Risk Factors for Unfavorable Outcomes of Tuberculosis in Korea: Implications for Patient-Centered Care in Tuberculosis Treatment.

BACKGROUND: The treatment success rate for tuberculosis (TB) has stagnated at 80-81% in South Korea, indicating unsatisfactory outcomes. Enhancing treatment success rate necessitates the development of individualized treatment approaches for each patient. This study aimed to identify the risk factors associated with unfavorable treatment outcomes to facilitate tailored TB care. METHODS: We retrospectively analyzed the data of patients with active TB between January 2019 and December 2020 at a single tertiary referral center. We classified unfavorable treatment outcomes according to the 2021 World Health Organization guidelines as follows: "lost to follow-up" (LTFU), "not evaluated" (NE), "death," and "treatment failure" (TF). Moreover, we analyzed risk factors for each unfavorable outcome using Cox proportional hazard regression analysis. RESULTS: A total of 659 patients (median age 62 years; male 54.3%) were included in the study. The total unfavorable outcomes were 28.1%: 4.6% LTFU, 9.6% NE, 9.1% deaths, and 4.9% TF. Multivariate analysis showed that a culture-confirmed diagnosis of TB was associated with a lower risk of LTFU (adjusted hazard ratio [aHR], 0.25; 95% confidence interval [CI], 0.10-0.63), whereas the occurrence of adverse drug reactions (ADRs) significantly increased the risk of LTFU (aHR, 6.63; 95% CI, 2.63-16.69). Patients living far from the hospital (aHR, 4.47; 95% CI, 2.50-7.97) and those with chronic kidney disease (aHR, 3.21; 95% CI, 1.33-7.75) were at higher risk of being transferred out to other health institutions (NE). Higher mortality was associated with older age (aHR, 1.06; 95% CI, 1.04-1.09) and comorbidities. The ADRs that occurred during TB treatment were a risk factor for TF (aHR, 6.88; 95% CI, 2.24-21.13). CONCLUSION: Unfavorable outcomes of patients with TB were substantial at a tertiary referral center, and the risk factors for each unfavorable outcome varied. To improve treatment outcomes, close monitoring and the provision of tailored care for patients with TB are necessary.

Clinical Characteristics and Treatment Outcomes of Pulmonary Diseases Caused by Coinfections With Multiple Nontuberculous Mycobacterial Species.

BACKGROUND: Coinfections with multiple nontuberculous mycobacterial (NTM) species have not been widely studied. We aimed to evaluate the clinical characteristics and treatment outcomes in patients with NTM-pulmonary disease (PD) caused by coinfection with multiple NTM species. METHODS: We retrospectively reviewed patients with NTM-PD at a tertiary referral hospital in Korea between March 2012 and December 2018. Coinfection was defined as two or more species of NTM pathogens isolated from the same respiratory specimen or different specimens within three months. RESULTS: Among 1,009 patients with NTM-PD, 147 (14.6%) NTM coinfections were observed (average age 64.7 years, 69.4% women). NTM species were identified more frequently (median 6 vs. 3 times, P < 0.001) in the coinfection group than in the single species group, and follow-up duration was also longer in the coinfection group (median 44.9 vs. 27.1 months, P < 0.001). Mycobacterium avium complex (MAC) and M. abscessus and M. massiliense (MAB) were the dominant combinations (n = 71, 48.3%). For patients treated for over six months in the MAC plus MAB group (n = 31), sputum culture conversion and microbiological cure were achieved in 67.7% and 41.9% of patients, respectively. We divided the MAC plus MAB coinfection group into three subgroups according to the target mycobacteria; however, no statistical differences were found in the treatment outcomes. CONCLUSION: In NTM-PD cases, a significant number of multiple NTM species coinfections occurred. Proper identification of all cultured NTM species through follow-up is necessary to detect multispecies coinfections. Further research is needed to understand the nature of NTM-PD in such cases.

