.004) and NALP volume (NALPV) (HR, 1.002 per mL; 95% CI, 1.000-1.004; = 0.019) were associated with a lower risk of critical events in the severe pneumonia group (n = 28).

Conclusion: CRP in the mild pneumonia group; NALP and NALPV in the severe pneumonia group; and sex, CRP, and CALP in the total cohort were independently associated with CEFS in patients with COVID-19.
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http://dx.doi.org/10.3348/kjr.2020.0567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462758PMC
November 2020

Imaging of COVID-19 pneumonia: Patterns, pathogenesis, and advances.

Br J Radiol 2020 Sep 6;93(1113):20200538. Epub 2020 Aug 6.

Department of Radiology, University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA.

COVID-19 pneumonia is a newly recognized lung infection. Initially, CT imaging was demonstrated to be one of the most sensitive tests for the detection of infection. Currently, with broader availability of polymerase chain reaction for disease diagnosis, CT is mainly used for the identification of complications and other defined clinical indications in hospitalized patients. Nonetheless, radiologists are interpreting lung imaging in unsuspected patients as well as in suspected patients with imaging obtained to rule out other relevant clinical indications. The knowledge of pathological findings is also crucial for imagers to better interpret various imaging findings. Identification of the imaging findings that are commonly seen with the disease is important to diagnose and suggest confirmatory testing in unsuspected cases. Proper precautionary measures will be important in such unsuspected patients to prevent further spread. In addition to understanding the imaging findings for the diagnosis of the disease, it is important to understand the growing set of tools provided by artificial intelligence. The goal of this review is to highlight common imaging findings using illustrative examples, describe the evolution of disease over time, discuss differences in imaging appearance of adult and pediatric patients and review the available literature on quantitative CT for COVID-19. We briefly address the known pathological findings of the COVID-19 lung disease that may help better understand the imaging appearance, and we provide a demonstration of novel display methodologies and artificial intelligence applications serving to support clinical observations.
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http://dx.doi.org/10.1259/bjr.20200538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465853PMC
September 2020

Clinical Impact of N-Terminal Prohormone of Brain Natriuretic Peptide on Patients Hospitalized with Community-Acquired Pneumonia.

Am J Med Sci 2020 10 2;360(4):383-391. Epub 2020 Jun 2.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.

Background: Risk stratification is important for the management of community-acquired pneumonia (CAP). The present study aimed to investigate the clinical impact of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) on prognosis and to identify clinical characteristics associated with NT-proBNP elevation in CAP patients.

Methods: This retrospective study included patients hospitalized for CAP at a tertiary referral center and who underwent measurement plasma NT-proBNP levels. Based on 30-day mortality, patients (n = 1,821) were divided into 2 groups, survivors (n = 150) and nonsurvivors (n = 1,671), and clinical and laboratory findings were compared.

Results: In multivariate analysis, blood levels of NT-proBNP (>942.5 pg/mL), albumin (<3.3 g/dL), and troponin I (>0.018 ng/mL) independently predicted 30-day mortality. Of these blood biomarkers, NT-proBNP exhibited the highest C-statistic, followed by albumin. NT-proBNP level/CURB-65 score and NT-proBNP level/pneumonia severity index (PSI) class exhibited significantly higher C-statistics than CURB-65 score and PSI class alone, respectively. The 3-test combinations of CURB-65 score/NT-proBNP level/albumin level and PSI class/NT-proBNP level/albumin level exhibited significantly higher C-statistics than the 2-test combinations. NT-proBNP elevation was associated with increased age, heart disease and chronic kidney disease and NT-proBNP levels only weakly or moderately correlated with other blood biomarkers.

Conclusions: NT-proBNP level was a useful marker for the prediction of 30-day mortality in patients hospitalized with CAP, and provided additional prognostic value to PSI or CURB-65 alone.
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http://dx.doi.org/10.1016/j.amjms.2020.05.042DOI Listing
October 2020

Association of Cost and Medical Service Satisfaction with Korean and Conventional Medicine Use before and after Surgery in Postsurgical Patients: A Questionnaire Survey of Korean Patients with Postsurgical Pain Visiting Korean Medicine Hospitals.

Evid Based Complement Alternat Med 2020 19;2020:8195241. Epub 2020 Mar 19.

Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, Republic of Korea.

