Development and validation of novel simple prognostic model for predicting mortality in Korean intensive care units using national insurance claims data.

BACKGROUND/AIMS: Intensive care unit (ICU) quality is largely determined by the mortality rate. Therefore, we aimed to develop and validate a novel prognostic model for predicting mortality in Korean ICUs, using national insurance claims data. METHODS: Data were obtained from the health insurance claims database maintained by the Health Insurance Review and Assessment Service of South Korea. From patients who underwent the third ICU adequacy evaluation, 42,489 cases were enrolled and randomly divided into the derivation and validation cohorts. Using the models derived from the derivation cohort, we analyzed whether they accurately predicted death in the validation cohort. The models were verified using data from one general and two tertiary hospitals. RESULTS: Two severity correction models were created from the derivation cohort data, by applying variables selected through statistical analysis, through clinical consensus, and from performing multiple logistic regression analysis. Model 1 included six categorical variables (age, sex, Charlson comorbidity index, ventilator use, hemodialysis or continuous renal replacement therapy, and vasopressor use). Model 2 additionally included presence/absence of ICU specialists and nursing grades. In external validation, the performance of models 1 and 2 for predicting in-hospital and ICU mortality was not inferior to that of pre-existing scoring systems. CONCLUSION: The novel and simple models could predict in-hospital and ICU mortality and were not inferior compared to the pre-existing scoring systems.

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.

Diagnosis of Primary Ciliary Dyskinesia via Whole Exome Sequencing and Histologic Findings.

PURPOSE: To assess the diagnostic potential of whole-exome sequencing (WES) and elucidate the clinical and genetic characteristics of primary ciliary dyskinesia (PCD) in the Korean population. MATERIALS AND METHODS: Forty-seven patients clinically suspected of having PCD were enrolled at a tertiary medical center. WES was performed in all patients, and seven patients received biopsy of cilia and transmission electron microscopy (TEM). RESULTS: Overall, PCD was diagnosed in 10 (21.3%) patients: eight by WES (8/47, 17%), four by TEM. Among patients diagnosed as PCD based on TEM results, two patients showed consistent results with WES and TEM of PCD (2/4, 50%). In addition, five patients, who were not included in the final PCD diagnosis group, had variants of unknown significance in PCD-related genes (5/47, 10.6%). The most frequent pathogenic (P)/likely pathogenic (LP) variants were detected in DNAH11 (n=4, 21.1%), DRC1 (n=4, 21.1%), and DNAH5 (n=4, 21.1%). Among the detected 17 P/LP variants in PCD-related genes in this study, 8 (47.1%) were identified as novel variants. Regarding the genotype-phenotype correlation in this study, the authors experienced severe PCD cases caused by the LP/P variants in MCIDAS, DRC1, and CCDC39. CONCLUSION: Through this study, we were able to confirm the value of WES as one of the diagnostic tools for PCD, which increases with TEM, rather than single gene tests. These results will prove useful to hospitals with limited access to PCD diagnostic testing but with relatively efficient in-house or outsourced access to genetic testing at a pre-symptomatic or early disease stage.

The deubiquitinase UCHL3 mediates p300-dependent chemokine signaling in alveolar type II cells to promote pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, fatal, fibrotic, interstitial lung disease of unknown cause. Despite extensive studies, the underlying mechanisms of IPF development remain unknown. Here, we found that p300 was upregulated in multiple epithelial cells in lung samples from patients with IPF and mouse models of lung fibrosis. Lung fibrosis was significantly diminished by the alveolar type II (ATII) cell-specific deletion of the p300 gene. Moreover, we found that ubiquitin C-terminal hydrolase L3 (UCHL3)-mediated deubiquitination of p300 led to the transcriptional activation of the chemokines Ccl2, Ccl7, and Ccl12 through the cooperative action of p300 and C/EBPß, which consequently promoted M2 macrophage polarization. Selective blockade of p300 activity in ATII cells resulted in the reprogramming of M2 macrophages into antifibrotic macrophages. These findings demonstrate a pivotal role for p300 in the development of lung fibrosis and suggest that p300 could serve as a promising target for IPF treatment.

Outstanding Characteristics of Birt-Hogg-Dube Syndrome in Korea.

