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Purpose@#The addition of immune checkpoint inhibitors to chemotherapy has improved survival outcomes in patients with extensive-stage small cell lung cancer (ES-SCLC). However, their real-world effectiveness remains unknown. Therefore, we investigated the effectiveness of atezolizumab plus chemotherapy in ES-SCLC in actual clinical settings. @*Materials and Methods@#In this multicenter prospective cohort study, patients with ES-SCLC receiving or scheduled to receive atezolizumab in combination with etoposide and carboplatin were enrolled between June 2021 and August 2022. The primary outcomes were progression-free survival (PFS) and the 1-year overall survival (OS) rate. @*Results@#A total of 100 patients with ES-SCLC were enrolled from seven centers. Median age was 69 years, and 6% had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2. The median PFS was 6.0 months, the 1-year OS rate was 62.2%, and the median OS was 13.5 months. An ECOG PS of 2-3 and progressive disease as the best response were poor prognostic factors for PFS, while an ECOG PS of 2-3 and brain metastasis were associated with poor prognosis for OS. In addition, consolidative thoracic radiotherapy was found to be an independent favorable prognostic factor for OS (hazard ratio, 0.336; p=0.021). Grade ≥ 3 treatment-related adverse events were observed in 7% of patients, with treatment-related deaths occurring in 2% of patients. @*Conclusion@#We provided evidence of the favorable real-world effectiveness and safety of atezolizumab plus chemotherapy in ES-SCLC patients, including in the elderly and those with poor ECOG PS. Additional consolidative thoracic radiotherapy may also benefit ES-SCLC patients.
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Background/Aims@#Epidermal growth factor receptor (EGFR) mutation is important in determining the treatment strategy for advanced lung cancer patients with malignant pleural effusion (MPE). Contrary to serum carcinoembryonic antigen (S-CEA) levels, the associations between pleural fluid CEA (PF-CEA) levels and EGFR mutation status as well as between PF-CEA levels and treatment efficacy have rarely been investigated in lung adenocarcinoma patients with MPE. @*Methods@#This retrospective study enrolled lung adenocarcinoma patients with MPE and available PF-CEA levels and EGFR mutation results. The patients were categorized based on PF-CEA levels: < 10 ng/mL, 10–100 ng/mL, 100–500 ng/mL, and ≥ 500 ng/mL. The association between PF-CEA levels and EGFR mutation status as well as their therapeutic impact on overall survival was compared among the four groups. @*Results@#This study included 188 patients. PF-CEA level was found to be an independent predictor of EGFR mutation but not S-CEA level. The EGFR mutation rates were higher as the PF-CEA levels increased, regardless of cytology results or sample types. Among EGFR-mutant lung adenocarcinoma patients receiving EGFR-tyrosine kinase inhibitor (TKI) treatment, those with high PF-CEA levels had significantly better survival outcomes than those with low PF-CEA levels. @*Conclusion@#High PF-CEA levels were associated with high EGFR mutation rate and may lead to a favorable clinical outcome of EGFR-TKI treatment in EGFR-mutant lung adenocarcinoma patients with MPE. These findings highlight the importance of actively investigating EGFR mutation detection in patients with suspected MPE and elevated PF-CEA levels despite negative cytology results.
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Purpose@#This study aimed to report the final analysis of time-on-treatment (TOT) and overall survival (OS) in patients with advanced-stage epidermal growth factor receptor (EGFR)+ non–small cell lung cancer (NSCLC) who received sequential afatinib and osimertinib and to compare the outcomes with other second-line regimens (comparator group). @*Materials and Methods@#In this updated report, the existing medical records were reviewed and rechecked. TOT and OS were updated and analyzed according to clinical features using the Kaplan-Meier method and log-rank test. TOT and OS were compared with those of the comparator group, in which most patients received pemetrexed-based treatments. A multivariable Cox proportional hazard model was used to evaluate features that could affect survival outcomes. @*Results@#The median observation time was 31.0 months. The follow-up period was extended to 20 months. A total of 401 patients who received first-line afatinib were analyzed (166 with T790M+ and second-line osimertinib, and 235 with unproven T790M and other second-line agents). Median TOTs on afatinib and osimertinib were 15.0 months (95% confidence interval [CI], 14.0 to 16.1) and 11.9 months (95% CI, 8.9 to 14.6), respectively. The median OS in the osimertinib group was 54.3 months (95% CI, 46.7 to 61.9), much longer than that in the comparator group. In patients who received osimertinib, the OS was longest with Del19+ (median, 59.1; 95% CI, 48.7 to 69.5). @*Conclusion@#This is one of the largest real-world studies reporting the encouraging activity of sequential afatinib and osimertinib in Asian patients with EGFR+ NSCLC who acquired the T790M mutation, particularly Del19+.
