Publications by authors named "Shin Yup Lee"

138 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

CD5L as an Extracellular Vesicle-Derived Biomarker for Liquid Biopsy of Lung Cancer.

Diagnostics (Basel) 2021 Mar 30;11(4). Epub 2021 Mar 30.

Division of Electronic Information System Research, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Techno-Jungangdaero 333, Dague 42988, Korea.

Cancer screening and diagnosis can be achieved by analyzing specific molecules within serum-derived extracellular vesicles (EVs). This study sought to profile EV-derived proteins to identify potential lung cancer biomarkers. EVs were isolated from 80 serum samples from healthy individuals and cancer patients via polyethylene glycol (PEG)-based precipitation and immunoaffinity separation using antibodies against CD9, CD63, CD81, and EpCAM. Proteomic analysis was performed using 2-D gel electrophoresis and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). The expression of proteins that were differentially upregulated in the EVs or tissue of lung cancer samples was validated by Western blotting. The area under the curve (AUC) was calculated to assess the predictability of each differentially expressed protein (DEP) for lung cancer. A total of 55 upregulated protein spots were selected, seven of which (CD5L, CLEC3B, ITIH4, SERFINF1, SAA4, SERFINC1, and C20ORF3) were found to be expressed at high levels in patient-derived EVs by Western blotting. Meanwhile, only the expression of EV CD5L correlated with that in cancer tissues. CD5L also demonstrated the highest AUC value (0.943) and was found to be the core regulator in a pathway related to cell dysfunction. Cumulatively, these results show that EV-derived CD5L may represent a potential biomarker-detected via a liquid biopsy-for the noninvasive diagnosis of lung cancer.
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http://dx.doi.org/10.3390/diagnostics11040620DOI 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

Clinical impact of rebiopsy among patients with epidermal growth factor receptor-mutant lung adenocarcinoma in a real-world clinical setting.

Thorac Cancer 2021 03 2;12(6):890-898. Epub 2021 Feb 2.

Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Background: In this study, we investigated the risk factors of acquired T790M mutation among patients with lung adenocarcinoma with epidermal growth factor receptor (EGFR) tyrosine mutation who were treated with EGFR-tyrosine kinase inhibitors (TKIs). The aim was to identify the clinical impact of rebiopsy.

Methods: This multicenter, retrospective cohort study was conducted in South Korea from January 2007 to June 2017. Patients with adenocarcinoma with EGFR mutation who underwent rebiopsy and were treated with EGFR-TKIs were included.

Results: Of a total of 352 patients, T790M mutation was identified in 156 (41.9%) at the time of rebiopsy. The median duration from initial biopsy to rebiopsy was 17 months. Univariate logistic regression analysis revealed associations of exon 19 deletion (odds ratio [OR], 1.643; p = 0.026), absence of L858R (OR, 0.627; p = 0.042), and previous EGFR-TKI treatment duration (OR, 1.039; p < 0.001) with T790M mutation. Previous EGFR-TKI treatment duration (OR, 3.580; p < 0.001) was independently associated with T790M mutation. A multivariate Cox proportional hazard model revealed that brain metastasis at initial diagnosis (hazard ratio, 1.390; p = 0.050) tended to be associated with T790M mutation. Among the patients with T790M mutation at rebiopsy, the osimertinib user group (n = 90) had a better one-year survival (68.7 vs. 58.3%, p = 0.048) than the osimertinib nonuser group (n = 66).

Conclusions: Rebiopsy might affect the clinical course of patients with EGFR-mutant adenocarcinoma who receive EGFR-TKIs.
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http://dx.doi.org/10.1111/1759-7714.13857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952806PMC
March 2021

Real-world outcomes of anti-PD1 antibodies in platinum-refractory, PD-L1-positive recurrent and/or metastatic non-small cell lung cancer, and its potential practical predictors: first report from Korean Cancer Study Group LU19-05.

J Cancer Res Clin Oncol 2021 Feb 1. Epub 2021 Feb 1.

Department of Medical Oncology, Seoul St. Mary's Hospital, The Catholic University, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.

Purpose: Although immune-checkpoint inhibitors have become a new therapeutic option for recurrent/metastatic non-small cell lung cancers (R/M-NSCLC), its clinical benefit in the real-world is still unclear.

Methods: We investigated 1181 Korean patients with programmed death-1 ligand 1 (PD-L1)-positive [tumor proportion score (TPS) ≥ 10% by the SP263 assay or ≥ 50% by the 22C3 assay] R/M-NSCLC treated with pembrolizumab or nivolumab after failure of platinum-based chemotherapy.

