Introduction: Smoking cessation activities incorporated into lung cancer screening programs have been broadly recommended, but studies to date have not shown increased quit rates associated with cessation programs in this setting. We aimed to determine the effectiveness of smoking cessation counseling in smokers presenting for lung cancer screening. Methods: This study is a randomized control trial of an intensive telephone-based smoking cessation counseling intervention incorporating lung cancer screening results versus usual care (information pamphlet). All active smokers enrolled in the Alberta Lung Cancer Screening Study cohort were randomized on a 1:1 ratio with a primary endpoint of self-reported 30-day abstinence at 12 months. Results: A total of 345 active smokers participating in the screening study were randomized to active smoking cessation counseling (n ¼ 171) or control arm (n ¼ 174). Thirty-day smoking abstinence at 12 months postrandomization was noted in 22 of 174 (12.6%) and 24 of 171 (14.0%) of participants in the control and intervention arms, respectively, a 1.4% difference (95% confidence interval:-5.9 to 8.7, p ¼ 0.7). No statistically significant differences in 7-day or point abstinence were noted, nor were differences at 6 months or 24 months. Conclusions: A telephone-based smoking cessation counseling intervention incorporating lung cancer screening results did not result in increased 12-month cessation rates versus written information alone in unselected smokers undergoing lung cancer screening. Routine referral of all current smokers to counseling-based cessation programs may not improve long-term cessation in this patient cohort. Future studies should specifically focus on this subgroup of

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Lung ischemia-reperfusion (I-R) is an important model of oxidant-mediated acute lung and vascular injury. Heme oxygenase-1 (HO-1) is a cytoprotective gene that is markedly induced by lung I-R injury. HO-1 mRNA is increased in mouse lung after 30 min of lung hilar clamping (ischemia) followed by 2-6 h of unclamping (reperfusion) compared with control mice. In a variety of vascular cell types, HO-1 mRNA is induced after 24 h of anoxia followed by 30 min-1 h of reoxygenation (A-R). Transfection studies reveal that the promoter and 5'-distal enhancer E1 are necessary and sufficient for increased HO-1 gene transcription after A-R. Immunoblotting studies show all three subfamilies of MAPKs (ERK, JNK, and p38) are activated by 15 min of reperfusion. We also demonstrate that HO-1 gene transcription after A-R involves ERK, JNK, and p38 MAPK pathways. Together, our data show that I-R not only induces HO-1 gene expression in mouse lungs and vascular cells but that gene transcription occurs via the promoter and E1 enhancer and involves upstream MAPK pathways.

Background Lung cancer is a major health problem. CT lung screening can reduce lung cancer mortality through early diagnosis by at least 20%. Screening high-risk individuals is most effective. Retrospective analyses suggest that identifying individuals for screening by accurate prediction models is more efficient than using categorical agesmoking criteria, such as the US Preventive Services Task Force (USPSTF) criteria. This study prospectively compared the effectiveness of the USPSTF2013 and PLCOm2012 model eligibility criteria. MethodsIn this prospective cohort study, participants from the International Lung Screening Trial (ILST), aged 55-80 years, who were current or former smokers (ie, had ≥30 pack-years smoking history or ≤15 quit-years since last permanently quitting), and who met USPSTF2013 criteria or a PLCOm2012 risk threshold of at least 1•51% within 6 years of screening, were recruited from nine screening sites in Canada, Australia, Hong Kong, and the UK. After enrolment, patients were assessed with the USPSTF2013 criteria and the PLCOm2012 risk model with a threshold of at least 1•70% at 6 years. Data were collected locally and centralised. Main outcomes were the comparison of lung cancer detection rates and cumulative life expectancies in patients with lung cancer between USPSTF2013 criteria and the PLCOm2012 model. In this Article, we present data from an interim analysis. To estimate the incidence of lung cancers in individuals who were USPSTF2013-negative and had PLCOm2012 of less than 1•51% at 6 years, ever-smokers in the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO) who met these criteria and their lung cancer incidence were applied to the ILST sample size for the mean follow-up occurring in the ILST. This trial is registered at ClinicalTrials.gov, NCT02871856. Study enrolment is almost complete.

M-T7 is a myxoma virus-encoded protein that has been found to bind and disrupt human chemokine gradients. This study examined whether purified M-T7 could prevent chronic rejection in a rat renal allograft model. Fisher F344 renal allografts were transplanted into Lewis rats. Recipients were randomly grouped into two groups: control animals treated with cyclosporine alone and animals treated with cyclosporine combined with low-, medium- and high-dose M-T7 viral protein. The survival rate was not significantly different between allograft groups. Renal allografts treated with high-dose M-T7 demonstrated a significant reduction in tubular atrophy, glomerular atrophy, vascular hyalinization, cortical scarring, and lymphocyte infiltration. Morphometric analyses demonstrated that the high-dose M-T7 group also showed a significantly decreased amount of glomerulosclerosis and transplant arteriosclerosis. These data demonstrate for the first time that the immunoregulatory viral protein M-T7 can effectively attenuate chronic rejection in rat renal allografts.

