Variable effects of underlying diseases on the prognosis of patients with COVID-19.

Underlying diseases might be risk factors for poor prognosis in patients with coronavirus disease (COVID-19); however, we still do not know whether these diseases are independent factors affecting prognosis, which type of underlying diseases are risk factors, and which type of clinical outcomes are affected. We retrospectively reviewed cohort data from 7,590 de-identified patients with COVID-19 who were diagnosed using severe acute respiratory syndrome-coronavirus-2 RNA polymerase chain reaction test up to May 15, 2020. We used linked-medical claims data provided by the Health Insurance Review and Assessment Service in South Korea. Underlying diseases were identified using the diagnostic codes in the patients' files from January 1, 2019 to December 31, 2019. The total mortality rate was 3.0% in patients with COVID-19. After adjusting for age, sex, and concomitant chronic conditions, we found that congestive heart failure, chronic pulmonary diseases, diabetes without chronic complications, renal diseases, and malignancy were factors that significantly increased the cost of treatment. Cerebrovascular disease, chronic pulmonary disease, and paralysis were found to be independent factors significant in prolonging hospital stay. Diabetes with chronic complications was independently associated with intensive care unit admission. In addition, underlying congestive heart failure (odds ratio [OR], 1.724; P = 0.003), dementia (OR, 1.598; P = 0.012), diabetes with and without chronic complications (OR, 1.821; P = 0.002 and OR, 1.518; P = 0.022, respectively), renal disease (OR, 2.299; P = 0.002), and malignancy (OR, 1.529; P = 0.039) were significant factors associated with death, even after adjustments. Underlying diseases were significant independent factors of the poor prognosis in patients with COVID-19. The effects were variable according to the type of underlying disease and clinical outcome. Therefore, patients with COVID-19 with underlying diseases should be monitored more closely because they are more at risk of a poor prognosis.

FEF25-75% Values in Patients with Normal Lung Function Can Predict the Development of Chronic Obstructive Pulmonary Disease.

Purpose: The forced mid-expiratory flow (FEF25-75%) value is a potentially sensitive marker of obstructive peripheral airflow. We aimed to assess whether FEF25-75% can be an early predictor of chronic obstructive pulmonary disease (COPD). Patients and Methods: Between July 1, 2007 and June 31, 2009, we identified 3624 patients who underwent a pulmonary function test (PFT) in Gangnam Severance Hospital. We selected 307 patients aged over 40 years without COPD who had normal PFT results at baseline and who had follow-up PFT records more than 1 year later. A FEF25-75% z-score less than -0.8435 was considered low. We defined COPD as a forced expiratory volume in one second/forced vital capacity value of less than 0.7 before July 31, 2019. Results: Among 307 patients, 91 (29.6%) had low FEF25-75% at baseline. After 10 years, the incidence rate of COPD in the low FEF25-75% group was significantly higher than that in the normal FEF25-75% group (41.8% vs 7.4%; P-value<0.001). The Cox proportional hazard model showed that age (hazard ratio [HR] 1.09; P-value<0.001), smoking status (occasional smoker HR, 4.59; P-value<0.001 and long-term smoker HR, 2.18; P-value=0.023), and low FEF25-75% (HR, 3.31; P-value<0.001) were predictive factors for the development of COPD. Conclusion: The FEF25-75% value in patients with normal lung function is a useful predictor for the development of COPD. We should carefully monitor patients who present with low FEF25-75% values, even if they have normal lung function.

Positive Effects of the National Cigarette Price Increase Policy on Smoking Cessation in South Korea.

BACKGROUND: In January 2015, South Korea's government raised the cigarette tax, and the retail price of cigarettes abruptly increased by 80% compared to the previous year. This research aimed to determine the effect of this increase on smoking cessation among South Korean smokers. METHODS: We analyzed data collected by the 2013-2015 South Korea National Health and Nutrition Examination Survey of 15,203 South Koreans over 19 years old using regression analysis. We examined the recent non-smoking period of nonsmoking people, prepared according to the survey, and analyzed the recent smoking cessation ratio. RESULTS: Among smokers, from 2013 to 2014, the smoking cessation rate was 7.2%, and it increased to 9.9% in 2015 after the increase in the cigarette tax. In 2015, the recent smoking cessation rate was higher among people over the age of 60 (odds ratio [OR], 2.67) compared to those between the ages of 40 and 49. The recent smoking cessation rate was higher among people with below elementary education (OR, 2.28) and above university education (OR, 1.94) compared to high school, higher for those with apartments (OR, 1.74) compared to general type residences, and higher among those with a household income in the low-middle quartile (Q2) (OR, 2.32) compared to the highest quartile (Q4). CONCLUSION: This innovative policy including increase in cigarette prices affected smoking cessation, and its impact varied by sub-group of smokers in South Korea.