This study aimed to assess the costs, health status, and medical service satisfaction with Korean and conventional medicine use before and after surgery of patients visiting Korean medicine hospitals for postsurgical musculoskeletal pain. The study population comprised patients who visited KM hospitals for the first time between June and November 2017 for persistent or recurrent pain and discomfort after low back, neck, shoulder, or knee surgery. Various validated questionnaires were used to collect data. A total of 100 participants were enrolled, and the majority had undergone low back surgery ( = 82). The participants had received 1.3 ± 0.7 magnetic resonance imaging (MRI) examinations and 2.4 ± 2.8 X-rays before surgery. Conventional interventions used before surgery were physical therapy (43%), medications (34%), and injections (28%), in descending order, while 48% of patients reported having received acupuncture 51.3 ± 81.1 times. The mean satisfaction score for surgery was 5.5 ± 2.8 points based on a 9-point Likert scale, while that for KM-based interventions was 6.3 ± 1.7 points. With respect to health-related information, the mean scores were 6.0 ± 2.2 points on the Numeric Rating Scale (NRS), 0.6 ± 0.2 points on the 5-Level EuroQol-5 Dimension (EQ-5D-5L), and 15.3 ± 10.2 on Beck's Depression Index II (BDI-II). The mean score on the Oswestry Disability Index (ODI) in patients with low back pain was 40.1 ± 19.2 points. Work impairment, as measured using the Work Productivity and Activity Impairment Questionnaire: General Health (WPAI-GH), was 62.5 ± 47.8%, while activity impairment was 5.9 ± 2.6%. Participants tended to show low satisfaction regarding surgery and high preference for KM-based interventions. In particular, low back surgery patients reported high ODI scores, indicating high dysfunctional levels and poor prognosis after surgery. It can be inferred that it is therefore important to provide appropriate presurgical and postsurgical care for patients with musculoskeletal pain to improve pain, function, and quality of life.
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http://dx.doi.org/10.1155/2020/8195241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106882PMC
March 2020

Polymorphisms in Glycolysis-Related Genes Are Associated with Clinical Outcomes of Paclitaxel-Cisplatin Chemotherapy in Non-Small Cell Lung Cancer.

Oncology 2020 6;98(7):468-477. Epub 2020 Apr 6.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea,

Objective: This study was conducted to investigate whether polymorphisms in glycolysis-related genes are associated with clinical outcomes of patients with advanced-stage non-small cell lung cancer (NSCLC) undergoing chemotherapy.

Methods: A total of 377 patients with NSCLC were enrolled. Sixty-five single-nucleotide polymorphisms in 26 genes involved in the glycolytic pathway were evaluated. The associations of the variants with the chemotherapy response and overall survival (OS) were analyzed.

Results: Among the 65 variants investigated, PFKL rs2073436C>G and GPI rs7248411C>G significantly correlated with clinical outcomes after chemotherapy in multivariate analyses. PFKL rs2073436C>G was significantly associated with both a worse response to chemotherapy (adjusted odds ratio [aOR] = 0.64, 95% CI = 0.45-0.90, p = 0.01) and a worse OS (adjusted hazard ratio [aHR] = 1.35, 95% CI = 1.14-1.61, p = 0.001). GPI rs7248411C>G was significantly associated with both a better chemotherapy response (aOR = 1.58, 95% CI = 1.07-2.23, p = 0.02) and a better OS (aHR = 0.80, 95% CI = 0.66-0.98, p = 0.03). When stratified by tumor histology, PFKL rs2073436C>G was significantly associated with OS only in squamous cell carcinoma, whereas GPI rs7248411C>G exhibited a significant association with the chemotherapy response and OS only in adenocarcinoma.

Conclusion: This result suggests that the PFKL rs2073436C>G and GPI rs7248411C>G are useful for predicting the clinical outcome of first-line paclitaxel-cisplatin chemotherapy in NSCLC.
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http://dx.doi.org/10.1159/000504175DOI Listing
July 2020

Ultrasound Assessment of Synchronous Thyroid Nodules in Patients With Papillary Thyroid Cancer: A Nodule-by-nodule Analysis Between Ultrasound and Pathology.

Anticancer Res 2020 Mar;40(3):1779-1786

Department of Radiology, School of Medicine, Kyungpook National University Chilgok Hospital, Kyungpook National University, Daegu, Republic of Korea.

Background/aim: The purpose of this study was to evaluate the diagnostic value of preoperative ultrasound (US) in the assessment of synchronous thyroid nodules in patients with papillary thyroid cancer (PTC) for determination of surgical extent.

Patients And Methods: A total of 210 consecutive patients who were surgically diagnosed with PTC were included in this study. Synchronous nodules, divided into probably benign and suspicious nodules based on US findings, were correlated with pathologic results using a nodule-by-nodule analysis.

