Mortality and outcomes in very elderly patients 90 years of age or older admitted to the ICU.

BACKGROUND: We evaluated the clinical characteristics and factors associated with mortality in very elderly patients ≥ 90 y of age admitted to the ICU. METHODS: We evaluated age-specific rates of admission and mortality in 16,935 subjects ≥ 18 y old and retrospectively analyzed the clinical data of 155 (0.92%) subjects ≥ 90 y old admitted to the ICU from January 2003 to July 2012. The clinical mortality index was defined as the ICU mortality rate associated with clinical risk factors including poor nutrition, do not resuscitate (DNR) order, pneumonia, chronic renal failure, cancer, mechanical ventilation, use of a vasopressor, and admission from a ward. RESULTS: The mortality rate of ICU subjects ≥ 90 y of age was 32.3%. A Cox's regression hazard model revealed that high glucose (P = .006), poor nutrition (P = .001), high Simplified Acute Physiology Scoring II scores (P < .001), DNR order (P = .002), and vasopressor treatment (P = .03) were independent predictive factors of mortality in subjects ≥ 90 y of age admitted to the ICU. An increasing number of clinical risk factors was associated with progressively higher mortality rates. All subjects with more than 5 risk factors died. CONCLUSIONS: The very elderly subjects (≥ 90 y) admitted to the ICU had a higher mortality rate compared with subjects of other ages. High Simplified Acute Physiology Scoring II scores, poor nutritional status, high glucose, use of vasopressors, and DNR orders should be considered as important predictors of mortality in very elderly ICU patients. The level of ICU treatment should be carefully considered in very elderly patients presenting with 5 or more risk factors.

A comparison between the efficiency of the Xpert MTB/RIF assay and nested PCR in identifying Mycobacterium tuberculosis during routine clinical practice.

OBJECTIVES: Polymerase chain reaction (PCR) for the detection of Mycobacterium tuberculosis (MTB) is more sensitive, specific, and rapid than the conventional methods of acid-fast bacilli (AFB) smear and culture. The aim of this study was to determine if the Xpert MTB/rifampicin (RIF) assay had additional advantages over nested PCR for the detection of MTB in a geographical area with intermediate tuberculosis (TB) incidence. METHODS: Between February and December 2013, the Xpert MTB/RIF assay and MTB nested PCR, as well as AFB smear and culture, were simultaneously performed on 198 clinical samples (160 pulmonary and 38 non-pulmonary specimens) collected from 171 patients hospitalized at Hallym University Medical Center for possible TB. The accuracy of the diagnosis of MTB culture-positive TB and the turnaround time of reporting laboratory results were calculated and compared. Rifampin resistance by the Xpert MTB/RIF assay was reviewed with that of conventional drug susceptibility testing (DST). RESULTS: The sensitivity, specificity, and positive and negative predictive values of the Xpert MTB/RIF assay and MTB nested PCR for diagnosis of MTB culture-positive pulmonary TB were 86.1% vs. 69.4% (P=0.1563), 97.8% vs. 94.1% (P=0.2173), 91.2% vs. 75.8% (P=0.1695), and 96.4% vs. 92.0% (P=0.2032), respectively. The median turnaround times of the Xpert MTB/RIF assay and MTB nested PCR were 0 [0-4] days and 4 [1-11] days, respectively (P<0.001). Two cases of rifampin resistance, as determined by the Xpert MTB/RIF assay, were found to be multi-drug resistant (MDR) pulmonary TB by DST. CONCLUSIONS: The Xpert MTB/RIF assay seemed to be sensitive, specific, and comparable to nested PCR for identifying MTB among clinically suspected TB patients, and the assay can be valuable in giving a timely identification of resistance to rifampin.

Complete mitochondrial genomes of Carcinoscorpius rotundicauda and Tachypleus tridentatus (Xiphosura, Arthropoda) and implications for chelicerate phylogenetic studies.

Horseshoe crabs (order Xiphosura) are often referred to as an ancient order of marine chelicerates and have been considered as keystone taxa for the understanding of chelicerate evolution. However, the mitochondrial genome of this order is only available from a single species, Limulus polyphemus. In the present study, we analyzed the complete mitochondrial genomes from two Asian horseshoe crabs, Carcinoscorpius rotundicauda and Tachypleus tridentatus to offer novel data for the evolutionary relationship within Xiphosura and their position in the chelicerate phylogeny. The mitochondrial genomes of C. rotundicauda (15,033 bp) and T. tridentatus (15,006 bp) encode 13 protein-coding genes, two ribosomal RNA (rRNA) genes, and 22 transfer RNA (tRNA) genes. Overall sequences and genome structure of two Asian species were highly similar to that of Limulus polyphemus, though clear differences among three were found in the stem-loop structure of the putative control region. In the phylogenetic analysis with complete mitochondrial genomes of 43 chelicerate species, C. rotundicauda and T. tridentatus were recovered as a monophyly, while L. polyphemus solely formed an independent clade. Xiphosuran species were placed at the basal root of the tree, and major other chelicerate taxa were clustered in a single monophyly, clearly confirming that horseshoe crabs composed an ancestral taxon among chelicerates. By contrast, the phylogenetic tree without the information of Asian horseshoe crabs did not support monophyletic clustering of other chelicerates. In conclusion, our analyses may provide more robust and reliable perspective on the study of evolutionary history for chelicerates than earlier analyses with a single Atlantic species.