Clinical impact of pneumothorax in patients with Pneumocystis jirovecii pneumonia and respiratory failure in an HIV-negative cohort.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) with acute respiratory failure can result in development of pneumothorax during treatment. This study aimed to identify the incidence and related factors of pneumothorax in patients with PCP and acute respiratory failure and to analyze their prognosis. METHODS: We retrospectively reviewed the occurrence of pneumothorax, including clinical characteristics and results of other examinations, in 119 non-human immunodeficiency virus patients with PCP and respiratory failure requiring mechanical ventilator treatment in a medical intensive care unit (ICU) at a tertiary-care center between July 2016 and April 2019. RESULTS: During follow up duration, twenty-two patients (18.5%) developed pneumothorax during ventilator treatment, with 45 (37.8%) eventually requiring a tracheostomy due to weaning failure. Cytomegalovirus co-infection (odds ratio 13.9; p = 0.013) was related with occurrence of pneumothorax in multivariate analysis. And development of pneumothorax was not associated with need for tracheostomy and mortality. Furthermore, analysis of survivor after 28 days in ICU, patients without pneumothorax were significantly more successful in weaning from mechanical ventilator than the patients with pneumothorax (44% vs. 13.3%, p = 0.037). PCP patients without pneumothorax showed successful home discharges compared to those who without pneumothorax (p = 0.010). CONCLUSIONS: The development of pneumothorax increased in PCP patient with cytomegalovirus co-infection, pneumothorax might have difficulty in and prolonged weaning from mechanical ventilators, which clinicians should be aware of when planning treatment for such patients.

Long- and short-term clinical impact of awake extracorporeal membrane oxygenation as bridging therapy for lung transplantation.

BACKGROUND: As lung transplantation (LTx) is becoming a standard treatment for end-stage lung disease, the use of bridging with extracorporeal membrane oxygenation (ECMO) is increasing. We examined the clinical impact of being awake during ECMO as bridging therapy in patients awaiting LTx. METHODS: In this single-center study, we retrospectively reviewed 241 consecutive LTx patients between October 2012 and March 2019; 64 patients received ECMO support while awaiting LTx. We divided into awake and non-awake groups and compared. RESULTS: Twenty-five patients (39.1%) were awake, and 39 (61.0%) were non-awake. The median age of awake patients was 59.0 (interquartile range, 52.5-63.0) years, and 80% of the group was men. The awake group had better post-operative outcomes than the non-awake group: statistically shorter post-operative intensive care unit length of stay [awake vs. non-awake, 6 (4-8.5) vs. 18 (11-36), p < 0.001], longer ventilator free days [awake vs. non-awake, 24 (17-26) vs. 0 (0-15), p < 0.001], and higher gait ability after LTx (awake vs. non-awake, 92% vs. 59%, p = 0.004), leading to higher 6-month and 1-year lung function (forced expiratory volume in 1 s: awake vs. non-awake, 6-month, 77.5% vs. 61%, p = 0.004, 1-year, 75% vs. 57%, p = 0.013). Furthermore, the awake group had significantly lower 6-month and 1-year mortality rates than the non-awake group (6-month 12% vs. 38.5%, p = 0.022, 1-year 24% vs. 53.8%, p = 0.018). CONCLUSIONS: In patients with end-stage lung disease, considering the long-term and short-term impacts, the awake ECMO strategy could be useful compared with the non-awake ECMO strategy.

Relationship of the lung microbiome with PD-L1 expression and immunotherapy response in lung cancer.

BACKGROUND: Lung cancer is the primary cause of cancer-related deaths worldwide. The human lung serves as a niche to a unique and dynamic bacterial community that is related to the development of multiple diseases. Here, we investigated the differences in the lung microbiomes of patients with lung cancer. METHODS: 16S rRNA sequencing was performed to evaluate the respiratory tract microbiome present in the bronchoalveolar lavage fluid. Patients were stratified based on programmed death-ligand 1 (PD-L1) expression levels and immunotherapy responses. RESULTS: In total, 84 patients were prospectively analyzed, of which 59 showed low (< 10%), and 25 showed high (≥ 10%) PD-L1 expression levels. The alpha and beta diversities did not significantly differ between the two groups. Veillonella dispar was dominant in the high-PD-L1 group; the population of Neisseria was significantly higher in the low-PD-L1 group than in the high-PD-L1 group. In the immunotherapy responder group, V. dispar was dominant, while Haemophilus influenzae and Neisseria perflava were dominant in the non-responder group. CONCLUSION: The abundances of Neisseria and V. dispar differed significantly in relation to PD-L1 expression levels and immunotherapy responses.