Results: The median age was 67 years, 13% of patients had ECOG-PS ≥ 2, and 27% were never-smokers. Adenocarcinoma was predominant (61%) and 18.1% harbored an EGFR activating mutation or ALK rearrangement. Pembrolizumab and nivolumab were administered to 51.3% and 48.7, respectively, and 42% received them beyond the third-line chemotherapy. Objective response rate (ORR) was 28.6%. Pembrolizumab group showed numerically higher ORR (30.7%) than the nivolumab group (26.4%), but it was comparable with that of the nivolumab group having PD-L1 TPS ≥ 50% (32.4%). Median progression-free survival (PFS) and overall survival (OS) were 2.9 (95% CI 0-27.9) and 10.7 months (95% CI 0-28.2), respectively. In multivariable analysis, concordance of TPS ≥ 50% in both PD-L1 assays and the development of immune-related adverse events (irAEs) were two significant predictors of better ORR, PFS, and OS. EGFR mutation could also predict significantly worse OS outcomes.

Conclusion: The real-world benefit of later-line anti-PD1 antibodies was comparable to clinical trials in patients with R/M-NSCLC, although patients generally were more heavily pretreated and had poorer ECOG-PS. Concordantly high PD-L1 TPS ≥ 50% and development of irAE could independently predict better treatment outcomes, while EGFR mutation negatively affected OS.
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http://dx.doi.org/10.1007/s00432-021-03527-4DOI 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

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

Etiological Distribution and Morphological Patterns of Granulomatous Pleurisy in a Tuberculosis-prevalent Country.

J Korean Med Sci 2021 Jan 4;36(1):e10. Epub 2021 Jan 4.

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

The cause of epithelioid granulomatous inflammation varies widely depending on the affected organ, geographic region, and whether the granulomas morphologically contain necrosis. Compared with other organs, the etiological distribution and morphological patterns of pleural epithelioid granulomas have rarely been investigated. We evaluated the final etiologies and morphological patterns of pleural epithelioid granulomatous inflammation in a tuberculosis (TB)-prevalent country. Of 83 patients with pleural granulomas, 50 (60.2%) had confirmed TB pleurisy (TB-P) and 29 (34.9%) had probable TB-P. Four patients (4.8%) with non-TB-P were diagnosed. With the exception of microbiological results, there was no significant difference in clinical characteristics and granuloma patterns between the confirmed TB-P and non-TB-P groups, or between patients with confirmed and probable TB-Ps. These findings suggest that most pleural granulomatous inflammation (95.2%) was attributable to TB-P in TB-endemic areas and that the granuloma patterns contributed little to the prediction of final diagnosis compared with other organs.
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http://dx.doi.org/10.3346/jkms.2021.36.e10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781852PMC
January 2021

Phase II open-label multicenter study to assess the antitumor activity of afatinib in lung cancer patients with activating epidermal growth factor receptor mutation from circulating tumor DNA: Liquid-Lung-A.

Thorac Cancer 2021 02 3;12(4):444-452. Epub 2020 Dec 3.

Department of Internal Medicine, Chonnam National University Medical School and CNU Hwasun Hospital, Hwasun, Jeonnam, Korea.

Background: Mutation analysis of circulating tumor DNA (ctDNA) is used for diagnosing lung cancer. This trial aimed to assess the efficacy of afatinib in treatment-naïve patients with lung cancer harboring epidermal growth factor receptor mutations (EGFRm, exon 19 deletions or exon 21 point mutations) detected based on ctDNA.

Methods: The primary objective was the objective response rate (ORR) in the response evaluable (RE) population. EGFRm analysis of ctDNA was performed using PANA Mutype. Of the 331 patients screened, ctDNA was positive in 21% (68/331) in the detection of activating EGFRm. Among 81 subjects with tumor EGFRm, 48 showed matched EGFRm in their ctDNA (59% sensitivity).

Results: Therapy with afatinib 40 mg was initiated in 21 (female, 17; adenocarcinoma, 20) patients (intention-to-treat, ITT); dose modifications were made in 15 (71%). The ORR was 74% in the RE population (14/19); 11 patients showed EGFRm only in ctDNA (Group A), whereas 10 exhibited the same EGFRm in their ctDNA and tumor DNA (Group B). There was no significant difference in ORR between Groups A and B (80% and 67% RE, respectively). Median progression-free survival (PFS) was 12.0 months, and no significant difference was observed according to the final afatinib dose, type of EGFRm, and Group A versus B. After progression, T790M mutation was found in 40% (6/15) of patients, and osimertinib was used as a second-line treatment.