COPD patients with exertional desaturation are at a higher risk of rapid decline in lung function.

PURPOSE: A recent study demonstrated that exertional desaturation is a predictor of rapid decline in lung function in patients with chronic obstructive pulmonary disease (COPD); however, the study was limited by its method used to detect exertional desaturation. The main purpose of this study was to explore whether exertional desaturation assessed using nadir oxygen saturation (SpO2) during the 6-minute walk test (6MWT) can predict rapid lung function decline in patients with COPD. MATERIALS AND METHODS: A retrospective analysis was performed on 57 patients with moderate to very severe COPD who underwent the 6MWT. Exertional desaturation was defined as a nadir SpO2 of <90% during the 6MWT. Rapid decline was defined as an annual rate of decline in forced expiratory volume in 1 second (FEV1)≥50 mL. Patients were divided into rapid decliner (n=26) and non-rapid decliner (n=31) groups. RESULTS: A statistically significant difference in exertional desaturation was observed between rapid decliners and non-rapid decliners (17 vs. 8, p=0.003). No differences were found between the groups for age, smoking status, BODE index, and FEV1. Multivariate analysis showed that exertional desaturation was a significant independent predictor of rapid decline in patients with COPD (relative risk, 6.8; 95% CI, 1.8 to 25.4; p=0.004). CONCLUSION: This study supports that exertional desaturation is a predictor of rapid lung function decline in male patients with COPD.

Bronchoscopic ethanolamine injection therapy in patients with persistent air leak from chest tube drainage.

BACKGROUND: Chest tube drainage (CTD) is an indication for the treatment of pneumothorax, hemothroax and is used after a thoracic surgery. But, in the case of incomplete lung expansion, and/or persistent air leak from CTD, medical or surgical thoracoscopy or, if that is unavailable, limited thoracotomy, should be considered. We evaluate the efficacy of bronchoscopic injection of ethanolamine to control the persistent air leak in patients with CTD. METHODS: Patients who had persistent or prolonged air leak from CTD were included, consecutively. We directly injected 1.0 mL solution of 5% ethanolamine oleate into a subsegmental or its distal bronchus, where it is a probable air leakage site, 1 to 21 times using an injection needle through a fiberoptic bronchoscope. RESULTS: A total of 15 patients were enrolled; 14 cases of spontaneous pneumothorax [idiopathic 9, chronic obstructive pulmonary disease (COPD) 3, post-tuberculosis 2] and one case of empyema associated with broncho-pleural fistula. Of these, five were patients with persistent air leak from CTD, just after a surgical therapy, wedge resection with plication for blebs or bullae. With an ethanolamine injection therapy, 12 were successful but three (idiopathic, COPD and post-tuberculosis) failed, and were followed by a surgery (2 cases) or pleurodesis (1 case). Some adverse reactions, such as fever, chest pain and increased radiographic opacities occurred transiently, but resolved without any further events. With success, the time from the procedure to discharge was about 3 days (median). CONCLUSION: Bronchoscopic ethanolamine injection therapy may be partially useful in controlling air leakage, and reducing the hospital stay in patients with persistent air leak from CTD.

Application of a new spirometric reference equation and its impact on the staging of Korean chronic obstructive pulmonary disease patients.

PURPOSE: A new spirometric reference equation was recently developed from the first national chronic obstructive pulmonary disease (COPD) survey in Korea. However, Morris' equation has been preferred for evaluating spirometric values instead. The objective of this study was to evaluate changes in severity staging in Korean COPD patients by adopting the newly developed Korean equation. MATERIALS AND METHODS: We evaluated the spirometric data of 441 COPD patients. The presence of airflow limitation was defined as an observed post-bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) less than 0.7, and the severity of airflow limitation was assessed according to GOLD stages. Spirometric values were reassessed using the new Korean equation, Morris' equation and other reference equations. RESULTS: The severity of airflow limitation was differently graded in 143 (32.4%) patients after application of the new Korean equation when compared with Morris' equation. All 143 patients were reallocated into more severe stages (49 at mild stage, 65 at moderate stage, and 29 at severe stage were changed to moderate, severe and very severe stages, respectively). Stages according to other reference equations were changed in 18.6-49.4% of the patients. CONCLUSION: These results indicate that equations from different ethnic groups do not sufficiently reflect the airflow limitation of Korean COPD patients. The Korean reference equation should be used for Korean COPD patients in order to administer proper treatment.

A phase II study of pemetrexed and carboplatin as a salvage therapy for platinum-pretreated patients with non-small cell lung cancer.

