Search

Induction of PM 2.5 -associated lung cancer in response to EGFR -tyrosine kinase inhibitors ( EGFR -TKI) remains unclear. Polycyclic aromatic hydrocarbons (PAHs) and their polar derivatives (oxygenated PAHs: OPAHs and azaarenes: AZAs) were characterized in fine particulates (PM 2.5 ) emitted from indoor coal combustion. Samples were collected in Xuanwei (Yunnan Province), a region in China with a high rate of lung cancer. Human lung adenocarcinoma cells A549 (with wild-type EGFR ) and HCC827 (with EGFR mutation) were exposed to the PM 2.5 , followed by treatment with EGFR -TKI. Two samples showed significant and dose-dependent reduction in the cell viability in A549. EGFR -TKI further demonstrated significantly decreased in cell viability in A549 after exposure to the coal emissions. Chrysene and triphenylene, dibenzo[ a , h ]anthracene, benzo[ ghi ]perylene, azaarenes and oxygenated polycyclic aromatic hydrocarbons (carbonyl-OPAHs) were all associated with EGFR -TKI–dependent reduced cell viability after 72-h exposure to the PM 2.5 . The findings suggest the coal emissions could influence the response of EGFR -TKI in lung cancer cells in Xuanwei. [ABSTRACT FROM AUTHOR]

Objective: Self-expandable metallic stents are used to relieve airway stenosis in selected patients; however, fracture of these stents may occur. This analysis aims to investigate the extent of tracheal torsion, assessed by a computed-generated reformatted 3-dimensional tracheal reconstruction from 2-dimensional computed tomographic images in predicting fracture of tracheal self-expandable metallic stents. Methods: From 2001 to 2007, 32 patients (aged 62.8 ± 14.1 years) with benign tracheal diseases received chest computed tomographic evaluation and Ultraflex (Boston Scientific, Natick, Mass) self-expandable metallic stents. The bending angles of the central axis and peripheral wall of the trachea at choke point were measured from the computed-generated 3-dimensional tracheal images. Results: Seventeen fractured stents were found among the patients. The median time for stent fracture was 865 days after implantation. Receiver operating characteristic curve analysis revealed that a 19° bending angle of the tracheal central axis (area under the curve, 0.929; 95% confidence interval, 0.847–1.012; P < .001) and a 44° maximal bending angle of the peripheral tracheal wall (area under the curve, 0.918; 95% confidence interval, 0.821–1.012; P < .001) had maximal power in predicting tracheal fracture of self-expandable metallic stents. Conclusions: Three-dimensional tracheal reconstructions from 2-dimensional chest computed tomographic data are useful in assessing the severity of tracheal torsion. Tortuous trachea with a central axis bending angle of 19° or more and peripheral tracheal wall maximal bending angle of 44° or more were associated with a high probability of fracture of the self-expandable metallic stent. [ABSTRACT FROM AUTHOR]

Objectives: We sought to compare the diagnostic yields of acid-fast bacilli smears and Mycobacterium tuberculosis cultures in terms of bronchoalveolar lavage fluid and histologic examination of transbronchial lung biopsy specimens for pulmonary tuberculosis by using bronchoscopy with versus without endobronchial ultrasonography in patients with negative acid-fast bacilli smears or no sputum production. Methods: From June 2005 to July 2006, a total of 451 patients were given diagnoses of and treated for pulmonary tuberculosis in a university-affiliated hospital. Among them, 121 patients who received bronchoscopy because of sputum-negative conditions were recruited. Of these, 73 patients received bronchoscopy with endobronchial ultrasonography, and 48 patients received conventional bronchoscopy. Results: Patients who received bronchoscopy with endobronchial ultrasonography had higher diagnostic yields of acid-fast bacilli smears (31.5% vs 12.5%, P = .018) in bronchoalveolar lavage fluid, M tuberculosis in bronchoalveolar lavage fluid (67.1% vs 47.9%, P = .024), and pathologic reports of tuberculosis in transbronchial lung biopsy specimens (32.9% vs 4.2%, P < .0001) than patients who received conventional bronchoscopy. With the aid of endobronchial ultrasonography, the overall diagnostic yield for tuberculosis by using bronchoscopic procedures (smears and cultures of bronchoalveolar lavage fluid and transbronchial lung biopsy specimens) was higher (80.8%) than for those who did not undergo endobronchial ultrasonography (58.3%, P = .035). Conclusions: The addition of endobronchial ultrasonography to diagnostic bronchoscopy increased the sensitivity for proving the presence of tuberculosis in a population of patients with negative acid-fast bacilli smears or no sputum production. [Copyright &y& Elsevier]

