Developing a Loop-Mediated Isothermal Amplification Assay for the Rapid Detection of Seven Respiratory Viruses including SARS-CoV-2.

Background and Objectives: The coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to be a pandemic even in 2022. As the initial symptoms of COVID-19 overlap with those of infections from other respiratory viruses, an accurate and rapid diagnosis of COVID-19 is essential for administering appropriate treatment to patients. Currently, the most widely used method for detecting respiratory viruses is based on real-time polymerase chain reaction (PCR) and includes reverse-transcription real-time quantitative PCR (RT-qPCR). However, RT-qPCR assays require sophisticated facilities and are time-consuming. This study aimed to develop a real-time quantitative loop-mediated isothermal amplification (RT-qLAMP) assay and compare its analytical performance with RT-qPCR. Materials and Methods: A total of 315 nasopharyngeal swabs from patients with symptoms of respiratory infections were included in this study. A primary screening of the specimens was performed using RT-qPCR. RNA/DNA from standard strains for respiratory viruses and heat-inactivated preparations of standard strains for SARS-CoV-2 were used to evaluate the accuracy and target specificity of the RT-qLAMP assay. Results: We successfully developed an RT-qLAMP assay for seven respiratory viruses: respiratory syncytial virus (RSV) A, RSV B, adenovirus, influenza (Flu) A (H1N1 and H3N2), Flu B, and SARS-CoV-2. RT-qLAMP was performed in a final reaction volume of 9.6 µL. No cross-reactivity was observed. Compared with the RT-PCR results, the sensitivity and specificity of the RT-qLAMP assay were 95.1% and 100%, respectively. The agreement between the two methods was 97.1%. The median amplification time to RT-qLAMP positivity was 22:34 min (range: 6:80-47:98 min). Conclusions: The RT-qLAMP assay requires a small number of reagents and samples and is performed with an isothermal reaction. This study established a fast, simple, and sensitive test that can be applied to point-of-care testing devices to facilitate the detection of respiratory viruses, including SARS-CoV-2.

Clinical Characteristics of Non-Smoking Chronic Obstructive Pulmonary Disease Patients: Findings from the KOCOSS Cohort.

Chronic obstructive pulmonary disease (COPD) has been regarded as a disease of smokers, but the prevalence of non-smoking COPD patients have been reported to be considerable. We investigated differences in clinical characteristics between smoking and non-smoking COPD patients. We used data from the Korea COPD Subgroup Study (KOCOSS) database, which is a multicenter cohort that recruits patients from 54 medical centres in Korea. Comprehensive comparisons of smoking and non-smoking COPD patients were performed based on general characteristics, exacerbations, symptom scores, radiological findings, and lung-function tests. Of the 2477 patients included in the study, 8.1% were non-smokers and 91.9% were smokers. Non-smoking COPD patients were more likely to be female and to have a higher body mass index and lower level of education. Non-smoking COPD patients had more comorbidities, including hypertension, osteoporosis, and gastroesophageal reflux disease, and experienced more respiratory and allergic diseases. No significant differences in exacerbation rates, symptom scores, or exercise capacity scores were observed between the two groups. Smoking COPD patients had more emphysematous lung according to the radiological findings, and non-smoking patients had more tuberculosis-destroyed lung and bronchiectasis. Lung-function testing revealed no significant difference in the forced expiratory capacity in 1 sec between the two groups, but smokers had more rapid lung-function decline in the 5 years of follow-up data. We found differences in general characteristics and radiological findings between smoking and non-smoking COPD patients. No significant differences in exacerbation or symptom scores were observed, but decline in lung function was less steep in non-smoking patients.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2053088 .

Longitudinal changes in forced expiratory volume in 1 s in patients with eosinophilic chronic obstructive pulmonary disease.