Results: Among the 302 synchronous nodules in 129 patients, 83 (27.5%) synchronous nodules in 73 patients were diagnosed as malignant after surgery. Ipsilateral probably benign nodules on US were more likely to be malignant than contralateral probably benign nodules (ipsilateral, 10.6%; contralateral, 2.0%, p=0.015). The presence of suspicious contralateral nodules on US and the number of synchronous nodules were significant factors related to contralateral cancer (p<0.001 and 0.030).

Conclusion: For evaluation of synchronous nodules in PTC patients, US assessment for synchronous nodules can be applied for preserving the contralateral lobe.
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http://dx.doi.org/10.21873/anticanres.14132DOI Listing
March 2020

Emphysema is associated with the aggressiveness of COPD-related adenocarcinomas.

Clin Respir J 2020 Apr 14;14(4):405-412. Epub 2020 Jan 14.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.

Objectives: To compare the differences in radiologic and pathologic features of surgically resected chronic obstructive pulmonary disease (COPD)-related adenocarcinomas according to the presence of emphysema.

Methods: A total of 216 smokers with surgically resected lung adenocarcinoma were included in this retrospective study, and 102 patients were diagnosed with COPD. We classified COPD patients as emphysematous or non-emphysematous group based on the emphysema severity on computed tomography (CT) and evaluated the differences in the CT and pathologic features between the two groups. The relationship between emphysema and disease-free survival was assessed using a Kaplan-Meier curve.

Results: Lung adenocarcinomas in emphysema group presented a more aggressive pathologic grade and higher prevalence of solid lesions (vs subsolid lesions) on CT than those in non-emphysematous group (P = 0.006 and <0.001, respectively). After adjustment for age, sex, smoking pack-years and tumor size, emphysema group had a greater risk for higher histologic grade and higher prevalence of solid lesions than non-emphysema group (odds ratio, 3.445; 95% confidence interval, 1.124-10.564; P = 0.030, odds ratio, 6.192; 95% confidence interval, 1.804-21.254; P = 0.004, respectively). Kaplan-Meier survival curves showed that patients with emphysema had significantly impaired disease-free survival compared with those without emphysema (median disease-free survival = 37.0 vs 57.5 months, P = 0.038).

Conclusion: Adenocarcinomas in emphysema-present COPD had more aggressive features of pathology and CT findings, and worse disease-free survival than those without emphysema. These findings might provide an insight into the different pathobiology and prognostic implications of lung adenocarcinomas according to the presence of emphysema in patients with COPD.
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http://dx.doi.org/10.1111/crj.13146DOI Listing
April 2020

Polymorphism in ASCL1 target gene DDC is associated with clinical outcomes of small cell lung cancer patients.

Thorac Cancer 2020 01 5;11(1):19-28. Epub 2019 Nov 5.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.

Background: Achaete-scute homolog 1 (ASCL1) is a basic helix-loop-helix transcription factor and is essential in the differentiation of neuroendocrine cells and neural tissues. ASCL1 is frequently overexpressed in small cell lung cancer (SCLC) and plays a crucial role in the pathogenesis of SCLC.

Methods: This study was conducted to identify the association between single nucleotide polymorphisms (SNPs) in ASCL1 target genes and clinical outcomes of patients with SCLC after chemotherapy. A total of 261 patients diagnosed with SCLC were enrolled in this study. The association between 103 SNPs in 58 ASCL1 target genes and the response to chemotherapy and survival of patients with SCLC were analyzed.

Results: Among the 103 SNPs, 10 SNPs were significantly associated with the response to chemotherapy, and 19 SNPs were associated with OS in multivariate analyses. Among these, Dopa Decarboxylase (DDC) rs12666409A>T was significantly associated with both a worse response to chemotherapy and worse OS (adjusted odds ratio [aOR] = 0.40, 95% CI = 0.18-0.90, P = 0.03; adjusted hazard ratio [aHR] = 1.52, 95% CI = 1.10-2.10, P = 0.01, respectively, under a dominant model). In a stage-stratified analysis, the association was significant only in the extensive disease subgroup (aOR = 0.19, 95% CI = 0.06-0.60, P = 0.01; aHR = 1.73, 95% CI = 1.16-2.56, P = 0.01, respectively, under a dominant model), but not in the limited disease subgroup.

Conclusion: The results of our study suggest that DDC rs12666409A>T may be useful markers for predicting the clinical outcomes of patients with SCLC undergoing chemotherapy.
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http://dx.doi.org/10.1111/1759-7714.13212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938757PMC
January 2020

Can emphysema influence size discrepancy between radiologic and pathologic size measurement in subsolid lung adenocarcinomas?

