Login to your account

Username *
Password *
Remember Me

Blog With Right Sidebar

    Vous êtes ici :  
  1. Accueil
  2. Blog With Right Sidebar

Smoking adversely affects treatment response, outcome and relapse in tuberculosis.

Related Articles

Smoking adversely affects treatment response, outcome and relapse in tuberculosis.

Eur Respir J. 2014 Oct 30;

Authors: Leung CC, Yew WW, Chan CK, Chang KC, Law WS, Lee SN, Tai LB, Leung EC, Au RK, Huang SS, Tam CM

Abstract
The impact of smoking on tuberculosis outcome was evaluated in a territory-wide treatment programme. 16 345 consecutive patients undergoing chemotherapy for active tuberculosis in government chest clinics in Hong Kong from 2001 to 2003 were followed up prospectively for 2 years for treatment outcome and subsequently tracked through the territory-wide tuberculosis notification registry for relapse until the end of 2012. Smoking was associated with more extensive lung disease, lung cavitation and positive sputum smear and culture at the baseline. In both current smokers and ex-smokers, sputum smears and cultures were significantly more likely to remain positive after 2 months of treatment. Both categories of smokers were significantly less likely to achieve cure or treatment completion within 2 years. Overall, 16.7% of unsuccessful treatment outcomes were attributable to smoking, with the key contributor being default in current smokers and death in ex-smokers. Among successful treatment completers, there was a clear gradient (hazard ratios of 1.00, 1.33, and 1.63) of relapse risk from never-smokers to ex-smokers and current smokers, with an overall population attributable risk of 19.4% (current smokers: 12.2%; ex-smokers: 7.2%). Smoking adversely affects baseline disease severity, bacteriological response, treatment outcome and relapse in tuberculosis. Smoking cessation likely reduces relapse and secondary transmission.

PMID: 25359352 [PubMed - as supplied by publisher]

Exosomes - structure, biogenesis and biological role in non small cell lung cancer.

Related Articles

Exosomes - structure, biogenesis and biological role in non small cell lung cancer.

Scand J Immunol. 2014 Oct 30;

Authors: Frydrychowicz M, Kolecka-Bednarczyk A, Madejczyk M, Yasar S, Dworacki G

Abstract
Many different cells produce and release membraneous microvesicles (MV) or exosomes into their microenvironment. Exosomes represent a specific subtype of secreted derived vesicles which are defined as homogenous vesicles of 30-100 nm lined by a lipid bilayer, that contain a specific set of proteins, lipids, and nucleic acids. There are clear evidences that they serve as important biological signals messangers and carriers in physiological as well as in pathological processes. Those derived from tumors (tumor-derived exosomes, TD-exosomes) function as pro-tumorigenic factors that can mediate intercellular communication in the tumor microenvironment and also contribute to cancer progression. The main functions of exosomes in the cancer microenvironment include: promotion of primary cancer growth, stimulation of angiogenesis, activation of stromal fibroblasts, sculpting the cancer ECM, generation of a pre-metastatic niche, and suppression of host immune response. Exosomes have recently emerged as potentially promising diagnostic and prognostic biomarkers in cancer and other diseases. This article is a summary of information about the structure and origin of exosomes, and also indicates the importance of exosomes, and microRNAs in lung cancer. The role of exosomes in NSCLC is little known, and its explanation requires thorough research. This article is protected by copyright. All rights reserved.

PMID: 25359529 [PubMed - as supplied by publisher]

Effect of circulating tumor cells combined with negative enrichment and CD45-FISH identification in diagnosis, therapy monitoring and prognosis of primary lung cancer.

fastcell2Circulating tumor cells (CTCs) are valuable for diagnosis, monitoring therapy and prognosis in primary lung cancer. Herein, we evaluated the clinical significance of lung cancer CTCs in this study.

Detection of CTCs was performed using epithelial cell adhesion molecule-independent enrichment and CD45 fluorescence in situ hybridization detection. CTCs ≥2/3.2 mL were considered as positive. The positive rates in primary lung cancer, benign lung disease and healthy control groups were 84, 0 and 4.2 %. CTCs count was significantly higher in lung cancer patients than healthy controls and benign lung disease, with an area under ROC curve of 0.917 (95 % confidence interval 0.855-0.979; p = 0.000) between lung cancer and nonmalignant diseases. CTCs count significantly increased with an increase in pathological stage with mean count of 2.3 ± 2.6 (stage I-II), 3.5 ± 3.3 (stage III) and 4.5 ± 4.3 (stage IV), respectively. The positive detection rate of CTCs for primary lung cancer diagnosis was higher than serum tumor markers.