BACKGROUND: Data on changes in lung function in eosinophilic chronic obstructive pulmonary disease (COPD) are limited. We investigated the longitudinal changes in forced expiratory volume in 1 s (FEV1) and effects of inhaled corticosteroid (ICS) in Korean COPD patients. METHODS: Stable COPD patients in the Korean COPD subgroup study (KOCOSS) cohort, aged 40 years or older, were included and classified as eosinophilic and non-eosinophilic COPD based on blood counts of eosinophils (greater or lesser than 300 cells/µL). FEV1 changes were analyzed over a 3-year follow-up period. RESULTS: Of 627 patients who underwent spirometry at least twice during the follow up, 150 and 477 patients were classified as eosinophilic and non-eosinophilic, respectively. ICS-containing inhalers were prescribed to 40% of the patients in each group. Exacerbations were more frequent in the eosinophilic group (adjusted odds ratio: 1.49; 95% confidence interval: 1.10-2.03). An accelerated FEV1 decline was observed in the non-eosinophilic group (adjusted annual rate of FEV1 change: - 12.2 mL/y and - 19.4 mL/y for eosinophilic and non-eosinophilic groups, respectively). In eosinophilic COPD, the adjusted rate of annual FEV1 decline was not significant regardless of ICS therapy, but the decline rate was greater in ICS users (- 19.2 mL/y and - 4.5 mL/y, with and without ICS therapy, respectively). CONCLUSIONS: The annual rate of decline in FEV1 was favorable in eosinophilic COPD compared to non-eosinophilic COPD, and ICS therapy had no beneficial effects on changes in FEV1.

Revised Korean Cough Guidelines, 2020: Recommendations and Summary Statements.

Cough is the most common respiratory symptom that can have various causes. It is a major clinical problem that can reduce a patient's quality of life. Thus, clinical guidelines for the treatment of cough were established in 2014 by the cough guideline committee under the Korean Academy of Tuberculosis and Respiratory Diseases. From October 2018 to July 2020, cough guidelines were revised by members of the committee based on the first guidelines. The purpose of these guidelines is to help clinicians efficiently diagnose and treat patients with cough. This article highlights the recommendations and summary of the revised Korean cough guidelines. It includes a revised algorithm for the evaluation of acute, subacute, and chronic cough. For a chronic cough, upper airway cough syndrome (UACS), cough variant asthma (CVA), and gastroesophageal reflux disease (GERD) should be considered in differential diagnoses. If UACS is suspected, first-generation antihistamines and nasal decongestants can be used empirically. In cases with CVA, inhaled corticosteroids are recommended to improve cough. In patients with suspected chronic cough due to symptomatic GERD, proton pump inhibitors are recommended. Chronic bronchitis, bronchiectasis, bronchiolitis, lung cancer, aspiration, intake of angiotensin-converting enzyme inhibitor, intake of dipeptidyl peptidase-4 inhibitor, habitual cough, psychogenic cough, interstitial lung disease, environmental and occupational factors, tuberculosis, obstructive sleep apnea, peritoneal dialysis, and unexplained cough can also be considered as causes of a chronic cough. Chronic cough due to laryngeal dysfunction syndrome has been newly added to the guidelines.

Longitudinal Changes in Clinical Features, Management, and Outcomes of Idiopathic Pulmonary Fibrosis. A Nationwide Cohort Study.

