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Background/Aims@#The optimal treatment (Tx) for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) remains to be determined. @*Methods@#A retrospective review was conducted on 77 NSCLC patients with synchronous BM who underwent first-line EGFR-tyrosine kinase inhibitor (TKI) Tx. The outcomes of patients were analyzed according to the clinicopathological characteristics including local Tx modalities. @*Results@#Fifty-nine patients underwent local Tx for BM (gamma knife surgery [GKS], 37; whole brain radiotherapy [WBRT], 18; others, four) concurrently or sequentially with EGFR-TKI. Patients treated with TKI alone showed significantly lower incidence of central nervous system (CNS) symptoms. The median progression-free survival (PFS) and overall survival (OS) after the initiation of EGFR-TKI for all patients were 9 and 19 months, respectively. In 60 patients with follow-up brain imaging, the median time to CNS progression was 15 months. Patients with EGFR exon 19 deletion had a significantly longer median OS than those with other mutations including L858R (23 months vs. 17 months). Other clinical characteristics, including CNS symptoms, number of BM, and the use of local Tx were not associated with OS, as well as PFS. In terms of the local optimal Tx modality, no difference was found between GKS and WBRT in the OS and PFS. @*Conclusions@#This study suggests that EGFR-TKI may result in a favorable outcome in NSCLC patients with synchronous BM, especially in deletion 19 mutant, regardless of the extent of BM lesions or local Tx modalities. Patients with asymptomatic BM can be treated with EGFR-TKI and careful surveillance.
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Background/Aims@#The study investigated the incidence of thromboembolic events (TEE) in head and neck (H&N) cancer patients who received concurrent chemoradiotherapy (CCRT) with cisplatin, and analyzed the factors affecting TEE occurrence @*Methods@#Two hundred and fifty-seven patients who started CCRT with cisplatin for H&N cancer from January 2005 to December 2019 were analyzed. @*Results@#TEE occurred in five patients, an incidence rate of 1.9%. The 2-, 4-, and 6-month cumulative incidences of TEE were 0.8%, 1.6%, and 1.9%, respectively. Khorana score was the only factor associated with TEE occurrence (p = 0.010). @*Conclusions@#The incidence of TEE in H&N cancer patients who underwent CCRT with cisplatin was relatively low when compared to other types of cancer. However, patients with a high Khorana score require more careful surveillance for possible TEE occurrence.
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BACKGROUND AND OBJECTIVES: Respiratory scoring guidelines for children and adults have been used for evaluating adolescents both in the 2007 and 2012 American Academy of Sleep Medicine (AASM) scoring manuals. We compared the scoring methods of polysomnography used in these scoring manuals, where pediatric and adult scoring rules were adopted for the diagnosis of sleep apnea in adolescents. SUBJECTS AND METHOD: 106 Korean subjects aged between 13 and 18 years were enrolled. All subjects underwent overnight polysomnography in a sleep laboratory. Data were scored according to both pediatric and adult guidelines in the 2007 and 2012 AASM scoring manuals. RESULTS: Both pediatric and adult apnea hypopnea index (AHI) using the 2012 method were significantly higher than those using the 2007 method. The difference in AHI compared between pediatric and adult scores with the 2012 AASM scoring system was markedly decreased from that with the 2007 method. There was a significant discordance in sleep apnea diagnosis between pediatric and adult scoring rules in the 2012 method. CONCLUSION: Both pediatric and adult rules were used for the diagnosis of adolescent sleep apnea in the 2012 method. However, there was significant discordance in the diagnosis between pediatric and adult scoring guidelines in the 2012 AASM manual, probably due to different cut-off values of AHI for the diagnosis of sleep apnea in pediatric (≥1) and adult (≥5) patients. Further studies are needed to determine a more reasonable cut-off value for the diagnosis of sleep apnea in adolescents.
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Adolescente , Adulto , Niño , Humanos , Apnea , Diagnóstico , Métodos , Polisomnografía , Proyectos de Investigación , Síndromes de la Apnea del SueñoRESUMEN
Diffuse alveolar hemorrhage (DAH) is a life-threatening condition associated with many disorders. Here, we report a case of 59-year-old female who had diffuse alveolar hemorrhage associated with methimazole. She had been treated with methimazole for two weeks due to the recurrence of Grave's disease, before visiting the emergency room. She had to be intubated on the 3rd day of hospitalization because of unabated massive hemoptysis and rapid progression of diffuse alveolar infiltration on chest radiographs. Since her clinical condition improved substantially after cessation of methimazole and steroid pulse therapy, she was extubated on the 9th day of hospitalization and then discharged. After discharge, DAH did not recur with cessation of steroid and she had radioactive iodine therapy for her Grave's disease. This was a rare and interesting case of life-threatening DAH associated with cytoplasmic-antineutrophil cytoplasmic antibody and methimazole.
