Effect of complicated, untreated and uncontrolled diabetes and pre-diabetes on treatment outcome among patients with pulmonary tuberculosis.

BACKGROUND AND OBJECTIVE: Patients with tuberculosis and diabetes have a higher risk of unfavourable anti-tuberculosis treatment outcomes. In the present study, we aimed to evaluate the effects of various diabetes statuses on the outcomes of patients with pulmonary tuberculosis. METHODS: Among the patients with pulmonary tuberculosis enrolled in the Korea Tuberculosis Cohort (KTBC) registry and the multicentre prospective cohort study of pulmonary tuberculosis (COSMOTB), those with diabetes and complicated diabetes were identified. The primary and secondary outcomes were unfavourable outcomes and mortality, respectively. The effect of diabetes and complicated diabetes on the outcomes was assessed using multivariable logistic regression analysis. Using COSMOTB, subgroup analyses were performed to assess the association between various diabetes statuses and outcomes. RESULTS: In the KTBC, diabetes (adjusted odds ratio [aOR] = 1.93, 95% CI = 1.64-2.26) and complicated diabetes (aOR = 1.96, 95% CI = 1.67-2.30) were significantly associated with unfavourable outcomes, consistent with the COSMOTB data analysis. Based on subgroup analysis, untreated diabetes at baseline was an independent risk factor for unfavourable outcomes (aOR = 2.72, 95% CI = 1.26-5.61). Prediabetes and uncontrolled diabetes increased unfavourable outcomes and mortality without statistical significance. CONCLUSION: Untreated and complicated diabetes at the time of tuberculosis diagnosis increases the risk of unfavourable outcomes and mortality.

Do patients attempt and succeed in quitting smoking during tuberculosis treatment? A prospective cohort study.

BACKGROUND: Despite a well-known relation between smoking tobacco and the tuberculosis epidemic, the factors associated with smoking cessation in tuberculosis patients are unclear. This study aims to examine the cascade of smoking cessation and the factors associated with persistent smoking among tuberculosis patients. METHODS: We conducted a prospective cohort study enrolling adult patients with pulmonary tuberculosis between 2016 and 2019 in the Republic of Korea. We examined the smoking status at baseline, followed the current smokers, re-examined their smoking status after 6 months of anti-tuberculosis treatment, and identified the factors associated with persistent smoking. RESULTS: Of the 419 enrolled patients, 109 (26.0%) were current smokers at baseline. Of the 79 current smokers who completed the 6-month survey, 24 (30.4%) succeeded in quitting smoking after 6 months of treatment. The adjusted odds ratio for persistent smoking was 6.57 (95% confidence interval [CI], 1.76-27.83) for drinking and 0.15 (95% CI, 0.03-0.68) for diabetes comorbidity. CONCLUSION: Drinking alcohol and diabetes comorbidity were important factors in smoking cessation. Only one third of the tuberculosis patients in our study cohort succeeded in quitting smoking during the 6-month treatment period. More aggressive interventions for smoking cessation should be adopted within the national anti-tuberculosis program.

Comparative Analysis of Preoperative High Frequency Color Doppler Ultrasound versus MR Lymphangiography versus ICG Lymphography of Lymphatic Vessels in Lymphovenous Anastomosis.

