Diagnostic utility of interferon-gamma release assay in extrapulmonary tuberculosis.

Early diagnosis of extrapulmonary tuberculosis (EP-TB) is essential. However, diagnosis of EP-TB is difficult. We evaluated the diagnostic utility of an interferon-gamma release assay (IGRA) in diagnosing active EP-TB among suspected patients in Korea. We retrospectively reviewed the clinical records of all patients with suspected EP-TB at Gangnam Severance Hospital in Seoul, Korea. Of the 418 patients with suspected EP-TB, 324 had active EP-TB. The tuberculosis (TB) group had a higher percentage of positive IGRAs (70.2%, 33/47) than the non-TB group (33.3%, 3/9) (P=0.034). The IGRA sensitivity and specificity were 70.2% (63.7-74.8%) and 66.7% (32.9-90.6%), respectively. The sensitivity and specificity of IGRAs in patients with TB lymphadenitis were 81.8% (61.4-90.4%) and 80.0% (35.1-98.9%), but 38.5% (31.2-45.7%) and 50.0% (2.7-97.3%) in patients with TB pleurisy. The diagnostic performance of IGRAs may vary depending on the site of EP-TB involvement. IGRA was potentially valuable for diagnosis of active EP-TB in TB lymphadenopathy.

Whole blood interferon-γ release assay is insufficient for the diagnosis of sputum smear negative pulmonary tuberculosis.

PURPOSE: We investigated the value of an interferon-γ release assay (IGRA) for the diagnosis of active pulmonary tuberculosis (PTB) among sputum smear negative PTB suspects in an environment with intermediate burden of PTB and high Bacillus Calmette-Guerin (BCG) vaccination rate. MATERIALS AND METHODS: We retrospectively reviewed IGRA, medical records, chest PA and CT scan of PTB suspects seen at Gangnam Severance Hospital, Seoul, Korea from Oct. 2007 to Apr. 2013. "Active PTB" was diagnosed when 1) M. tuberculosis culture positive, 2) confirmation by pathologic examination; or 3) clinical findings compatible with TB. RESULTS: Of 224 sputum smear negative PTB suspects, 94 were confirmed as having active PTB. There were no statistically significant differences in the diagnostic yield of IGRA between immunocompromised and immunocompetent sputum smear negative PTB suspects. IGRA did show superior sensitivity [81.9%, 95% confidence interval (CI); 74.13-89.70%] in the diagnosis of sputum smear negative PTB when compared with chest high-resolution computed tomography (HRCT), tuberculin skin test (TST), and chest X-ray (p<0.001). Also, IGRA showed highest negative predictive value (82.7%, 95% CI; 75.16-90.15%) when compared with HRCT, TST and chest X-ray (p=0.023). However, combining the results of IGRA with those of HRCT, TST, or both did not increase any diagnostic parameters. CONCLUSION: Failure to increase diagnostic yields by combination with other diagnostic modalities suggests that additional enforcement with IGRA may be insufficient to exclude other diagnoses in sputum smear negative PTB suspects and to screen active PTB in an environment with intermediate TB prevalence and a high BCG vaccination rate.

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.

Late respiratory infection after lung transplantation.

BACKGROUND: Aiming to improve outcome of lung transplantation (LTx) patients, we reviewed risk factors and treatment practices for the LTx recipients who experienced respiratory infection in the late post-LTx period (>1 month after LTx). METHODS: We analyzed the clinical data of 48 recipients and donors from 61 LTx, who experienced late respiratory infections. Late respiratory infections were classified according to the etiology, time of occurrence, and frequency of donor-to-host transmission or colonization of the recipient prior to transplantation. RESULTS: During the period of observation, 42 episodes of respiratory infections occurred. The organisms most frequently involved were gram (-) bacteria: Acinetobacter baumannii (n=13, 31.0%), Pseudomonas aeruginosa (n=7, 16.7%), and Klebsiella pneumoniae (n=4, 10.0%). Among the 42 episodes recorded, 14 occurred in the late post-LTx period. These were bacterial (n=6, 42.9%), fungal (n=2, 14.3%), viral (n=4, 28.5%), and mycobacterial (n=2, 14.3%) infections. Of 6 bacterial infections, 2 were from multidrug-resistant (MDR) A. baumannii and one from each of MDR P. aeruginosa, extended spectrum ß-lactamase (+) K. pneumoniae, methicillin-resistant Staphylococcus aureus and Streptococcus pneumoniae. Infection-related death occurred in 6 of the 14 episodes (43%). CONCLUSION: Although the frequency of respiratory infection decreased sharply in the late post-LTx period, respiratory infection was still a major cause of mortality. Gram (-) MDR bacteria were the agents most commonly identified in these infections.

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.