Objective: This retrospective study was to determine factors that contribute to self-expandable metallic stent fracture in patients with tracheobronchial disease. Methods: From 2001 to 2006, 139 patients (age, 62.1 ± 15.4 years; range, 23–87 years) with benign (n = 62) and malignant (n = 77) tracheobronchial disease received 192 Ultraflex (Boston Scientific, Natick, Mass) self-expandable metallic stents (98 in patients with benign disease and 94 in patients with malignant disease). Results: Seventeen fractured self-expandable metallic stents were found; the incidence was 12.2% (17/139 patients) among patients with tracheobronchial disease. Tortuous airway (odds ratio, 4.06; 95% confidence interval, 1.04–18.34; P = .04) independently predicted self-expandable metallic stent fracture. Most self-expandable metallic stent fractures (64.7%, 11/17) were detected 500 to 1000 days after self-expandable metallic stent implantation. Clinical presentations for patients with fractured self-expandable metallic stents included dyspnea exacerbation (70.6%, 12/17) and cough (23.5%, 4/17). Conclusions: Self-expandable metallic stent fracture is not uncommon in patients with tracheobronchial disease. Tortuous airway is an independent predictor for it. Although management of the fractured self-expandable metallic stent in our study was feasible and safe, self-expandable metallic stents should be restricted to a more select population. [Copyright &y& Elsevier]

Abstract: Objectives: The aim of the study was to investigate the risk factors of developing early-onset delirium in mechanically ventilated patients and determine the subsequent clinical outcomes. Methods: Confusion assessment method for the intensive care unit (ICU) was used to assess the enrolled mechanically ventilated patients for delirium. The risk factors of developing delirium and clinical outcomes were determined in these subjects. Results: Delirium was present in 31 (21.7%) of 143 patients in the first 5 days. In multivariable analysis, hypoalbuminemia (odds ratio, 5.94; 95% confidence interval, 1.23-28.77) and sepsis (odds ratio, 3.65; 95% confidence interval, 1.03-12.9) increased the risk of developing delirium in mechanically ventilated patients. The patients with delirium had a higher in-hospital mortality (67.7% vs 33.9%, respectively; P = .001) and longer duration of mechanical ventilation (19.5 ± 15.8 vs 9.3 ± 8.8 days, respectively; P = .003) than patients without delirium. The incidence of nosocomial pneumonia was increased in delirious patients (64.5% vs 38.4%, P = .01) compared with nondelirious patients, whereas the lengths of ICU or hospital stay were similar between both groups. Conclusions: Mechanically ventilated patients with sepsis or hypoalbuminemia were more vulnerable to develop delirium in their early stay in the ICU. Early-onset delirium is associated with prolonged duration of mechanical ventilation and higher incidence of nosocomial pneumonia, leading to a higher mortality. [Copyright &y& Elsevier]

Summary: Endobronchial tuberculosis (TB) often leads to some degree of tracheobronchial stenosis. Because matrix metalloproteinases (MMPs) play an essential role in tissue remodeling in the airways, we investigated the role of MMP-1 polymorphism in patients with endobronchial TB. One hundred and one cases of pulmonary TB in Taiwanese patients were genotyped for the 1G/2G polymorphism of MMP-1 promoter (−1607bp). Bronchoscopic examination was performed to determine the presence of endobronchial involvement. Levels of MMP-1 in peripheral blood monocytes and in bronchial biopsies were also determined. 1G genotypes of MMP-1 polymorphism, containing at least one 1G allele, were associated with the presence of endobronchial TB. Using multivariate analysis, 1G genotypes and female gender were independent predictors of the development of endobronchial TB. Endobronchial TB patients with 1G genotypes had a 9.86-fold greater risk of developing tracheobronchial stenosis. IL-1β increased levels of MMP-1 in peripheral blood monocytes of TB patients with 1G genotypes. MMP-1 activity was also present in the endobronchial TB granuloma from patients with 1G/1G genotype. 1G genotypes of MMP-1 polymorphism were associated with a greater risk of developing tracheobronchial stenosis through up-regulation of MMP-1 activity. [Copyright &y& Elsevier]

