Publications by authors named "Yong Hoon Lee"

90 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

Birefringent whispering gallery cavities designed by linear transformation optics.

Opt Express 2021 Mar;29(6):9242-9251

It was reported that whispering gallery cavities designed by conformal transformation optics can support high-Q resonant modes with emission directionality. Intrinsically, these cavities have gradient index profiles implementing conformal mappings in physical space. In this paper, using the linear coordinate transformation, we propose another design scheme of whispering gallery cavities with (piecewise-) homogeneous, anisotropic index profile. We numerically show that so-designed cavities are also able to support high-Q whispering gallery modes with directional far-field emission patterns. We verify such characteristics by using a phase space representation (called the Poincaré Husimi function) of the intracavity wave function.
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http://dx.doi.org/10.1364/OE.417744DOI Listing
March 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

Clinical features and prognostic factors of critically ill patients with COVID-19 in Daegu, South Korea: A multi-center retrospective study.

Medicine (Baltimore) 2021 Feb;100(7):e24437

Division of Pulmonary and Critical Care Medicine, Yeungnam University Medical Center, Daegu, Republic of Korea.

Abstract: To describe the clinical and demographic characteristics of critically ill patients with COVID-19 in Daegu, South Korea, and to explore the risk factors for in-hospital mortality in these patients.Retrospective cohort study of 110 critically ill patients with COVID-19 admitted to the ICU in Daegu, South Korea, between February 18 and April 5, 2020. The final date of follow-up was April 20, 2020.A total of 110 patient medical records were reviewed. The median age was 71 years (interquartile range [IQR] = 63-78 years). During the study period, 47 patients (42.7%) died in the hospital. The most common SARS-CoV-2 infection related complication was acute respiratory distress syndrome (ARDS) in 95 patients (86.4%). Of the 79 patients (71.8%) who received invasive mechanical ventilation, 46 (58.2%) received neuromuscular blockade injection, and 19 (24.1%) received ECMO treatment. All patients received antibiotic injection, 99 patients (90%) received hydroxychloroquine, 96 patients (87.3%) received lopinavir-ritonavir antiviral medication, and 14 patients (12.7%) received other antiviral agents, including darunavir-cobicistat and emtricitabine-tenofovir. In the multivariable logistic regression model, the odds ratio of in-hospital death was higher with APACHE II score (OR = 1.126; 95% CI = 1.014-1.252; P  = .027).The in-hospital mortality rate of critically ill patients with COVID-19 was approximately 40%. Higher APACHE II score at admission was an independent risk factor for death in these patients.
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http://dx.doi.org/10.1097/MD.0000000000024437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899898PMC
February 2021

Impact of immune checkpoint gene CD155 Ala67Thr and CD226 Gly307Ser polymorphisms on small cell lung cancer clinical outcome.

Sci Rep 2021 Jan 19;11(1):1794. Epub 2021 Jan 19.

Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea.

This study was conducted to investigate the impact of genetic variants of immune checkpoint genes on the treatment outcome in small cell lung cancer (SCLC). In the present study, 261 platinum doublet-treated SCLC patients were enrolled. A total of 96 polymorphisms in 33 immune checkpoint-related genes were selected, and their association with chemotherapy response and survival outcomes were analyzed. Among the polymorphisms studied, CD155 rs1058402G > A (Ala67Thr, A67T) and CD226 rs763361C > T (Gly307Ser, G307S) were significantly associated with SCLC treatment outcome. The rs1058402G > A had a worse chemotherapy response and overall survival (under a dominant model, adjusted odds ratio [aOR] = 0.52, 95% confidence interval [CI] = 0.27-0.99, P = 0.05; adjusted hazard ratio [aHR] = 1.55, 95% CI = 1.12-2.14, P = 0.01, respectively). The rs763361C > T had better chemotherapy response and overall survival (under a dominant model, aOR = 2.03, 95% CI = 1.10-3.75, P = 0.02; aHR = 0.69, 95% CI = 0.51-0.94, P = 0.02, respectively). When the rs1058402GA/AA and rs763361CC genotypes were combined, the chemotherapy response and overall survival were significantly decreased as the number of bad genotypes increased (aOR = 0.52, 95% CI = 0.33-0.81, Ptrend = 0.004; aHR = 1.48, 95% CI = 1.19-1.84, Ptrend = 4 × 10, respectively). The 3-D structural model showed that CD155 A67T created a new hydrogen bond and structural change on CD155. These changes resulted in extending the distance and losing the hydrogen bonds between CD155 and CD226, thus weakening CD155/CD226 binding activity. In conclusion, CD155 rs1058402G > A and CD226 rs763361C > T may be useful for predicting the clinical outcomes of SCLC patients after chemotherapy.
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http://dx.doi.org/10.1038/s41598-021-81260-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815735PMC
January 2021