Thorac Cancer 2019 10 12;10(10):1919-1927. Epub 2019 Aug 12.

Department of Pathology, School of Medicine, Kyungpook National University, Daegu, South Korea.

Background: To investigate the difference in the measured diameter of subsolid lung adenocarcinomas of thin-section computed tomography (TSCT) and pathology according to presence of emphysema.

Methods: A total of 268 surgically resected pathologic T1 or T2 adenocarcinomas visualized as subsolid nodules (SSNs) on TSCT were analyzed in 252 patients. Two observers measured the greatest diameters of the whole tumor (WTsize) and solid tumor (STsize) on TSCT in lung windows, classified nodules as part-solid or nonsolid, and recorded the presence of regional emphysema. Interobserver variability was determined with intraclass correlation coefficients (ICC). CT measurements were compared to pathologic size (Psize) and invasive size (PIsize) using the Wilcoxon signed-rank test.

Results: The interobserver agreement between the diameters measured by the two observers was strong for WTsize (ICC = 0.968 [95% confidence interval, 0.960-0.975]) and STsize (ICC = 0.966 [95% CI, 0.950-0.969]). Radiologic WTsize was significantly greater than Psize (P < 0.001), while STsize was less than PIsize. The WTsize of the emphysema group was better correlated with Psize than WTsize of the normal lung group (P = 0.001), while the STsize of the normal lung group was better correlated with PIsize than STsize of the emphysema group. The concordance rate in T staging between CT and pathologic analysis was better correlated in patients with normal lungs than in those with emphysema (P = 0.023).

Conclusion: STsize on TSCT was underestimated in patients with emphysema, resulting in higher discordance in T staging between TSCT and pathologic analysis for subsolid lung adenocarcinomas.
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http://dx.doi.org/10.1111/1759-7714.13165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775004PMC
October 2019

Clinical relevance of chronic respiratory disease in Korean patients with pulmonary thromboembolism.

J Thorac Dis 2019 Jun;11(6):2410-2419

Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Korea.

Background: Data regarding clinical and radiological features of patients with pulmonary thromboembolism (PTE) and concomitant chronic respiratory disease (CRD) are limited. Accordingly, the aim of the present study was to investigate clinico-radiological features of this patient population.

Methods: Patients with PTE were retrospectively classified into one of two groups: those with and without CRD. Clinical characteristics, blood biomarkers, and computed tomographic (CT) findings were compared between the groups.

Results: Of 1,207 PTE patients included, CRD was detected in 128 (11%). The most common CRD was chronic obstructive pulmonary disease [41 (32%)], followed by bronchial anthracofibrosis [32 (25%)]. In multivariate analysis, unprovoked PTE [odds ratio (OR) 1.99, 95% confidence interval (CI): 1.29-3.05, P=0.002], dyspnea (OR 1.54, 95% CI: 1.11-2.34, P=0.041), lower respiratory tract infection (LRTI) (OR 3.90, 95% CI: 2.13-7.14, P<0.001), Pulmonary Embolism Severity Index (PESI) class IV-V (OR 5.24, 95% CI: 3.43-8.00, P<0.001), in-situ pulmonary artery thrombosis (OR 10.62, 95% CI: 3.71-30.45, P<0.001), and pulmonary artery enlargement (OR 1.65, 95% CI: 3.71-30.45, P<0.001) were found to be independent clinical factors related to CRD in patients with PTE. CRD was an independent predictor of PTE-related in-hospital mortality (OR 3.96, 95% CI: 1.32-11.88, P=0.014).

Conclusions: Patients with PTE and concomitant CRD were characterized by higher incidences of dyspnea, LRTI, PESI class IV-V, and pulmonary artery thrombosis, compared with non-CRD patients. In these patients, CRD was a predictor of PTE-related in-hospital mortality.
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http://dx.doi.org/10.21037/jtd.2019.05.53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626803PMC
June 2019

Genetic Variant of Notch Regulator DTX1 Predicts Survival After Lung Cancer Surgery.

Ann Surg Oncol 2019 Oct 16;26(11):3756-3764. Epub 2019 Jul 16.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Korea.

Background: We evaluated the association between genetic variants in the Notch pathway and survival outcomes of patients with surgically resected NSCLC.

Methods: Sixty-four single nucleotide polymorphisms (SNPs) in the Notch pathway genes were evaluated in the discovery study (n = 354) and two sequential validation studies (n = 772 and n = 746, respectively). The association of genotype with overall survival (OS) and disease-free survival (DFS) was evaluated.