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Femenino , Humanos , Persona de Mediana Edad , Anticuerpos Anticitoplasma de Neutrófilos , Citoplasma , Servicio de Urgencia en Hospital , Hemoptisis , Hemorragia , Hospitalización , Yodo , Metimazol , Radiografía Torácica , RecurrenciaRESUMEN
BACKGROUND: Apoptosis plays a role in the development of pleural effusion. Caspase-cleaved cytokeratin 18, a marker for epithelial cell apoptosis, was evaluated in pleural effusion. METHODS: A total of 79 patients with pleural effusion were enrolled. The underlying causes were lung cancer (n=24), parapneumonic effusion (n=15), tuberculous effusion (n=28), and transudates (n=12). The levels of M30, an epitope of caspase-cleaved cytokeratin 18, were measured in blood and pleural fluids using enzyme-linked immunosorbent assay along with routine cellular and biochemical parameters. The expression of M30 was evaluated in the pleural tissues using immunohistochemistry for M30. RESULTS: The M30 levels in pleural fluid were significantly higher in patients with tuberculosis (2,632.1+/-1,467.3 U/mL) than in patients with lung cancer (956.5+/-618.5 U/mL), parapneumonic effusion (689.9+/-413.6 U/mL), and transudates (273.6+/-144.5 U/mL; all p<0.01). The serum levels were not significantly different among the disease groups. Based on receiver operating characteristics analysis, the area under the curve of M30 for differentiating tuberculous pleural effusion from all other effusions was 0.93. In the immunohistochemical analysis of M30, all pathologic types of cancer cells showed moderate to high expression, and the epithelioid cells in granulomas showed high expression in tuberculous pleural tissues. CONCLUSION: Caspase-cleaved cytokeratin 18 was most prominently observed in tuberculous pleural effusion and showed utility as a clinical marker. The main source of M30 was found to be the epithelioid cells of granulomas in tuberculous pleural tissues.
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Humanos , Apoptosis , Biomarcadores , Citoesqueleto , Ensayo de Inmunoadsorción Enzimática , Células Epiteliales , Células Epitelioides , Exudados y Transudados , Granuloma , Inmunohistoquímica , Queratina-18 , Queratinas , Neoplasias Pulmonares , Derrame Pleural , Curva ROC , Tuberculosis , Tuberculosis PleuralRESUMEN
BACKGROUND: Although airway obstruction in chronic obstructive pulmonary disease (COPD) is due to pathologic processes in both the airways and the lung parenchyma, the contribution of these processes, as well as other factors, have not yet been evaluated quantitatively. We therefore quantitatively evaluated the factors contributing to airflow limitation in patients with COPD. METHODS: The 213 COPD patients were aged >45 years, had smoked >10 pack-years of cigarettes, and had a post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) <0.7. All patients were evaluated by medical interviews, physical examination, spirometry, bronchodilator reversibility tests, lung volume, and 6-minute walk tests. In addition, volumetric computed tomography (CT) was performed to evaluate airway wall thickness, emphysema severity, and mean lung density ratio at full expiration and inspiration. Multiple linear regression analysis was performed to identify the variables independently associated with FEV1 - the index of the severity of airflow limitation. RESULTS: Multiple linear regression analysis showed that CT measurements of mean lung density ratio (standardized coefficient beta=-0.46; p<0.001), emphysema severity (volume fraction of the lung less than -950 HU at full inspiration; beta=-0.24; p<0.001), and airway wall thickness (mean wall area %; beta=-0.19, p=0.001), as well as current smoking status (beta=-0.14; p=0.009) were independent contributors to FEV1. CONCLUSION: Mean lung density ratio, emphysema severity, and airway wall thickness evaluated by volumetric CT and smoking status could independently contribute to the severity of airflow limitation in patients with COPD.