Metabolite Profile of Cucurbitane-Type Triterpenoids of Bitter Melon (Fruit of ) and Their Inhibitory Activity against Protein Tyrosine Phosphatases Relevant to Insulin Resistance.

J Agric Food Chem 2021 Feb 6;69(6):1816-1830. Epub 2021 Jan 6.

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.

Qualitative analysis of cucurbitane-type triterpenoids of bitter melon (fruit of L.) using ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry revealed 27 promising cucurbitane-type triterpenoids, and LC/MS-guided chemical analysis of fruit extract led to the isolation and structural characterization of 22 cucurbitane-type triterpenoids (), including 8 new cucurbitane-type triterpenoidal saponins, yeojoosides A-H (). The structures of the new compounds () were elucidated by spectroscopic methods, including 1D and 2D NMR and high-resolution electrospray ionization mass spectrometry. Their absolute configurations were assigned by quantum chemical electronic circular dichroism calculations, chemical reactions, and DP4+ analysis using gauge-including atomic orbital NMR chemical shift calculations. All isolated compounds () were examined for inhibitory activity against protein tyrosine phosphatases relevant to insulin resistance. Nine compounds (, , , , , , , , and ) showed selective inhibitory effects of over 70% against PTPN2. The present results suggested that these compounds would be potential antidiabetic agents.
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http://dx.doi.org/10.1021/acs.jafc.0c06085DOI Listing
February 2021

Hepatoprotective Potency of Chrysophanol 8--Glucoside from L. against Hepatic Fibrosis via Regulation of the STAT3 Signaling Pathway.

Int J Mol Sci 2020 Nov 27;21(23). Epub 2020 Nov 27.

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.

Rhubarb is a well-known herb worldwide and includes approximately 60 species of the genus. One of the representative plants is , which is prescribed as official rhubarb due to its pharmacological potential in the Korean and Chinese pharmacopoeia. In our bioactive screening, we found out that the EtOH extract of inhibited hepatic stellate cell (HSC) activation by transforming growth factor β1 (TGF-β1). Chemical investigation of the EtOH extract led to the isolation of chrysophanol 8--glucoside, which was determined by structural analysis using NMR spectroscopic techniques and electrospray ionization mass spectrometry (ESIMS). To elucidate the effects of chrysophanol 8--glucoside on HSC activation, activated LX-2 cells were treated for 48 h with chrysophanol 8--glucoside, and α-SMA and collagen, HSC activation markers, were measured by comparative quantitative real-time PCR (qPCR) and western blotting analysis. Chrysophanol 8--glucoside significantly inhibited the protein and mRNA expression of α-SMA and collagen compared with that in TGF-β1-treated LX-2 cells. Next, the expression of phosphorylated SMAD2 (p-SMAD2) and p-STAT3 was measured and the translocation of p-STAT3 to the nucleus was analyzed by western blotting analysis. The expression of p-SMAD2 and p-STAT3 showed that chrysophanol 8--glucoside strongly downregulated STAT3 phosphorylation by inhibiting the nuclear translocation of p-STAT3, which is an important mechanism in HSC activation. Moreover, chrysophanol 8--glucoside suppressed the expression of p-p38, not that of p-JNK or p-Erk, which can activate STAT3 phosphorylation and inhibit MMP2 expression, the downstream target of STAT3 signaling. These findings provided experimental evidence concerning the hepatoprotective effects of chrysophanol 8--glucoside against liver damage and revealed the molecular basis underlying its anti-fibrotic effects through the blocking of HSC activation.
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http://dx.doi.org/10.3390/ijms21239044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730872PMC
November 2020

Toxicity of humidifier disinfectant polyhexamethylene guanidine hydrochloride by two-week whole body-inhalation exposure in rats.