BACKGROUND: Despite the extensive use of various imaging modalities, there is limited literature on comparing the reliability between indocyanine green (ICG) lymphography, MR Lymphangiogram (MRL), and high frequency color Doppler ultrasound (HFCDU) to identify lymphatic vessels. METHOD: In this study of 124 patients, the correlation between preoperative image findings to the actual lymphatic vessel leading to lymphovenous anastomosis (LVA) was evaluated. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and simple detection were calculated. Subgroup analysis was also performed according to the severity of lymphedema. RESULTS: Total of 328 LVAs were performed. The HFCDU overall had significantly higher sensitivity for identifying lymphatic vessels (99%) over MRL (83.5%) and ICG lymphography (82.3%)(p < 0.0001). Both ICG lymphography and HFCDU had 100% specificity and PPV. The NPV was 3.6%, 6.5% and 57.1% respectively for MRL, ICG lymphography, and HFCDU. All modalities showed high sensitivity for early stage 2 lymphedema while HFCDU showed a significantly higher sensitivity for late stage 2 (MRL:79.7%, ICG:83.1%, HFCDU:97%) and stage 3 (MRL:79.7%, ICG:79.7%, HFCDU:100%) over the other two modalities (p < 0.0001). CONCLUSION: This study demonstrated while all three modalities are able to provide good information, the sensitivity may alter as the severity of lymphedema progresses. The HFCDU will provide the best detection for lymphatic vessels throughout all stages of lymphedema. However, as each modality provides different and unique information, combining and evaluating the data according to the stage of lymphedema will be able to maximize the chance for a successful surgical outcome.

Burnout of Faculty Members of Medical Schools in Korea.

BACKGROUND: There is no national survey on medical school faculty members' burnout in Korea. This study aimed to investigate burnout levels and explore possible factors related to burnout among faculty members of Korean medical schools. METHODS: An anonymous online questionnaire was distributed to 40 Korean medical schools from October 2020 to December 2020. Burnout was measured by a modified and revalidated version of the Maslach Burnout Inventory-Human Service Survey. RESULTS: A total of 996 faculty members participated in the survey. Of them, 855 answered the burnout questions, and 829 completed all the questions in the questionnaire. A significant number of faculty members showed a high level of burnout in each sub-dimension: 34% in emotional exhaustion, 66.3% in depersonalization, and 92.4% in reduced personal accomplishment. A total of 31.5% of faculty members revealed a high level of burnout in two sub-dimensions, while 30.5% revealed a high level of burnout in all three sub-dimensions. Woman faculty members or those younger than 40 reported significantly higher emotional exhaustion and depersonalization. Long working hours (≥ 80 hours/week) showed the highest reduced personal accomplishment scores (F = 4.023, P = 0.018). The most significant stressor or burnout source was "excessive regulation by the government or university." The research was the most exasperating task, but the education was the least stressful. CONCLUSION: This first nationwide study alerts that a significant number of faculty members in Korean medical schools seem to suffer from a high level of burnout. Further studies are necessary for identifying the burnout rate, related factors, and strategies to overcome physician burnout.

Perceptions on good-life, good-death, and advance care planning in Koreans with non-cancerous chronic diseases.

AIMS: This study explored perceptions on a good-life, good-death, and advance care planning in Koreans with non-cancerous chronic diseases with the goal to develop a culture-specific advance care planning intervention in this population. DESIGN: A qualitative descriptive design was used. METHODS: Data collections were conducted between September 2017 - June 2018. Twenty-nine patients aged 41-82 years (85.8% men) participated in the interviews lasting 40-60 min. The verbatim transcriptions of the semi-structured interview data were analysed using conventional content analysis. RESULTS: Good-life was described as 'present with physical and financial independence,' 'not burdensome to the family,' 'completed life responsibility', and 'helping others.' Some participants described good-death as 'prepared death' while others considered it as 'sudden death during sleep.' All participants wanted to have a painless death and not burden the family. Advance care planning was a new concept to many participants. It was likened to 'insurance.' Some participants believed that decision-making on life-sustaining treatment should be done by their family, not themselves, because of economic or emotional distress. Some participants wanted to discuss medical and non-medical care services to reduce the burden on self and family. CONCLUSION: Family is key when it comes to the meaning of good-life and good-death. Cultural adaptation is necessary to meet the advance care planning needs of Koreans with non-cancerous chronic diseases. IMPACT: Successfully implementing advance care planning in Koreans with non-cancerous chronic diseases depends on how it is adapted to the disease-specific characteristics compared with cancer, and the cultural norms and social context. Nurses need to be prepared to offer advance care planning to persons with non-cancerous chronic diseases based on a keen sense of and empathetic cultural competence.