High versus low attenuation thresholds to determine the solid component of ground-glass opacity nodules.

OBJECTIVES: To evaluate and compare the diagnostic accuracy of high versus low attenuation thresholds for determining the solid component of ground-glass opacity nodules (GGNs) for the differential diagnosis of adenocarcinoma in situ (AIS) from minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA). METHODS: Eighty-six pathologically confirmed GGNs < 3 cm observed in 86 patients (27 male, 59 female; mean age, 59.3 ± 11.0 years) between January 2013 and December 2015 were retrospectively included. The solid component of each GGN was defined using two different attenuation thresholds: high (-160 Hounsfield units [HU]) and low (-400 HU). According to the presence or absence of solid portions, each GGN was categorized as a pure GGN or part-solid GGN. Solid components were regarded as indicators of invasive foci, suggesting MIA or IA. RESULTS: Among the 86 GGNs, there were 57 cases of IA, 19 of MIA, and 10 of AIS. Using the high attenuation threshold, 44 were categorized as pure GGNs and 42 as part-solid GGNs. Using the low attenuation threshold, 13 were categorized as pure GGNs and 73 as part-solid GGNs. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for the invasive focus were 55.2%, 100%, 100%, 22.7%, and 60.4%, respectively, for the high attenuation threshold, and 93.4%, 80%, 97.2%, 61.5%, and 91.8%, respectively, for the low attenuation threshold. CONCLUSION: The low attenuation threshold was better than the conventional high attenuation threshold for determining the solid components of GGNs, which indicate invasive foci.

Efficacy of adjuvant chemotherapy for completely resected stage IB non-small cell lung cancer: a retrospective study.

BACKGROUND: Lung cancer is being increasingly detected in the early stages, highlighting the importance of lung cancer screening. However, there is no consensus on the post-operative management of stage IB non-small cell lung cancer (NSCLC). Therefore, this study aimed to identify the predictive factors for prognosis of stage IB NSCLC and determine the efficacy of adjuvant chemotherapy on recurrence and survival. METHODS: We enrolled 89 patients with stage IB NSCLC who underwent complete resection surgery at Gangnam Severance Hospital from Jan 2008 to Dec 2014. As per the National Comprehensive Cancer Network guidelines, patients were considered to be at high risk when they showed poorly differentiated tumors, lymphovascular invasion, tumor size >4 cm, and visceral pleural invasion (VPI). RESULTS: Among the 89 patients, 27 underwent adjuvant chemotherapy. Young patients or patients with squamous cell lung cancer received adjuvant chemotherapy frequently. Adjuvant chemotherapy was not a significant factor for disease-free survival and overall survival. Adjuvant chemotherapy did not show a significant protective effect for survival, even for high-risk patients. However, VPI was a significant risk factor for disease-free survival [hazard ratio (HR): 7.051; 95% confidence interval (CI): 1.570-31.659; P=0.011] and overall survival (HR: 8.289; 95% CI: 1.036-66.307; P=0.046), even after adjustment for various factors. CONCLUSIONS: Adjuvant chemotherapy does not affect the prognosis of stage IB NSCLC, even in high-risk patients. Additionally, VPI is a strong prognostic factor of stage IB NSCLC.

Hepatitis C virus p7 induces mitochondrial depolarization of isolated liver mitochondria.

Hepatitis C virus (HCV)­encoded protein p7 is a viroporin that acts as an ion channel and is indispensable for HCV particle production. Although the main target of HCV p7 is the endoplasmic reticulum, it also targets mitochondria. HCV­infected cells show mitochondrial depolarization and ATP depletion; however, the function of HCV p7 in mitochondria is not fully understood. The present study demonstrated that treatment of isolated mouse liver mitochondria with the synthesized HCV p7 protein induced mitochondrial dysfunction. It also demonstrated that HCV p7 targeted isolated mouse liver mitochondria and induced mitochondrial depolarization. In addition, HCV p7 triggered matrix acidification and, ultimately, a decrease in ATP synthesis in isolated mitochondria. These findings indicate that targeting of mitochondria by HCV p7 in infected cells causes mitochondrial dysfunction to support HCV particle production. The present study provided evidence for the role of HCV p7 in mitochondria, and may lead to the development of novel strategies for HCV therapy.