J Toxicol Pathol 2020 Oct 9;33(4):265-277. Epub 2020 Aug 9.

Inhalation Toxicity Research Center, Chemicals Research Bureau, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency, 339-30 Expo-ro, Yuseong-gu, Daejeon 305-380, Republic of Korea.

The use of polyhexamethylene guanidine hydrochloride (PHMG·HCl) as a humidifier disinfectant caused an outbreak of pulmonary disease, leading to the deaths of pregnant women and children in South Korea. However, limited information is available on the inhalation toxicity of PHMG·HCl. Therefore, this study aimed to characterize the subacute inhalation toxicity of PHMG·HCl by whole-body exposure in rats. F344 rats were exposed to 0 mg/m, 1 mg/m, 5 mg/m, or 25 mg/m of PHMG·HCl for 6 h/day, 5 days/week for two weeks via whole-body inhalation. Emaciation and rale were observed in rats in the 25 mg/m PHMG·HCl group. Significant changes in body weight, hematology, serum chemistry and organ weight were observed in all PHMG·HCl-exposed groups. Gross lesions showed ballooning or red focus in the lungs of rats in the PHMG·HCl-exposed groups. In histopathological examination, most of histological lesions (including degeneration, atrophy, ulcer, inflammatory cell infiltration, inflammation, and fibrosis in nasal cavity, larynx, trachea, and lungs) indicated tissue damage by PHMG·HCl in all PHMG·HCl-exposed groups. Additionally, atrophy of the spleen, thymus, and reproductive organs; immaturity of the testes; and cell debris in the epididymides were affected by the reduction in body weight in PHMG·HCl-exposed groups. In conclusion, two-week repeated whole-body inhalation exposure of rats to PHMG·HCl reveled toxic effects on the respiratory system and secondary effects on other organs. The results of this study indicate that the no observable adverse effect level (NOAEL) for PHMG·HCl is below 1 mg/m.
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http://dx.doi.org/10.1293/tox.2020-0043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677626PMC
October 2020

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

Universal light-guiding geometry for on-chip resonators having extremely high Q-factor.

Nat Commun 2020 Nov 23;11(1):5933. Epub 2020 Nov 23.

Department of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.

By providing an effective way to leverage nonlinear phenomena in integrated devices, high-Q optical resonators have led to recent advances in on-chip photonics. However, developing fabrication processes to shape any new material into a resonator with extremely smooth surfaces on a chip has been an exceptionally challenging task. Here, we describe a universal method to implement ultra-high-Q resonators with any new material having desirable properties that can be deposited by physical vapor deposition. Using this method light-guiding cores with surface roughness on the molecular-scale are created automatically on pre-patterned substrates. Its efficacy has been verified using AsS, a chalcogenide glass that has high-nonlinearity. The Q-factor of the AsS resonator so-developed approached the propagation loss record achieved in chalcogenide fibers which were limited by material losses. Owing to the boosted Q-factor, lasing by stimulated Brillouin scattering has been demonstrated with 100 times lower threshold power than the previous record.
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http://dx.doi.org/10.1038/s41467-020-19799-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683556PMC
November 2020

Adverse impact of renin-angiotensin system blockade on the clinical course in hospitalized patients with severe COVID-19: a retrospective cohort study.

Sci Rep 2020 11 20;10(1):20250. Epub 2020 Nov 20.