Abstract: Defensins play a pivotal role in antimicrobial reactions, inflammatory responses, wound repair, and specific immunity. In inflammatory and infectious lung diseases, α-defensins are released from recruited neutrophils, and modulate a variety of lung cell functions. We found that human bronchial and alveolar epithelial cells treated with low and moderate concentrations (5 and 10 μg/ml) of purified neutrophil-derived α-defensin-1 secreted more interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 in a dose- and time-dependent manner. Under moderate and high concentrations (10 and 20 μg/ml) of α-defensin-1, we observed typical apoptotic changes in the lung epithelial cells after stimulation for 24 h. Furthermore, α-defensin-1 triggered lung cell detachment in a time- and dose-dependent manner at moderate and high concentrations. Prior to the detachment, caspase-3 activity significantly increased. On confocal laser microscopy, rapid translocation of α-defensin-1 to the endoplasmic reticulum (ER) was noted. These findings suggest that neutrophil-derived α-defensin-1 has pro-inflammatory and apoptotic effects in human bronchial and alveolar epithelial cells, which are concentration-dependent and may be associated with ER activity. [Copyright &y& Elsevier]

Abstract: Context: Since the development of palliative care in the 1980s, “do not resuscitate” (DNR) has been promoted worldwide to avoid unnecessary resuscitation in terminally ill cancer patients. Objectives: This study aimed to evaluate the effect of a palliative care consultation service (PCCS) on DNR designation and to identify a subgroup of patients who would potentially benefit from care by the PCCS with respect to DNR designation. Methods: In total, 2995 terminally ill cancer patients (with a predicted life expectancy of less than six months by clinician estimate) who received care by the PCCS between January 2006 and December 2010 at a single medical center in Taiwan were selected. Among these, the characteristics of 2020 (67.4%) patients who were not designated as DNR at the beginning of care by the PCCS were retrospectively analyzed to identify variables pertinent to DNR designation. Results: A total of 1301 (64%) of 2020 patients were designated as DNR at the end of care by the PCCS. Male gender and primary liver cancer were characteristics more predominantly found among DNR-designated patients who also had worse performance status, higher prevalence of physical distress, and shorter intervals from palliative care referral to death than did patients without DNR designation. On univariate analysis, a higher probability of DNR designation was associated with male gender, duration of care by the PCCS of more than 14 days, patients' prognostic awareness, family's diagnostic and prognostic awareness, and high Palliative Prognostic Index (PPI) scores. On multivariate analysis, duration of care by the PCCS, patients' prognostic awareness, family's diagnostic and prognostic awareness, and a high PPI score constituted independent variables predicting DNR-designated patients at the end of care by the PCCS. Conclusion: DNR designation was late in terminally ill cancer patients. DNR-designated cancer patient indicators were high PPI scores, patients' prognostic awareness, family's diagnostic and prognostic awareness, and longer durations of care by the PCCS. [Copyright &y& Elsevier]

Abstract: To recognize patients with inhibitory and neutralizing auto-antibodies to interferon-γ (AutoAbs-IFN-γ) presenting with the sporadic phenotype of Mendelian Susceptibility to Mycobacterial Disease (MSMD) mainly characterized by recurrent intracellular mycobacterium or/and salmonella infections, we comprehensively investigated IL12/23-IFN-γ signaling, candidate genetic sequencings or/and protein expressions of IL12RB1, IFNRG1, IL12p40, IFNRG2, STAT1, IKKA, NEMO, CYBB and IRF8 in four patients. Their serum was further titrated to detect AutoAbs-IFN-γ, for which the biological activity was assessed in Jurkat T cells. The patients mainly presented with recurrent non-tuberculous mycobacterium osteomyelitis and lymphadenopathy (Mycobacterium abscessus, chelonae and avium intracellular complex), and salmonella sepsis (S. enterica serogroup B, C2 and D). Additionally, Penicillium marneffei, varicella-zoster virus, and herpes simplex virus infections occurred. Inhibitory and neutralizing IFN-γ downstream signaling was elucidated in Jurkat cell lines as decreased MHC class I and phosphorylated STAT1 expression. Together with 24 patients from the PubMed search, the majority of the AutoAbs-IFN-γ patients were Asian (25/28). The most common involvement was lymph nodes (in 22/28), lungs (19/28) and bones (12/28). Mycobacterium avium complex (in 14) and chelonae (7) were the most common pathogens from 40 isolations. In contrast to those with the mild form of MSMD phenotype, AutoAbs-IFN-γ patients, in the absence of BCG-induced diseases, had a more persistent course and poor response to IFN-γ treatment. In conclusion, AutoAbs-IFN-γ patients may have a sporadic adult-onset MSMD phenotype in Asian regions endemic for mycobacterial infections. [Copyright &y& Elsevier]