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Purpose@#Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. @*Materials and Methods@#Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. @*Results@#A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. @*Conclusion@#Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.
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Background@#Neurogenic differentiation 1 (NeuroD1) is a representative small cell lung cancer (SCLC) transcription regulator involved in the carcinogenesis and behavior of SCLC.Histone modifications play an important role in transcription, and H3 lysine 4 trimethylation (H3K4me3) is primarily associated with promoter regions. @*Methods@#We investigated the association between single nucleotide polymorphisms (SNPs) in NeuroD1 and H3K4me3 coincident regions, selected using ChIP sequencing (ChIP-seq), and the clinical outcomes of 261 patients with SCLC. @*Results@#Among 230 SNPs, two were significantly associated with both the chemotherapy response and overall survival (OS) of patients with SCLC. RNF145 rs2043268A>G was associated with worse chemotherapy response and OS (under a recessive model, adjusted odds ratio [aOR], 0.50, 95% confidence interval [CI], 0.26–0.94, P = 0.031, and adjusted hazard ratio [aHR], 1.88, 95% CI, 1.38–2.57, P G was also associated with worse chemotherapy response and OS (under a dominant model, aOR, 0.47, 95% CI, 0.23–0.99, P = 0.046, and aHR, 2.03, 95% CI, 1.47–2.82, P G and CINP rs762105A>G were associated with clinical outcomes in patients with SCLC and also affected the promoter activity of each gene.
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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 f luid 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 f luid carcinoembryonic antigen (CEA), and pleural nodularity were independent discriminators between high-ADA MPE and high-ADA TPE groups. Using pleural ADA level of 40 to 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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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 TBP. 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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BackgroundCoronavirus 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.MethodsWe 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.ResultsCompared with the non-DM group (n=847), patients with DM (n=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.ConclusionDM 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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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. @*Conclusions@#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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We retrospectively reviewed patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections who wereadmitted to an intensive care unit in Daegu, South Korea. The outcomes of patients who did (cases) or did not (controls) receivedarunavir-cobicistat (800–150 mg) therapy were compared. Fourteen patients received darunavir-cobicistat treatment, and 96 receivedother antiviral therapy (controls). Overall, the darunavir-cobicistat group comprised patients with milder illness, and thecrude 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, p=0.035]. After 1:2 propensity-score matching, there were 14 patients in the darunavir-cobicistatgroup, and 28 patients in the controls. In propensity score-matched analysis, the darunavir-cobicistat group had lower mortalitythan the controls (OR 0.07, 95% CI 0.01–0.52, p=0.009). In conclusion, darunavir-cobicistat therapy was found to be associatedwith a significant survival benefit in critically ill patients with SARS-CoV-2 infection.
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BACKGROUND@#Information regarding the incidence and risk factors for deep vein thrombosis (DVT) detected by follow-up computed tomographic (CT) venography after pulmonary embolism (PE) is sparse. The aim of the present study was to identify the predictors of DVT in follow-up CT images, and to elucidate their clinical significance.@*METHODS@#Patients with PE were classified into the following three cohorts based on the time of indirect CT venography follow-up: within 1 month, 1 to 3 months, and 3 to 9 months after the initial CT scan. Each cohort was subdivided into patients with or without DVT detected by follow-up CT. Clinical variables were compared between the two groups.@*RESULTS@#Follow-up CT revealed DVT in 61% of patients with PE within 1 month, in 15% of patients with PE at 1 to 3 months, and in 9% of patients with PE at 3 to 9 months after the initial CT scan. Right ventricular (RV) dilation on the initial CT (odds ratio [OR], 8.30; 95% confidence interval [CI], 1.89–36.40; p=0.005) and proximal DVT at the initial presentation (OR, 6.93; 95% CI, 1.90–25.20; p=0.003) were found to independently predict DVT in follow-up CT images within 1 month, proximal DVT at the initial presentation was found to independently predict DVT in follow-up CT images at 1 to 3 months (OR, 6.69; 95% CI, 1.53–29.23; p=0.012), and central PE was found to independently predict DVT in follow-up CT images at 3 to 9 months (OR, 4.25; 95% CI, 1.22–4.83; p=0.023) after the initial CT scan. Furthermore, the detection of DVT by follow-up CT independently predicted the recurrence of venous thromboembolism (VTE) (OR, 4.67; 95% CI, 2.24–9.74; p < 0.001).@*CONCLUSION@#Three months after PE, DVT was not detected by follow-up CT in most patients with PE. RV dilation on the initial CT, central PE, and proximal DVT at the initial presentation were found to predict DVT on follow-up CT, which might predict VTE recurrence.