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Anciano , Humanos , Obstrucción de las Vías Aéreas , Tomografía Computarizada de Haz Cónico , Enfisema , Volumen Espiratorio Forzado , Modelos Lineales , Pulmón , Procesos Patológicos , Examen Físico , Enfermedad Pulmonar Obstructiva Crónica , Humo , Fumar , Espirometría , Productos de Tabaco , Tomografía Computarizada por Rayos X , Capacidad VitalRESUMEN
BACKGROUND: Adequate assessment and control of sedation play crucial roles in the proper performance of mechanical ventilation. METHODS: A total of 30 patients with various pulmonary diseases were prospectively enrolled. The study population was randomized into two groups. The sedation assessment group (SAG) received active protocol-based control of sedation, and in the empiric control group (ECG), the sedation levels were empirically adjusted. Subsequently, daily interruption of sedation (DIS) was conducted in the SAG. RESULTS: In the SAG, the dose of midazolam was significantly reduced by control of sedation (day 1, 1.3+/-0.5 microg/kg/min; day 2, 0.9+/-0.4 microg/kg/min; p<0.01), and was significantly lower than the ECG on day 2 (p<0.01). Likewise, on day 2, sedation levels were significantly lower in the SAG than in the ECG. Significant relationship was found between Ramsay sedation scale and Richmond agitation-sedation scale (RASS; rs=-0.57), Ramsay Sedation Scale and Bispectral Index (BIS; rs=0.77), and RASS and BIS (rs=-0.79). In 10 patients, who didn't require re-sedation after DIS, BIS showed the earliest and most significant changes among the sedation scales. Ventilatory parameters showed significant but less prominent changes, and hemodynamic parameters didn't show significant changes. No seriously adverse events ensued after the implementation of DIS. CONCLUSION: Active assessment and control of sedation significantly reduced the dosage of sedatives in patients receiving mechanical ventilation. DIS, conducted in limited cases, suggested its potential efficacy and tolerability.
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Humanos , Sedación Consciente , Monitores de Conciencia , Electrocardiografía , Hemodinámica , Hipnóticos y Sedantes , Enfermedades Pulmonares , Midazolam , Estudios Prospectivos , Respiración Artificial , Ventiladores Mecánicos , Pesos y MedidasRESUMEN
To date, clinico-physiologic indices have not been compared with quantitative CT imaging indices in determining the risk of chronic obstructive pulmonary disease (COPD) exacerbation. We therefore compared clinico-physiologic and CT imaging indices as risk factors for COPD exacerbation in patients with COPD. We retrospectively analyzed 260 COPD patients from pulmonary clinics at 11 hospitals in Korea from June 2005 to November 2009 and followed-up for at least one year. At the time of enrollment, none of these patients had COPD exacerbations for at least 2 months. All underwent clinico-physiologic and radiological evaluation for risk factors of COPD exacerbation. After 1 yr, 106 of the 260 patients had at least one exacerbation of COPD. Multiple logistic regression analysis showed that old age, high Charlson Index, and low FEV1 were significant in a clinico-physiologic model, with C-statistics of 0.69, and that increased age and emphysema index were significant in a radiologic model, with C-statistics of 0.64. The difference between the two models was statistically significant (P = 0.04 by bootstrap analysis). Combinations of clinico-physiologic risk factors may be better than those of imaging risk factors in predicting COPD exacerbation.
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Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Progresión de la Enfermedad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Adaptive support ventilation (ASV), an automated closed-loop ventilation mode, adapts to the mechanical characteristics of the respiratory system by continuous measurement and adjustment of the respiratory parameters. The adequacy of ASV was evaluated in the patients with acute lung injury (ALI). METHODS: A total of 36 patients (19 normal lungs and 17 ALIs) were enrolled. The patients' breathing patterns and respiratory mechanics parameters were recorded under the passive ventilation using the ASV mode. RESULTS: The ALI patients showed lower tidal volumes and higher respiratory rates (RR) compared to patients with normal lungs (7.1+/-0.9 mL/kg vs. 8.6+/-1.3 mL/kg IBW; 19.7+/-4.8 b/min vs. 14.6+/-4.6 b/min; p<0.05, respectively). The expiratory time constant (RCe) was lower in ALI patients than in those with normal lungs, and the expiratory time/RCe was maintained above 3 in both groups. In all patients, RR was correlated with RCe and peak inspiratory flow (rs=-0.40; rs=0.43; p<0.05, respectively). In ALI patients, significant correlations were found between RR and RCe (rs=-0.76, p<0.01), peak inspiratory flow and RR (rs=-0.53, p<0.05), and RCe and peak inspiratory flow (rs=-0.53, p<0.05). CONCLUSION: ASV was found to operate adequately according to the respiratory mechanical characteristics in the ALI patients. Discrepancies with the ARDS Network recommendations, such as a somewhat higher tidal volume, have yet to be addressed in further studies.