The ratio of plasma angiopoietin-2 to angiopoietin-1 as a prognostic biomarker in patients with sepsis.

BACKGROUND: We aimed to investigate the role of angiopoietin (Angpt) as a predictive biomarker for sepsis by evaluating associations between plasma Angpt and various inflammatory cytokines and mortality in critically ill patients with sepsis. METHODS: This study was a retrospective cohort study of the prospectively collected samples and clinical data of 145 patients with sepsis who were admitted to the medical intensive care unit (ICU) of a 2000-bed university tertiary referral hospital in South Korea. We collected plasma within 24 h of medical ICU admission, and several biomarkers (Angpt-1 and -2, Tie2, vascular endothelial growth factor, interleukin (IL)-1ß, IL-10, IL-18, IL-6, interferon gamma-induced protein-10, and tumor necrosis factor-α) were measured using a Human Magnetic Luminex Screening Assay kit. RESULTS: Plasma Angpt-2 was correlated with IL-6 (rs = 0.555) and tumor necrosis factor-α (rs = 0.559). Plasma Angpt-2 (rs = 0.530) and Angpt-2/1 (rs = 0.562) were correlated with the Sequential Organ Failure Assessment (SOFA) score. The area under the curve (AUC) for the 28-day mortality prediction for the plasma Angpt-2/1 ratio was 0.736; AUCs for the Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 0.659 and 0.745, respectively. Using multivariate Cox proportional hazard regression analysis for 28-day mortality, we found that acute respiratory distress syndrome (hazard ratio (HR) = 2.235, 95% CI = 1.163-4.296,p = 0.016), APACHE II score (HR = 1.127, 95% CI = 1.037-1.224,p = 0.005), and Angpt-2/1 > 3.2 (HR = 2.522, 95% CI = 1.205-5.278,p = 0.014) were risk factors for 28-day mortality. CONCLUSIONS: Plasma Angpt-2 was related to cytokines, but Angpt-2/1 ratio was a good predictor of 28-day mortality in patients with sepsis.

Spatial profiling of non-small cell lung cancer provides insights into tumorigenesis and immunotherapy response.

Lung cancer is the second most common cancer worldwide and a leading cause of cancer-related deaths. Despite advances in targeted therapy and immunotherapy, the prognosis remains unfavorable, especially in metastatic cases. This study aims to identify molecular changes in non-small cell lung cancer (NSCLC) patients based on their response to treatment. Using tumor and matched immune cell rich peritumoral tissues, we perform a retrospective, comprehensive spatial transcriptomic analysis of a proven malignant NSCLC sample treated with immune checkpoint inhibitor (ICI). In addition to T cells, other immune cell types, such as B cells and macrophages, were also activated in responders to ICI treatment. In particular, B cells and B cell-mediated immunity pathways are consistently found to be activated. Analysis of the histologic subgroup (lung squamous cell carcinoma, LUSC; lung adenocarcinoma, LUAD) of NSCLC also confirms activation of B cell mediated immunity. Analysis of B cell subtypes shows that B cell subtypes were more activated in immune cell-rich tissues near tumor tissue. Furthermore, increased expression of B cell immunity-related genes is associated with better prognosis. These findings provide insight into predicting ICI treatment responses and identifying appropriate candidates for immunotherapy in NSCLC patients.

Factors affecting accuracy of clinical staging in resectable non-small cell lung cancer in a real-world study.