Birt-Hogg-Dube (BHD) is a rare genetic disorder characterized by multiple lung cysts, typical skin manifestations, and renal tumors. We prospectively enrolled thirty-one subjects from four South Korean institutions with typical lung cysts, and next-generation sequencing was conducted. We prospectively enrolled thirty-one subjects from four Korean institutions with typical lung cysts. Next-generation sequencing was performed to investigate mutations in the following genes: FLCN, TSC1, TSC2, CFTR, EFEMP2, ELN, FBLN5, LTBP4, and SERPINA1. BHD was diagnosed in 11 of the 31 enrolled subjects (35.5%; FLCN mutations). Notably, we identified three novel mutations (c.1098G>A, c.139G>T, and c.1335del) that have not been previously reported. In addition to FLCN mutations, we also observed mutations in CFTR (16.1%), LTBP4 (9.7%), TSC2 (9.7%), TSC1 (3.2%), ELN (3.2%), and SERPINA1 (3.2%). According to a systematic review of 45 South Korean patients with BHD, the prevalence of pneumothorax (72.7%) was greater in South Korea than in the rest of the world (50.9%; p = 0.003). The prevalence of skin manifestations (13.6%) and renal tumors (9.1%) was lower in Korea than in the rest of the world, at 47.9% [p < 0.001] and 22.5% [p = 0.027], respectively). This study confirmed a significant prediction model for BHD based on age, number of lung cysts (>40), and maximal diameter of lung cysts (>2 cm) regardless of skin manifestations and renal tumors. Importantly, three novel mutations (c.1098G>A, c.139G>T, and c.1335del) were identified. In conclusion, South Korean patients with BHD display characteristics that are different from those observed in patients of other nationalities. Detailed characterization of lung cysts is needed to define BHD, especially in South Korea, even if patients do not present with skin or renal lesions.

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.

Longitudinal association between adiposity changes and lung function deterioration.

BACKGROUND: The longitudinal relationship between adiposity and lung function is controversial. We aimed to investigate the long-term association between adiposity changes and lung function in a middle-aged general Asian population. METHODS: In total, 5011 participants (average age, 54 years; 45% men) were enrolled from a community-based prospective cohort. During the follow-up period (median 8 years), both spirometry and bio-electrical impedance analysis were performed biannually. Individual slopes of the fat mass index (FMI; fat mass divided by the square of height in meters) and waist-to-hip ratio (WHR) were calculated using linear regression analysis. Multivariate linear mixed regression analysis was used to determine the long-term association between adiposity changes and lung function. RESULTS: The FMI was inversely associated with forced vital capacity (FVC) (estimated: - 31.8 mL in men, - 27.8 mL in women) and forced expiratory volume in 1 s (FEV1) (estimated: - 38.2 mL in men, - 17.8 mL in women) after adjusting for baseline age, height, residential area, smoking exposure (pack-years, men only), initial adiposity indices, and baseline lung function. The WHR was also inversely associated with FVC (estimated = - 1242.2 mL) and FEV1 (estimated = - 849.8 mL) in men. The WHR-increased group showed a more rapid decline in lung function than the WHR-decreased group in both the fat-gain and fat-loss groups. CONCLUSION: Adiposity was associated with the long-term impairment of lung function. Central obesity was the main driver of lung function impairment in the middle-aged general Asian population, regardless of fat mass changes.

Clinical Outcomes and Prognosis of Patients With Interstitial Lung Disease Undergoing Lung Cancer Surgery: A Propensity Score Matching Study.

BACKGROUND: Patients with interstitial lung disease (ILD) may have a poor prognosis after lung cancer surgery because of respiratory complications and increased recurrence rates due to limited resection. Few studies have investigated prognosis after surgery by matching clinical variables between patients with and without ILD. PATIENTS AND METHODS: Medical records of patients who underwent lung cancer surgery between January 2010 and August 2020 at a referral hospital in South Korea were reviewed. Patients with ILD were identified based on preoperative computed tomography findings. Through propensity score matching, the clinical outcomes and prognoses of patients with (ILD group) and without ILD (control group) were compared. RESULTS: Of 1629 patients, 113 (6.9%) patients with ILD were identified, of whom 104 patients were matched. Before matching, patients with ILD had higher mean age, proportion of men, and rates of sublobar resection and squamous cell carcinoma than those without ILD. After matching, there was no significant difference in postoperative mortality rates between the control and ILD groups. The 5-year survival rate was significantly lower in the ILD group (66%) than in the control group (78.8%; P= .007). The 5-year survival rate of the ILD-GAP (Gender, Age, Physiology) stage III group (12.6%) was significantly lower than that of the ILD-GAP stage I (73.5%) and II groups (72.6%; P< .0001). Multivariable Cox analysis demonstrated that idiopathic pulmonary fibrosis, higher clinical stage, and recurrence were independent prognostic factors for mortality. CONCLUSION: Concomitant ILD negatively affects long-term prognosis after lung cancer surgery, and ILD subtype and physiological severity assessment help predict prognosis after surgery.

