A genetic variation in microRNA target site of KRT81 gene is associated with survival in early-stage non-small-cell lung cancer.

BACKGROUND: MicroRNAs (miRNAs) have a key role in carcinogenesis through negative regulation of their target genes. Therefore, genetic variations in miRNAs or their target sites may affect miRNA-mRNA interactions, thereby result in altered expression of target genes. This study was conducted to investigate the associations between single-nucleotide polymorphisms (SNP) located in the miRNA target sites (poly-miRTSs) and survival of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: Using public SNP database and miRNA target sites prediction program, 354 poly-miRTSs were selected for genotyping. Among these, 154 SNPs applicable to Sequenom's MassARRAY platform were investigated in 357 patients. A replication study was carried out on an independent patient population (n = 479). Renilla luciferase assay and reverse transcription-polymerase chain reaction were conducted to examine functional relevance of potentially functional poly-miRTSs. RESULTS: Of the 154 SNPs analyzed in a discovery set, 14 SNPs were significantly associated with survival outcomes. Among these, KRT81 rs3660G>C was found to be associated with survival outcomes in the validation cohort. In the combined analysis, patients with the rs3660 GC + CC genotype had a significantly better overall survival compared with those with GG genotype [adjusted hazard ratio (aHR) for OS, 0.65; 95% confidence interval (CI) 0.50-0.85; P = 0.001]. An increased expression of the reporter gene for the C allele of rs3660 compared with the G allele was observed by luciferase assay. Consistently, the C allele was associated with higher relative expression level of KRT81 in tumor tissues. CONCLUSION: The rs3660G>C affects KRT81 expression and thus influences survival in early-stage NSCLC. The analysis of the rs3660G>C polymorphism may be useful to identify patients at high risk of a poor disease outcome.

Radiologic and laboratory differences in patients with tuberculous and parapneumonic pleural effusions showing non-lymphocytic predominance and high adenosine deaminase levels.

PURPOSE: Tuberculous pleural effusion (TPE) is characterized by lymphocytic predominance and high adenosine deaminase (ADA) levels. However, TPEs sometimes present non-lymphocytic predominance, and parapneumonic effusion (PPE) often exceeds the cutoff value of ADA for TPE. Thus, the differential diagnosis of cases with pleural fluid (PF) showing non-lymphocytic predominance and high ADA levels is challenging. However, limited data concerning the clinical differences in these patients are available. METHODS: A retrospective study was conducted on TPE and PPE patients with PF showing non-lymphocytic predominance and ADA levels ≥40 U/L in 2009-2013 in a South Korean tertiary referral hospital. The clinical, laboratory, and computed tomography (CT) findings between the groups were analyzed using multivariate logistic regression to develop a prediction model with independent factors for TPE. RESULTS: Among 353 patients with TPE, 24 (6.8 %) showed PF with non-lymphocytic predominance and ADA levels of ≥40 U/L. Twenty-eight PPE patients who presented PF findings comparable with those of TPE patients were included in the control group. In the final analysis, PF ADA levels >58 U/L and nodular lung lesions on CT were independent positive predictors, while loculated effusion was an independent negative predictor for TPE. Using the prediction model, a score ≥ +3 provided a sensitivity of 88 %, specificity of 93 %, positive predictive value of 91 %, and negative predictive value of 90 % for TPE. CONCLUSION: PF ADA levels, nodular lung lesions, and loculated pleural effusion may help differentiate TPE from PPE in patients with PF showing non-lymphocytic predominance and ADA levels ≥40 U/L.

Comparison of the incidence between tuberculosis and nontuberculous mycobacterial disease after gastrectomy.

