Care of patients with sepsis has improved over the last decade. However, in the recent two years, there was no significant progress in the development of a new drug for critically ill patients. In January 2011, it was announced that the worldwide phase 3 randomized trial of a novel anti-Toll-like receptor-4 compound, eritoran tetrasodium, had failed to demonstrate an improvement in the mortality of patients with severe sepsis. In October 2011, Xigris (drotrecogin alfa, a recombinant activated protein C) was withdrawn from the market following the failure of its worldwide trial that had attempted to demonstrate improved outcome. These announcements were disappointing. The recent failure of 2 promising drugs to further reduce mortality suggests that new approaches are needed. A study was published showing that sepsis can be associated to a state of immunosuppression and loss of immune function in human. However, the timing, incidence, and nature of the immunosuppression remain poorly characterized, especially in humans. This emphasizes the need for a better understanding of sepsis as well as new therapeutic strategies. Many clinical experiences of the extracorporeal membrane oxygenator (ECMO) treatment for adult acute respiratory distress syndrome (ARDS) patients, which is caused by the H1N1 influenza A virus, were reported. The use of ECMO in severe respiratory failure, particularly in the treatment of adult ARDS, is occurring more commonly.
Background: While qualitative analysis of methylation has been reviewed, the quantitative analysis of methylation has rarely been studied. We evaluated the methylation status of CDKN2A, RARβ, and RASSF1A promoter regions in non-small cell lung carcinomas (NSCLCs) by using pyrosequencing. Then, we evaluated the association between methylation at the promoter regions of these tumor suppressor genes and the clinicopathological parameters of the NSCLCs. Methods: We collected tumor tissues from a total of 53 patients with NSCLCs and analyzed the methylation level of the CDKN2A, RARβ, and RASSF1A promoter regions by using pyrosequencing. In addition, we investigated the correlation between the hypermethylation of CDKN2A and the loss of p16INK4A immunoexpression. Results: Hypermethylation of CDKN2A, RARβ, and RASSF1A promoter regions were 16 (30.2%), 22 (41.5%), and 21 tumors (39.6%), respectively. The incidence of hypermethylation at the CDKN2A promoter in the tumors was higher in undifferentiated large cell carcinomas than in other subtypes (p=0.002). Hyperrmethylation of CDKN2A was significantly associated with p16INK4A immunoexpression loss (p=0.045). With regard to the clinicopathological characteristics of NSCLC, certain histopathological subtypes were found to be strongly associated with the loss of p16INK4A immunoexpression (p=0.016). Squamous cell carcinoma and undifferentiated large cell carcinoma showed p16INK4A immunoexpression loss more frequently. The Kaplan-Meier survival curves analysis showed that methylation level and patient survival were barely related to one another. Conclusion: We quantitatively analyzed the promoter methylation status by using pyrosequencing. We showed a significant correlation between CDKN2A hypermethylation and p16INK4A immunoexpression loss.
Background: Oxidation plays an important role in acute lung injury. This study was conducted in order to elucidate the effect of repetitive post-treatment of N-acetylcysteine (NAC) in lipopolysaccaride (LPS)-induced acute lung injury (ALI) of rats. Methods: Six-week-old male Sprague-Dawley rats were divided into 4 groups. LPS (Escherichia coli 5 mg/kg) was administered intravenously via the tail vein. NAC (20 mg/kg) was injected intraperitoneally 3, 6, and 12 hours after LPS injection. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the ALI at 24 hours after LPS injection. The concentration of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)were measured in BALF. Nuclear factor κB (NF-κB), lipid peroxidation (LPO), and myeloperoxidase (MPO) were measured using lung tissues. Micro-computed tomography (micro-CT) images were examined in each group at 72 hours apart from the main experiments in order to observe the delayed effects of NAC. Results: TNF-α and IL-1β concentration in BALF were not different between LPS and NAC treatment groups. The concentration of LPO in NAC treatment group was significantly lower than that of LPS group (5.5±2.8 nmol/mL vs. 16.5±1.6 nmol/mL) (p=0.001). The activity of MPO in NAC treatment group was significantly lower than that of LPS group (6.4±1.8 unit/g vs. 11.2±6.3 unit/g, tissue) (p＜0.048). The concentration of NF-κB in NAC treatment group was significantly lower than that of LPS group (0.3±0.1 ng/μL vs. 0.4±0.2 ng/μL) (p=0.0001). Micro-CT showed less extent of lung injury in NAC treatment than LPS group. Conclusion: After induction of ALI with lipopolysaccharide, the therapeutic administration of NAC partially attenuated the extent of ALI through the inhibition of NF-κB activation.