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.

Medical Complications of Lung Transplantation.

Lung transplantation (LT) is now considered as an effective treatment option for end-stage lung diseases that improves the short and long-term survival rates and quality of life. As increasingly many LT procedures are being performed, the medical complications of LT are also increasing in frequency and emerging as a very important issue for transplant clinicians. Although chronic lung allograft dysfunction and infection are major causes of death after LT, many medical complications, several of which result from immunosuppressive treatment, contribute to increased mortality and morbidity. This article reviews the most frequent and important medical complications of LT, accompanied by a review of the literature and studies from South Korea, including lung allograft rejection, infection, and non-allograft organ systemic complications.

Long-term clinical course and progression of lymphangioleiomyomatosis in a single lung transplant referral centre in Korea.

We aimed to describe the clinical features of lymphangioleiomyomatosis (LAM) in Korean patients and identify factors associated with progressive disease (PD). Clinical features of 54 patients with definite or probable LAM from 2005 to 2018 were retrospectively analysed. Common features were pneumothorax (66.7%) and abdominal lymphadenopathy (50.0%). Twenty-three (42.6%) patients were initially treated with mechanistic target of rapamycin (mTOR) inhibitors. Lung transplantation (LT) was performed in 13 (24.1%) patients. Grouped based on the annual decline in forced expiratory volume in 1 s (FEV1) from baseline and LT, 36 (66.7%) patients exhibited stable disease (SD). All six deaths (11.1%) occurred in PD. Proportion of SD was higher in those treated initially with mTOR inhibitors than in those under observation (p = 0.043). Univariate analysis revealed sirolimus use, and baseline forced vital capacity, FEV1, and diffusing capacity of the lungs for carbon monoxide are associated with PD. Multivariate analysis showed that only sirolimus use (odds ratio 0.141, 95% confidence interval 0.021-0.949, p = 0.044) reduced PD. Kaplan-Meier analysis estimates overall survival of 92.0% and 74.7% at 5 and 10 years, respectively. A considerable proportion of LAM patients remain clinically stable without treatment. LT is an increasingly viable option for patients with severe lung function decline.

NADPH oxidase 4 signaling in a ventilator-induced lung injury mouse model.

BACKGROUND: For patients with acute respiratory distress syndrome, a ventilator is essential to supply oxygen to tissues, but it may also cause lung damage. In this study, we investigated the role of NOX4 using NOX4 knockout (KO) mice and NOX4 inhibitors in a ventilator-induced lung injury (VILI) model. METHODS: Wild-type (WT) male C57BL/6J mice and NOX4 knockout (KO) male mice were divided into five groups: (1) control group; (2) high tidal ventilation (HTV) group: WT mice + HTV ± DMSO; (3) NOX4 KO group; (4) NOX4 KO with HTV group; (5) NOX4 inhibitor group: WT mice + HTV + NOX4 inhibitor. In the VILI model, the supine position was maintained at 24 mL/kg volume, 0 cm H2O PEEP, 100/min respiratory rate, and 0.21 inspired oxygen fraction. In the NOX4 inhibitor group, 50 µL anti-GKT 137831 inhibitor was injected intraperitoneally, 2 h after ventilator use. After 5 h of HTV, mice in the ventilator group were euthanized, and their lung tissues were obtained for further analysis. In addition, the relationship between EphA2 (which is related to lung injury) and NOX4 was investigated using EphA2 KO mice, and NOX4 and EphA2 levels in the bronchoalveolar lavage fluid (BALF) of 38 patients with pneumonia were examined. RESULTS: Cell counts from BALFs were significantly lower in the NOX4 KO with HTV group (p < 0.01) and EphA2 KO with HTV group (p < 0.001) compared to that in the HTV group. In the NOX4 inhibitor group, cell counts and protein concentrations from BALF were significantly lower than those in the HTV group (both, p < 0.001). In the NOX4 KO group and the NOX4 inhibitor group, EphA2 levels were significantly lower than those in the HTV group (p < 0.001). In patients with respiratory disease, NOX4 and EphA2 levels were significantly higher in patients with pneumonia and patients who received ventilator treatment in the intensive care unit. CONCLUSION: In the VILI model with high tidal volume, NOX4 KO, EphA2 KO or monoclonal antibodies attenuated the VILI. NOX4 and EphA2 levels were significantly higher in patients with pneumonia and especially in mechanical ventilated in the ICU. Inhibition of Nox4 is a potential therapeutic target for the prevention and reduction of VILI.