BACKGROUND: The clinical staging of non-small cell lung cancer (NSCLC) is well known to be related to their prognosis. However, there is usually a discrepancy between clinical staging and pathological staging. There are few analyses of clinical staging accuracy in patients with NSCLC. We compared the concordance rate between clinical and pathological staging of NSCLC and evaluated factors affecting the accuracy in real-world data. METHODS: Altogether, 811 patients with primary NSCLC who had undergone curative lung resection surgery in Severance Hospital from January 2019 to December 2020 were retrospectively reviewed. We used the eighth edition of the American Joint Committee on Cancer TNM staging. RESULTS: Among 811 patients, endobronchial ultrasound (EBUS) and positron emission tomography (PET-CT) were performed in 31.6% and 96.7%, respectively. The concordance rates between clinical and pathological TNM staging, T factor, and N factor, were 68.7%, 77.7%, and 85.8%, respectively. With multivariable logistic regression analysis, current smokers (OR 0.49; 95% CI: 0.32-0.76, p = 0.001) and a higher clinical stage (p < 0.001) contributed to the clinical staging inaccuracy. Additionally, the presence of a bronchoscopy specialist was significantly associated with clinical staging accuracy (OR 1.53; 95% CI: 1.10-2.13, p = 0.011). CONCLUSION: Clinical staging accuracy in NSCLC improved compared to before the widespread use of PET-CT and EBUS in clinical staging work-up. Smoking history and absence of expert bronchoscopy specialists showed a meaningful correlation with the inaccuracy of clinical staging. Thus, training more bronchoscopy experts would improve the staging accuracy of NSCLC, which could positively affect the prognosis of NSCLC.

Malnutrition is associated with mortality in Sjögren's syndrome-associated interstitial lung disease.

The role of nutritional status as a prognostic factor in patients with Sjögren's syndrome-associated interstitial lung disease (SjS-ILD) is currently unclear. This study aimed to predict the prognosis of patients with SjS-ILD through their nutritional status assessment. In this retrospective observational study, nutritional status was evaluated at the time of diagnosis using body mass index (BMI) and nutritional markers such as controlling nutritional status (CONUT), the Glasgow prognostic score (GPS), and prognostic nutrition index (PNI) for all participants. Receiver operating characteristic (ROC) analyses were performed using BMI and each nutritional marker data to compare the area under the ROC curve (AUC) and find the cutoff value using the maximum Youden index. Kaplan-Meier analysis and Cox proportional hazards regression analysis were performed to predict the prognosis of SjS-ILD patients. A total of 112 SjS-ILD patients were enrolled in the study, and 8.9% died during the follow-up period. The median time from diagnosis to follow-up period was 4.2 years. The AUC for PNI was the highest among nutritional markers and BMI, and PNI cutoff value was used to distinguish between the PNI < 47.7 and PNI ≥ 47.7 groups. A statistical difference was observed in the Kaplan-Meier analysis and log-rank test (p = 0.005). In multivariable analyses, PNI < 47.7 (hazard ratio 9.40, 95% confidence interval 1.54-57.21) is associated with increased mortality, suggesting the importance of early nutritional intervention for malnutrition in SjS-ILD patients.

New Targeted Therapy for Non-Small Cell Lung Cancer.

Lung cancer ranks first in cancer mortality in Korea and cancer incidence in Korean men. More than half of Korean lung cancer patients undergo chemotherapy, including adjuvant therapy. Cytotoxic agents, targeted therapy, and immune checkpoint inhibitors are used in chemotherapy according to the biopsy and genetic test results. Among chemotherapy, the one that has developed rapidly is targeted therapy. The National Comprehensive Cancer Network (NCCN) guidelines have been updated recently for targeted therapy of multiple gene mutations, and targeted therapy is used not only for chemotherapy but also for adjuvant therapy. While previously targeted therapies have been developed for common genetic mutations, recently targeted therapies have been developed to overcome uncommon mutations or drug resistance that have occurred since previous targeted therapy. Therefore, this study describes recent, rapidly developing targeted therapies.

Usefulness of bronchial washing fluid for detection of EGFR mutations in non-small cell lung cancer.