Differences of lung microbiome in patients with clinically stable and exacerbated bronchiectasis.

BACKGROUND: Molecular-based diagnostic techniques can compensate for the inherent limitations of culture-based microbiology and provide a more comprehensive description of an entire community of bacteria at a particular anatomical site. Using culture-independent DNA-based molecular techniques, the aim of the present study was to characterize, differentiate, and compare the composition of lower airway bacterial microbiome between clinically stable and acutely infected patients with bronchiectasis experiencing exacerbation. METHODS: Patients with clinically stable bronchiectasis and those experiencing acutely exacerbated bronchiectasis were recruited. All patients underwent bronchoscopy. Paired sputum and bronchoalveolar lavage (BAL) samples were collected for microbiological tests. Molecular analysis was performed for BAL samples using 16S ribosomal RNA (rRNA) gene sequencing. RESULTS: The mean age of the 14 recruited patients was 60 years (range 42 to 78 years), and nine (64%) were female. Using quantitative culture and 16S rRNA sequencing, the common organisms identified from 14 BAL samples were Haemophilus influenzae, Pseudomonas aeruginosa and Moraxella catarrhalis, and Prevotella. Molecular techniques revealed Prevotella and Veillonella as potentially pathogenic anaerobic species. 16S rRNA gene sequencing yielded similar relative abundances and distributions of taxa in the stable and exacerbated bronchiectasis groups. Alpha diversity with richness, Simpson's and Shannon indices, and beta diversity using principal coordinate analysis revealed no significant differences in lung microbiome between patients with clinically stable and exacerbated bronchiectasis. CONCLUSION: Culture-based microbiological and molecular-based techniques did not reveal significant differences in the lung microbiome of patients who were clinically stable and those experiencing exacerbated bronchiectasis. Patient-specific microbial communities were dominated by one or several genera, regardless of clinical status. DNA sequencing could identify potentially pathogenic organisms unable to be identified using microbiological methods.

Sarcopenia correlates with systemic inflammation in COPD.

BACKGROUND: Muscle wasting and chronic inflammation are predominant features of patients with COPD. Systemic inflammation is associated with an accelerated decline in lung function. In this study, the prevalence of sarcopenia and the relationships between sarcopenia and systemic inflammations in patients with stable COPD were investigated. MATERIALS AND METHODS: In a cross-sectional design, muscle strength and muscle mass were measured by handgrip strength (HGS) and bioelectrical impedance analysis in 80 patients with stable COPD. Patients (≥40 years old) diagnosed with COPD were recruited from outpatient clinics, and then COPD stages were classified. Sarcopenia was defined as the presence of both low muscle strength (by HGS) and low muscle mass (skeletal muscle mass index [SMMI]). Levels of circulating inflammatory biomarkers (IL-6 and high-sensitivity TNFα [hsTNFα]) were measured. RESULTS: Sarcopenia was prevalent in 20 (25%) patients. Patients with sarcopenia were older, had lower body mass index, and a higher percentage of cardiovascular diseases. In addition, they had significantly higher modified Medical Research Council scores and lower 6-minute walk distance than those without sarcopenia. HGS was significantly correlated with age, modified Medical Research Council score, and COPD Assessment Test scores. Both HGS and SMMI had associations with IL-6 and hsTNFα (HGS, r=-0.35, P=0.002; SMMI, r=-0.246, P=0.044) level. In multivariate analysis, old age, lower body mass index, presence of cardiovascular comorbidities, and higher hsTNFα levels were significant determinants for sarcopenia in patients with stable COPD. CONCLUSION: Sarcopenia is very common in patients with stable COPD, and is associated with more severe dyspnea-scale scores and lower exercise tolerance. Systemic inflammation could be an important contributor to sarcopenia in the stable COPD population.

Birt-Hogg-Dube syndrome prospectively detected by review of chest computed tomography scans.