PURPOSE: Gastrectomy is a well-known risk factor for tuberculosis (TB). However, little data are available regarding the relationship between gastrectomy and the risk of nontuberculous mycobacterial (NTM) disease. Here, we investigated the incidence of TB and NTM lung disease in gastrectomized patients. METHOD: New cases of TB and NTM lung infection or disease were examined among patients who had undergone gastrectomy due to gastric cancer from 2003 to 2009 at a tertiary referral hospital in South Korea. Annualized incidence rates for cases were compared with those of the general population. RESULTS: This study included a total of 2,684 patients. New mycobacterial cases were found in 41 patients. Cases of TB and NTM lung infection were 35 (85 %) and 6 (15 %) including 2 NTM lung disease cases, respectively. Annualized crude incidence rates for TB, NTM lung infection, and NTM lung disease were 327/100,000, 56/100,000, and 19/100,000, respectively. The age-standardized incidence rate of TB was significantly higher in gastrectomized patients than in the general population. However, the standardized incidences of NTM lung infection and disease were not significantly different from those of non-gastrectomized patients. Patients with NTM lung infection frequently exhibited comorbid chronic lung disease, while those with TB were more frequently found to have fibronodular lesions on preoperative chest radiography. CONCLUSIONS: Gastrectomy does not appear to increase the risk of NTM lung disease. However, NTM lung infection or disease should be considered as a differential diagnosis of pulmonary TB in gastrectomized patients accompanying chronic lung disease.

Predictive factors for tuberculosis in patients with a TB-PCR-negative bronchial aspirate.

PURPOSE: Pulmonary tuberculosis (PTB), with a tuberculosis (TB)-polymerase chain reaction (PCR)-negative bronchial aspirate (BA), but a positive culture result is often encountered in clinical practice. However, limited data are available concerning clinical judgment in patients with suspected PTB and a TB-PCR-negative BA pending culture results. The present study aimed to identify predictors for PTB in patients with a TB-PCR-negative BA. METHODS: A retrospective study was conducted on patients who had undergone a bronchoscopy because of suspected PTB. Clinical, laboratory, and computed tomography (CT) findings were investigated in PTB patients with TB-PCR-negative but positive culture BA results, and non-PTB patients with a radiographic lesion comparable to the former. RESULTS: Of 250 patients screened, 31 (12 %) were diagnosed with PTB by positive culture results only. Of these 31 patients, 30 (97 %) had a lesion within one-third of the hemithorax as determined by chest radiography. In the final analysis of 30 PTB and 65 non-PTB patients with comparable radiographic lesions, a positive QuantiFERON-TB Gold In-Tube (QFT) result was independently associated with an increased risk of a positive TB culture. CT findings of consolidation were a negative predictor for PTB. Patients with a negative QFT result and consolidation had a negative predictive value of 95 % for PTB, while patients with a positive QFT result and nodular CT abnormalities without consolidation had a positive predictive value of 86 % for PTB. CONCLUSION: The simple combination of CT findings of consolidation and QFT test results may help clinicians to refine decision-making in patients with a TB-PCR-negative BA.

The clinical course of respiratory tuberculosis in lung cancer patients.

OBJECTIVE: To determine the clinical features of lung cancer patients with respiratory tuberculosis (TB), thereby elucidating the clinical course. SETTING: A tertiary referral hospital in Korea, with intermediate TB prevalence. DESIGN: A retrospective case-control study involving lung cancer patients in whom respiratory TB was diagnosed concurrently or sequentially. RESULTS: Of 36 lung cancer patients, 10 (27.8%) were diagnosed with TB concurrently with the diagnosis of lung cancer, while 26 (72.2%) were diagnosed with TB after the diagnosis of lung cancer. The median time from the diagnosis of lung cancer to the diagnosis of TB was 4 months (range -1-47). Five lung cancer patients presented with incidental microbiological or pathological findings. Of the 36 lung cancer patients, eight (22%) had no remarkable changes on chest radiography, while all control group patients had identifiable abnormalities (P < 0.001). In both groups, most patients completed the initially prescribed anti-tuberculosis medications, with some modest modifications. The most common cause of death in the lung cancer group was progression of lung cancer (89.5%). CONCLUSION: The clinical course of respiratory TB in lung cancer patients does not differ from that in patients without malignancy, suggesting that respiratory TB may not influence the clinical course of lung cancer patients if properly treated.

Polymorphisms in the type IV collagen alpha3 gene and the risk of COPD.