Results: Of the 64 SNPs analyzed in the discovery study, 9 were significantly associated with OS or DFS. Among them, the association remained significant only for Deltex-1 (DTX1) rs1732786A>G in the first validation study. The second validation study confirmed again the association between DTX1 rs1732786A>G and survival outcomes. In the combined analysis, rs1732786A>G was significantly associated with better OS and DFS (adjusted HR ·aHR· for OS, 0.75; 95% CI 0.64-0.87; P = 0.0002; aHR for DFS, 0.79; 95% CI 0.71-0.89; P = 0.0001). In vitro luciferase assay showed that the rs1732786G allele was associated with higher promoter activity compared to rs1732786A allele. Consistently, relative mRNA expression level of DTX1 showed significant positive correlation with rs1732786 A-to-G change (P = 0.02) in tumor tissues.

Conclusions: These results suggest that DTX1 rs1732786 is a potential prognostic factor that may have clinical utility in the management of early stage NSCLC.
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http://dx.doi.org/10.1245/s10434-019-07614-2DOI Listing
October 2019

Gait Ignition Failure in JNPL3 Human Tau-mutant Mice.

Exp Neurobiol 2019 Jun 26;28(3):404-413. Epub 2019 Jun 26.

Department of Structure and Function of Neural Network, Korea Brain Research Institute, Daegu 41062, Korea.

Cognitive impairments and motor dysfunction are commonly observed behavioral phenotypes in genetic animal models of neurodegenerative diseases. JNPL3 transgenic mice expressing human P301L-mutant tau display motor disturbances with age- and gene dose-dependent development of neurofibrillary tangles, suggesting that tau pathology causes neurodegeneration associated with motor behavioral abnormalities. Although gait ignition failure (GIF), a syndrome marked by difficulty in initiating locomotion, has been described in patients with certain forms of tauopathies, transgenic mouse models mirroring human GIF syndrome have yet to be reported. Using the open field and balance beam tests, here we discovered that JNPL3 homozygous mice exhibit a marked delay of movement initiation. The elevated plus maze excluded the possibility that hesitation to start in JNPL3 mice was caused by enhanced levels of anxiety. Considering the normal gait ignition in rTg4510 mice expressing the same mutant tau in the forebrain, GIF in JNPL3 mice seems to arise from abnormal tau deposition in the hindbrain areas involved in locomotor initiation. Accordingly, immunohistochemistry revealed highly phosphorylated paired helical filament tau in JNPL3 brainstem areas associated with gait initiation. Together, these findings demonstrate a novel behavioral phenotype of impaired gait initiation in JNPL3 mice and underscore the value of this mouse line as a tool to study the neural mechanisms and potential treatments for human GIF syndrome.
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http://dx.doi.org/10.5607/en.2019.28.3.404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614071PMC
June 2019

Nonsurgical integrative inpatient treatments for symptomatic lumbar spinal stenosis: a multi-arm randomized controlled pilot trial.

J Pain Res 2019 28;12:1103-1113. Epub 2019 Mar 28.

Department of Anesthesiology, Division of Pain Medicine, Mayo Clinic, Rochester, MN, USA,

Background: Lumbar spinal stenosis (LSS) is a chronic condition that causes low back pain and neurogenic claudication, often resulting in significant limitation of daily activities. In this open-label randomized controlled pilot study, we assessed the safety and feasibility of 4-week novel integrative inpatient treatments for LSS.

Methods: Thirty-six symptomatic LSS patients were randomly and equally allocated to one of the three groups: Mokhuri Chuna treatment 1 (MT1) group, Mokhuri Chuna treatment 2 (MT2) group, or conventional management treatment (CMT) group. MT1 patients were treated with herbal medication, Mokhuri Chuna, and acupuncture, and received daily physician consultation; MT2 patients were treated with Mokhuri Chuna and acupuncture without any herbal medication, and received daily physician consultation; and CMT patients received conventional pain management therapy that included epidural steroid injection, oral NSAID, and muscle relaxant medication, along with daily physiotherapy. The primary outcome of this pilot study was safety as measured by the type and incidence of adverse events (AEs). The secondary outcome measures included VAS score for low back pain and leg pain, Oswestry Disability Index, Oxford Claudication Score (OCS), walking capacity on a 50 m flat track and treadmill, and EuroQol-5D score. Magnetic resonance imaging was also performed up to 6 months after treatment cessation.