Background: This study evaluates the bacterial pathogens of Ventilator-associated pneumonia (VAP) in a tertiary referral hospital. Methods: A total of 109 bacterial pathogens from 91 adult patients with VAP, who were admitted to the medical intensive care unit from January 2008 to December 2009, were examined. Clinical characteristics, bacterial pathogens, and resistance profiles were analyzed. Results: Staphylococcus aureus (44%) was the most frequently isolated. Acinetobacter baumanii (30%), Pseudomonas aeruginosa (12%), Stenotrophomonas maltophilia (7%), Klebsiella pneumoniae (6%), and Serratia marcescens (2%) were isolated from the transtracheal aspirates or bronchoalveolar lavage in patients with VAP. There was no significant difference of bacterial pathogens between early and late onset VAP. All isolated S. aureus were methicillin resistant S. aureus; the imipenem resistance rate of A. baumanii was 69%. Conclusion: The two most frequent pathogens of VAP were S. aureus and A. baumanii. There were no pathogenic differences between early and late onset VAP.
Background: The prevalence rate of pulmonary tuberculosis (PTB) is steadily decreasing in South Korea. However, PTB is a disease with relatively high mortality and morbidity rates throughout Korea. Although there are many studies and statistics about the risk factors of PTB mortality in many countries, there are only a limited number of domestic papers on this topic. The aim of this study is to determine predictive factors for mortality among in-hospital patients associated with PTB. Methods: From December 2006 to January 2011, we reviewed medical records of 2,122 adult patients diagnosed with tuberculosis at a single tertiary hospital in a suburban area. In this study period, 960 patients were diagnosed with PTB by positive Acid fast bacilli smear and/or mycobacterial culture of the respiratory specimen. We compared the groups of patients deceased and patients discharged alive with PTB. The number of dead patients was 82(47 males, 35 females). Results: Mortality was significantly associated with increased values of white blood cells (WBC), blood urine nitrogen (BUN), creatinine, C-reactive protein (CRP), numbers of involved lung field, and length of hospitalization. Also, it was associated with the decreased values of hemoglobin, lymphocyte, sodium, albumin, and cholesterol. Furthermore, admission through the emergency department, initial intensive care unit admission, and drug resistant PTB affected mortality in PTB patients. Independent predictors associated with PTB mortality are BUN, initial intensive care unit care, and admission during treatment of tuberculosis. Conclusion: In our study, mortality of pulmonary tuberculosis was related with parameters associated with nutritional status, disease severity at the time of admission, and drug resistance.
Background: The epidemiology of tuberculosis (TB) has been assessed based on the data of the analysis of TB patients notified to the surveillance system in Korea. However, the national status of TB is not validated through this surveillance system. The objective is to determine the epidemiology of TB and to understand the accurate status of TB patients treated in private institutions. Methods: Medical records of 53,579 patients who had been diagnosed with TB in 2008 were analyzed. Results: Among 53,579 patients, the number of sputum smear positive cases was 15,639(29.2%) and the number of new cases was 39,191 (73.1%). The drug resistance rate of new cases was 5.3%, while the rate stood at 13.3%for TB patients with treatment history. The number of multi-drug resistant TB (MDR-TB) patients was 2,472 (4.6%), which consists of 2.9% of new cases and 9.3% of TB patients with prior treatment history. The number of extensively drug-resistant TB patients was 749 (1.4%), consisting of 1.1% of new cases and 2.2% of TB patients with prior treatment history. In terms of treatment outcomes, 66.4% of all TB patients, 70.5% of new cases, 64.4%of relapse cases, and 46.8% of MDR-TB cases were cured or completed. It was inferred that in 2008, the total number of TB patients reached 70,767, 145.6 per 100,000 people (95% confidence interval, 145.5∼145.7). Conclusion: We conclude that the medical records review of the Health Insurance Review and Assessment Service (HIRA) data can be very effective in promoting the understanding of the current status of TB in private institutions.
A patient who has multiple lung masses with a history of malignancy in organs other than the lung is more likely to be diagnosed with metastatic rather than primary lung cancer. Rarely, metastatic cancer can coexist with primary. We experienced a case of concurrent diagnosis of primary small cell lung cancer and pulmonary metastasis of uterine malignant mixed Müllerian tumor (MMMT). The patient was a 52-year-old female with femur fracture and multiple lung masses with a history of an operation for uterine MMMT. The small cell lung cancer was diagnosed by bronchoscopic biopsy. The central lung mass decreased after chemotherapy for small cell lung cancer but multiple peripheral masses increased. A percutaneous biopsy for one of peripheral masses revealed metastatic uterine MMMT. We suggest that we have to consider the possible presence of concomitant malignancies of different origins in one organ especially with patients who had a history of malignancy in another organ.
Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (extranodal MZL) is a distinct subgroup of non-Hodgkin's lymphoma. Pulmonary extranodal MZL is a rare entity and accounts for less than 0.5% of primary pulmonary malignancies. Only a few cases of simultaneous occurrence of lung cancer and pulmonary extranodal MZL have been reported. A 60-year-old woman was referred to our hospital with a pulmonary nodule. She was diagnosed with lung adenocarcinoma by percutaneous needle biopsy. The protrusions into the left main bronchus were found by accident while performing bronchoscopy during lung cancer evaluation. The bronchial lesions were diagnosed as extranodal MZL. Although the patient underwent surgical resection for the lung adenocarcinoma, the pulmonary extranodal MZL was left untreated; it was monitored during follow-up visits. To our knowledge, this is the first report of synchronous lung adenocarcinoma and primary extranodal MZL of the main bronchus.