Suppression of Mig-6 overcomes the acquired EGFR-TKI resistance of lung adenocarcinoma.

BACKGROUND: The resistance of lung cancer to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is one of the unconquered frontiers in chemotherapy. Mitogen-inducible gene 6 (Mig-6) is known to inhibit the kinase activity of epidermal growth factor receptor (EGFR). Similarly, numerous studies of mouse models suggested tumor suppressive function of Mig-6 in lung cancer. On the contrary, the results of clinical investigations revealed that lung cancer patients with elevated expression of Mig-6 are associated with a poor prognosis. More recent work showed that unlike wild type (WT) EGFR, mutant EGFR phosphorylates Mig-6 and phosphorylated Mig-6 negatively regulates the degradation of EGFR mutants in lung adenocarcinoma. Here, we tried to untangle the controversies surrounding Mig-6 function as a protagonist or an antagonist of EGFR-TKI resistant lung cancer. METHODS: We compared the expression and phosphorylation status of Mig-6 in the EGFR-TKI resistant lung adenocarcinoma (PC9/GR cells) to EGFR-TKI sensitive lung adenocarcinoma (PC9 cells). We investigated the function of Mig-6 by either depletion or overexpression of Mig-6 in those cells and evaluated the efficacy of combining of Mig-6 knock-down and EGFR-TKI treatment in PC9/GR. The correlation between Mig-6 expressions and the prognoses of lung adenocarcinoma was examined by The Cancer Genome Atlas (TCGA) data and clinical samples. RESULTS: Our results indicated that the expression of Mig-6 was significantly increased in PC9/GR cells compared to that of PC9 cells. The significant portion of Mig-6 existed as a phosphorylated form in PC9 and PC9/GR cells. Moreover, overexpression of Mig-6 significantly increased the cell proliferation, invasion and epithelial mesenchymal transition (EMT) in PC9 cells. Combination of Mig-6 knock-down and EGFR-TKI treatment significantly overcame the EGFR-TKI resistance of PC9/GR cells. In addition, our analyses of clinical samples confirmed that high Mig-6 expressions positively correlate with a poor prognosis and EGFR-TKI resistance in lung adenocarcinoma. CONCLUSION: Our findings reinforce scientific notion of Mig-6 as an oncoprotein in the context of EGFR-TKI resistant lung adenocarcinoma. We propose that targeting Mig-6 may be a promising strategy to overcome the EGFR-TKI resistance in lung cancer.

Clinical profiles of subclinical disease among pulmonary tuberculosis patients: a prospective cohort study in South Korea.

BACKGROUND: Subclinical tuberculosis (TB) is a potential target for public health intervention because its early identification may reduce TB transmission. We aimed to describe the clinical and laboratory findings of subclinical disease among pulmonary TB patients and compared treatment outcomes for subclinical and active diseases. METHODS: In this prospective cohort study, we enrolled adult patients aged ≥ 19 years with pulmonary TB between 2016 and 2018. Subclinical TB was defined as radiographic or microbiologic test results consistent with TB without clinical symptoms. We implemented a two-stage symptom assessment using a predefined TB symptom checklist. Demographic, clinical, and laboratory data were compared between subclinical and active diseases using multivariable binary logistic regression analysis. We evaluated treatment outcomes in the drug-susceptible cohort. RESULTS: Among 420 enrolled patients, 81 (19.3%) had subclinical TB. Multivariable analysis showed that age < 65 years was the only variable significantly associated with subclinical disease. Subclinical disease had a significantly lower proportion of acid-fast bacilli smear and culture positivity and multiple lobe involvement compared to active disease. The white blood cell counts, platelet counts, and C-reactive protein levels were significantly higher among patients with active disease than among those with subclinical disease. Among 319 patients with treatment success in the drug-susceptible cohort, six (1.9%) recurrent cases were identified, and all were active disease. Patients with subclinical disease had a higher proportion of favourable outcomes; however, its odds ratio was insignificant. CONCLUSIONS: Nearly one-fifth of tuberculosis cases were subclinical in South Korea. Despite its milder clinical presentation and lower level of inflammatory markers, the treatment outcomes of subclinical TB were not significantly different from that of active disease.