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BACKGROUND: Information regarding the incidence and risk factors for deep vein thrombosis (DVT) detected by follow-up computed tomographic (CT) venography after pulmonary embolism (PE) is sparse. The aim of the present study was to identify the predictors of DVT in follow-up CT images, and to elucidate their clinical significance. METHODS: Patients with PE were classified into the following three cohorts based on the time of indirect CT venography follow-up: within 1 month, 1 to 3 months, and 3 to 9 months after the initial CT scan. Each cohort was subdivided into patients with or without DVT detected by follow-up CT. Clinical variables were compared between the two groups. RESULTS: Follow-up CT revealed DVT in 61% of patients with PE within 1 month, in 15% of patients with PE at 1 to 3 months, and in 9% of patients with PE at 3 to 9 months after the initial CT scan. Right ventricular (RV) dilation on the initial CT (odds ratio [OR], 8.30; 95% confidence interval [CI], 1.89–36.40; p=0.005) and proximal DVT at the initial presentation (OR, 6.93; 95% CI, 1.90–25.20; p=0.003) were found to independently predict DVT in follow-up CT images within 1 month, proximal DVT at the initial presentation was found to independently predict DVT in follow-up CT images at 1 to 3 months (OR, 6.69; 95% CI, 1.53–29.23; p=0.012), and central PE was found to independently predict DVT in follow-up CT images at 3 to 9 months (OR, 4.25; 95% CI, 1.22–4.83; p=0.023) after the initial CT scan. Furthermore, the detection of DVT by follow-up CT independently predicted the recurrence of venous thromboembolism (VTE) (OR, 4.67; 95% CI, 2.24–9.74; p < 0.001). CONCLUSION: Three months after PE, DVT was not detected by follow-up CT in most patients with PE. RV dilation on the initial CT, central PE, and proximal DVT at the initial presentation were found to predict DVT on follow-up CT, which might predict VTE recurrence.
Subject(s)
Humans , Cohort Studies , Follow-Up Studies , Incidence , Multidetector Computed Tomography , Phlebography , Pulmonary Embolism , Recurrence , Risk Factors , Tomography, X-Ray Computed , Venous Thromboembolism , Venous ThrombosisABSTRACT
The cause of death in patients with tuberculosis (TB) may differ according to the phase of anti-tuberculosis treatment. However, there are limited data regarding this issue in Korea. We compared the cause of death of TB patients who died during the early intensive and late continuation phase of treatment. Twenty (56%) of the 36 early deaths were due to TB-related causes, whereas 34 (89%) of the 38 late deaths were due to TB-unrelated causes. This finding suggests that TB-related early deaths mainly attributable to delayed diagnosis should be improved to further reduce the overall TB deaths.
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Recently, genetic variants in the WNT signaling pathway have been reported to affect the survival outcome of Caucasian patients with early stage non-small cell lung cancer (NSCLC). We therefore attempted to determine whether these same WNT signaling pathway gene variants had similar impacts on the survival outcome of NSCLC patients in a Korean population. A total of 761 patients with stages I-IIIA NSCLC were enrolled in this study. Eight variants of WNT pathway genes were genotyped and their association with overall survival and disease-free survival were analyzed. None of the eight variants were significantly associated with overall survival or disease-free survival. There were no differences in survival outcome after stratifying the subjects according to age, gender, smoking status, and histological type. These results suggest that genetic variants in the WNT signaling pathway may not affect the survival outcome of NSCLC in a Korean population.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Asian People/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Demography , Disease-Free Survival , Genotype , Kaplan-Meier Estimate , Lung Neoplasms/genetics , Polymorphism, Single Nucleotide , Republic of Korea , Smoking , Wnt Signaling Pathway/geneticsABSTRACT
Vascular endothelial growth factor (VEGF) contributes to tumor angiogenesis. The role of VEGF single nucleotide polymorphisms (SNPs) in lung cancer susceptibility and its prognosis remains inconclusive and controversial. This study was performed to investigate whether VEGF polymorphisms affect survival outcomes of patients with early stage non-small cell lung cancer (NSCLC) after surgery. Three potentially functional VEGF SNPs (rs833061T>C, rs2010963G>C, and rs3025039C>T) were genotyped. A total of 782 NSCLC patients who were treated with surgical resection were enrolled. The association of the SNPs with overall survival (OS) and disease free survival (DFS) was analyzed. In overall population, none of the three polymorphisms were significantly associated with OS or DFS. However, when the patients were stratified by tumor histology, squamous cell carcinoma (SCC) and adenocarcinoma (AC) had significantly different OS (Adjusted hazard ratio [aHR] = 0.76, 95% CI = 0.56–1.03 in SCC; aHR = 1.33, 95% CI = 0.98–1.82 in AC; P for heterogeneity = 0.01) and DFS (aHR = 0.75, 95% CI = 0.58–0.97 in SCC; aHR = 1.26, 95% CI = 1.00–1.60 in AC; P for heterogeneity = 0.004) according to the rs833061T>C genotypes. Our results suggest that the prognostic role of VEGF rs833061T>C may differ depending on tumor histology.