A number of genome-wide linkage analyses have identified the 2q33.3-2q37.2 region as the most likely to contain the genes that contribute to the susceptibility to chronic obstructive pulmonary disease (COPD). It was hypothesised that the type IV collagen alpha3 (COL4A3) gene, which is one of the genes located in the 2q33.3-2q37.2 region, may act as a low-penetrance susceptibility gene for COPD. To test this hypothesis, the association of COL4A3 -1162T>C, IVS2+12C>A, P141L, G162E, H451R, P574L and *315C>A polymorphisms with the risk of COPD was investigated in a case-control study of 311 COPD patients and 386 controls. The presence of at least one 451R allele was associated with a significantly higher risk of COPD compared with the 451 H/H genotype (adjusted odds ratio 1.48, 95% confidence interval (1.03-2.14)). When the subjects were stratified according to age and COPD severity, the 451R allele was associated with a significantly higher risk of COPD only in younger individuals with severe COPD (3.02 (1.37-6.67)). In conclusion, these findings suggest that the type IV collagen alpha3 gene contributes to the genetic susceptibility to chronic obstructive pulmonary disease.

Outcomes of standard and tailored anti-tuberculosis regimens in patients with tuberculous pleural effusion.

BACKGROUND: In an era of increasing concerns about drug resistance, there are limited data on treatment outcomes and recurrence rates after standard short-course anti-tuberculosis treatment in patients with culture-negative tuberculous pleural effusion (TPE). OBJECTIVE: To compare treatment outcomes and recurrence rates between a standard anti-tuberculosis regimen with negative culture and unavailable drug susceptibility testing (DST) data, and a tailored anti-tuberculosis regimen based on individual DST data. DESIGN: We analysed the data of all patients with TPE from the TB registry database at Kyungpook National University Hospital, South Korea, during 2008-2012. The study population was divided into two groups according to regimen. RESULTS: Standard and tailored anti-tuberculosis regimens were administered to respectively 124 and 146 patients with TPE. Drug resistance was detected in 10% of patients with TPE, about a quarter of whom were multidrug-resistant. The treatment completion rate was not significantly different between the two groups (91% vs. 93%). During a median 20-month follow-up, the recurrence rate was also similar in both groups (1% vs.1%). CONCLUSIONS: Despite limited statistical power, these preliminary results support the hypothesis that immunocompetent patients with culture-negative TPE can be appropriately managed with a standard short-course anti-tuberculosis regimen, even in this era of increasing concerns about drug resistance.

Lymphoid interstitial pneumonia: clinical features, associations and prognosis.

Lymphoid interstitial pneumonia (LIP) is rare and its clinical course incompletely described. The aim of this study was to examine the clinical features, associations and prognosis of surgical lung biopsy-proven LIP. The study group consisted of 15 subjects encountered over a 14-yr period. The majority of subjects were females (n = 11) and the mean age was 47 yrs (range 17-78 yrs). Underlying systemic immune disorders were frequent, including Sjögren's syndrome (n = 8), rheumatoid arthritis, systemic lupus erythematosus, polymyositis, common variable immunodeficiency and dysproteinaemia. Only three patients were classified as "idiopathic". Presenting symptoms were dominated by dyspnoea and cough. Restrictive physiology, reduced diffusion capacity (62.5+/-18.4% predicted) and bronchoalveolar lavage lymphocytosis (30.5+/-29.1% pred) were noted. Thirteen patients received corticosteroid therapy. Of the nine whose response could be assessed, four showed clinical improvement and four were stable. Overall, median survival was 11.5 yrs. Of the seven patients who died, respiratory problems were the primary cause of death in three. Conversion to lymphoma was not identified. In conclusion, histopathological lymphoid interstitial pneumonia is commonly associated with immune system dysregulation, with idiopathic lymphoid interstitial pneumonia being extremely rare. Clinical stability or improvement with corticosteroids can be expected; however, survival remains impaired.

Extraordinary Strengthening Effect of Carbon Nanotubes in Metal-Matrix Nanocomposites Processed by Molecular-Level Mixing.

Carbon-nanotube-reinforced Cu matrix nanocomposites have been fabricated by molecular-level mixing of functionalized carbon nanotubes (CNTs) with Cu ions, followed by spark plasma sintering. The compressive strengths and Young's moduli of CNT-reinforced nanocomposites are considerably higher than those of the Cu matrix due to the homogeneously dispersed CNTs embedded in the Cu matrix.