Clinical Role of the Chronic Obstructive Pulmonary Disease Assessment Test in Prediction of the Response to Treatment for Exacerbations.

BACKGROUND: The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is a validated, eight-item questionnaire used to quantify the health status of patients. The aim of this study was to evaluate the usefulness of the CAT questionnaire as a tool to assess the response to treatment in acute exacerbations of COPD in an outpatient setting. METHODS: A multicenter, phase 3 randomized controlled trial was conducted previously to examine the efficacy and safety of oral zabofloxacin for the treatment of COPD exacerbations. In the present post hoc analysis of the original study, patients with COPD exacerbation were categorized as responders or non-responders according to the respiratory symptoms persisting on day 10 (visit 3) of treatment. The CAT questionnaire was completed daily by patients at home from the initial visit to the second visit on day 5. Subsequently, the questionnaire was completed in the presence of a physician on days 10 (visit 3) and 36 (visit 4). Multivariate regression analysis was performed to determine the association between CAT scores and the therapeutic response. RESULTS: The CAT scores decreased more rapidly in responders compared to non-responders during the first 5 days (23.3-20.4 vs. 23.5-22). Among responders, patients with higher severity of illness also revealed higher CAT scores on the first day of an exacerbation (mild, 19.8; moderate, 21.4; severe, 23.8; very severe, 28.6). Multivariate analysis revealed that a change in the CAT score during the first 3 days influenced the therapeutic response. A significant decrease in scores in the domains of sputum production, chest tightness, and activities of daily living was seen among responders. CONCLUSION: Early improvement in CAT scores may be associated with a more favorable response to the treatment of COPD exacerbations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01658020. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0000532.

Efficacy of Vinorelbine Monotherapy as Third- or Further-Line Therapy in Patients with Advanced Non-Small-Cell Lung Cancer.

BACKGROUND: The survival rate of patients with lung cancer has increased significantly over the years, but there has been no further progress in third- or fourth-line therapy. We investigated the efficacy and tolerability of monotherapy with weekly vinorelbine, a semi-synthetic vinca alkaloid, in advanced non-small-cell lung cancer (NSCLC) patients who had previously been treated several times. METHODS: In all, 159 NSCLC patients who received vinorelbine monotherapy as third- or further-line therapy between January 2008 and July 2017 were included in this study. Patients received vinorelbine intravenously at a dose of 25-30 mg/m2/week. RESULTS: Their mean age was 62.4 years. The histologic types of tumor were adenocarcinoma (50.9%), squamous cell carcinoma (42.8%), and others (6.2%). The overall response rate was 19.5% (31/159). The median progression-free survival (PFS) was 3.0 months (95% confidence interval [CI] 2.5-3.5 months), and the median overall survival (OS) after vinorelbine use was 7.6 months (95% CI 6.2-9.0 months). Vinorelbine therapy showed significantly higher efficacy in patients with adenocarcinoma, and these patients had a longer PFS than patients with other types of cancer. Patients who received vinorelbine as fifth- or further-line treatment had a higher response rate and longer PFS and OS than those who received vinorelbine as third- or fourth-line treatment. CONCLUSIONS: Weekly vinorelbine monotherapy may be a feasible therapeutic option for patients with heavily treated, advanced NSCLC, particularly lung adenocarcinoma.

Hippo effector YAP directly regulates the expression of PD-L1 transcripts in EGFR-TKI-resistant lung adenocarcinoma.