Conclusions: Afatinib showed similar ORR and PFS in patients with lung cancer harboring EGFRm in their ctDNA regardless of tumor EGFRm results.

Key Points: SIGNIFICANT FINDINGS OF THE STUDY: Afatinib showed favorable ORR and PFS regardless of the tumor EGFR mutation status results, similar to the findings of previous trials assessing afatinib as first-line treatment of EGFR-mutated non-small cell lung cancer based on tumor genotyping.

What This Study Adds: Our findings emphasize that the survival benefit of afatinib treatment can be achieved not only by appropriate dose reduction with frequent and detailed monitoring of toxicities, but also by using noninvasive (ctDNA) assays in a real-world setting.
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http://dx.doi.org/10.1111/1759-7714.13763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882376PMC
February 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

Laboratory and radiological discrimination between tuberculous and malignant pleural effusions with high adenosine deaminase levels.

Korean J Intern Med 2020 Sep 29. Epub 2020 Sep 29.

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

Background/aims: Pleural fluid adenosine deaminase (ADA) levels are useful in discriminating tuberculous pleural effusions (TPEs) from malignant pleural effusions (MPEs). However, some patients with MPE exhibit high-ADA levels, which may mimic TPEs. There is limited data regarding the differential diagnosis between high-ADA MPE and high-ADA TPE. This study aimed to identify the predictors for distinguishing high-ADA MPEs from high-ADA TPEs.

Methods: Patients with TPE and MPE with pleural fluid ADA levels ≥40 IU/L were included in this study. Clinical, laboratory, and radiological data were compared between the two groups. Independent predictors and their diagnostic performance for high-ADA MPEs were evaluated using multivariate logistic regression analysis and receiver operating characteristic curve.

Results: A total of 200 patients (high-ADA MPE, n = 30, and high-ADA TPE, n = 170) were retrospectively included. In the multivariate analysis, pleural fluid ADA, pleural fluid carcinoembryonic antigen (CEA), and pleural nodularity were independent discriminators between high-ADA MPE and high-ADA TPE groups. Using pleural ADA level of 40-56 IU/L (3 points), pleural CEA level ≥6 ng/mL (6 points), and presence of pleural nodularity (3 points) for predicting high-ADA MPEs, a sum score ≥6 points yielded a sensitivity of 90%, specificity of 96%, positive predictive value of 82%, negative predictive value of 98%, and area under the receiver operating characteristic curve of 0.965.

Conclusions: A scoring system using three parameters may be helpful in guiding the differential diagnosis between high-ADA MPEs and high-ADA TPEs.
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http://dx.doi.org/10.3904/kjim.2020.246DOI Listing
September 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

Use of Darunavir-Cobicistat as a Treatment Option for Critically Ill Patients with SARS-CoV-2 Infection.

Yonsei Med J 2020 Sep;61(9):826-830

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

We retrospectively reviewed patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections who were admitted to an intensive care unit in Daegu, South Korea. The outcomes of patients who did (cases) or did not (controls) receive darunavir-cobicistat (800-150 mg) therapy were compared. Fourteen patients received darunavir-cobicistat treatment, and 96 received other antiviral therapy (controls). Overall, the darunavir-cobicistat group comprised patients with milder illness, and the crude mortality rate of all patients in the darunavir-cobicistat group was lower than that in the controls [odds ratio (OR) 0.20, 95% confidence interval (CI) 0.04-0.89, =0.035]. After 1:2 propensity-score matching, there were 14 patients in the darunavir-cobicistat group, and 28 patients in the controls. In propensity score-matched analysis, the darunavir-cobicistat group had lower mortality than the controls (OR 0.07, 95% CI 0.01-0.52, =0.009). In conclusion, darunavir-cobicistat therapy was found to be associated with a significant survival benefit in critically ill patients with SARS-CoV-2 infection.
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http://dx.doi.org/10.3349/ymj.2020.61.9.826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471078PMC
September 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

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

Comparison of biochemical parameters and chemokine levels in pleural fluid between patients with anergic and non-anergic tuberculous pleural effusion.

Tuberculosis (Edinb) 2020 07 13;123:101940. Epub 2020 May 13.