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Humanos , Lesión Pulmonar Aguda , Automatización , Pulmón , Respiración , Mecánica Respiratoria , Frecuencia Respiratoria , Sistema Respiratorio , Volumen de Ventilación Pulmonar , Ventilación , Lesión Pulmonar Inducida por Ventilación Mecánica , Ventiladores MecánicosRESUMEN
BACKGROUND: Adaptive support ventilation (ASV), an automated closed-loop ventilation mode, adapts to the mechanical characteristics of the respiratory system by continuous measurement and adjustment of the respiratory parameters. The adequacy of ASV was evaluated in the patients with acute lung injury (ALI). METHODS: A total of 36 patients (19 normal lungs and 17 ALIs) were enrolled. The patients' breathing patterns and respiratory mechanics parameters were recorded under the passive ventilation using the ASV mode. RESULTS: The ALI patients showed lower tidal volumes and higher respiratory rates (RR) compared to patients with normal lungs (7.1+/-0.9 mL/kg vs. 8.6+/-1.3 mL/kg IBW; 19.7+/-4.8 b/min vs. 14.6+/-4.6 b/min; p<0.05, respectively). The expiratory time constant (RCe) was lower in ALI patients than in those with normal lungs, and the expiratory time/RCe was maintained above 3 in both groups. In all patients, RR was correlated with RCe and peak inspiratory flow (rs=-0.40; rs=0.43; p<0.05, respectively). In ALI patients, significant correlations were found between RR and RCe (rs=-0.76, p<0.01), peak inspiratory flow and RR (rs=-0.53, p<0.05), and RCe and peak inspiratory flow (rs=-0.53, p<0.05). CONCLUSION: ASV was found to operate adequately according to the respiratory mechanical characteristics in the ALI patients. Discrepancies with the ARDS Network recommendations, such as a somewhat higher tidal volume, have yet to be addressed in further studies.
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Humanos , Lesión Pulmonar Aguda , Automatización , Pulmón , Respiración , Mecánica Respiratoria , Frecuencia Respiratoria , Sistema Respiratorio , Volumen de Ventilación Pulmonar , Ventilación , Lesión Pulmonar Inducida por Ventilación Mecánica , Ventiladores MecánicosRESUMEN
OBJECTIVE: The aim of this study was to examine whether or not levofloxacin has any relationship with QT prolongation in a real clinical setting by analyzing a clinical data warehouse of data collected from different hospital information systems. METHODS: Electronic prescription data and medical charts from 3 different hospitals spanning the past 9 years were reviewed, and a clinical data warehouse was constructed. Patients who were both administrated levofloxacin and given electrocardiograms (ECG) were selected. The correlations between various patient characteristics, concomitant drugs, corrected QT (QTc) prolongation, and the interval difference in QTc before and after levofloxacin administration were analyzed. RESULTS: A total of 2,176 patients from 3 different hospitals were included in the study. QTc prolongation was found in 364 patients (16.7%). The study revealed that age (OR 1.026, p < 0.001), gender (OR 0.676, p = 0.007), body temperature (OR 1.267, p = 0.024), and cigarette smoking (OR 1.641, p = 0.022) were related with QTc prolongation. After adjusting for related factors, 12 drugs concomitant with levofloxacin were associated with QTc prolongation. For patients who took ECGs before and after administration of levofloxacin during their hospitalization (n = 112), there was no significant difference in QTc prolongation. CONCLUSIONS: The age, gender, body temperature, cigarette smoking and various concomitant drugs might be related with QTc prolongation. However, there was no definite causal relationship or interaction between levofloxacin and QTc prolongation. Alternative surveillance methods utilizing the massive accumulation of electronic medical data seem to be essential to adverse drug reaction surveillance in future.