Results: Thirty-four treated patients were included in the analysis, based on the modified intention-to-treat principle. No serious AEs were observed or reported. Compared to the CMT group, the MT1 and MT2 groups did show significant improvement at 3 and 6 months in various domains, including pain (VAS score for leg and back pain) and function (OCS and treadmill walking).

Conclusion: These novel multimodal integrative treatments for LSS are both clinically safe and logistically feasible. Larger, adequately powered randomized controlled trials will be necessary to assess comparative efficacy and thoroughly analyze the cost-effectiveness of each treatment approach.

Clinical Trial Registration Number Cris: KCT0001218.
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http://dx.doi.org/10.2147/JPR.S173178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445233PMC
March 2019

Glucose transporter 3 gene variant is associated with survival outcome of patients with non-small cell lung cancer after surgical resection.

Gene 2019 Jun 4;703:58-64. Epub 2019 Apr 4.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Lung Cancer Center, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea; Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address:

This study was conducted to explore whether polymorphisms of glucose transporter 3 (GLUT3) gene affect the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. Four single nucleotide polymorphisms (SNPs) in GLUT3 were investigated in a total of 782 patients with NSCLC who underwent curative surgery. The association of the SNPs with overall survival (OS) and disease free survival (DFS) was analyzed. Among the four SNPs investigated, GLUT3 rs7309332C>T was significantly associated with OS and DFS in multivariate analyses. The SNP was associated with significantly worse OS (adjusted hazard ratio [aHR] = 1.62, 95% confidence interval [CI] = 1.04-2.53, P = 0.03, under recessive model), and worse DFS (aHR = 1.64, 95% CI = 1.18-2.29, P = 0.003, under recessive model). When stratified by tumor histology, the association between the GLUT3 rs7309332C>T and OS/DFS was not limited to either squamous cell carcinoma (SCC) or adenocarcinoma (AC), although the significant association remained only in AC for OS (P = 0.40 for SCC and P = 0.04 for OS) and only in SCC for DFS (P = 0.03 for SCC and P = 0.08 for OS). When AC patients were stratified according to EGFR mutation status, the SNP was significantly associated with DFS in patients with EGFR mutant tumors (aHR = 2.47, 95% CI = 1.15-5.30, P = 0.02, under recessive model), but not in those with EGFR wild-type tumors. This study suggests that genetic variation in GLUT3 may be useful in predicting survival of patients with early stage NSCLC.
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http://dx.doi.org/10.1016/j.gene.2019.04.013DOI Listing
June 2019

Prediction of high nodal burden with ultrasound and magnetic resonance imaging in clinically node-negative breast cancer patients.

Cancer Imaging 2019 Feb 1;19(1). Epub 2019 Feb 1.

Department of Radiology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, South Korea.

Background: Although the role of axillary imaging has been redirected for predicting high nodal burden rather than predicting nodal metastases since ACOSOG Z1011 trial, it remains unclear whether and how axillary lymph node (ALN) characteristics predicts high nodal burden. Our study was aimed to evaluate the predictive value of imaging characteristics of ALNs at ultrasound and magnetic resonance imaging (MRI) for prediction of high nodal burden (≥3 metastatic ALNs) in clinically node-negative breast cancer patients.

Methods: Clinicopathological and imaging characteristics were evaluated in patients with ultrasound (n = 312) and MRI (n = 256). Imaging characteristics include number of suspicious ALNs and cortical morphologic changes (grade 1, cortical thickness < 2 mm; grade 2, 2-5 mm; grade 3, ≥5 mm or fatty hilum loss). Odds ratios (ORs) were calculated using multivariate analysis.

Results: For ultrasound, higher (≥2) T stage (OR = 5.65, P = .005), higher number of suspicious ALNs (2 suspicious ALNs, OR = 6.52, P = .019; ≥ 3 suspicious ALNs, OR = 21.08, P = .005), and grade 3 of cortical morphologic changes (OR = 9.85, P = .023) independently associated with high nodal burden. For MRI, higher (≥2) T stage (OR = 5.17, P = .011) and higher number of suspicious ALNs (2 suspicious ALNs, OR = 69.00, P = .001; ≥ 3 suspicious ALNs, OR = 93.55, P < .001) were independently associated with high nodal burden. Among patients with 2 suspicious ALNs, those with grade 3 cortical morphologic change at ultrasound had a higher rate of high nodal burden than those with grade 2 (60.0% [3/5] vs. 25.0% [2/8]).