Department of Internal Medicine, Kyungpook National University, School of Medicine, Daegu, South Korea; Kyungpook National University Bio-Medical Research Institute, Daegu, South Korea. Electronic address:

Pleural fluid (PF) immune response in anergic tuberculous pleural effusion (TPE) patients is poorly understood. This study aimed to compare PF biochemical parameters and chemokine levels between anergic and non-anergic TPE patients. Chemokine arrays, cytokine measurements, and flow cytometry were performed in 58 patients (TPE [non-anergic (n = 32) and anergic (n = 10)] and malignant pleural effusion (MPE) [n = 16]). PF adenosine deaminase 2 (ADA2) levels were significantly lower in anergic TPE patients than in non-anergic TPE patients (p = 0.048). Among the 40 chemokines tested, PF CCL27 levels were significantly higher in anergic TPE patients than in non-anergic TPE and MPE patients (p < 0.001). The percentage of CD4CCR10T cells in PF was higher in anergic TPE patients than in non-anergic TPE and MPE patients (p = 0.001). We reported here that CCL27/CCR10 interactions might contribute to pathophysiology in anergic TPE. PF CCL27 and CD4CCR10T cells may help in diagnosing TPE in patients with moderate elevation of PF ADA levels.
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http://dx.doi.org/10.1016/j.tube.2020.101940DOI Listing
July 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

Idiopathic Pleural Effusions: Characteristics and Discrimination From Cytology-Negative Malignant Pleural Effusions.

Am J Med Sci 2020 09 25;360(3):236-242. Epub 2020 Apr 25.

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

Background: The etiology of pleural effusions often remained unknown notwithstanding surgical pleural biopsy and further clinical observation. A better understanding of clinical characteristics of patients with idiopathic pleural effusion (IPE) may improve the ability to differentiate between IPEs and cytology-negative malignant pleural effusions (MPEs) and facilitate the identification of patients requiring invasive investigation. However, little is known about the clinical factors that can help distinguish patients with IPE from those with cytology-negative MPE.

Materials And Methods: Patients who were diagnosed with IPE or cytology-negative MPE between 2010 and 2017 were enrolled in this retrospective study. Clinical, laboratory and radiologic characteristics were compared between patients with IPE and cytology-negative MPE. Diagnostic performances of predictors for IPE were assessed using receiver operating characteristic curves.

Results: Of 146 patients undergoing pleural biopsy owing to cytology-negative pleural effusion of uncertain cause, MPE was confirmed in 54 patients. IPE was ultimately diagnosed in 22 patients. Multivariate analysis demonstrated that a minimal amount of pleural effusion (odds ratio [OR] = 12.41, P = 0.039), presence of pleural nodularity (OR = 0.01, P < 0.001) and pleural fluid carcinoembryonic antigen levels less than 14 ng/mL (OR = 87.59, P = 0.002) were independent factors for distinguishing IPEs from cytology-negative MPEs. A combination of the absence of pleural nodularity with pleural fluid carcinoembryonic antigen levels less than 14 ng/mL yielded an area under the curve of 0.94 (sensitivity = 91% and specificity = 96%).

Conclusions: Using these readily available parameters to identify IPE in patients with cytology-negative exudative effusion of unknown cause can help guide decision-making when choosing to perform an invasive pleural biopsy or to take a conservative approach.
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http://dx.doi.org/10.1016/j.amjms.2020.04.020DOI Listing
September 2020

Crucial role of temporary airborne infection isolation rooms in an intensive care unit: containing the COVID-19 outbreak in South Korea.

Crit Care 2020 May 18;24(1):238. Epub 2020 May 18.

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

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http://dx.doi.org/10.1186/s13054-020-02944-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234817PMC
May 2020

Characteristics and survival impact of polymorphonuclear leucocyte-predominant malignant pleural effusions secondary to lung cancer.

Clin Respir J 2020 Apr 15. Epub 2020 Apr 15.

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

Introduction: In comparison with mononuclear leucocyte (MNL)-predominant malignant pleural effusions (MPEs), polymorphonuclear leucocyte (PMNL)-predominant MPEs have rarely been investigated and may be associated with a poorer prognosis.

Objectives: To investigate the characteristics and survival impact of PMNL-predominant MPEs secondary to lung cancer.

Methods: This retrospective study included patients with MPE secondary to lung cancer, which were classified into the PMNL- and MNL-predominant groups according to cellular predominance in the pleural fluid. Clinical, hematological, radiological, and pleural fluid data were compared between the groups, and the survival impact of PMNL predominance in MPE was evaluated.

Results: Of the 193 MPEs included, 37 (19%) were characterised by PMNL predominance. Compared to the MNL-predominant group, the PMNL-predominant group showed significantly poorer patient performances (P = .001), higher white blood cell counts (P = .009), higher neutrophil counts, higher blood neutrophil-to-lymphocyte ratio (P = .046), higher serum C-reactive protein (P = .003), lower serum albumin (P < .001), lower pleural fluid pH (P = .002) and higher pleural fluid lactate dehydrogenase (P = .029) levels. In contrast, most clinical and radiological findings, including the duration of symptoms, showed no significant intergroup differences. A shift towards MNL predominance was observed in only 38% of the PMNL-predominant patients who underwent repeat thoracentesis. Overall survival of the PMNL-predominant group was significantly shorter than the MNL-predominant group (P = .003).