PURPOSE: Birt-Hogg-Dube syndrome (BHD) is a rare disorder caused by mutations in the gene that encodes folliculin (FLCN) and is inherited in an autosomal dominant manner. BHD is commonly accompanied by fibrofolliculomas, renal tumors, multiple pulmonary cysts, and spontaneous pneumothorax. The aim of this study was to detect BHD prospectively in patients undergoing chest computed tomography (CT) scans and to evaluate further the characteristics of BHD in Korea. METHODS: We prospectively checked and reviewed the chest CT scans obtained for 10,883 patients at Gangnam Severance Hospital, Seoul, Korea, from June 1, 2015 to May 31, 2016. Seventeen patients met the study inclusion criteria and underwent screening for FLCN mutation to confirm BHD. We analyzed the characteristics of the patients confirmed to have BHD and those for a further 6 patients who had previously been described in Korea. RESULTS: Six (0.06%) of the 10,883 patients reviewed were diagnosed with BHD. There was no difference in demographic or clinical features between the patients with BHD (n = 6) and those without BHD (n = 11). Pneumothorax was present in 50% of the patients with BHD but typical skin and renal lesions were absent. The maximum size of the cysts in the BHD group (median 39.4 mm; interquartile range [IQR] 11.4 mm) was significantly larger than that in the non-BHD group (median 15.8 mm; IQR 7.8 mm; P = 0.001). Variable morphology was seen in 100.0% of the cysts in the BHD group but in only 18.2% of the cysts in the non-BHD group (P = 0.002). Nine (95%) of the total of 12 Korean patients with BHD had experienced pneumothorax. Typical skin and renal lesions were present in 20.0% of patients with BHD. CONCLUSIONS: Our findings suggest that BHD can be detected if chest CT scans are read in detail.

Dietary vitamin C intake protects against COPD: the Korea National Health and Nutrition Examination Survey in 2012.

BACKGROUND: Vitamin C, as an antioxidant, has recently been suggested to provide protection against COPD; however, only few national cohort studies have investigated these effects. We aimed to confirm the protective effects of vitamin C against COPD in Korean patients. PATIENTS AND METHODS: We analyzed the data of 3,283 adults aged ≥40 years (representing 23,541,704 subjects) who underwent pulmonary function tests and responded to questionnaires on smoking history and vitamin C intake, with stratification variables and sampling weight designated by the Korea 2012 National Health and Nutrition Examination Survey. RESULTS: Among all the subjects, 512 (representing 3,459,679 subjects; 15.6%) were diagnosed as having COPD based on pulmonary function test results. Male gender, old age, residence in suburban/rural regions, low household income, low educational level, an occupation in agriculture or fisheries, and heavy smoking were significantly associated with COPD. Low intake of nutrients, including potassium, vitamin A, carotene, retinol, and vitamin C, was significantly associated with COPD. The prevalence of COPD in heavy smokers with the lowest quartile (Q1, <48.50 mg; 63.0%) and low-middle quartile (Q2, 48.50-84.38 mg; 56.4%) of vitamin C intake was significantly higher than that in subjects with the high-middle quartile (Q3, 84.38-141.63 mg; 29.5%) and highest quartile (Q4, >141.63 mg; 32.6%) of vitamin C intake (P=0.015). In multivariate analysis, male gender, old age, heavy smoking, and a low intake of vitamin C were significant independent risk factors for COPD. A significant reduction of 76.7% in COPD risk was observed with a Q3 vitamin C intake compared to Q1 vitamin C intake (odds ratio, 0.233; 95% confidence interval, 0.094-0.576) in heavy smokers. CONCLUSION: This large-scale national study suggests that dietary vitamin C provides protection against COPD, independent of smoking history, in the general Korean population.

A rare case of primary thymic adenocarcinoma mimicking small cell lung cancer.

Primary thymic adenocarcinoma is a very rare malignancy of the anterior mediastinum with no standardized treatment. A 36-year-old male patient presented with hoarseness over the past 3 months. A chest computed tomography (CT) scan showed an infiltrative mass to the proximal vessels and aortic arch in left upper mediastinum (4.1×3.1×5.4 cm). Brain magnetic resonance imaging (MRI) showed focal lesions, suggesting metastasis in the left frontal lobe. A thoracoscopic biopsy of the mediastinal mass confirmed a primary thymic adenocarcinoma forming a glandular structure with atypia of tumor cells. The patient received four cycles of systemic chemotherapy, consisting of etoposide and cisplatin, with concurrent radiotherapy (6,000 cGy/30 fractions) to the mediastinal lesion and the metastatic brain lesion (4,200 cGy/12 fractions). A follow-up chest CT scan and brain MRI showed a decrease in the size of the left upper mediastinal mass and brain lesion. We report a rare case of the primary thymic adenocarcinoma with a literature review.