INTRODUCTION: The implementation of bronchial washing fluid (BWF) as a diagnostic specimen may complement the low diagnostic yields of plasma in detecting EGFR mutation (mEGFR) in non-small cell lung cancer. However, the diagnostic value of BWF in detecting mEGFR has yet to be clarified. MATERIALS AND METHODS: From March 2021 to August 2022, patients with histologically confirmed NSCLC with matched tumor tissue, BWF, and/or plasma samples were enrolled. Patients were classified into either initial diagnosis or rebiopsy groups. Diagnostic yields of mEGFR in BWF and plasma were evaluated using droplet digital polymerase chain reaction and compared to mEGFR in tumor tissue as standard. RESULTS: The study included 123 patients (74.1 %) in the initial diagnosis and 43 patients (25.9 %) in the rebiopsy group. BWF showed higher sensitivity, specificity, and concordance rates than plasma in both the initial diagnosis (57.4 %, 96.4 %, and 74.0 % vs. 16.4 %, 96.2 %, and 53.1 %) and the rebiopsy group (87.9 %, 60.0 %, and 81.4 % vs. 25.0 %, 75.0 %, and 41.7 %). In the initial diagnosis group, mEGFR was detected in the BWF of 13 out of 16 patients, even in the absence of tumor cells in the tissue biopsy. In these cases, EGFR test results obtained from BWF showed concordance with EGFR test results from the tumor tissue obtained through repeated biopsy or surgery later. In the rebiopsy group, T790M was detected in 16 patients (37.2 %) by tissue biopsy. The combined use of tissue biopsy and BWF increased detection, confirming T790M in 22 patients (51.2 %). DISCUSSION: The detection of mEGFR using BWF shows higher diagnostic yields than plasma for both initial diagnosis and rebiopsy. T790M was detected earlier in BWF than in tissue rebiopsy in some cases, providing patients with an early opportunity to access third-generation EGFR-TKIs. The complementary use of BWF with tumor tissue may improve precision in EGFR-mutated NSCLC treatment strategies.

Clinical features and molecular genetics associated with brain metastasis in suspected early-stage non-small cell lung cancer.

Introduction: Regarding whether brain magnetic resonance imaging (MRI) should be routine in patients with suspected early-stage lung cancer, guideline recommendations are inconsistent. Therefore, we performed this study to evaluate the incidence of and risk factors for brain metastasis (BM) in patients with suspected early-stage non-small-cell lung cancer (NSCLC). Methods: A review of the medical charts of consecutive NSCLC patients diagnosed between January 2006 and May 2020 was performed. We identified 1,382 NSCLC patients with clinical staging of T1/2aN0M0 (excluding BM), and investigated the incidence, clinical predictors, and prognosis of BM in the cohort. We also performed RNA-sequencing differential expression analysis using transcriptome of 8 patients, using DESeq2 package (version 1.32.0) with R (version 4.1.0). Results: Among 1,382 patients, nine hundred forty-nine patients (68.7%) underwent brain MRI during staging, and 34 patients (3.6%) were shown to have BM. Firth's bias-reduced logistic regression showed that tumor size (OR 1.056; 95% CI 1.009-1.106, p=0.018) was the only predictor of BM, and pathologic type was not a predictor of BM in our cohort (p>0.05). The median overall survival for patients with brain metastasis was 5.5 years, which is better than previously reported in the literature. RNA-sequencing differential expression analysis revealed the top 10 significantly upregulated genes and top 10 significantly downregulated genes. Among the genes involved in BM, Unc-79 homolog, non-selective sodium leak channel (NALCN) channel complex subunit (UNC79) was the most highly expressed gene in the lung adenocarcinoma tissues from the BM group, and an in vitro assay using A549 cells revealed that the NALCN inhibitor suppressed lung cancer cell proliferation and migration. Conclusions: Given the incidence and favorable outcome of BM in patients with suspected early-stage NSCLC, selective screening with brain MRI may be considered, especially in patients with high-risk features.

Aspergillus Galactomannan Titer as a Diagnostic Marker of Invasive Pulmonary Aspergillosis in Lung Transplant Recipients: A Single-Center Retrospective Cohort Study.