In total, 25 metastasis lung cancer patients participated in the follow-up. Changes in CTCs count after two cycles of chemotherapy were consistent with radiographic appearance. Moreover, CTCs count was better than serum tumor markers for monitoring chemotherapy response. Median progression-free survival (PFS) was 2.05, 3.25 and 8.348 months (p < 0.05) in group in which post-treatment CTCs count was increased, unchanged and decreased, respectively.

Furthermore, PFS in patients whose post-treatment CTCs count increased or were unchanged accompanied by a baseline CTCs count <3 was significantly shorter than those whose post-treatment CTCs count decreased or was unchanged accompanied with baseline value ≥3 (1.85 vs. 8.22 months, p = 0.000). Therefore, CTCs are a reproducible indicator of disease status that may be superior to imaging.

Pathogenesis of post primary tuberculosis: immunity and hypersensitivity in the development of cavities.

M. Tuberculosis (MTB) is an obligate human parasite even though humans are more resistant than any of the animals used for study. It is a human parasite because only humans develop post primary tuberculosis (TB) in their lungs that mediates transmission of infection to new hosts.

The extreme paucity of human lung tissue with post primary TB has forced scientists to study animal models and human tissues that do not have the disease. Consequently, the unique features of post primary TB remain largely unknown and misconceptions are widely accepted. This manuscript presents a revised pathogenesis of post primary TB based on studies of lung tissues of thousands of patients by multiple authors and related literature.

Primary TB stimulates systemic immunity that kills organisms and heals granulomas resulting in both protection from disseminated TB and resistance to new infection. Post primary TB, in contrast, requires systemic immunity that it subverts to produce local susceptibility in the apex of the lung. It begins in the part of lung with the lowest ventilation, perfusion and movement and then proceeds to paralyze alveolar macrophages, block the exits and suppress inflammation to further isolate the area with post obstructive pneumonia. This provides a safe place for a small number of MTB to drive prolonged accumulation of host lipids and mycobacterial antigens in an otherwise immune person. After many months, the affected lung suddenly undergoes caseation necrosis with vanishingly few MTB. The necrotic tissue fragments to produce a cavity or hardens to develop fibrocaseous disease.

Evidence suggests that this is triggered by a hypersensitivity reaction against cord factor and then progresses as the Koch phenomenon against many antigens. MTB grow in perfusion only in dead tissue or on a cavity wall.

We anticipate that a more accurate understanding of the pathogenesis of post primary TB will facilitate focusing modern technologies to produce rapid advances in understanding and combating TB.

Tracking a tuberculosis outbreak over 21 years: strain-specific single nucleotide polymorphism-typing combined with targeted whole genome sequencing.

Whole genome sequencing (WGS) is increasingly used in molecular-epidemiological investigations of bacterial pathogens, despite cost- and time-intensive analyses. We combined strain-specific single nucleotide polymorphism (SNP)-typing and targeted WGS to investigate a tuberculosis cluster spanning 21 years in Bern, Switzerland.

METHODS:  Based on genome sequences of three historical outbreak Mycobacterium tuberculosis isolates, we developed a strain-specific SNP-typing assay to identify further cases. We screened 1,642 patient isolates, and performed WGS on all identified cluster isolates. We extracted SNPs to construct genomic networks. Clinical and social data were retrospectively collected.

RESULTS:  We identified 68 patients associated with the outbreak strain. Most were diagnosed in 1991-1995, but cases were observed until 2011. Two thirds belonged to the homeless and substance abuser milieu. Targeted WGS revealed 133 variable SNP positions among outbreak isolates. Genomic network analyses suggested a single origin of the outbreak, with subsequent division into three sub-clusters. Isolates from patients with confirmed epidemiological links differed by 0-11 SNPs.

CONCLUSIONS:  Strain-specific SNP-genotyping allowed rapid and inexpensive identification of M. tuberculosis outbreak isolates in a population-based strain collection. Subsequent targeted WGS provided detailed insights into transmission dynamics. This combined approach could be applied to track bacterial pathogens in real-time and at high resolution.

Search

Search