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.

Reference values of skeletal muscle area for diagnosis of sarcopenia using chest computed tomography in Asian general population.

BACKGROUND: Diagnostic cutoff points for sarcopenia in chest computed tomography (CT) have not been established although CT is widely used for investigating skeletal muscles. This study aimed to determine reference values for sarcopenia of thoracic skeletal muscles acquired from chest CT scans and to analyse variables related to sarcopenia using the cutoff values determined in a general Asian population. METHODS: We retrospectively reviewed chest CT scans of 4470 participants (mean age 54.8 ± 9.9 years, 65.8% male) performed at a check-up centre in South Korea (January 2016-August 2017). To determine cutoffs, 335 participants aged 19-39 years (mean age 35.2 ± 3.6 years, 75.2% male) were selected as the healthy and younger reference group, and 4135 participants aged ≥40 years (mean age 56.4 ± 8.4 years, 65.1% male) were selected as the study group. We measured the following: cross-sectional area (CSA) of the pectoralis, intercostalis, paraspinal, serratus, and latissimus muscles at the 4th vertebral region (T4CSA ); T4CSA divided by height2 (T4MI); pectoralis muscle area (PMCSA ); and PMCSA divided by height2 (PMI) at the 4th vertebral region. Sarcopenia cutoff was defined as sex-specific values of less than -2 SD below the mean from the reference group. RESULTS: In the reference group, T4CSA , T4MI, PMCSA , and PMI cutoffs for sarcopenia were 100.06cm2 , 33.69cm2 /m2 , 29.00cm2 , and 10.17cm2 /m2 in male, and 66.93cm2 , 26.01cm2 /m2 , 18.29cm2 , and 7.31cm2 /m2 in female, respectively. The prevalence of sarcopenia in the study group measured with T4CSA , T4MI, PMCSA and PMI cutoffs were 11.4%, 8.7%, 8.5%, and 10.1%, respectively. Correlations were observed between appendicular skeletal mass divided by height2 measured by bioelectrical impedance analysis (BIA) and T4CSA (r = 0.82; P < 0.001)/T4MI (r = 0.68; P < 0.001), and ASM/height2 measured by BIA and PMCSA (r = 0.72; P < 0.001)/PMI (r = 0.63; P < 0.001). In the multivariate logistic regression models, sarcopenia defined by T4CSA /T4MI were related to age [odds ratio (95% confidence interval), P-values: 1.09 (1.07-1.11), <0.001/1.05 (1.04-1.07), <0.001] and diabetes [1.60 (1.14-2.25), 0.007/1.47 (1.01-2.14), 0.043]. Sarcopenia defined by PMCSA /PMI were related to age [1.09 (1.08-1.10), <0.001/1.05 (1.03-1.06), <0.001], male sex [0.23 (0.18-0.30), <0.001/0.47 (0.32-0.71), <0.001], diabetes [2.30 (1.73-3.05), <0.001/1.63 (1.15-2.32), 0.007], history of cancer [2.51 (1.78-3.55), <0.001/1.61 (1.04-2.48), 0.033], and sufficient physical activity [0.67 (0.50-0.89), 0.007/0.74 (0.56-0.99), 0.042]. CONCLUSIONS: The reference cutoff values of a general population reported here will enable sex-specific standardization of thoracic muscle mass quantification and sarcopenia assessment.

Nontuberculous mycobacterial infection after lung transplantation: A single-center experience in South Korea.