Purpose: MicroRNAs (miRNAs) post-transcriptionally regulate hundreds of gene targets involved in tumorigenesis thereby controlling vital biological processes, including cellular proliferation, di erentiation and apoptosis. MiRNA pro ling is an emerging tool for the potential early detection of a variety of malignancies. is study was conducyed to assess the feasibility and methodological robustness of quantifying sputum miRNAs, employing quantitative real-time polymerase chain reaction (RT-qPCR) and cluster analysis on an optimized miRNA pro le as a novel approach for the early detection of non-small cell lung cancer (NSCLC).Methods: e relative expressions of 11 miRNAs in sputum (miR-21, miR-145, miR-155, miR-205, miR-210, miR-92, miR-17-5p, miR-143, miR-182, miR-372, and let-7a) in addition to U6 were retrospectively assessed in four NSCLC-positive and four negative controls. Subsequently, a set of ve miRNAs (miR-21, miR-143, miR-155, miR-210, miR-372) was selected because of degree of relatedness observed in the cluster analysis and tested in the same sputum sample set. e ve optimized miRNAs accurately clustered these eight retrospective patients into NSCLC positive cases and negative controls. e ve miRNA panel was then prospectively quanti ed in the sputum of 30 study patients (24 NSCLC cases and six negative controls) in a double-blind fashion to validate a ve miRNA panel using hierarchical cluster analysis.Results: e optimized ve miRNA panel detected NSCLC (83.3% sensitivity and 100% speci city) in 30 prospectively accrued study patients.Conclusion: Sputum miRNA pro ling using cluster analysis is a promising approach for the early detection of non-small cell lung cancer. Further investigation using this approach is warranted.

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was as follows: In adults with unilateral diaphragmatic paralysis, does diaphragmatic plication offer functional improvement in dyspnoea, better pulmonary function tests (PFTs) and return to activity? A total of 126 papers were found using the reported search, of which 13 represented the best evidence to answer the clinical question. The authors, date and country of publication, patient group studied, surgical approach, study type, relevant outcomes and results of these articles are tabulated. Those articles reporting improvement in PFTs following plication, documented this benefit in the following parameters: mean forced vital capacity (range 17-40%), forced expiratory volume at 1 sec (range 21-27%), functional residual capacity (range 20-21%) and total lung capacity (range 16-19%). The percentage of postoperative improvement in shortness of breath as measured by a dyspnoea score was reported to be between 90 and 96% in the thoracotomy group and 100% in the Video Assisted Thoracoscopic Surgery (VATS) group, the dyspnoea score that was used in all the studies was a visual analogue scale between 0 and 10 where 0 is no dyspnoea and 10 is the worst dyspnoea a patient can have. One of the studies reported postoperative normalization in ventilation perfusion scan (VQ) scan parameters when compared with the preoperative mismatch. Complication rate was similar between the two groups, while the mortality rate was 4% in the thoracotomy group and 0% in the VATS group. The total number of patients included in all the studies combined was 161. All reports included in this review are observational studies (one cohort study and the remainder being case series); therefore, the risk of selection, information and publication biases are high and conclusions should be implemented with caution. We conclude that diaphragmatic plication can improve the functional status, shortness of breath and PFTs of patients with unilateral diaphragm paralysis. Patients undergoing a VATS approach appear to have more advantages in objective and subjective measures (including PFTs, dyspnoea score, length of hospital stay and postoperative complications). Further research with high-quality study designs is advised, focussing mainly on the long-term benefits and assessment of health-related quality of life.

Lung cancer is the leading cause of cancer related morbidity and mortality worldwide. Currently, the vast majority of lung cancers are diagnosed at a late stage, when patients become symptomatic leading to dismal, less than 15% five-year survival rates. Evidence has demonstrated that screening computed tomography scans can be used to detect lung cancer, but these scans have high false positive rates. Therefore, there is a continued need for the development of minimally-invasive methods to screen the high risk population and diagnose lung cancer at an earlier, curable stage. One such promising area is the use micro-RNAs. These are short, non-coding RNA molecules that have been shown in previous research to be dysregulated in cancers. This review will focus on the potential use of miRNA levels in various biological fluids (whole blood, plasma, serum, and sputum) and demonstrate their potential utility as screening and diagnostic biomarkers for lung cancer. Current research will be analyzed and compared, and future directions in establishing the use of miRNAs for detecting lung cancer will be discussed.