Subject(s)
Humans , Adenocarcinoma , Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Disease-Free Survival , Genotype , Lung Neoplasms , Polymorphism, Single Nucleotide , Population Characteristics , Prognosis , Vascular Endothelial Growth Factor AABSTRACT
BACKGROUND: Viridans streptococci (VS) are a large group of streptococcal bacteria that are causative agents of community-acquired respiratory tract infection. However, data regarding their clinical characteristics are limited. The purpose of the present study was to investigate the clinical and radiologic features of community-acquired pneumonia (CAP) with or without parapneumonic effusion caused by VS. METHODS: Of 455 consecutive CAP patients with or without parapneumonic effusion, VS were isolated from the blood or pleural fluid in 27 (VS group, 5.9%) patients. Streptococcus pneumoniae was identified as a single etiologic agent in 70 (control group) patients. We compared various clinical parameters between the VS group and the control group. RESULTS: In univariate analysis, the VS group was characterized by more frequent complicated parapneumonic effusion or empyema and bed-ridden status, lower incidences of productive cough, elevated procalcitonin (>0.5 ng/mL), lower age-adjusted Charlson comorbidity index score, and more frequent ground glass opacity (GGO) or consolidation on computed tomography (CT) scans. Multivariate analysis demonstrated that complicated parapneumonic effusion or empyema, productive cough, bed-ridden status, and GGO or consolidation on CT scans were independent predictors of community-acquired respiratory tract infection caused by VS. CONCLUSION: CAP caused by VS commonly presents as complicated parapneumonic effusion or empyema. It is characterized by less frequent productive cough, more frequent bed-ridden status, and less common CT pulmonary parenchymal lesions. However, its treatment outcome and clinical course are similar to those of pneumococcal pneumonia.
Subject(s)
Humans , Bacteria , Comorbidity , Cough , Empyema , Glass , Incidence , Methods , Multivariate Analysis , Pneumonia , Pneumonia, Pneumococcal , Respiratory Tract Infections , Streptococcus pneumoniae , Tomography, X-Ray Computed , Treatment Outcome , Viridans StreptococciABSTRACT
BACKGROUND: Although organizing pneumonia (OP) responds well to corticosteroid therapy, relapse is common during dose reduction or follow-up. Predictors of relapse in OP patients remain to be established. The aim of the present study was to identify factors related to relapse in OP patients. METHODS: This study was retrospectively performed in a tertiary referral center. Of 66 OP patients who were improved with or without treatment, 20 (30%) experienced relapse. The clinical and radiologic parameters in the relapse patient group (n=20) were compared to that in the non-relapse group (n=46). RESULTS: Multivariate analysis demonstrated that percent predicted forced vital capacity (FVC), PaO2/FiO2, and serum protein level were significant predictors of relapse in OP patients (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.70-0.97; p=0.018; OR, 1.02; 95% CI, 1.00-1.04; p=0.042; and OR, 0.06; 95% CI, 0.01-0.87; p=0.039, respectively). CONCLUSION: This study shows that FVC, PaO2/FiO2 and serum protein level at presentation can significantly predict relapse in OP patients.