Conclusions: A higher number of suspicious ALNs is an independent predictor for high nodal burden. Further stratification can be achieved by incorporating assessment of ultrasound-based cortical morphologic changes.
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http://dx.doi.org/10.1186/s40644-019-0191-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359788PMC
February 2019

Community-Acquired Pneumonia with Negative Chest Radiography Findings: Clinical and Radiological Features.

Respiration 2019;97(6):508-517. Epub 2019 Jan 9.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea.

Background: Data regarding community-acquired pneumonia (CAP) identified on chest computed tomography (CT) but not on chest radiography (CR) are limited.

Objectives: The present study aimed to investigate the clinical and radiological features of these patients.

Methods: We retrospectively compared the clinical characteristics, etiological agents, treatment outcomes, and CT findings between CAP patients with negative CR and positive CT findings (negative CR group) and those with positive CR as well as CT findings (control group).

Results: Of 1,925 patients, 94 patients (4.9%) were included in the negative CR group. Negative CR findings could be attributed to the location of the lesions (e.g., those located in the dependent lung) and CT pattern with a low attenuation, such as ground-glass opacity (GGO). The negative CR group was characterized by a higher frequency of aspiration pneumonia, lower incidences of complicated parapneumonic effusion or empyema and pleural drainage, and lower blood levels of inflammatory markers than the control group. On CT, the negative CR group exhibited higher rates of GGO- and bronchiolitis-predominant patterns and a lower rate of consolidation pattern. Despite shorter length of hospital stay in the negative CR group, 30-day and in-hospital mortalities were similar between the two groups.

Conclusions: CAP patients with negative CR findings are characterized by lower blood levels of inflammatory markers, a higher incidence of aspiration pneumonia, and a lower incidence of complicated para-pneumonic effusion or empyema than those with positive CR findings. Chest CT scan should be considered in suspected CAP patients with a negative CR, especially in bedridden patients.
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http://dx.doi.org/10.1159/000495068DOI Listing
September 2020

Moxibustion for prehypertension and stage I hypertension: a pilot randomized controlled trial.

Integr Med Res 2019 Mar 24;8(1):1-7. Epub 2018 Nov 24.

Korea Institute of Oriental Medicine, Daejeon, South Korea.

Background: Prehypertension and hypertension are associated with cardiovascular disease, ischemic heart disease, and stroke morbidity. The purpose of this study is to evaluate the effectiveness and safety of moxibustion in patients with prehypertension or hypertension.

Methods: Forty-five subjects with prehypertension or stage I hypertension were randomized into three groups: moxibustion treatment group A (2 sessions/week for 4 weeks), moxibustion treatment group B (3 sessions/week for 4 weeks), and control group (nontreated group). The primary outcome measure was the change in blood pressure after 4 weeks of treatment. Safety was assessed at every visit.

Results: There were no significant differences in systolic blood pressure (SBP) or diastolic blood pressure (DBP) among three groups after 4 weeks of treatment ( = 0.4798 and  = 0.3252, respectively). In treatment group B, there was a significant decrease in SBP and DBP from baseline to 4 weeks of treatment (mean difference (MD) -9.55;  = 0.0225, MD -7.55;  = 0.0098, respectively). There were no significant differences among groups in secondary outcome measures after 4 weeks of treatment. Six adverse events (AEs) in the treatment group A and 12 AEs in the treatment group B occurred related to the moxibustion treatment.

Conclusion: In conclusion, the results of this study show that moxibustion (3 sessions/week for 4 weeks) might lower blood pressure in patients with prehypertension or stage I hypertension and treatment frequency might affect effectiveness of moxibustion in BP regulation. Further randomized controlled trials with a large sample size on prehypertension and hypertension should be conducted.

Trial Registration: This study was registered with the 'Clinical Research Information Service (CRIS)', Republic of Korea (KCT0000469), and the protocol for this study was presented orally at the 15th International Council of Medical Acupuncture and Related Techniques (ICMART) in Athens, 25-27 May 2012.
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http://dx.doi.org/10.1016/j.imr.2018.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309023PMC
March 2019

TSC2 genetic variant and prognosis in non-small cell lung cancer after curative surgery.

Thorac Cancer 2019 02 26;10(2):335-340. Epub 2018 Dec 26.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.