Developments of EGFR-TKI and immunotherapy targeting the PD1/PD-L1 pathway are considered most important medical breakthroughs in lung cancer treatment. Nowadays, 3rd generation EGFR TKI is widely used for T790M positive 1st and 2nd EGFR-TKI resistant lung cancer patients. Immunotherapy is powerful option for lung cancer patients without drug targets and chemotherapy resistant patients. It also has changed the concept of conventional anti-cancer therapy in the point of regulating tumor microenvironment. There are many studies linking these two important pathways. Recent studies demonstrated that PD-L1 expression is significantly correlated to the mutation status of EGFR, and activation of EGFR signaling can also induce the expression of PD-L1. However, the real linker between PD-L1 and EGFR signaling remains to be revealed. Our previous study revealed that the Hippo pathway effector YAP confers EGFR-TKI resistance in lung adenocarcinoma, and inhibition of YAP restores sensitivity to EGFR-TKIs. Thus, we examined whether PD-L1 is relevant, in terms of conferring EGFR-TKI resistance and whether YAP directly regulates the expression of PD-L1 in this context. First, we compared the expression levels of PD-L1 and YAP between EGFR-TKI-resistant PC9 cells and the parental PC9 adenocarcinoma cells. The expression levels of both YAP and PD-L1 were markedly higher in the EGFR-TKI-resistant cells compared to the parental cells, suggesting differential expression pattern between two cell types. YAP knockdown significantly decreased the expression of PD-L1 in the EGFR-TKI-resistant cells, while YAP overexpression increased the expression of PD-L1 in the parental PC9 cells. Then, our results revealed that YAP regulates the transcription of PD-L1, and the YAP/TEAD complex binds to the PD-L1 promoter. Surprisingly, knockdown of PD-L1 was sufficient to decrease cell proliferation and wound healing in the EGFR-TKI-resistant PC9 cells. These data suggest a PD1-independent oncogenic function of PD-L1. The Hippo effector YAP plays a crucial role in linking the PD-L1 and EGFR-TKI resistance by directly regulating the expression of PD-L1 in lung cancer. Targeting PD-L1 directly or via YAP could provide an effective therapeutic strategy for EGFR-TKI-resistant lung adenocarcinoma.

Hippo pathway effector YAP inhibition restores the sensitivity of EGFR-TKI in lung adenocarcinoma having primary or acquired EGFR-TKI resistance.

The efficacy of EGFR-tyrosine kinase inhibitors (TKIs) is significantly limited by various resistance mechanisms to those drugs. The resistance to EGFR-TKI is largely divided by two classes; acquired resistance after EGFR-TKI treatment, and primary resistance marked by cancer cell's dependence on other oncogene, such as KRAS. YAP has emerged as critical oncogene in conferring drug resistance against targeted therapy. In this study, we evaluated the role of YAP in primary and acquired EGFR-TKI resistance using gefitinib-resistant A549 and PC9 cells and their parental cell lines. Our study revealed that EGFR-TKI resistance is associated with enhanced YAP activity. Notably, YAP activation was independent of the Hippo pathway. We confirmed that AXL is a downstream target of YAP that confers EGFR-TKI resistance. And our results showed that YAP can induce ERK activation in lung adenocarcinoma. The combination of YAP inhibition with EGFR-TKI overcomes primary and acquired EGFR-TKI resistance. We also found increased YAP expression in human lung cancer after acquiring EGFR-TKI resistance. Collectively, we suggest a novel EGFR-TKI resistance mechanism involving YAP activation and suggest targeting YAP and EGFR simultaneously may be a breakthrough treatment of primary and acquired EGFR-TKI resistant lung cancer.

The E3 ubiquitin ligase CHIP selectively regulates mutant epidermal growth factor receptor by ubiquitination and degradation.