Conclusions: PMNL predominance in MPEs secondary to lung cancer may be observed in variable phases with respect to the duration of symptoms and the time of thoracentesis. Overall, PMNL-predominant MPEs were associated with more advanced stages and poorer survival outcomes, compared to MNL-predominant MPEs.
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http://dx.doi.org/10.1111/crj.13195DOI Listing
April 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

A Case of Paraneoplastic Neurological Syndrome Expressing Dual Antineuronal Antibodies: Anti-Hu and Recoverin.

Ann Indian Acad Neurol 2020 Jan-Feb;23(1):133-135

Department of Neurology, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea.

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http://dx.doi.org/10.4103/aian.AIAN_185_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001452PMC
February 2020

Clinical characteristics and outcome in patients with pulmonary embolism undergoing coronary angiography.

Vasc Med 2020 04 7;25(2):157-159. Epub 2020 Feb 7.

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

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http://dx.doi.org/10.1177/1358863X19900239DOI Listing
April 2020

A single nucleotide polymorphism rs12898 is associated with primary hepatic cancer in a Chinese population.

Int J Clin Exp Pathol 2019 1;12(8):3063-3069. Epub 2019 Aug 1.

Department of Intensive Care Unit, Yanbian University Hospital Yanji, Jilin, China.

Background & Aims: Primary hepatic cancer (PHC) is a common malignant tumor and the third most frequent cause of cancer-related death worldwide. However, the molecular mechanisms underlying hepatic cancer remain unknown. is considered a biomarker of cancer as it can facilitate tumor progression. We aimed to investigate the association between genetic polymorphisms of potential regulatory SNPs in the gene and PHC.

Methods: The relationship between rs12898 and PHC was analyzed in a case-control study with a Chinese population of 608 PHC patients and 608 healthy individuals using SPSS 21.0.

Results: PHC was significantly associated with alcohol consumption ( < 0.001), history of hepatitis ( < 0.001), and liver cirrhosis ( < 0.001), but not with smoking ( = 0.168), age ( = 0.175), or sex ( = 0.051). Distribution of three genotypes (GG, GA, and AA) of rs12898 significantly differed between the cases and controls ( < 0.001). Compared with the GG genotype, the GA and AA genotype was associated with a significantly increased risk of PHC (OR = 1.425, 95% CI = 1.099-1.848, = 0.007; and OR = 2.220, 95% CI = 1.574-3.132, < 0.001, respectively). rs12898 was associated with a significantly increased risk of PHC under a dominant model (OR = 1.592, 95% CI = 1.243-2.040, < 0.001), and under a recessive model (OR = 1.771, 95% CI = 1.311-2.393, < 0.001) for the variant A allele.

Conclusion: Results suggest that rs12898G > A may play a role in the pathogenesis of PHC, and may be a marker for susceptibility to PHC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949695PMC
August 2019

The effect of susceptibility variants, identified in never-smoking female lung cancer cases, on male smokers.

Korean J Intern Med 2020 07 30;35(4):929-935. Epub 2019 Dec 30.

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

Background/aims: Genome wide and candidate gene association studies have identified polymorphisms associated with the risk of lung cancer in never-smokers. This study was conducted to evaluate the association between 11 polymorphisms identified in female never smokers and the lung cancer risk in male smokers.

Methods: This study included 714 lung cancer patients and 626 healthy controls. The polymorphisms were genotyped using SEQUENOM MassARRAY iPLEX assay or Taq-Man assay.

Results: Two polymorphisms were associated with the risk of lung cancer in male smokers, as in female never smokers. Male smokers carrying the rs4975616 variant allele had a significantly decreased risk of lung cancer (in a codominant model: odds ratio, 0.77; 95% confidence interval, 0.61 to 0.96; p = 0.02). The rs9387478 polymorphism also reduced lung cancer risk in male smokers (in a codominant model: odds ratio, 0.85; 95% confidence interval, 0.73 to 0.997; p = 0.046). In a stratified analysis, the association between these polymorphisms and the risk of lung cancer was predominant in lighter smokers and for cases of adenocarcinoma.

Conclusion: These results suggest that a subset of polymorphisms known to be associated with the risk of lung cancer in female never smokers is also associated with the risk of lung cancer in male smokers.
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http://dx.doi.org/10.3904/kjim.2018.417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373985PMC
July 2020