Rationale: In recent decades, diagnosis and treatment recommendations for idiopathic pulmonary fibrosis (IPF) have changed. In Korea, the average life expectancy has increased, unmet healthcare needs have been reduced, and the number of computed tomographic examinations performed has nearly doubled. The Korean Interstitial Lung Disease Study Group conducted a nationwide cohort study for idiopathic interstitial pneumonia, including IPF, and established a registry for IPF.Objectives: Using study data collected by the study group, this study aimed to evaluate longitudinal changes in clinical features, diagnosis, treatment, and mortality and analyze the extent to which changes in medication usage affected IPF-associated mortality.Methods: The study population included newly diagnosed patients with IPF from a cohort study (January 2002 to September 2008, n = 1,839, 2008 group) and prospective registry (January 2012 to August 2018, n = 1,345, 2018 group). Survival curves were estimated using the Kaplan-Meier method, and Cox regression models were used to identify mortality-associated risk factors in each group.Results: The 2018 group was younger, had fewer symptoms, had less honeycombing, underwent more serologic autoimmune marker and pulmonary function tests, had higher oxygen partial pressure and lower carbon dioxide partial pressure values, was less frequently diagnosed by surgical biopsy, and had better survival than the 2008 group. Steroid use and conservative care declined, whereas N-acetylcysteine use increased in this group. Antifibrotic agents were used in only the 2018 group. In the 2008 group, N-acetylcysteine was associated with lower mortality, whereas conservative care was associated with higher mortality. In the 2018 group, the use of antifibrotic agents was associated with lower mortality, and steroid use was associated with higher mortality. The survival rates in the 2008 and 2018 non-antifibrotic agent subgroups were similar.Conclusions: This study analyzed national IPF cohort data spanning 17 years. In clinical practice, the IPF diagnosis was made earlier, steroid and immunosuppressive agent use was reduced, and antifibrotic agents were administered. The survival of patients with IPF has improved over the decades, and antifibrotic use was consistently associated with improved survival.Clinical trial registered with clinicaltrials.gov (NCT04160715).

Clinical Characteristics of Chronic Obstructive Pulmonary Disease in Female Patients: Findings from a KOCOSS Cohort.

Purpose: The prevalence of chronic obstructive pulmonary disease (COPD) in females has increased, changing the concept of COPD as a disease mostly limited to males. In this study, the clinical characteristics of COPD in females were investigated. Patients and Methods: The study was based on a multicenter cohort of COPD patients recruited from 54 medical centers in South Korea. Sex-based differences in general characteristics, exposure risk factors, depression scores, results of pulmonary function tests, COPD exacerbation, symptom scores, and radiologic findings were evaluated. Sex-related differences in the annual FEV1 change over 5 years were analyzed in a linear mixed model. Results: Of the 2515 patients enrolled in this study, 8.1% were female. Female patients who had a higher BMI and a lower level of education were less likely to be smokers, were more exposed to passive smoking/biomass, and were more depressed compared to males. The rates of bronchiectasis, previous childhood respiratory infection, and asthma were higher in females. Female patients also had more symptoms and a poorer exercise capacity than males, but no significant differences were observed in terms of exacerbations. Radiologic findings revealed that male patients had worse emphysema, and female patients had worse bronchiectasis, as determined based on chest X-ray and computed tomography findings. On pulmonary function tests, female patients had less obstruction and less annual FEV1 loss over 5 years. Conclusion: This study revealed differences in the clinical parameters between male and female patients with COPD, including general characteristics, disease characteristics, and clinical outcomes.

Prevalence of chronic cough and possible causes in the general population based on the Korean National Health and Nutrition Examination Survey.

Although chronic cough is very common, its prevalence and causes have been rarely reported in the large general population including smokers. This study aimed to identify the prevalence of possible causes of chronic cough and their clinical impact.From Korean National Health and Nutrition Examination Survey (KNHANES) data including 119,280 adults aged over 40 years, 302 individuals with chronic cough were recruited irrespective of smoking status. Data from questionnaire, laboratory tests including spirometry, chest radiographs, and otorhinolaryngologic examination were analyzed.The prevalence of chronic cough in adults was 2.5% ±â€Š0.2%. Current smokers occupied 47.7% ±â€Š3.8% of study population and 46.8% ±â€Š3.9% of the subjects showed upper airway cough syndrome (UACS). Based on spirometry, chronic obstructive pulmonary disease (COPD) was identified in 26.4% ±â€Š3.5%. Asthma explained for 14.5% ±â€Š2.8% of chronic cough. Only 4.1% ±â€Š1.6% showed chronic laryngitis suggesting gastro-esophageal reflux-related cough. Abnormalities on chest radiography were found in 4.0% ±â€Š1.2%. Interestingly, 50.3% ±â€Š4.5% of study subjects had coexisting causes. In multivariate analysis, only current smoking (odds ratio [OR] 3.16, P < 0.001), UACS (OR 2.50, P < 0.001), COPD (OR 2.41, P < 0.001), asthma (OR 8.89, P < 0.001), and chest radiographic abnormalities (OR 2.74, P = 0.003) were independent risk factor for chronic cough. This pattern was not different according to smoking status excepting the prevalence of COPD.Smoking, COPD, and chest radiographic abnormalities should be considered as causes of chronic cough, along with UACS and asthma. Gastro-esophageal reflux-related cough is not prevalent in study population.