Somatic mutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) is a decisive factor for the therapeutic response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma. The stability of mutant EGFR is maintained by various regulators, including heat shock protein 90 (Hsp90). The C terminus of Hsc70-interacting protein (CHIP) is a Hsp70/Hsp90 co-chaperone and exhibits E3 ubiquitin ligase activity. The high-affinity Hsp90-CHIP complex recognizes and selectively regulates their client proteins. CHIP also works with its own E3 ligase activity independently of Hsp70/Hsp90. Here, we investigated the role of CHIP in regulating EGFR in lung adenocarcinoma and also evaluated the specificity of CHIP's effects on mutant EGFR. In HEK 293T cells transfected with either WT EGFR or EGFR mutants, the overexpression of CHIP selectively decreased the expression of certain EGFR mutants (G719S, L747_E749del A750P and L858R) but not WT EGFR. In a pull-down assay, CHIP selectively interacted with EGFR mutants and simultaneously induced their ubiquitination and proteasomal degradation. The expressions of mutant EGFR in PC9 and H1975 were diminished by CHIP, while the expression of WT EGFR in A549 was nearly not affected. In addition, CHIP overexpression inhibited cell proliferation and xenograft's tumor growth of EGFR mutant cell lines, but not WT EGFR cell lines. EGFR mutant specific ubiquitination by CHIP may provide a crucial regulating mechanism for EGFR in lung adenocarcinoma. Our results suggest that CHIP can be novel therapeutic target for overcoming the EGFR TKI resistance.

Visual Assessment of Chest Computed Tomography Findings in Anti-cyclic Citrullinated Peptide Antibody Positive Rheumatoid Arthritis: Is it Associated with Airway Abnormalities?

INTRODUCTION: We aimed to evaluate the association between specific anti-cyclic citrullinated peptide antibody (ACCPA) and pulmonary abnormalities in rheumatoid arthritis (RA) subjects. METHODS: Computed tomography (CT) images of 83 subjects with RA were evaluated in a blind fashion. Enrolled subjects underwent autoantibody testing to determinate titer of ACCPA and rheumatoid factor, and pulmonary function testing. Visual CT assessment included lobar analysis for extent of semi-quantitative total interstitial lung disease score (ILDS) and each airway abnormality score (bronchiectasis, bronchial wall thickening, centrilobular nodules, and expiratory air trapping). Correlation tests, and simple and multiple regression analyses were performed to determine the relationship between the visual CT abnormalities, physiologic parameters, and autoantibody titers. RESULTS: ACCPA-positive subjects had a greater extent and higher prevalence of small airway abnormalities including centrilobular nodules and air trapping compared to ACCPA-negative subjects (all p < 0.05). Bronchiectasis and bronchial wall thickening correlated with the ratio of forced expiratory volume in 1 s and forced vital capacity (FVC) (r = -0.236 and r = -0.329, all p < 0.05), and ILDS correlated with FVC and the diffusing capacity of the lung for carbon monoxide (r = -0.218 and r = -0.366, all p < 0.05). Bronchial wall thickening and air trapping correlated with ACCPA titers (r = 0.235 and r = 0.264, all p < 0.05). Air trapping and bronchial wall thickening were significantly associated with ACCPA titers. CONCLUSION: In ACCPA (+) RA, visual CT assessment of large and small airways beyond RA-ILD, which is attributable to RA-related autoimmunity, can provide valuable information regarding airway abnormalities, regardless of the patients' physiologic airflow limitations.

Carbon monoxide negatively regulates NLRP3 inflammasome activation in macrophages.

Inflammasomes are cytosolic protein complexes that promote the cleavage of caspase-1, which leads to the maturation and secretion of proinflammatory cytokines, including interleukin-1ß (IL-1ß) and IL-18. Among the known inflammasomes, the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3)-dependent inflammasome is critically involved in the pathogenesis of various acute or chronic inflammatory diseases. Carbon monoxide (CO), a gaseous molecule physiologically produced in cells and tissues during heme catabolism, can act as an anti-inflammatory molecule and a potent negative regulator of Toll-like receptor signaling pathways. To date, the role of CO in inflammasome-mediated immune responses has not been fully investigated. Here, we demonstrated that CO inhibited caspase-1 activation and the secretion of IL-1ß and IL-18 in response to lipopolysaccharide (LPS) and ATP treatment in bone marrow-derived macrophages. CO also inhibited IL-18 secretion in response to LPS and nigericin treatment, another NLRP3 inflammasome activation model. In contrast, CO did not suppress IL-18 secretion in response to LPS and poly(dA:dT), an absent in melanoma 2 (AIM2)-mediated inflammasome model. LPS and ATP stimulation induced the formation of complexes between NLRP3 and apoptosis-associated speck-like protein, or NLRP3 and caspase-1. CO treatment inhibited these molecular interactions that were induced by LPS and ATP. Furthermore, CO inhibited mitochondrial ROS generation and the decrease of mitochondrial membrane potential induced by LPS and ATP in macrophages. We also observed that the inhibitory effect of CO on the translocation of mitochondrial DNA into the cytosol was associated with suppression of cytokine secretion. Our results suggest that CO negatively regulates NLRP3 inflammasome activation by preventing mitochondrial dysfunction.