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

The association between angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB) and the risk of mortality in hospitalized patients with severe coronavirus disease 2019 (COVID-19) was investigated. This retrospective cohort study was performed in all hospitalized patients with COVID-19 in tertiary hospitals in Daegu, Korea. Patients were classified based on whether they received ACE-I or ARB before COVID-19 diagnosis. The analysis of the primary outcome, in-hospital mortality, was performed using the Cox proportional hazards regression model. Of 130 patients with COVID-19, 30 (23.1%) who received ACE-I or ARB exhibited an increased risk of in-hospital mortality (adjusted hazard ratio, 2.20; 95% confidence interval [CI], 1.10-4.38; P = 0.025). ACE-I or ARB was also associated with severe complications, such as acute respiratory distress syndrome (ARDS) (adjusted odds ratio [aOR], 2.58; 95% CI, 1.02-6.51; P = 0.045) and acute kidney injury (AKI) (aOR, 3.06; 95% CI, 1.15-8.15; P = 0.026). Among the patients with ACE-I or ARB therapy, 8 patients (26.7%) used high equivalent doses of ACE-I or ARB and they had higher in-hospital mortality and an increased risk of ARDS and AKI (all, P < 0.05). ACE-I or ARB therapy in patients with severe COVID-19 was associated with the occurrence of severe complications and increased in-hospital mortality. The potentially harmful effect of ACE-I or ARB therapy may be higher in patients who received high doses.
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http://dx.doi.org/10.1038/s41598-020-76915-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680105PMC
November 2020

Assessment of the Contribution of Antagonistic Secondary Metabolites to the Antifungal and Biocontrol Activities of NBC275.

Plant Pathol J 2020 Oct;36(5):491-496

Division of Biotechnology, Jeonbuk National University, Iksan 55496, Korea.

An understanding of the contribution of secondary metabolites (SMs) to the antagonistic and biocontrol activities of bacterial biocontrol agents serves to improve biocontrol potential of the strain. In this study, to evaluate the contribution of each SM produced by NBC275 (Pf275) to its antifungal and biocontrol activity, we combined analysis of the genome with our previous study of transposon (Tn) mutants. Thirteen Tn mutants, which belonged to 6 biosynthetic gene clusters (BGCs) of a total 14 BGCs predicted by the antiSMASH tool were identified by the reduction of antifungal activity. The biocontrol performance of Pf275 was significantly dependent on 2,4-diacetylphloroglucinol and pyoverdine. The clusters that encode for arylpolyene and an unidentified small linear lipopeptide influenced antifungal and biocontrol activities. To our knowledge, our study identified the contribution of SMs, such as a small linear lipopeptide and arylpolyene, to biocontrol efficacy for the first time.
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http://dx.doi.org/10.5423/PPJ.FT.08.2020.0149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542033PMC
October 2020

Evaluation of 1-Propanol Toxicity in B6C3F1 Mice via Repeated Inhalation over 28 and 90 Days.

J Toxicol 2020 24;2020:9172569. Epub 2020 Sep 24.

Chemical Research Bureau, Occupational Safety and Health Research Institute, KOSHA, Daejeon 34122, Republic of Korea.

We evaluated the toxicity of 1-propanol exposure following repeated inhalation over 28- and 90-day periods in male and female B6C3F1 mice to confirm the potential target organs and to determine the no-observable-adverse-effect levels (NOAELs). Five mice of each sex were exposed to 1-propanol at concentrations of 0, 100, 400, or 1600 ppm for 28 days and showed no consequent toxicity. Following this, ten mice of each sex were exposed at concentrations of 0, 500, 1600, or 5200 ppm for 90 days. We observed no effects on food consumption, body weight, organ weight, clinical signs, hematology and biochemistry parameters, or gross or histological features even at the maximum concentration. Therefore, the NOAEL of inhaled 1-propanol was defined as 5200 ppm (12.8 mg/L) for male and female mice under study conditions.
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http://dx.doi.org/10.1155/2020/9172569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532428PMC
September 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

Clinical Significance of Timing of Intubation in Critically Ill Patients with COVID-19: A Multi-Center Retrospective Study.

J Clin Med 2020 Sep 2;9(9). Epub 2020 Sep 2.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea.