Association of the Neutrophil-to-Lymphocyte Ratio with Lung Function and Exacerbations in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: The ratio of neutrophils to lymphocytes (NLR) is a widely available marker of inflammation. Several types of inflammatory cells and mediators have been found to be involved in the progression of chronic obstructive pulmonary disease (COPD). We sought to evaluate the association of the NLR with severity of airflow limitation and disease exacerbations in a COPD population. METHODS: We analyzed 885 patients from the Korean COPD Subtype Study cohort that recruited subjects with COPD from 44 referral hospitals. We determined the relationship of NLR levels to severity of lung function using a linear regression model. In addition, we analyzed the experiences of COPD exacerbation according to the NLR quartiles. RESULTS: NLR levels were inversely associated with severity of airflow limitation as measured by FEV1% predicted and absolute values after adjustments for age, gender, body mass index, pack-years of smoking, and the use of inhaled corticosteroid (P<0.001, respectively). In the multivariate binary regression model, the NLR 4th quartile (vs. 1st quartile) was found to be a significant predictor of exacerbations during 1-year follow-up (OR = 2.05, 95% CI = 1.03 to 4.06, P = 0.041). Adding an NLR to FEV1 significantly improved prediction for exacerbations during 1-year follow-up as measured by the net reclassification improvement (NRI = 7.8%, P = 0.032) and the integrated discrimination improvement (IDI = 0.014, P = 0.021). CONCLUSIONS: The NLR showed a significant inverse relationship to airflow limitation and was a prognostic marker for future exacerbations in patients with COPD.

The Korean Cough Guideline: Recommendation and Summary Statement.

Cough is one of the most common symptom of many respiratory diseases. The Korean Academy of Tuberculosis and Respiratory Diseases organized cough guideline committee and cough guideline was developed by this committee. The purpose of this guideline is to help clinicians to diagnose correctly and treat efficiently patients with cough. In this article, we have stated recommendation and summary of Korean cough guideline. We also provided algorithm for acute, subacute, and chronic cough. For chronic cough, upper airway cough syndrome (UACS), cough variant asthma (CVA), and gastroesophageal reflux disease (GERD) should be considered. If UACS is suspicious, first generation anti-histamine and nasal decongestant can be used empirically. In CVA, inhaled corticosteroid is recommended in order to improve cough. In GERD, proton pump inhibitor is recommended in order to improve cough. Chronic bronchitis, bronchiectasis, bronchiolitis, lung cancer, aspiration, angiotensin converting enzyme inhibitor, habit, psychogenic cough, interstitial lung disease, environmental and occupational factor, tuberculosis, obstructive sleep apnea, peritoneal dialysis, and idiopathic cough can be also considered as cause of chronic cough. Level of evidence for treatment is mostly low. Thus, in this guideline, many recommendations are based on expert opinion. Further study regarding treatment for cough is mandatory.

Factors that Predict Negative Results of QuantiFERON-TB Gold In-Tube Test in Patients with Culture-Confirmed Tuberculosis: A Multicenter Retrospective Cohort Study.