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Humanos , Temperatura Corporal , Minería de Datos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Electrocardiografía , Prescripción Electrónica , Electrónica , Electrones , Sistemas de Información en Hospital , Hospitalización , Síndrome de QT Prolongado , Ofloxacino , FumarRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality throughout the world and is the only major disease that is continuing to increase in both prevalence and mortality. The second Korean National Health and Nutrition Survey revealed that the prevalence of COPD in Korean subjects aged > or =45 years was 17.2% in 2001. Further surveys on the prevalence of COPD were not available until 2007. Here, we report the prevalence of spirometrically detected COPD in Korea, using data from the fourth Korean National Health and Nutrition Survey (KNHANES IV) which was conducted in 2007~2009. METHODS: Based on the Korean Statistical Office census that used nationwide stratified random sampling, 10,523 subjects aged > or =40 years underwent spirometry. Place of residence, levels of education, income, and smoking status, as well as other results from a COPD survey questionnaire were also assessed. RESULTS: The prevalence of COPD (defined as forced expiratory volume in 1 sec/forced vital capacity or =40 years) was 12.9% (men, 18.7%; women, 7.5%). In total, 96.5% of patients with COPD had mild-to-moderate disease; only 2.5% had been diagnosed by physicians, and only 1.7% had been treated. The independent risk factors for COPD were smoking, advanced age, and male gender. CONCLUSION: The prevalence of COPD was 12.9% in the KNHANES IV data. Most patients with COPD were undiagnosed and untreated. Based on these results, a strategy for early COPD intervention is warranted in high risk subjects.
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Anciano , Femenino , Humanos , Masculino , Censos , Volumen Espiratorio Forzado , Hipogonadismo , Corea (Geográfico) , Enfermedades Mitocondriales , Encuestas Nutricionales , Oftalmoplejía , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica , Encuestas y Cuestionarios , Factores de Riesgo , Humo , Fumar , Espirometría , Capacidad VitalRESUMEN
BACKGROUND/AIMS: Oxidative stress results in protein oxidation and is implicated in carcinogenesis. Sulfiredoxin (Srx) is responsible for the enzymatic reversal of inactivated peroxiredoxin (Prx). Nuclear factor E2-related factor 2 (Nrf2) binds to antioxidant responsive elements and upregulates the expression of Srx and Prx during oxidative stress. We aimed to elucidate the biological functions and potential roles of Srx in lung cancer. METHODS: To study the roles of Srx and Prx III in lung cancer, we compared the protein levels of Nrf2, Prxs, thioredoxin, and Srx in 40 surgically resected human lung cancer tissues using immunoblot and immunohistochemical analyses. Transforming growth factor-beta1, tumor necrosis factor-alpha, and camptothecin treatment were used to examine Prx III inactivation in Mv1Lu mink lung epithelial cells and A549 lung cancer cells. RESULTS: Prx I and Prx III proteins were markedly overexpressed in lung cancer tissues. A significant increase in the oxidized form of a cysteine sulfhydryl at the catalytic site of Prxs was found in carcinogenic lung tissue compared to normal lung tissue. Densitometric analyses of immunoblot data revealed significant Srx expression, which was higher in squamous cell carcinoma tissue (60%, 12/20) than in adenocarcinoma (20%, 4/20). Also, Nrf2 was present in the nuclear compartment of cancer cells. CONCLUSIONS: Srx and Prx III proteins were markedly overexpressed in human squamous cell carcinoma, suggesting that these proteins may play a protective role against oxidative injury and compensate for the high rate of mitochondrial metabolism in lung cancer.
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Animales , Humanos , Adenocarcinoma/enzimología , Antineoplásicos Fitogénicos/farmacología , Western Blotting , Camptotecina/farmacología , Carcinoma de Células Escamosas/enzimología , Línea Celular Tumoral , Inmunohistoquímica , Neoplasias Pulmonares/enzimología , Visón , Factor 2 Relacionado con NF-E2/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/genética , Peroxiredoxina III/metabolismo , Peroxirredoxinas/metabolismo , Pronóstico , Interferencia de ARN , Especies Reactivas de Oxígeno/metabolismo , Transfección , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia ArribaRESUMEN
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and responses to therapies are highly variable. The aim of this study was to identify the predictors of pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD. A total of 127 patients with stable COPD from the Korean Obstructive Lung Disease (KOLD) Cohort, which were prospectively recruited from June 2005 to September 2009, were analyzed retrospectively. The prediction models for the FEV1, FVC and IC/TLC changes after 3 months of treatment with salmeterol/fluticasone were constructed by using multiple, stepwise, linear regression analysis. The prediction model for the FEV1 change after 3 months of treatment included wheezing history, pre-bronchodilator FEV1, post-bronchodilator FEV1 change and emphysema extent on CT (R = 0.578). The prediction models for the FVC change after 3 months of treatment included pre-bronchodilator FVC, post-bronchodilator FVC change (R = 0.533), and those of IC/ TLC change after 3 months of treatment did pre-bronchodilator IC/TLC and post-bronchodilator FEV1 change (R = 0.401). Wheezing history, pre-bronchodilator pulmonary function, bronchodilator responsiveness, and emphysema extent may be used for predicting the pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD.