PURPOSE: Nontuberculous mycobacteria (NTM) infection is an important issue after lung transplantation. However, a large-scale epidemiological study on this issue in Korea is lacking. We aimed to evaluate the epidemiology of NTM infection after lung transplant surgery in Korea. METHODS: Between October 2012 and December 2018, we retrospectively evaluated lung transplant recipients in a referral hospital in South Korea. A total of 215 recipients were enrolled. The median age at transplantation was 56 years (range, 17-75), and 62% were men. Bronchoscopy was performed according to the surveillance protocol and clinical indications. A diagnosis of NTM infection was defined as a positive NTM culture from a bronchial washing, bronchoalveolar lavage sample, or two separate sputum samples. We determined NTM pulmonary disease (NTM-PD) according to the American Thoracic Society/Infectious Disease Society of America 2007 guidelines. The Kaplan-Meier method and log-rank test were used for conditional survival analysis in patients with follow-up of ≥12 months. RESULTS: Fourteen patients (6.5%) were diagnosed with NTM infection at a median of 11.8 months (range, 0.3-51.4) after transplantation. Nine patients (4.2%) were diagnosed with NTM-PD, and the incidence rate was 1980/100,000 person-years. Mycobacterium abscessus was the most common species causing NTM-PD (66%), followed by M. avium complex (33%). The presence of NTM infection did not influence all-cause mortality among those who underwent follow-up for ≥12 months (N = 133, log-rank P = 0.816). CONCLUSION: The incidence of NTM-PD was considerably high among lung-transplant recipients. M. abscessus was the most common causative species of NTM-PD after lung transplantation.

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.

WITHDRAWN: Effect of Disease Type on Changes in Total Lung Volume After Lung Transplantation.

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Association of protein consumption and energy intake on sarcopenia in tuberculosis survivors.

BACKGROUND: Tuberculosis (TB) causes undernutrition, and it has a long recovery time after treatment. It is accompanied by adverse health outcomes, such as sarcopenia. OBJECTIVE: We aimed to evaluate the prevalence of sarcopenia and its association with protein and total energy intakes among Korean TB survivors. METHODS: Data of the population-based Korea National Health and Nutrition Examination Survey (2008-2011) were analyzed, including 9,203 participants aged ⩾ 40 years. We used three definitions for sarcopenia-appendicular skeletal muscle mass (ASM, kg) divided by body mass index (BMI, kg/m2), weight (kg), or height squared (m2). Daily protein and total energy intakes were estimated with a 24-h recall method. Multiple logistic regression was used to evaluate the association between dietary protein/total energy intake and sarcopenia among TB survivors. RESULTS: The prevalence of sarcopenia was 11.2%, 10.7%, and 24.3% among TB survivors with sarcopenia defined by ASM divided by BMI, weight, and height squared, respectively. The prevalence of sarcopenia among TB survivors was higher than among those without TB. After adjusting for age, weight, sex, education level, employment status, smoking status, and drinking status, sufficient protein and total energy intakes were associated with a lower risk of sarcopenia in TB survivors. CONCLUSION: The prevalence of sarcopenia was higher in TB survivors than in those without TB. We suggest consuming sufficient protein intake along with increasing total energy intake in TB survivors.

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.

Risk factors and mortality of acute kidney injury within 1 month after lung transplantation.

After lung transplantation (LT), some patients are at risk of acute kidney injury (AKI), which is associated with worse outcomes and increased mortality. Previous studies focused on AKI development from 72 h to 1 week within LT, and reported main risk factors for AKI such as intraoperative hypotension, need of ECMO support, ischemia time or longer time on waiting list. However, this period interval rarely reflects medical risk factors probably happen in longer post-operative period. So, in this study we aimed to describe the incidence and risk factor of AKI within post-operative 1 month, which is longer follow up duration. Among 161 patients who underwent LT at Severance hospital in Seoul, Korea from October 2012 to September 2017, 148 patients were retrospectively enrolled. Multivariable logistic regression and Cox proportional hazard models were utilized. Among 148 patients, 59 (39.8%) developed AKI within 1-month after LT. Stage I or II, and stage III AKI were recorded in 26 (17.5%) and 33 (22.2%), respectively. We also classified AKI according to occurrence time, within 1 week as early AKI, from 1 week within 1 month was defined as late AKI. AKI III usually occurred within 7 days after transplantation (early vs. late AKI III, 72.5% vs 21.1%). Risk factor for AKI development was pre-operative anemia, higher units of red blood cells transfused during surgery, colistin intravenous infusion for treating multi drug resistant pathogens were independent risk factors for AKI development. Post-operative bleeding, grade 3 PGD within 72 h, and sepsis were more common complication in the AKI group. Patients with AKI III ([24/33] 72.7%) had significantly higher 1-year mortality than the no-AKI ([18/89] 20.2%), and AKI I or II group ([9/26] 34.6%), log-rank test, P < 0.001). AKI was associated with worse post-operative outcome, 3-month, and 1-year mortality after LT. Severity of AKI was usually determined in early post op period (ex. within 7 days) after LT, so optimal post-operative management as well as recipients selection should be considered.