Incidence and clinical predictors of endobronchial tuberculosis in patients with pulmonary tuberculosis.

BACKGROUND AND OBJECTIVE: Incidence and predictors of endobronchial tuberculosis (EBTB) remain unknown because of the lack of prospective studies. Our objective was to assess the incidence and predictors of concomitant EBTB in patients with active pulmonary tuberculosis (PTB). METHODS: We prospectively performed routine bronchoscopic examination in all patients with PTB to detect EBTB. Clinical and bronchoscopic findings were analyzed to elucidate predictors of EBTB. RESULTS: Bronchoscopies of 429 PTB patients were performed at a tertiary referral hospital in Korea. Among those, 233 patients (54.3%) had EBTB. Female gender (odds ratio (OR) 4.35, 95% confidence interval (CI) 1.78-10.63), longer symptom duration (>4 weeks; OR 1.86, 95% CI 1.05-5.46), and no previous history of tuberculosis (OR 4.16, 95% CI 1.22-14.18) were found to be the independent predictors of concomitant EBTB in patients with active PTB. Most of the EBTB/PTB patients had mild stenosis, and more than 20% of them had severe stenosis at the time of diagnosis. Patients with EBTB had follow-up bronchoscopy to evaluate persistent airway stenosis. Persistent bronchostenosis with the lumen narrowed by more than one third occurred in 20.7% (30/145) of patients. The involvement length and decreased forced expiratory volume in 1 s were the risk factors for persistent bronchostenosis. CONCLUSIONS: In patients with active PTB, 50% or more have EBTB. Female gender and longer duration of symptoms are the main predictors of concomitant EBTB. Immediate diagnostic bronchoscopy in patients with active PTB should be considered in selected patients for detection of brocnhostenosis.

Prevalence of Spirometrically-defined Restrictive Ventilatory Defect in Korea: The Fourth-2, 3, and Fifth Korean National Health and Nutrition Examination Survey, 2008-2012.

The aim of the study was to evaluate the prevalence of restrictive ventilatory defect and to determine the risk factors in subjects with spirometrically-defined restrictive ventilatory defect. We used the population-based, fourth-2, 3 (2008, 2009) and fifth (2010-2012) Korea National Health and Nutrition Examination Survey (KNHANES) to analyze 15,073 subjects, aged ≥40 yr who underwent spirometry. Chest radiographs were also analyzed to identify restrictive lung disease. Spirometrically-defined restrictive ventilatory defect (FEV1/FVC≥70% and FVC<80% of mean predicted value) was detected in 11.3% (n= 1,709) of subjects aged ≥40 yr. The prevalence increased to 12.3% on using the lower limit of normal (LLN) criteria. Approximately 99.4% of subjects were classified as mild restrictive. Among these, 11.3% had inactive tuberculosis (TB) lesion, 2.2% cardiac disease, 2.0% previous operation scar or radiation injury and/or mediastinal disease, and 7.4% other pulmonary disease suggestive of restrictive lung diseases on chest radiograph. Evidence of previous TB history was independently associated with restrictive ventilatory defect (odds ratios [OR], 1.78; 95% confidence interval, 1.45-2.18) after adjustment for gender, age, smoking, area for residence and body mass index. The prevalence of restrictive ventilatory defect among the nationwide population in Korea was 11.3% with fixed ratio criterion and 12.3% with LLN criterion. Most cases were of the mild restrictive category and previous TB history is the independent risk factor for restrictive ventilatory defect.