Efficacy of surgical treatment for brain metastasis in patients with non-small cell lung cancer.

PURPOSE: Patients with non-small cell lung cancer (NSCLC) and simultaneously having brain metastases at the initial diagnosis, presenting symptoms related brain metastasis, survived shorter duration and showed poor quality of life. We analyzed our experiences on surgical treatment of brain metastasis in patients with NSCLC. MATERIALS AND METHODS: We performed a single-center, retrospective review of 36 patients with NSCLC and synchronous brain metastases between April 2006 and December 2011. Patients were categorized according to the presence of neurological symptoms and having a brain surgery. As a result, 14 patients did not show neurological symptoms and 22 patients presented neurological symptoms. Symptomatic 22 patients were divided into two groups according to undergoing brain surgery (neurosurgery group; n=11, non-neurosurgery group; n=11). We analyzed overall surgery (OS), intracranial progression-free survival (PFS), and quality of life. RESULTS: Survival analysis showed there was no difference between patients with neurosurgery (OS, 12.1 months) and non-neurosurgery (OS, 10.2 months; p=0.550). Likewise for intracranial PFS, there was no significant difference between patients with neurosurgery (PFS, 6.3 months) and non-neurosurgery (PFS, 5.3 months; p=0.666). Reliable neurological one month follow up by the Medical Research Council neurological function evaluation scale were performed in symptomatic 22 patients. The scale improved in eight (73%) patients in the neurosurgery group, but only in three (27%) patients in the non-neurosurgery group (p=0.0495). CONCLUSION: Patients with NSCLC and synchronous brain metastases, presenting neurological symptoms showed no survival benefit from neurosurgical resection, although quality of life was improved due to early control of neurological symptoms.

KRAS oncogene substitutions in Korean NSCLC patients: clinical implication and relationship with pAKT and RalGTPases expression.

OBJECTIVES: Since different conformation of each KRAS mutant leads to inherent downstream signaling, its distribution, influence on the clinical outcome, and effect on the signaling mediators were investigated in the Korean NSCLC patients whose tumor have KRAS mutation. MATERIALS AND METHODS: Mutation at KRAS codons 12 and 13 was evaluated in 1420 Korean NSCLC by direct sequencing and expression of RalA, RalB, and pAKT-Ser473 was evaluated by immunohistochemistry in 30 cases whose KRAS mutant tumor tissues were available. RESULTS: Eighty-two (5.8%) out of 1420 patients harbored a KRAS mutation either in codon 12 or 13. Gly12Asp was the most frequent (34.1%), followed by Gly12Cys (22.0%) and Gly12Val (13.4%). Transversion at codons 12 and 13, which includes Gly12Cys, Gly12Val, Gly12Ala, Gly13Cys, and Gly12Phe was detected in 45 cases (54.9%) and transition, including Gly12Asp, Gly12Ser, and Gly13Asp was detected in 37 cases (45.1%). Male and smoking history were associated with transversion (p=0.001 and 0.006, respectively; χ(2)-test), and multivariate analysis showed that gender was an independent influencing factor (p=0.026; Cochran-Mantel-Haenszel test). Multivariate analysis on survival revealed that KRAS mutation subtype did not influence overall survival of the patients with KRAS mutations after adjustment for age, gender, performance status, and stage. There were no differences in the nuclear and cytoplasmic expression of pAKT-Ser473 between transversion and transition mutants. Expression of Ral-GTPases, RalA and RalB, did not differ between transversion and transition mutants, however, strong expression of RalB in the tissue of patients with KRAS mutants was associated with advanced stages (P-value=0.020, χ(2)-test). CONCLUSIONS: In this study population, not only the frequency of KRAS mutation but also the distribution of its subtypes differed from those of Western studies, with unique influencing factors. Clinical outcome and expression of pAKT-Ser473, RalA, and RalB did not differ among subtypes.

Inhibition of mTORC1 induces loss of E-cadherin through AKT/GSK-3ß signaling-mediated upregulation of E-cadherin repressor complexes in non-small cell lung cancer cells.