Clinical outcomes of tigecycline in the treatment of multidrug-resistant Acinetobacter baumannii infection.

PURPOSE: Acinetobacter baumannii (A. baumannii) has emerged as a major cause of nosocomial pneumonia and sepsis in seriously ill patients. Multidrug-resistant A. baumannii (MDRAB) is increasing in frequency, and the management of it's infections is consequently difficult. Therefore, tigecycline is considered to be the drug of choice for MDRAB treatment. The aim of our study was to evaluate the microbiological eradication and clinical effectiveness of tigecycline against MDRAB in seriously ill patients, including patients with ventilator-associated pneumonia (VAP). MATERIALS AND METHODS: We conducted a retrospective study including patients with A. baumannii infections who were treated with tigecycline between April 1, 2009 and March 31, 2010. We treated 27 patients with tigecycline for MDRAB infections. RESULTS: The mean age of patients was 66.2 years, and 20 (74.1%) patients were male. The median length of stay at hospital was 74.6 days. MDRAB was eradicated from the site of infection in 23 cases (85.2%), however, only 17 cases (63.0%) showed positive clinical responses. Overall, an in-hospital mortality rate of 51.9% was observed, and 4 cases of death were attributable to sepsis. The combination therapy showed better clinical and microbial success rates than the monotherapy without significant difference. CONCLUSION: We observed the relatively low clinical success rate although the microbial eradication rate was high, probably due to superinfections in VAP and bacteremia. We suggest that clinicians should limit tigecycline monotherapy for MDRAB infection in critically ill patients, until large controlled clinical trials should be conducted.

Overexpression of Romo1 promotes production of reactive oxygen species and invasiveness of hepatic tumor cells.

BACKGROUND & AIMS: Chronic oxidative stress from reactive oxygen species (ROS) produced by the mitochondria promotes hepatocarcinogenesis and tumor progression. However, the exact mechanism by which mitochondrial ROS contributes to tumor cell invasion is not known. We investigated the role of ROS modulator 1 (Romo1) in hepatocellular carcinoma (HCC) development and tumor cell invasiveness. METHODS: We performed real-time, semi-quantitative, reverse transcriptase polymerase chain reaction; invasion and luciferase assays; and immunofluorescence and immunohistochemical analyses. The formation of pulmonary metastatic nodules after tumor cell injection was tested in severe combined immunodeficient mice. We analyzed Romo1 expression in HCC cell lines and tissues (n = 95). RESULTS: Expression of Romo1 was increased in HCC cells, compared with normal human lung fibroblast cells. Exogenous expression of Romo1 in HCC cells increased their invasive activity, compared with control cells. Knockdown of Romo1 in Hep3B and Huh-7 HCC cells reduced their invasive activity in response to stimulation with 12-O-tetradecanoylphorbol-13-acetate. Levels of Romo1 were increased compared with normal liver tissues in 63 of 95 HCC samples from patients. In HCC samples from patients, there was an inverse correlation between Romo1 overexpression and patient survival times. Increased levels of Romo1 also correlated with vascular invasion by the tumors, reduced differentiation, and larger tumor size. CONCLUSIONS: Romo1 is a biomarker of HCC progression that might be used in diagnosis. Reagents that inhibit activity of Romo1 and suppress mitochondrial ROS production, rather than eliminate up-regulated intracellular ROS, might be developed as cancer therapies.

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.

Stress-induced cardiomyopathy following cephalosporin-induced anaphylactic shock during general anesthesia.

PURPOSE: Anaphylaxis may be caused by various agents during general anesthesia. Sympathetic discharge may occur during anaphylaxis, which can trigger transient cardiomyopathy. We describe a case of stress-induced cardiomyopathy that occurred in association with an anaphylactic reaction during general anesthesia. CLINICAL FEATURES: A 32-year-old female undergoing laparoscopic enucleation of an ovarian cyst developed a severe anaphylactic reaction after cephalosporin infusion during general anesthesia. Her vital signs responded favourably to immediate resuscitative maneuvers, but cardiovascular collapse reappeared with transient ventricular tachycardia shortly after her transfer to the intensive care unit. ST-segment elevation appeared in electrocardiographic leads V(2)-V(6) and echocardiography showed diffuse regional wall motion abnormalities in the midventricular level. Increased MB fractions of creatine kinase and troponin T levels indicated myocardial necrosis, but cardiac catheterization demonstrated normal coronary arteries. Management was supportive and she was discharged 2 days after the onset of anaphylactic symptoms, without sequelae. A diagnosis of stress-induced cardiomyopathy of a midventricular type following anaphylaxis was made on the basis of the clinical features and the findings of cardiac evaluations. CONCLUSIONS: Transient, reversible left-ventricular dysfunction is a recently recognized phenomenon that may occur in the setting of anaphylactic reactions during the perioperative period.