BACKGROUND: Interferon-γ release assays such as the QuantiFERON-TB Gold In-Tube Test (QFT-GIT) are designed to detect Mycobacterium tuberculosis infections, whether latent or manifesting as disease. However, a substantial number of persons with culture-confirmed tuberculosis (TB) have negative QFT-GITs. Information on host factors contributing to false-negative and indeterminate results are limited. METHODS: A multicenter retrospective cohort study was performed with 1,264 culture-confirmed TB patients older than 18 years who were subjected to the QFT-GIT at one of the six hospitals between May 2007 and February 2014. Patients with human immunodeficiency virus infection were excluded. Clinical and laboratory data were collected in South Korea. RESULTS: Of all patients, 87.6% (1,107/1,264) were diagnosed with pulmonary TB and 12.4% (157/1,264) with extrapulmonary TB. The rate of negative results was 14.4% (182/1,264). The following factors were highly correlated with false-negative results in the QFT-GIT: advanced age (age ≥ 65 years, odds ratio [OR] 1.57, 95% confidence interval [CI] 1.03-2.39), bilateral disease as determined by chest radiography (OR 1.75, 95% CI 1.13-2.72), malignancy (OR 2.42, 95% CI 1.30-4.49), and lymphocytopenia (total lymphocyte count < 1.0 × 109/L, OR 1.86, 95% CI 1.21-2.87). CONCLUSIONS: Consequently, QFT-GIT results need to be interpreted with caution in patients with these host risk factors such as the elderly, bilateral disease on chest radiography, or malignancy, or lymphocytopenia.

Risk factors for death during pulmonary tuberculosis treatment in Korea: a multicenter retrospective cohort study.

The data regarding risk factors for death during tuberculosis (TB) treatment are inconsistent, and few studies examined this issue in Korea. The purpose of this study was to evaluate baseline prognostic factors for death during treatment of adult patients with pulmonary TB in Korea. A multicenter retrospective cohort study of 2,481 patients who received TB treatment at eight hospitals from January 2009 to December 2010 was performed. Successful treatment included cure (1,129, 45.5%) and treatment completion (1,204, 48.5%) in 2,333 patients (94.0%). Unsuccessful treatment included death (85, 3.4%) and treatment failure (63, 2.5%) occurred in 148 patients (6.0%). In multivariate analysis, male sex, anemia, dyspnea, chronic heart disease, malignancy, and intensive care unit (ICU) admission were significant risk factors for death during TB treatment. Therefore, male sex, anemia, dyspnea, chronic heart disease, malignancy, and ICU admission could be baseline prognostic factors for death during treatment of adult patients with pulmonary TB in Korea.

Pleomorphic adenoma presenting with a mediastinal mass.

Pleomorphic adenoma is the most common type of salivary gland tumor. Although it rarely affects the trachea and bronchus, it usually grows in the airway and presents as an endobronchial mass. We recently experienced a case of pleomorphic adenoma originating in the bronchus and growing outward into the mediastinum. We present this case with review of the computed tomography (CT) scan of the patient's chest, the endoscopic ultrasound (EUS), and the histopathology report.

Gastric tuberculosis presenting with a huge abdominal mass.

Tuberculosis of the stomach is extremely rare. We report the case of a 38-year-old woman who presented with epigastric discomfort and a palpable mass that persisted for a period of one month. We also report our findings from the abdominal computed tomographic, upper endoscopic and endoscopic ultrasonographic examinations of the patient. Abdominal computed tomography (CT) showed the presence of a large mass with an irregularly contoured low attenuation lesion. Upper endoscopy and endoscopic ultrasonography revealed a protruding ulcerative mass with an ill-defined heteroechoic subepithelial lesion originating from the gastric submucosal layer. This was previously misdiagnosed as a gastrointestinal stromal tumour. Endoscopic biopsy specimen was positive on acid-fast bacillus staining, and polymerase chain reaction for Mycobacterium tuberculosis was also positive. Abdominal CT and endoscopy at the patient's three-month follow-up showed near complete resolution of the lesion.

Clinical significance of incidental thyroid nodules identified on low-dose CT for lung cancer screening.