Invasive pulmonary aspergillosis (IPA) can occur in immunocompromised patients, and an early detection and intensive treatment are crucial. We sought to determine the potential of Aspergillus galactomannan antigen titer (AGT) in serum and bronchoalveolar lavage fluid (BALF) and serum titers of beta-D-glucan (BDG) to predict IPA in lung transplantation recipients, as opposed to pneumonia unrelated to IPA. We retrospectively reviewed the medical records of 192 lung transplant recipients. Overall, 26 recipients had been diagnosed with proven IPA, 40 recipients with probable IPA, and 75 recipients with pneumonia unrelated to IPA. We analyzed AGT levels in IPA and non-IPA pneumonia patients and used ROC curves to determine the diagnostic cutoff value. The Serum AGT cutoff value was 0.560 (index level), with a sensitivity of 50%, specificity of 91%, and AUC of 0.724, and the BALF AGT cutoff value was 0.600, with a sensitivity of 85%, specificity of 85%, and AUC of 0.895. Revised EORTC suggests a diagnostic cutoff value of 1.0 in both serum and BALF AGT when IPA is highly suspicious. In our group, serum AGT of 1.0 showed a sensitivity of 27% and a specificity of 97%, and BALF AGT of 1.0 showed a sensitivity of 60% and a specificity of 95%. The result suggested that a lower cutoff could be beneficial in the lung transplant group. In multivariable analysis, serum and BALF AGT, with a minimal correlation between the two, showed a correlation with a history of diabetes mellitus.

Characteristics and risk factors of mortality in patients with systemic sclerosis-associated interstitial lung disease.

BACKGROUND: Systemic sclerosis (SSc) is a heterogeneous autoimmune disease characterized by dysregulation of fibroblast function, which often involves the lungs. Interstitial lung disease (ILD) associated with SSc (SSc-ILD) is a major cause of death among patients with SSc. Our study aimed to identify risk factors for mortality and compare the clinical characteristics of patients with SSc-ILD. PATIENTS AND METHODS: Patients were retrospectively enrolled between 2010 and 2018 in a tertiary hospital in Korea. Patients with SSc-ILD were classified depending on the first pulmonary function test or radiologic findings: extensive (n = 46, >20% disease extent on computed tomography (CT) or forced vital capacity [FVC] < 70% in indeterminate cases) and limited (n = 60, <20% disease extent on CT or FVC ≥70% in indeterminate cases). RESULTS: Patients in the extensive group were younger (mean age ± SD 49.3 ± 11.5) than those in the limited group (53.9 ± 12.5, p = .067) at diagnosis. The extensive group showed frequent pulmonary hypertension (43.5% vs. 16.7%, p = .009) and higher erythrocyte sedimentation rate (61.3 ± 33.7 vs. 42.1 ± 26.0, p = .003) and mortality (32.6%, mean duration of follow-up, 100.0 ± 44.7 months vs. 10.0%, 86.0 ± 53.4 months, p = .011). ILD was detected within five years from the first visit (median years 3.5 (1.0, 6.0) vs. 4.5 (0.6, 9.0), survivors vs. non-survivors), and mortality occurred in 19.8% of all patients during a 15-year follow-up. Older age, lower FVC, and initial disease stage (limited or extensive) were associated with mortality, but FVC decline was similar in the limited and extensive groups, such as 15-20% in the first year and 8-10% in the next year, regardless of the initial extent of the disease. CONCLUSIONS: Approximately 10% of patients with SSc-ILD in the limited and extensive group showed progression. ILD was detected at a median of less than five years from the first visit; therefore, it is necessary to carefully monitor patients' symptoms and signs from an early stage. Long-term surveillance is also required.Key messagesPatients with systemic sclerosis-interstitial lung disease manifested a heterogeneous disease course.Approximately 10% of the patients in the limited group showed progression, which was similar to the proportion of patients in the extensive group.Interstitial lung disease was detected at a median of less than five years from the first visit.

Identification of nontuberculous mycobacteria isolated from household showerheads of patients with nontuberculous mycobacteria.

This study aimed to examine whether nontuberculous mycobacteria (NTM) inside household showerheads are identical to those in patients with NTM-pulmonary disease (PD) since household water is one of the potential NTM sources. Samples were obtained from 32 household showerheads of patients with NTM-PD recruited through the Pulmonary Outpatient Department at the Severance Hospital between October 2018 and October 2019. All isolates from patients with NTM-PD were diagnosed using a reverse-hybridization line probe assay based on the ropB gene. To determine the mycobacterial compositions, the washing fluids were collected and investigated using multiplex polymerase chain reaction assay and NTM culture; suspected microbial isolates in these fluids and culture were identified using sequencing analysis of 16S rRNA gene. NTM species causing the PD in the patients were Mycobacterium avium, M. intracellulare, M. abscessus, M. massiliense, and M. fortuitum complex. The mycobacteria isolated from the showerhead were M. lentiflavum, M. gordonae, M. triplex, M. phocaicum, M. mucogenicum, M. florentinum, M. gilvum, M. llatzerense, and M. peregrinum. However, the species identified in the showerheads did not match those of the patients. Despite NTM species in the showerheads, clinical implications in the main pathogenesis associated with the disease in the patients studied were not elucidated.