BACKGROUND: mTOR, which can form mTOR Complex 1 (mTORC1) or mTOR Complex 2 (mTORC2) depending on its binding partners, is frequently deregulated in the pulmonary neoplastic conditions and interstitial lung diseases of the patients treated with rapalogs. In this study, we investigated the relationship between mTOR signaling and epithelial mesenchymal transition (EMT) by dissecting mTOR pathways. METHODS: Components of mTOR signaling pathway were silenced by shRNA in a panel of non-small cell lung cancer cell lines and protein expression of epithelial and mesenchymal markers were evaluated by immunoblotting and immunocytochemistry. mRNA level of the E-cadherin repressor complexes were evaluated by qRT-PCR. RESULTS: IGF-1 treatment decreased expression of the E-cadherin and rapamycin increased its expression, suggesting hyperactivation of mTOR signaling relates to the loss of E-cadherin. Genetic ablation of rapamycin-insensitive companion of mTOR (Rictor), a component of mTORC2, did not influence E-cadherin expression, whereas genetic ablation of regulatory-associated protein of mTOR (Raptor), a component of mTORC1, led to a decrease in E-cadherin expression at the mRNA level. Increased phosphorylation of AKT at Ser473 and GSK-3ß at Ser9 were observed in the Raptor-silenced NSCLC cells. Of the E-cadherin repressor complexes tested, Snail, Zeb2, and Twist1 mRNAs were elevated in raptor-silenced A549 cells, and Zeb2 and Twist1 mRNAs were elevated in Raptor-silenced H2009 cells. These findings were recapitulated by treatment with the GSK-3ß inhibitor, LiCl. Raptor knockdown A549 cells showed increased expression of N-cadherin and vimentin with mesenchymal phenotypic changes. CONCLUSIONS: In conclusion, selective inhibition of mTORC1 leads to hyperactivation of the AKT/GSK-3ß pathway, inducing E-cadherin repressor complexes and EMT. These findings imply the existence of a feedback inhibition loop of mTORC1 onto mTORC2 that plays a role in the homeostasis of E-cadherin expression and EMT, requiring caution in the clinical use of rapalog and selective mTORC1 inhibitors.

Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells.

Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H2O2) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H2O2 treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells.

Notch1 destabilizes the adherens junction complex through upregulation of the Snail family of E-cadherin repressors in non-small cell lung cancer.

One of the critical steps driving cancer cell migration and metastasis is the repression of cell adhesion molecules resulting in loss of cell­to-cell adhesion. Although interactions between Notch1 and components of the adherens junction complex have been suggested, little is known concerning the consequence of their interactions. In this study, we investigated the interaction between the Notch1 and the E­cadherin/ß­catenin complex, its effect on the expression of adherens junction complex components and its influence on non-small cell lung cancer (NSCLC) cell proliferation. With progression of lung neoplastic lesions in LSL K-ras G12D mice, the expression of E­cadherin was inhibited whereas that of Notch1 was increased with frequent nuclear localization, suggesting an inverse relationship between E­cadherin and Notch1 expression with tumor progression. Transduction of the human Notch1 intracellular domain (N1ICD) into NSCLC cells inhibited expression of E­cadherin and ß­catenin and induced changes in the localization of adherens junction molecules. The loss of E­cadherin was mediated through upregulation of the Snail family of transcription factors, Snail and Slug. Experiments in which siRNA against E-cadherin was introduced into NSCLC cells revealed that N1ICD decreased the expression of ß­catenin in an E­cadherin­independent manner, leading to inhibition of markers of Wnt/ß­catenin signaling activation. Despite inhibition of Wnt/ß­catenin signaling in the N1ICD­transduced cells, cells transduced with N1ICD showed no difference in cell cycle progression when compared with that of the control vector-transduced cells. In conclusion, Notch1 inhibited the expression of E­cadherin through upregulation of the Snail family of transcriptional factors, resulting in inhibition of expression of ß­catenin and destabilization of adherens junctions.

A case of locally advanced well-differentiated fetal adenocarcinoma of the lung treated with concurrent chemoradiation therapy.

Fetal adenocarcinoma is a rare adenocarcinoma subtype of pulmonary blastoma. A 48-year-old male patient is being referred to our hospital due to progressive dyspnea. A chest X-ray showed a lung mass of unknown origin that was obstructing the right main bronchus. After relieving the airway obstruction with stent insertion via bronchoscopy, a diagnosis of fetal adenocarcinoma is being confirmed through thoracoscopic biopsy. Due to the locally advanced state of the lung cancer, it seemed to be inoperable, and concurrent chemo-radiation therapy was being administered with docetaxel. The stent was removed after improvements in the airway obstruction followed by a lung mass shrinkage. Comparing to other contexts which describe fetal adenocarcinoma as lower grade malignancy with low-associated mortality, herein, we describe a case of locally-advanced fetal adenocarcinoma (T4N3M0). This is the first documented case being treated with concurrent chemoradiation therapy. The followed-up image studies represent a partial response and the patient is currently under further observations.