BACKGROUND: Incidental thyroid nodules (ITNs) are defined as newly encountered nodules identified on imaging performed for an unrelated purpose. In practice, ITNs are often detected on chest computed tomography (CT). We investigated the prevalence and clinical significance of ITNs detected on low-dose chest CT (LDCT) for lung cancer screening. METHODS: We retrospectively reviewed the electronic medical records of patients with no history of thyroid disease who underwent LDCT for lung cancer screening between March 2009 and February 2012 at Jeju National University Hospital (Korea). RESULTS: Among 1,941 patients that underwent LDCT, 55(2.8%) were found to have ITNs. Seven (12.7%) of those cases were malignant. The positive and negative predictive values of chest LDCT for the detection of incidental malignant thyroid nodules were 26.9% and 73.4%, respectively. Factors considered to be predictive of malignancy on LDCT were a mean attenuation value of 55 HU or more (p = 0.036) and the presence of dense calcifications (p = 0.048). Sex, age, location of the nodule, longest diameter of the lesion, AP/T (anteroposterior/transverse dimension) ratio, margins, density, presence of punctate calcifications, and thyroid enlargement had no significant predictive value in discriminating benign and malignant nodules. On multivariate analyses, a mean attenuation value above 55 was the only statistically significant feature (p = 0.048). CONCLUSIONS: A mean attenuation value greater than 55 HU on LDCT may be a useful predictive factor for differentiating malignant from benign lesions. Therefore, a careful assessment of the thyroid gland is necessary for patients undergoing LDCT for lung cancer screening.

Multiple endotracheal and endobronchial metastases after pneumonectomy for a primary lung cancer: A case report.

Endotracheal metastasis of primary lung cancer is extremely rare. We report the case of a 51-year-old male patient who had undergone right pneumonectomy for squamous cell carcinoma one year earlier. The post-operative chest computed tomography (CT) image revealed a very small endotracheal nodule with contrast enhancement. This finding was erroneously regarded as endotracheal phlegm because of the nodular size and the rarity of endotracheal metastases from primary lung cancer. This case indicates that a thorough evaluation should be performed with a high level of suspicion for malignancy when a nodule-like lesion with contrast enhancement or tracheal thickening is detected on follow-up CT scan, in patients who undergo surgery for lung cancer.

Comparison of clinical characteristics between healthcare-associated pneumonia and community-acquired pneumonia in patients admitted to secondary hospitals

BACKGROUND: Since healthcare-associated pneumonia (HCAP) is heterogeneous, clinical characteristics and outcomes are different from region to region. There can also be differences between HCAP patients hospitalized in secondary or tertiary hospitals. This study aimed to evaluate the clinical characteristics of HCAP patients admitted into secondary community hospitals. METHODS: This was a retrospective study conducted in patients with HCAP or community-acquired pneumonia (CAP) hospitalized in two secondary hospitals between March 2009 and January 2011. RESULTS: Of a total of 303 patients, 96 (31.7%) had HCAP. 42 patients (43.7%) resided in a nursing home or long-term care facility, 36 (37.5%) were hospitalized in an acute care hospital for > 2 days within 90 days, ten received outpatient intravenous therapy, and eight attended a hospital clinic or dialysis center. HCAP patients were older. The rates of patients with CURB65 scores of 3 or more (22.9% vs. 9.1%; p = 0.001) and PSI class IV or more (82.2% vs. 34.7%; p < 0.001) were higher in the HCAP group. Drug-resistant pathogens were more frequently detected in the HCAP group (23.9% vs. 0.4%; p < 0.001). However, Streptococcus pneumoniae was the most common pathogen in both groups. The rates of antibiotic change, use of inappropriate antibiotics, and failure of initial antibiotic therapy in the HCAP group were significantly higher. Although the overall survival rate of the HCAP group was significantly lower (82.3% vs. 96.8%; p < 0.001), multivariate analyses failed to show that HCAP itself was a prognostic factor for mortality (p = 0.826). Only PSI class IV or more was associated with increased mortality (p = 0.005). CONCLUSIONS: HCAP should be distinguished from CAP because of the different clinical features. However, the current definition of HCAP does not appear to be a prognostic for death. In addition, the use of broad-spectrum antibiotics for HCAP should be reassessed because S. pneumoniae was most frequently identified even in HCAP patients.

