Promoter-Specific Variants in NeuroD1 and H3K4me3 Coincident Regions and Clinical Outcomes of Small Cell Lung Cancer

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.

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

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.

A Multicenter Study to Identify the Respiratory Pathogens Associated with Exacerbation of Chronic Obstructive Pulmonary Disease in Korea / 결핵및호흡기질환

Background@#Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea. @*Methods@#A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma–COPD (ACO) and pure COPD was performed. @*Results@#We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were detected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016). @*Conclusion@#Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.

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

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.

Prognostic Implication of Volumetric Quantitative CT Analysis in Patients with COVID-19: A Multicenter Study in 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; p = 0.004), C-reactive protein (CRP) (HR, 1.080 per mg/dL;95% CI, 1.010–1.156; p = 0.025), and COVID-affected lung proportion (CALP) (HR, 1.067 per percentage; 95% CI, 1.033– 1.101;p < 0.001) were significantly associated with CEFS. CRP (HR, 1.164 per mg/dL; 95% CI, 1.006–1.347; p = 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; p = 0.004) and NALP volume (NALPV) (HR, 1.002 per mL; 95% CI, 1.000–1.004;p = 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.

The socioeconomic impact of Korean dental health insurance policy on the elderly: a nationwide cohort study in South Korea

PURPOSE: The purpose of this retrospective study was to investigate the relationships of types of dental insurance coverage in Korea with sociodemographic characteristics and the prevalence of systemic and oral diseases, as well as to evaluate the socioeconomic impact of Korean dental insurance policies. METHODS: Sample cohort data from 2006 to 2015 were obtained from the National Health Insurance Service. Patients were divided into 2 groups. The exposed group comprised patients who received insurance benefits for complete dentures, removable partial dentures, and implant care, while the control group comprised patients who did not receive these benefits. The type of insurance coverage and the prevalence of systemic and oral diseases were compared between the 2 groups. RESULTS: Patients who received benefits in the form of complete dentures, removable partial dentures, and implants had similar sociodemographic characteristics in terms of sex, age, income quintile, and type of insurance coverage to the control group. The prevalence of hypertension, anemia, renal disease, rheumatoid arthritis, osteoporosis, asthma, and cerebral infarction was higher in the exposed group than in the control group (P<0.05). The prevalence of periodontal diseases and dental caries was also higher in the exposed group. CONCLUSIONS: Korean dental health insurance policy has been beneficial for the medical expenses of low-income and elderly people suffering from a cost burden due to systemic diseases. However, since there is a tendency to avoid invasive interventions in older patients due to the high risk of systemic diseases, insurance coverage of dentures may be more helpful from a socioeconomic perspective than coverage of dental implant treatments.

Bosentan and Rifampin Interactions Modulate Influx Transporter and Cytochrome P450 Expression and Activities in Primary Human Hepatocytes

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with 20 μM bosentan+200 μM rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.

Predictors of Relapse in Patients with Organizing Pneumonia / 결핵및호흡기질환

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.

Clinical Characteristics of Community-Acquired Viridans Streptococcal Pneumonia / 결핵및호흡기질환

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.

A Case of Venlafaxine-Induced Interstitial Lung Disease / 결핵및호흡기질환

A patient treated with venlafaxine for major depression developed an interstitial lung disease (ILD) with the characteristic clinical, radiological and pathological features of chronic hypersensitivity pneumonitis. A high resolution computed tomography scan demonstrated ground glass opacity, mosaic perfusion with air-trapping and traction bronchiectasis in both lungs. The pathological findings were consistent with a nonspecific interstitial pneumonia pattern. Clinical and radiological improvements were noted after the discontinuation of venlafaxine and the administration of a corticosteroid. This report provides further evidence that the anti-depressant venlafaxine can cause ILD.

A Case of Community-Acquired Methicillin-Resistant Staphylococcus aureus Pneumonia / 대한내과학회지

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has received considerable attention in recent years as the cause of infections in individuals in the community who do not have traditional risk factors for MRSA infection, such as hospitalization or contact with healthcare services. CA-MRSA strains have different molecular and antimicrobial susceptibilities, as compared to hospital-associated MRSA. Although CA-MRSA strains are primarily associated with skin and soft tissue infections, they can cause more invasive infections, such as severe community-acquired pneumonia. Reports on CA-MRSA pneumonia in Korea are sparse. Therefore, we report a case of CA-MRSA pneumonia with molecular typing of the MRSA isolate.

A Case of Multicentric Castleman's Disease Presenting with Follicular Bronchiolitis / 결핵및호흡기질환

Multicentric Castleman's disease (CD) is a rare atypical lymphoproliferative disorder, which is characterized by various systemic manifestations. Some patients with multicentric CD may have concomitant lung parenchymal lesions, for which lymphoid interstitial pneumonia (LIP) is known to be the most common pathologic finding. Follicular bronchiolitis and LIP are considered to be on the same spectrum of the disease. We describe a case of multicentric CD with pulmonary involvement, which was pathologically proven as follicular bronchiolitis.