Validity Study for Clinical Use of Hand-Held Spirometer in Patients with Chronic Obstructive Pulmonary Disease.

A spirometer is a medical device frequently used clinically for the diagnosis and prediction of lung disease. This study aimed to investigate the clinical usefulness of a hand-held spirometer (The Spirokit), compared with conventional spirometry in patients with chronic obstructive pulmonary disease (COPD). This study was conducted from February 2022 to October 2022. Measurements from 80 patients with COPD (male: 53, female: 27) were obtained using The Spirokit and PC-based pulmonary function test equipment, and the resulting values were compared and analyzed. For the concurrent validity comparison of The Spirokit, the intra-class correlation (ICC 2, 1), coefficients of variation (CVME), 95% limits of agreement (95% LOA), and Cohen's Kappa Index were analyzed. The Spirokit showed high agreement (ICC: 0.929-0.989; 95% LOA: -0.525 to 2.559; and CVME: 0.05-0.08) with the PC-based pulmonary function tester. Using the Cohen's kappa coefficients, the device showed high sensitivity, specificity, and accuracy scores of Pa: 0.90, Pc: 0.52, and K: 0.79, respectively, indicating considerable agreement. The Spirokit, a portable pulmonary function test device, is a piece of equipment with high validity and portability, with high potential for replacing PC-based pulmonary function test equipment.

The Matrix Stiffness Coordinates the Cell Proliferation and PD-L1 Expression via YAP in Lung Adenocarcinoma.

The extracellular matrix (ECM) exerts physiological activity, facilitates cell-to-cell communication, promotes cell proliferation and metastasis, and provides mechanical support for tumor cells. The development of solid tumors is often associated with increased stiffness. A stiff ECM promotes mechanotransduction, and the predominant transcription factors implicated in this phenomenon are YAP/TAZ, ß-catenin, and NF-κB. In this study, we aimed to investigate whether YAP is a critical mediator linking matrix stiffness and PD-L1 in lung adenocarcinoma. We confirmed that YAP, PD-L1, and Ki-67, a marker of cell proliferation, increase as the matrix stiffness increases in vitro using the lung adenocarcinoma cell lines PC9 and HCC827 cells. The knockdown of YAP decreased the expression of PD-L1 and Ki-67, and conversely, the overexpression of YAP increased the expression of PD-L1 and K-67 in a stiff-matrix environment (20.0 kPa). Additionally, lung cancer cells were cultured in a 3D environment, which provides a more physiologically relevant setting, and compared to the results obtained from 2D culture. Similar to the findings in 2D culture, it was confirmed that YAP influenced the expression of PD-L1 and K-67 in the 3D culture experiment. Our results suggest that matrix stiffness controls PD-L1 expression via YAP activation, ultimately contributing to cell proliferation.

Contralateral bone conducted sound wave propagation on the skull bones in fresh frozen cadaver.

The study aimed to investigate the efficient pathway for BC sound transmission by measuring vibrations on the opposite side of the skull bone, referred to as the mastoid position. The realistic contralateral transmission pathway of bone conduction (BC) vibrations is investigated through each osseous structure in the midlines of the fresh-frozen whole head. BC stimulation is applied to the mastoid using a bone vibrator, and acceleration responses are observed on the contralateral mastoid bone and seven midline points of skull bones using triaxial accelerometers. The study finds that the range showing the highest contralateral transmission efficiency of bone vibration is the intermediate frequency range with contralateral direction. Within this range, a significant amplitude of acceleration response is measured at the face-side points and the back and upper parts of the head. The thesis suggests that signal transmission from the specific midline to the mastoid can be more efficient than the conventional configuration of BC from the mastoid to the mastoid.