Surgical decortication as the first-line treatment for pleural empyema.

OBJECTIVE: The study objective was to evaluate the clinical outcomes of surgical decortication as the first line of treatment for pleural empyema. METHODS: We analyzed the medical records of 111 patients who presented with empyema and were treated with simple drainage or surgical decortication as the first line of treatment at Gangnam Severance Hospital, a tertiary referral medical center in Seoul, Korea. RESULTS: Of 111 patients with empyema, 27 underwent surgical decortication as the first intervention. Surgical decortication showed a better treatment success rate in all study subjects (96.3%, 26/27 patients) compared with simple drainage (58.3%, 49/84 patients; P < .0001 for method comparison). After propensity-scored matching, decortication resulted in a better outcome (95.0%, 19/20 patients) versus drainage (56.7%, 17/30 patients; P = .003). Surgical decortication as the first line of treatment for empyema was the best predictor of treatment success after adjustment for compounding factors (odds ratio, 14.529; 95% confidence interval, 1.715-123.074; P = .014). CONCLUSIONS: The first treatment choice for pleural empyema is a critical determinant of ultimate therapeutic success. After adjusting for confounding variables, surgical decortication is the optimal first treatment choice for advanced empyema.

Fiberoptic bronchoscopy for the rapid diagnosis of smear-negative pulmonary tuberculosis.

BACKGROUND: This study was aimed to investigate the diagnostic value of fiberoptic bronchoscopy (FOB) with chest high-resolution computed tomography (HRCT) for the rapid diagnosis of active pulmonary tuberculosis (PTB) in patients suspected of PTB but found to have a negative sputum acid-fast bacilli (AFB) smear. METHODS: We evaluated the diagnostic accuracy of results from FOB and HRCT in 126 patients at Gangnam Severance Hospital (Seoul, Korea) who were suspected of having PTB. RESULTS: Of 126 patients who had negative sputum AFB smears but were suspected of having PTB, 54 patients were confirmed as having active PTB. Hemoptysis was negatively correlated with active PTB. Tree-in-bud appearance on HRCT was significantly associated with active PTB. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FOB alone was 75.9%, 97.2%, 95.3%, and 84.3%, respectively, for the rapid diagnosis of active PTB. The combination of FOB and HRCT improved the sensitivity to 96.3% and the NPV to 96.2%. CONCLUSIONS: FOB is a useful tool in the rapid diagnosis of active PTB with a high sensitivity, specificity, PPV and NPV in sputum smear-negative PTB-suspected patients. HRCT improves the sensitivity of FOB when used in combination with FOB in sputum smear-negative patients suspected of having PTB.

A rotational ablation tool for calcified atherosclerotic plaque removal.

Atherosclerosis is a major cardiovascular disease involving accumulations of lipids, white blood cells, and other materials on the inside of artery walls. Since the calcification found in the advanced stage of atherosclerosis dramatically enhances the mechanical properties of the plaque, restoring the original lumen of the artery remains a challenge. High-speed rotational atherectomy, when performed with an ablating grinder to remove the plaque, produces much better results in the treatment of calcified plaque compared to other methods. However, the high-speed rotation of the Rotablator commercial rotational atherectomy device produces microcavitation, which should be avoided because of the serious complications it can cause. This research involves the development of a high-speed rotational ablation tool that does not generate microcavitation. It relies on surface modification to achieve the required surface roughness. The surface roughness of the tool for differential cutting was designed based on lubrication theory, and the surface of the tool was modified using Nd:YAG laser beam engraving. Electron microscope images and profiles indicated that the engraved surface of the tool had approximately 1 µm of root mean square surface roughness. The ablation experiment was performed on hydroxyapatite/polylactide composite with an elastic modulus similar to that of calcified plaque. In addition, differential cutting was verified on silicone rubber with an elastic modulus similar to that of a normal artery. The tool performance and reliability were evaluated by measuring the ablation force exerted, the size of the debris generated during ablation, and through visual inspection of the silicone rubber surface.