This study was conducted to investigate the associations between polymorphisms of genes involved in the LKB1 pathway and the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. Twenty-three single nucleotide polymorphisms (SNPs) in the LKB1 pathway were investigated in 782 patients with NSCLC who underwent curative surgery. The association of SNPs with overall survival (OS) and disease-free survival (DFS) were analyzed. Among the 23 SNPs investigated, TSC2 rs30259G > A was associated with significantly worse OS and DFS (adjusted hazard ratio for OS 1.88, 95% confidence interval 1.21-2.91, P = 0.005; adjusted hazard ratio for DFS 1.65, 95% confidence interval 1.15-2.38, P = 0.01, under codominant models, respectively). Subgroup analysis showed that SNPs were significantly associated with survival outcomes in squamous cell carcinoma, ever-smokers, and stage I, but not in adenocarcinoma, never-smokers, and stage II-IIIA. The results suggest that TSC2 rs30259G > A may be useful to predict prognosis in patients with NSCLC, especially squamous cell carcinoma, after curative surgery.
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http://dx.doi.org/10.1111/1759-7714.12951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360237PMC
February 2019

Axillary Pathologic Complete Response to Neoadjuvant Chemotherapy in Clinically Node-Positive Breast Cancer Patients: A Predictive Model Integrating the Imaging Characteristics of Ultrasound Restaging with Known Clinicopathologic Characteristics.

Ultrasound Med Biol 2019 03 17;45(3):702-709. Epub 2018 Dec 17.

Department of Radiology, School of Medicine, Kyungpook National University, Daegu, South Korea; Department of Radiology, Kyungpook National University Hospital, Daegu, South Korea.

The goal of this study was to evaluate various clinicopathologic and imaging characteristics as independent predictors of axillary pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) and to determine the added value of a model that integrates imaging characteristics of ultrasound (US) restaging with known clinicopathologic characteristics. A total of 227 clinically node-positive breast cancer patients underwent axillary US after NAC (termed US restaging) before surgery. We constructed a clinicopathologic model with independent predictors of clinicopathologic characteristics in multivariate analyses. A combined model was created by integrating imaging characteristics with clinicopathologic characteristics. The predictive values of the models were compared using the area under the receiver operating characteristic curve. Of the 227 patients, 106 (46.7%) achieved axillary pCR. Multivariate analysis revealed that higher histologic grades (odds ratio [OR] = 4.21 and 10.11 for moderate and high grade, respectively), negative hormonal receptor status (OR = 2.88), smaller (≤1.5 cm) residual tumor size (OR = 2.83), absence of fatty hilum loss (OR = 14.06) and absence of eccentric cortical thickening of the axillary lymph node (OR = 4.42) were independently associated with the axillary pCR (all p values < 0.05). Integrating the imaging characteristics of the US restaging significantly increased the predictive capability of the model that applied only the clinicopathologic characteristics (c-index, 0.783 vs. 0.657; p < 0.001). Imaging characteristics of the US restaging were independently associated with axillary pCR after NAC and they significantly improved the predictive capability of the model that used only the clinicopathologic characteristics.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2018.10.026DOI Listing
March 2019

An expression quantitative trait locus variant for LKB1 gene predicts the clinical outcomes of chemotherapy in patients with non-small cell lung cancer.

Cancer Genet 2018 12 16;228-229:73-82. Epub 2018 Oct 16.

Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Lung Cancer Center, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, Kyungpook National University, Daegu, Republic of Korea. Electronic address:

Background: We conducted this study to identify regulatory variants in cancer-related pathway genes which can predict clinical outcomes of chemotherapy in advanced NSCLC, using a comprehensive list of regulatory SNPs prioritized by RegulomeDB.

Methods: A total of 509 potentially functional SNPs in cancer-related pathway genes were evaluated. The SNPs were analyzed in a discovery set (n = 198), and an independent validation set (n = 181). The associations of the SNPs with chemotherapy response and overall survival (OS) were analyzed.

Results: In the discovery set, 95 SNPs were significantly associated with clinical outcomes. Among the 95 SNPs, only rs10414193A > G in the intronic region of ARID3A, an eQTL for LKB1, was consistently associated with chemotherapy response and OS in the validation set. In combined analysis, the rs10414193A > G was significantly associated with worse response to chemotherapy (adjusted odds ratio = 0.63, 95% CI = 0.47-0.85, P = 0.002), and with worse OS (adjusted hazard ratio = 1.25, 95% CI = 1.08-1.45, P = 0.004). Luciferase assay showed a significantly higher LKB1 promoter activity associated with rs10414193G allele compared with rs10414193A allele (P = 0.0009).

Conclusions: Our results suggest that rs10414193A > G may be useful for the prediction of clinical outcomes of chemotherapy in advanced NSCLC.
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http://dx.doi.org/10.1016/j.cancergen.2018.10.002DOI Listing
December 2018