Subject(s)
Humans , Cryptogenic Organizing Pneumonia , Follow-Up Studies , Methods , Multivariate Analysis , Pneumonia , Recurrence , Retrospective Studies , Tertiary Care Centers , Vital CapacityABSTRACT
Short telomeres are known as one of the risk factors for human cancers. The present study was conducted to evaluate the association between 6 polymorphisms, which were related with short telomere length in the Korean population, and lung cancer risk using 1,100 cases and 1,096 controls. Among the 6 polymorphisms, TERT rs2853669 was significantly associated with increased lung cancer risk under a recessive model (odds ratio [OR]=1.38, 95% confidence interval [CI]=1.05-1.81, P=0.02). The effect of rs2853669 on lung cancer risk was significant in younger individuals (OR=1.73, 95% CI=1.18-2.54, P=0.005) and adenocarcinoma (OR=1.50, 95% CI=1.07-2.07, P=0.02). Our results suggest that a common functional promoter polymorphism, TERT rs2853669, may influence both telomere length and lung cancer risk in the Korean population.
Subject(s)
Female , Humans , Male , Middle Aged , Adenocarcinoma/epidemiology , Case-Control Studies , Gene Frequency/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Lung Neoplasms/epidemiology , Polymorphism, Single Nucleotide/genetics , Promoter Regions, Genetic/genetics , Republic of Korea/epidemiology , Telomerase/genetics , Telomere/physiology , Telomere Homeostasis/geneticsABSTRACT
BACKGROUND/AIMS: A number of genome-wide and candidate gene association studies have identified polymorphisms associated with telomere length in Caucasian populations. This study was conducted to determine the impacts of 17 polymorphisms identified in Caucasians on telomere length in a Korean population. METHODS: Ninety-four healthy individuals were enrolled in this study. Relative telomere length of chromosomes from peripheral blood samples was measured using quantitative polymerase chain reaction. RESULTS: Two polymorphisms, rs10936599 of MYNN and rs412658 of ZNF676, were found to be associated w ith telomere length (under dominant model, p = 0.04; under recessive model, p = 0.001). Three polymorphisms, rs2853669, rs7705526, and rs2736108, at the TERT locus were also associated with telomere length (under recessive model, p = 0.01, p = 0.02, and p = 0.01, respectively). The genotypes of the five polymorphisms associated with short telomere length were considered bad genotypes; telomere length was significantly decreased with increasing number of bad genotypes (p= 1.7 x 10(-5)). CONCLUSIONS: We have identified polymorphisms associated with telomere length in a Korean population.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Asian People/genetics , Case-Control Studies , DNA-Binding Proteins/genetics , Genome-Wide Association Study , Genotype , Kruppel-Like Transcription Factors/genetics , Phenotype , Polymorphism, Single Nucleotide , Republic of Korea , Telomerase/genetics , Telomere/genetics , Telomere Homeostasis , Zinc FingersABSTRACT
BACKGROUND: Information regarding prognostic value of growth differentiation factor 15 (GDF-15) and heart-type fatty acid-binding protein (H-FABP) in patients with chronic obstructive pulmonary disease (COPD) exacerbation is limited. The aim of this study was to investigate whether serum levels of GDF-15 and H-FABP predict an adverse outcome for COPD exacerbation. METHODS: Clinical variables, including serum GDF-15 and H-FABP levels were compared in prospectively enrolled patients with COPD exacerbation that did or did not experience an adverse outcome. An adverse outcome included 30-day mortality and need for endotracheal intubation or inotropic support. RESULTS: Ninety-seven patients were included and allocated into an adverse outcome (n=10) or a control (n=87) group. Frequencies of mental change and PaCO2>37 mm Hg were significantly higher in the adverse outcome group (mental change: 30% vs. 6%, p=0.034 and PaCO2>37 mm Hg: 80% vs. 22%, p1,600 pg/mL) was more common in the adverse outcome group (80% vs. 43%, p=0.041). However, serum H-FABP level and frequency of serum H-FABP elevation (>755 pg/mL) did not differ between the two groups. Multivariate analysis showed that an elevated serum GDF-15 and PaCO2>37 mm Hg were significant predictors of an adverse outcome (odds ratio [OR], 25.8; 95% confidence interval [CI], 2.7-243.8; p=0.005 and OR, 11.8; 95% CI, 1.2-115.3; p=0.034, respectively). CONCLUSION: Elevated serum GDF-15 level and PaCO2>37 mm Hg were found to predict an adverse outcome independently in patients with COPD exacerbation, suggesting the possibility that serum GDF-15 could be used as a prognostic biomarker of COPD exacerbation.