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Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Albuterol/análogos & derivados , Androstadienos/uso terapéutico , Broncodilatadores/uso terapéutico , Enfisema , Modelos Lineales , Pulmón/fisiopatología , Pronóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , República de Corea , Pruebas de Función Respiratoria , Estudios Retrospectivos , Tomógrafos Computarizados por Rayos X , Resultado del TratamientoRESUMEN
It is unclear whether emphysema, regardless of airflow limitation, is a predictive factor associated with survival after lung cancer resection. Therefore, we investigated whether emphysema was a risk factor associated with the outcome after resection for lung cancer. This study enrolled 237 patients with non small cell lung cancer with stage I or II who had surgical removal. Patient outcome was analyzed based on emphysema. Emphysema was found in 43.4% of all patients. Patients with emphysema were predominantly men and smokers, and had a lower body mass index than the patients without emphysema. The patients without emphysema (n=133) survived longer (mean 51.2+/-3.0 vs. 40.6+/-3.1 months, P=0.042) than those with emphysema (n=104). The univariate analysis showed a younger age, higher FEV1/FVC, higher body mass index, cancer stage I, and a lower emphysema score were significant predictors of better survival. The multivariate analysis revealed a younger age, higher body mass index, and cancer stage I were independent parameters associated with better survival, however, emphysema was not. This study suggests that unfavorable outcomes after surgical resection of lung cancer should not be attributed to emphysema itself.
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Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Edad , Índice de Masa Corporal , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Enfisema/complicaciones , Neoplasias Pulmonares/complicaciones , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Factores de Riesgo , Fumar , Tasa de SupervivenciaRESUMEN
BACKGROUND/AIMS: Peroxiredoxin (Prx) belongs to a ubiquitous family of antioxidant enzymes that regulates many cellular processes through intracellular oxidative signal transduction pathways. Silica-induced lung damage involves reactive oxygen species (ROS) that trigger subsequent toxic effects and inflammatory responses in alveolar epithelial cells resulting in fibrosis. Therefore, we investigated the role of Prx in the development of lung oxidant injury caused by silicosis, and determined the implication of ROS in that process. METHODS: Lung epithelial cell lines A549 and WI26 were treated with 1% silica for 0, 24, or 48 hours, following pretreatment of the A549 cells with N-acetyl-L-cysteine and diphenylene iodonium and no pretreatment of the WI26 cells. We transfected an HA-ubiquitin construct into the A549 cell line and then analyzed the cells via Western blotting and co-immunoprecipitation. RESULTS: Silica treatment induced cell death in the A549 lung epithelial cell line and selectively degraded Prx I without impairing protein synthesis in the A549 cells, even when the ROS effect was blocked chemically by N-acetyl-L-cysteine. A co-immunoprecipitation study revealed that Prx I did not undergo ubiquitination. CONCLUSIONS: Silica treatment induces a decrease of Prx I expression in lung epithelial cell lines regardless of the presence of ROS. The silica-induced degradation of Prx does not involve the ubiquitin-proteasomal pathway.
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Humanos , Línea Celular , Células Epiteliales/efectos de los fármacos , Pulmón/química , Peroxirredoxinas/análisis , Isoformas de Proteínas , Especies Reactivas de Oxígeno/metabolismo , Dióxido de Silicio/toxicidad , Ubiquitina/metabolismoRESUMEN
PURPOSE: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Paclitaxel is an active agent against NSCLC and it has a radiosensitizing effect. We investigated the efficacy and toxicity of weekly paclitaxel administration along with concurrent radiotherapy for treating locally advanced and locally recurrent NSCLC. MATERIALS AND METHODS: Twenty-five previously untreated stage III or locally recurrent NSCLC patients received weekly paclitaxel (60 mg/m2) and concurrent radiotherapy. Chemotherapy was given on days 1, 8, 15 and 22. Concurrent radiotherapy at 1.5 Gy was given twice a day to a total dose of 54 Gy in 3.5 weeks. After the completion of CCRT, consolidation chemotherapy was delivered if possible. RESULTS: The overall response rate was 72% with one complete response and 17 partial responses. The median overall survival was 16 months with a 2 year survival rate and a 5 year survival rate of 38% and 24%, respectively. The rate of grade > 3 radiation pneumonitis was 16% (4 patients) and 2 patients were died from the pneumonitis. The rate of grade 3 radiation esophagitis was 12% (3 patients) and the hematologic toxicities were not significant. CONCLUSION: Weekly paclitaxel with concurrent radiotherapy is effective for treating locally advanced and locally recurrent NSCLC, but radiation pneumonitis is the major toxicity and this is potentially fatal.