Two cases of pulmonary and pleural sparganosis confirmed by tissue biopsy and immunoserology.

Sparganosis in humans is an incidental infection and is known to be associated with eating insufficiently cooked meat of frogs and snakes or drinking unboiled stream water. Although it can involve various internal organs, pulmonary and pleural involvement due to sparganum is rare. Because we recently experienced two cases involving lung parenchyma and pleura that were misdiagnosed as bacterial pneumonia and lung cancer, we herein intend to present them in detail.

Two cases of pulmonary and pleural sparganosis confirmed by tissue biopsy and immunoserology

Sparganosis in humans is an incidental infection and is known to be associated with eating insufficiently cooked meat of frogs and snakes or drinking unboiled stream water. Although it can involve various internal organs, pulmonary and pleural involvement due to sparganum is rare. Because we recently experienced two cases involving lung parenchyma and pleura that were misdiagnosed as bacterial pneumonia and lung cancer, we herein intend to present them in detail.

The immunohistochemical overexpression of ribonucleotide reductase regulatory subunit M1 (RRM1) protein is a predictor of shorter survival to gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC).

We evaluated whether ribonucleotide reductase regulatory subunit M1 (RRM1) protein expression by immunohistochemistry (IHC) is a predictor of survival and response in gemcitabine-treated, advanced non-small cell lung cancer (NSCLC). We retrospectively collected 40 formalin-fixed, paraffin-embedded NSCLC tissues to investigate the protein expression of RRM1 by IHC with a purified rabbit anti-human RRM1 polyclonal antibody (ProteinTech Group, Chicago, IL, USA). RRM1 expression was positive in 14 (35%) and negative in 26 (65%) cases. Ten (25%) patients were treated as first-line and 30 (75%) patients as second-line. The median age was 61 years and M/F was 31/9. Stage IIIB/IV was 7/33 and adenocarcinoma/squamous cell carcinoma/other cell type was 20/16/4. Other characteristics, including age, gender, stage, cell type and first/second-line were not statistically different in the RRM-positive and RRM-negative groups. The overall survival of RRM1-positive groups was significantly shorter than RRM-negative groups (5.1 months vs. 12.9 months, p = 0.022). The response rates of 38 out of 40 patients were assessable. Disease control rate (PR+SD) of the RRM1-positive groups was significantly lower than that of RRM1-negative groups (23% vs. 56%, p = 0.053). In patients with gemcitabine-treated advanced NSCLC, patients with RRM1-positive tumors had worse overall survival and disease control than patients with RRM1-negative tumors.

The use of etanercept in a patient with disseminated tuberculosis.

Tumor necrosis factor (TNF) is a central regulator of chronic inflammatory diseases and plays a major role in the host immune system against tuberculosis (TB). TNF antagonists, infliximab and etanercept are effective in treating chronic inflammatory diseases by inhibiting TNF, but increase the risk of TB as a result of immunosuppression. Previous studies have shown that the risk of TB is greater in patients who received infliximab than in those who received etanercept and several hypotheses on the action mechanisms of the two agents have been presented in order to explain this difference in the risk of TB. As the clinical use of TNF antagonists increase, the incidence rate of TB may increase. Therefore, it is necessary that clinicians considering the use of TNF antagonists pay much attention to the prevention and control of TB and understand the mechanisms of action of the TNF antagonists. This case shows that etanercept treatment can be safely administered during the treatment of TB. In the future, additional studies will be needed to determine the safety of etanercept and the optimal time for the administration of etanercept during the TB treatment.