Malignant thoracic lymph node classification with deep convolutional neural networks on real-time endobronchial ultrasound (EBUS) images.

BACKGROUND: Thoracic lymph node (LN) evaluation is essential for the accurate diagnosis of lung cancer and deciding the appropriate course of treatment. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is considered a standard method for mediastinal nodal staging. This study aims to build a deep convolutional neural network (CNN) for the automatic classification of metastatic malignancies involving thoracic LN, using EBUS-TBNA. METHODS: Patients who underwent EBUS-TBNAs to assess the presence of malignancy in mediastinal LNs during a ten-month period at Severance Hospital, Seoul, Republic of Korea, were included in the study. Corresponding LN ultrasound images, pathology reports, demographic data, and clinical history were collected and analyzed. RESULTS: A total of 2,394 endobronchial ultrasound (EBUS) images of 1,459 benign LNs from 193 patients, and 935 malignant LNs from 177 patients, were collected. We employed the visual geometry group (VGG)-16 network to classify malignant LNs using only traditional cross-entropy for classification loss. The sensitivity, specificity, and accuracy of predicting malignancy were 69.7%, 74.3%, and 72.0%, respectively, and the overall area under the curve (AUC) was 0.782. We applied the new loss function to train the network and, using the modified VGG-16, the AUC improved to a value of 0.8. The sensitivity, specificity, and accuracy improved to 72.7%, 79.0%, and 75.8%, respectively. In addition, the proposed network can process 63 images per second on a single mainstream graphics processing unit (GPU) device, making it suitable for real-time analysis of EBUS images. CONCLUSIONS: Deep CNNs can effectively classify malignant LNs from EBUS images. Selecting LNs that require biopsy using real-time EBUS image analysis with deep learning is expected to shorten the EBUS-TBNA procedure time, increase lung cancer nodal staging accuracy, and improve patient safety.

Protective effect of methotrexate on lung function and mortality in rheumatoid arthritis-related interstitial lung disease: a retrospective cohort study.

BACKGROUND: Studies on the risk and protective factors for lung function decline and mortality in rheumatoid arthritis-related interstitial lung disease (RA-ILD) are limited. OBJECTIVES: We aimed to investigate clinical factors and medication uses associated with lung function decline and mortality in RA-ILD. METHODS: This retrospective cohort study examined the medical records of patients with RA-ILD who visited Severance Hospital between January 2006 and December 2019. We selected 170 patients with RA-ILD who had undergone at least one spirometry test and chest computed tomography scan. An absolute decline of ⩾10% in the functional vital capacity (FVC) was defined as significant decline in pulmonary function. Data for analysis were retrieved from electronic medical records. RESULTS: Ninety patients (52.9%) were female; the mean age was 64.0 ± 10.2 years. Multivariate logistic regression showed that a high erythrocyte sediment rate level at baseline [odds ratio (OR) = 3.056; 95% confidence interval (CI) = 1.183-7.890] and methotrexate (MTX) use (OR = 0.269; 95% CI = 0.094-0.769) were risk and protective factors for lung function decline, respectively. Multivariate Cox regression analysis indicated that age ⩾65 years (OR = 2.723; 95% CI = 1.142-6.491), radiologic pattern of usual interstitial pneumonia (UIP) or probable UIP (OR = 3.948; 95% CI = 1.522-10.242), baseline functional vital capacity (FVC) % predicted (OR = 0.971; 95% CI = 0.948-0.994), and MTX use (OR = 0.284; 95% CI = 0.091-0.880) were predictive of mortality. CONCLUSION: We identified risk and protective factors for lung function decline and mortality in patients with RA-ILD. MTX use was associated with favorable outcome in terms of both lung function and mortality in our cohort.

Impact of non-cystic fibrosis bronchiectasis on critically ill patients in Korea: a retrospective observational study.