BACKGROUND: Although platinum-based doublet chemotherapy is considered as standard of care for patients with advanced non-small cell lung cancer (NSCLC), most of them are eventually supposed to experience disease progression. Pemetrexed, docetaxel, erlotinib, and gefitinib have been shown to be active as monotherapy for pretreated patients. In this study, the efficacy of pemetrexed and carboplatin as a salvage therapy for patients with advanced NSCLC is evaluated. PATIENTS AND METHODS: From March 2007 to February 2009, 32 patients who were diagnosed with inoperable NSCLC and treated with one or more prior cisplatin-based chemotherapies were enrolled. Treatment consisted of pemetrexed 500 mg/m(2) over a 10-min intravenous infusion and carboplatin at an AUC 5 mg/mL/min over a 30-min intravenous infusion on Day 1 of a 21-day cycle. All patients were supplemented with folic acid and vitamin B12 to reduce the hematological toxicity of pemetrexed. RESULTS: There were one (3.1%) complete response and five partial (15.6%) responses. The overall response rate was 18.8% and the median response duration was 4.4 months. Among the responders, four patients had adenocarcinoma and two had squamous cell carcinoma. Nine patients had stable disease, and the disease control rate was 46.9%. With a median follow up duration of 9.4 months, the median time to progression was 2.3 months and the median OS was 9.4 months. Seven patients (21.9%) experienced grade 3 and 4 hematologic toxicities; one anemia (3.1%), six neutropenia (18.8%), and six thrombocytopenia (18.8%). Two patients experienced grade 4 febrile neutropenia with infection. Four patients (12.5%) experienced grade 3 non-hematologic toxicities; four asthenia (12.5%), two anorexia (6.3%), and one stomatitis (3.1%). Grade 1-2 peripheral neuropathy developed in 13 patients (40.6%). CONCLUSION: The combination of pemetrexed and carboplatin showed favorable toxicity profiles and activity in the pretreated patients with advanced NSCLC. It is suggested that this regimen can be a good chemotherapeutic option as a salvage therapy for patients with NSCLC.

Clinical efficacy of direct DNA sequencing analysis on sputum specimens for early detection of drug-resistant Mycobacterium tuberculosis in a clinical setting.

BACKGROUND: Early detection of drug-resistant Mycobacterium tuberculosis is important for the control and prevention of disease transmission. However, conventional drug susceptibility tests for drug-resistant M tuberculosis take at least 3 to 8 weeks. Here, we report the clinical efficacy of direct DNA sequencing analysis for detecting drug-resistant TB on sputum specimens in a clinical setting. METHODS: A total of 113 sputum specimens from 111 patients, who were suspected of having drug-resistant TB by clinicians, were used for DNA sequencing of katG, rpoB, embB, and pncA genes for isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide (PZA) resistance, respectively, and the results were compared with drug susceptibility tests. The optimization of antituberculosis drugs according to the results of DNA sequencing and the treatment outcomes of the patients were also analyzed. RESULTS: Turnaround time of the direct DNA sequencing analysis was 3.8 +/- 1.8 days. We found mutations related to drug resistance in 30 clinical specimens for katG, 39 for rpoB, 13 for embB, and 24 for pncA. The sensitivity and specificity of the assay were 63.6% and 94.6% for INH, 96.2 and 93.9% for RIF, 69.2% and 97.5% for EMB, and 100% and 92.6% for PZA, respectively. Of the patients with RIF resistance, including multidrug-resistant TB by the assay, 92.5% of the patients with initial first-line antituberculosis drugs were changed to second-line antituberculosis drugs, and treatment was successful in 61.9% of these cases. CONCLUSION: Direct DNA sequencing analysis of clinical sputum specimens is a rapid and useful method for the detection and treatment of drug-resistant TB.

Comparison of the prevalence of chronic obstructive pulmonary disease diagnosed by lower limit of normal and fixed ratio criteria.

The Global Initiative of Chronic Obstructive Lung Disease (GOLD) guidelines define chronic obstructive pulmonary disease (COPD) in subjects with FEV(1)/FVC <0.7. However, the use of this fixed ratio may result in over-diagnosis of COPD in the elderly, especially with mild degree of COPD. The lower limit of normal (LLN) can be used to minimize the potential misclassification. The aim of this study was to evaluate the impact of different definitions of airflow obstruction (LLN or fixed ratio of FEV(1)/FVC) on the estimated prevalence of COPD in a population-based sample. We compared the prevalence of COPD and its difference diagnosed by different methods using either fixed ratio (FEV(1)/FVC <0.7) or LLN criterion (FEV(1)/FVC below LLN). Among the 4,816 subjects who had performed spirometry, 2,728 subjects met new ATS/ERS spirometry criteria for acceptability and repeatability. The prevalence of COPD was 10.9% (14.7% in men, 7.2% in women) by LLN criterion and 15.5% (21.8% in men, 9.1% in women) by fixed ratio of FEV(1)/FVC among subjects older than 45 yr. The difference of prevalence between LLN and fixed ratio of FEV(1)/FVC was even higher among subjects with age >/=65, 14.9% and 31.1%, respectively. In conclusion, the prevalence of COPD by LLN criterion was significantly lower in elderly compared to fixed ratio of FEV(1)/FVC. Implementing LLN criterion instead of fixed ratio of FEV(1)/FVC may reduce the risk of over-diagnosis of COPD in elderly people.