The effect of intubation timing on the prognosis of critically ill patients with coronavirus 2019 (COVID-19) is not yet well understood. We investigated whether early intubation is associated with the survival of COVID-19 patients with acute respiratory distress syndrome (ARDS). This multicenter, retrospective, observational study was done on 47 adult COVID-19 patients with ARDS who were admitted to the intensive care unit (ICU) in Daegu, Korea between February 17 and April 23, 2020. Clinical characteristics and in-hospital mortality were compared between the early intubation and initially non-intubated groups, and between the early and late intubation groups, respectively. Of the 47 patients studied, 23 (48.9%) were intubated on the day of meeting ARDS criteria (early intubation), while 24 (51.1%) were not initially intubated. Eight patients were never intubated during the in-hospital course. Median follow-up duration was 46 days, and 21 patients (44.7%) died in the hospital. No significant difference in in-hospital mortality rate was noted between the early group and initially non-intubated groups (56.5% vs. 33.3%, = 0.110). Furthermore, the risk of in-hospital death in the early intubation group was not significantly different compared to the initially non-intubated group on multivariate adjusted analysis ( = 0.385). Results were similar between early and late intubation in the subgroup analysis of 39 patients treated with mechanical ventilation. In conclusion, in this study of critically ill COVID-19 patients with ARDS, early intubation was not associated with improved survival. This result may help in the efficient allocation of limited medical resources, such as ventilators.
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http://dx.doi.org/10.3390/jcm9092847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564702PMC
September 2020

Coronavirus disease 2019 pneumonia may present as an acute exacerbation of idiopathic pulmonary fibrosis.

J Thorac Dis 2020 Jul;12(7):3902-3904

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

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http://dx.doi.org/10.21037/jtd-20-1658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399424PMC
July 2020

The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea.

Diabetes Metab J 2020 08 12;44(4):602-613. Epub 2020 Aug 12.

Department of Internal Medicine, Daegu Catholic University Hospital, Daegu Catholic University School of Medicine, Daegu, Korea.

Background: Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes.

Methods: We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group.

Results: Compared with the non-DM group (=847), patients with DM (=235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease.

Conclusion: DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.
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http://dx.doi.org/10.4093/dmj.2020.0146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453989PMC
August 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

Expression of key regulatory genes in necroptosis and its effect on the prognosis in non-small cell lung cancer.

J Cancer 2020 11;11(18):5503-5510. Epub 2020 Jul 11.

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

Accumulating evidence suggests that necroptosis, or programmed necrotic cell death, may play a significant role in cancer. We evaluated the expression of key molecules in necroptosis and their association with clinical features and prognosis in NSCLC. A total of 253 NSCLC patients (96 squamous cell carcinoma [SCC] cases and 157 adenocarcinoma [AC] cases) who underwent curative resection were included. Tumor tissues and corresponding normal tissues were investigated for relative mRNA expression levels of , , and . Difference in disease free survival (DFS) was analyzed according to the expression levels of these molecules in tumor tissues. NSCLC tissues had significantly lower expression of , , and than normal tissues ( = 1 x 10, = 8 x 10, and = 4 x 10, respectively). In subgroup analysis, SCCs had significantly lower , , and expression ( = 5 x 10, = 3 x 10, = 1 x 10, respectively), and ACs had significantly lower and expression ( = 0.01 and = 6 x 10, respectively) than normal tissues. Low expression of , , and in tumors was associated with a worse DFS (HR = 1.71, = 0.01; HR = 1.53, = 0.04; and HR = 1.53, = 0.04, respectively) in a multivariate analysis. In SCC, none of the , , and expression was significantly associated with DFS. However, in AC, low expression of , , and was significantly associated with worse DFS (HR = 1.67, = 0.03; HR = 1.70, = 0.03; and HR = 1.81, = 0.02, respectively). Key regulatory genes in necroptosis, , , and , were downregulated in NSCLC, and their lower expression in NSCLC may be used to predict early recurrence after curative resection, especially in AC.
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http://dx.doi.org/10.7150/jca.46172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391199PMC
July 2020

Effect of genetic variation in Notch regulator DTX1 on SCLC prognosis compared with the effect on NSCLC prongosis.

Thorac Cancer 2020 09 22;11(9):2698-2703. Epub 2020 Jul 22.