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Humanos , Carcinoma de Pulmón de Células no Pequeñas , Quimioradioterapia , Quimioterapia de Consolidación , Esofagitis , Paclitaxel , Neumonía , Neumonitis por Radiación , Fármacos Sensibilizantes a Radiaciones , Tasa de SupervivenciaRESUMEN
BACKGROUND: The nitric oxide (NO) released by inducible NO synthase (iNOS) plays an important role in the pathophysiology of sepsis. Corticosteroids also play a role in the hemodynamic and inflammatory reactions in sepsis. Both have been shown to have a relationship theoretically, but their correlation and clinical impacts have rarely been evaluated. METHODS: 26 patients with sepsis and 14 healthy controls were enrolled in this study. The initial random plasma total NO and the serum cortisol levels were measured. The same measurements were serially carried out on the 3rd, 5th, and 7th days. RESULTS: The initial total plasma levels of NO and cortisol were higher in the patients with sepsis than in the healthy controls. The total NO levels were higher in patients with severe sepsis than in the those with mild sepsis. There was a correlation between the total NO and cortisol level throughout the study. CONCLUSION: In patients with sepsis, the levels of plasma NO and cortisol were well correlated during the first week of sepsis, which suggests an interrelationship. However, the clinical and pathogenetic implications await further evaluation.
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Humanos , Corticoesteroides , Hemodinámica , Hidrocortisona , Óxido Nítrico Sintasa , Óxido Nítrico , Plasma , Sepsis , Choque SépticoRESUMEN
BACKGROUND: The purpose of this study is to assess a score system for operative risk evaluation of CABG. MATERIAL AND METHOD: From January 2001 to September 2005, retrospective study for various perioperative factors of 2993 cases was done. RESULT: The early operative mortality was 2.4% and the beta coefficients of 7 core variables related to it (preoperative LV dysfuction, preoperative renal failure, MI within 1 week, reoperation, combined surgery, preoperative atrial fibrillation, preoperative IABP) were adjusted to score system. ROC curve and Hosmer and Lemeshow goodness of fit test was done. CONCLUSION: This score system was effective in assessing operative risk of CABG. But It is necessary to gather larger volume of case and perform multicenter study.
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Fibrilación Atrial , Puente de Arteria Coronaria , Vasos Coronarios , Mortalidad , Insuficiencia Renal , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Curva ROCRESUMEN
BACKGROUND: IS6110 DNA fingerprint is a very useful tool for investigating the transmission of tuberculosis. The aim of this study was to identify the epidemiological situations within a given area (one province). METHODS: The 681 Mycbobacterium tuberculosis isolates from patients, who were registered at health centers in Gyeonggi Province from May to December in 2004, were subjected to IS6110 DNA fingerprinting. Patients belonging to clusters were interviewed by health-workers to determine their previous contacts or household TB history. RESULTS: The number of IS6110 copies of the 681 isolates showed diverse fingerprint patterns from 0 to 21 of which the most prevalent copy number was 10 from 120 isolates (17.6%). Thirty-three isolates (4.8%) belonged to the K strain, and 128 isolates (18.8%) belonged to the K family. There were 180 (26.4%) isolates belonged belonging to fifty clusters, of which two clusters were within household transmission. Forty-three (23.9%) out of 180 patients resided in an area under the same health center control. The rate of clusters in those aged 60-70 was higher than in any other age group ( 95% CI of RR : 1.072 ~ 1.988). CONCLUSION: This is the first report of an epidemiological survey based on a whole province using a DNA fingerprinting technique for M. tuberculosis. These results will be helpful in developing a program or policies to prevent the transmission of TB.