This study investigated the impact of bronchiectasis on patients admitted to the intensive care unit (ICU) at a hospital in Korea. Patients with bronchiectasis were diagnosed using results of chest computed tomography performed before ICU admission. The severity of bronchiectasis was based on the number of affected lobes, and patients with ≥ 3 bronchiectatic lobes were classified into the severe bronchiectasis group. Overall, 823 patients were enrolled. The mean age was 66.0 ± 13.9 years, and 63.4% were men. Bronchiectasis and severe bronchiectasis were present in 148 (18.0%) and 108 (13.1%) patients, respectively. The increase in the number of bronchiectatic lobes was related to the rise in ICU mortality (P for trend = 0.012) and in-hospital mortality (P for trend = 0.004). Patients with severe bronchiectasis had higher odds for 28-day mortality [odds ratio (OR) 1.122, 95% confidence interval (CI) 1.024-1.230], ICU mortality (OR 1.119, 95% CI 1.023-1.223), and in-hospital mortality (OR 1.208, 95% CI 1.092-1.337). The severe bronchiectasis group showed lower overall survival (log-rank P < 0.001), and the adjusted hazard ratio was 1.535 (95% CI 1.178-2.001). Severe bronchiectasis had a negative impact on all-cause mortality during ICU and hospital stays, resulting in a lower survival rate.

The Association between Behavioral Risk Factors and Nontuberculous Mycobacterial Pulmonary Disease.

PURPOSE: We aimed to determine the relationship between environmental exposure and nontuberculous mycobacterial pulmonary disease (NTM-PD) in Korea. MATERIALS AND METHODS: A group of 150 patients with NTM-PD and a control group of 217 patients with other respiratory diseases were prospectively enrolled between June 2018 and December 2020 in Seoul, Korea. They were surveyed with a standardized questionnaire, and their medical records were reviewed. Odds ratio (OR) and 95% confidence intervals (CI) were calculated with multivariate logistic regression analysis. RESULTS: The mean ages of the NTM-PD and control groups were similar (63.8±9.2 years vs. 63.5±10.0 years; p=0.737), and most patients were female (76.0% vs. 68.7%; p=0.157) and nonsmokers (82.0% vs. 72.8%; p=0.021). Mycobacterium avium (49.3%) was the most commonly identified strain among NTM-PD patients, followed by M. intracellulare (32.0%) and M. abscessus subspecies massiliense (12.7%). There were no differences in housing type or frequency of soil- or pet-related exposure between the case and the control groups. However, in subgroup analysis excluding patients with M. intracellulare infection, more case patients frequently visited public baths ≥1 time/week (35.3% vs. 19.4%, p=0.003); this remained significant after multivariate analysis (OR, 2.84; 95% CI, 1.58-5.17). CONCLUSION: Frequent exposure to water at public baths might affect the odds of contracting NTM-PD, excluding individuals infected with M. intracellulare strains.

Correlation between serum carbohydrate antigen 19-9 levels and computed tomography severity score in patients with nontuberculous mycobacterial pulmonary disease.

There is no validated clinical biomarker for disease severity or treatment response for nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the correlation between elevated serum carbohydrate antigen (CA) 19-9 levels and NTM-PD disease activity, defined using an imaging severity score based on chest computed tomography (CT). We retrospectively examined 79 patients with NTM-PD who underwent serum CA19-9 level assessments and chest CT less than 1 month apart. NTM-PD severity was rated using a CT-based scoring system. The correlation between the CT score and serum CA19-9 levels was evaluated. Chest CT revealed nodular bronchiectasis without cavitation in most patients (78.5%). Serum CA19-9 levels were elevated in 19 (24%) patients. Serum CA19-9 levels were positively correlated with the total CT score and bronchiectasis, bronchiolitis, cavity, and consolidation subscores. Partial correlation analysis revealed a significant positive correlation between serum CA19-9 levels and CT scores for total score and bronchiectasis, bronchiolitis, cavitation, and consolidation subscores after controlling for age, sex, and BMI. Serum CA19-9 levels were positively correlated with the CT severity score for NTM-PD. Serum CA19-9 may be useful in evaluating disease activity or therapeutic response in patients with NTM-PD.