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

Deltex-1 (DTX1) is a negative regulator of the Notch signaling pathway. Here, we investigated the clinical effect of DTX1 rs1732786A > G, which is associated with better prognosis in patients with early-stage non-small cell lung cancer (NSCLC), in 261 patients with small cell lung cancer (SCLC). DTX1 rs1732786A > G was associated with a significantly worse chemotherapy response and lower overall survival in the codominant model (odds ratio = 0.42, 95% confidence interval [CI]: 0.26-0.66, P = 2 × 10 ; hazard ratio = 1.47, 95% CI: 1.17-1.84, P = 0.001, respectively). An in vitro luciferase assay was performed, and the 1732786G allele demonstrated significantly higher promoter activity than the 1732786A allele (P = 2 × 10 ). In summary, DTX1 rs1732786A > G was associated with poor prognosis in patients with SCLC as opposed to patients with NSCLC. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: DTX1 rs1732786A > G was associated with better prognosis in patients with early-stage non-small cell lung cancer (NSCLC) in our previous study. WHAT THIS STUDY ADDS: DTX1 rs1732786A > G was associated with a significantly worse chemotherapy response and lower overall survival in small cell lung cancer (SCLC).
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http://dx.doi.org/10.1111/1759-7714.13566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471053PMC
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

A Case of COVID-19 with Acute Myocardial Infarction and Cardiogenic Shock.

J Korean Med Sci 2020 Jul 13;35(27):e258. Epub 2020 Jul 13.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea.

A 60-year-old male patient with coronavirus disease-2019 showed new onset ST-segment elevation in V1-V2 leads on electrocardiogram and cardiac enzyme elevation in intensive care unit. He had a history of type 2 diabetes mellitus, hypertension, and dyslipidemia. He was receiving mechanical ventilation and veno-venous extracorporeal membrane oxygenation treatment for severe hypoxia. Two-D echocardiogram showed regional wall motion abnormalities. We performed primary percutaneous coronary intervention for acute myocardial infarction complicating cardiogenic shock under hemodynamic support. He expired on the 16th day of admission because of cardiogenic shock and multi-organ failure. Active surveillance and intensive treatment strategy are important for saving lives of COVID-19 patients with acute myocardial infarction.
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http://dx.doi.org/10.3346/jkms.2020.35.e258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358062PMC
July 2020

Clinical Course of Asymptomatic and Mildly Symptomatic Patients with Coronavirus Disease Admitted to Community Treatment Centers, South Korea.

Emerg Infect Dis 2020 10 22;26(10):2346-2352. Epub 2020 Jun 22.

We evaluated the clinical course of asymptomatic and mildly symptomatic patients with laboratory-confirmed coronavirus disease (COVID-19) admitted to community treatment centers (CTCs) for isolation in South Korea. Of 632 patients, 75 (11.9%) had symptoms at admission, 186 (29.4%) were asymptomatic at admission but developed symptoms during their stay, and 371 (58.7%) remained asymptomatic during their entire clinical course. Nineteen (3.0%) patients were transferred to hospitals, but 94.3% (573/613) of the remaining patients were discharged from CTCs upon virologic remission. The mean virologic remission period was 20.1 days (SD + 7.7 days). Nearly 20% of patients remained in the CTCs for 4 weeks after diagnosis. The virologic remission period was longer in symptomatic patients than in asymptomatic patients. In mildly symptomatic patients, the mean duration from symptom onset to virologic remission was 11.7 days (SD + 8.2 days). These data could help in planning for isolation centers and formulating self-isolation guidelines.
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http://dx.doi.org/10.3201/eid2610.201620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510714PMC
October 2020

Fatal Outcomes of COVID-19 in Patients with Severe Acute Kidney Injury.

J Clin Med 2020 Jun 3;9(6). Epub 2020 Jun 3.

Division of Nephrology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu 41944, Korea.

The outcome of coronavirus disease 2019 (COVID-19) is associated with organ damage; however, the information about the relationship between acute kidney injury (AKI) and COVID-19 is still rare. We evaluated the clinical features and prognosis of COVID-19 patients with AKI according to the AKI severity. Medical data of hospitalized COVID-19 patients in two university-based hospitals during an outbreak in Daegu, South Korea, were retrospectively analyzed. AKI and its severity were defined according to the Acute Kidney Injury Network. Of the 164 hospitalized patients with COVID-19, 30 patients (18.3%) had AKI; 14, 4, and 12 patients had stage 1, 2, and 3, respectively. The median age was significantly higher in AKI patients than in non-AKI patients (75.5 vs. 67.0 years, = 0.005). There were 17 deaths (56.7%) among AKI patients; 4 (28.6%), 1 (25.0%), and 12 (100.0%), respectively. In-hospital mortality was higher in AKI patients than in non-AKI patients (56.7% vs. 20.8%, < 0.001). After adjusting for potential confounding factors, stage 3 AKI was associated with higher mortality than either non-AKI or stage 1 AKI (hazard ratio (HR) = 3.62 (95% confidence interval (CI) = 1.75-7.48), = 0.001; HR = 15.65 (95% CI = 2.43-100.64), = 0.004). Among the AKI patients, acute respiratory distress syndrome and low serum albumin on admission were considered independent risk factors for stage 3 AKI (both 0.05). Five patients with stage 3 AKI underwent dialysis and eventually died. In conclusion, COVID-19 patients with severe AKI had fatal outcomes.
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http://dx.doi.org/10.3390/jcm9061718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355571PMC
June 2020

Outcomes of COVID-19 among Patients on In-Center Hemodialysis: An Experience from the Epicenter in South Korea.

J Clin Med 2020 Jun 2;9(6). Epub 2020 Jun 2.

Division of Nephrology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.

Patients with advanced chronic kidney disease (CKD) or who are on hemodialysis (HD) could have increased susceptibility to the 2019 coronavirus disease (COVID-19) given their pre-existing comorbidities, older age, compromised immune system, and regular visits to populated outpatient dialysis centers. This study included 14 consecutive patients on HD or with advanced CKD who initiated HD after being diagnosed with laboratory-confirmed COVID-19 from February to April 2020 in hospitals throughout Daegu, South Korea. The included patients, 42.9% of whom were men, had a mean age of 63.5 years. Four patients had a history of contact with a patient suffering from COVID-19. The most common symptom was cough (50.0%), followed by dyspnea (35.7%). The mean time from symptom onset to diagnosis and admission was 2.6 and 3.5 days, respectively. Patients exhibited lymphopenia and elevated inflammatory markers, including C-reactive protein and ferritin. Chest radiography findings showed pulmonary infiltration in 10 patients. All patients underwent regular HD in a negative pressure room and received antiviral agents. Four patients received mechanical ventilation and continuous renal replacement therapy at a median duration of 14.0 and 8.5 days, respectively. One patient underwent extracorporeal membrane oxygenation for three days. Among the 14 patients included, two died due to acute respiratory distress syndrome, nine were discharged from the hospital, and three remained hospitalized. Despite the high-risk conditions associated with worse outcomes, patients on HD did not exhibit extremely poor overall COVID-19 outcomes perhaps due to early diagnosis, prompt hospitalization, and antiviral therapy.
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http://dx.doi.org/10.3390/jcm9061688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355817PMC
June 2020

Electrocardiographic changes as a prognostic tool for hospitalized patients with pulmonary embolism.

Thromb Res 2020 08 19;192:61-63. Epub 2020 Mar 19.

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

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http://dx.doi.org/10.1016/j.thromres.2020.03.013DOI Listing
August 2020

Acute Hyperglycemic Crises with Coronavirus Disease-19: Case Reports.

Diabetes Metab J 2020 04;44(2):349-353

Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea.

Since the first case was contracted by coronavirus disease-19 (COVID-19) in Daegu, Korea in February 2020, about 6,800 cases and 130 deaths have been reported on April 9, 2020. Recent studies have reported that patients with diabetes showed higher mortality and they had a worse prognosis than the group without diabetes. In poorly controlled patients with diabetes, acute hyperglycemic crises such as diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) also might be precipitated by COVID-19. Thus, intensive monitoring and aggressive supportive care should be needed to inadequately controlled patients with diabetes and COVID-19 infection. Here, we report two cases of severe COVID-19 patients with acute hyperglycemic crises in Korea.
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http://dx.doi.org/10.4093/dmj.2020.0091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188962PMC
April 2020