The First Pulmonary Hypertension Registry in the United Arab Emirates (UAEPH): Clinical Characteristics, Hemodynamic Parameters with Focus on Treatment and Outcomes for Patients with Group 1-PH.

BACKGROUND: The aim of this study is to present the first United Arab Emirates pulmonary hypertension registry of patients' clinical characteristics, hemodynamic parameters and treatment outcomes. METHOD: This is a retrospective study describing all the adult patients who underwent a right heart catheterization for evaluation of pulmonary hypertension (PH) between January 2015 and December 2021 in a tertiary referral center in Abu Dhabi, United Arab Emirates. RESULTS: A total of 164 consecutive patients were diagnosed with PH during the five years of the study. Eighty-three patients (50.6%) were World Symposium PH Group 1-PH; nineteen patients (11.6%) were Group 2-PH due to left heart disease; twenty-three patients (14.0%) were Group 3-PH due to chronic lung disease; thirty-four patients (20.7%) were Group 4-PH due to chronic thromboembolic lung disease, and five patients (3.0%) were Group 5-PH. Among Group 1-PH, twenty-five (30%) had idiopathic, twenty-seven (33%) had connective tissue disease, twenty-six (31%) had congenital heart disease, and five patients (6%) had porto-pulmonary hypertension. The median follow-up was 55.6 months. Most of the patients were started on dual then sequentially escalated to triple combination therapy. The 1-, 3- and 5-year cumulative probabilities of survival for Group 1-PH were 86% (95% CI, 75-92%), 69% (95% CI, 54-80%) and 69% (95% CI, 54-80%). CONCLUSIONS: This is the first registry of Group 1-PH from a single tertiary referral center in the UAE. Our cohort was younger with a higher percentage of patients with congenital heart disease compared to cohorts from Western countries but similar to registries from other Asian countries. Mortality is comparable to other major registries. Adopting the new guideline recommendations and improving the availability and adherence to medications are likely to play a significant role in improving outcomes in the future.

Corrigendum to "Assessment of Bone Mineral Density in Male Patients with Chronic Obstructive Pulmonary Disease by DXA and Quantitative Computed Tomography".

[This corrects the article DOI: 10.1155/2016/6169721.].

The annual direct costs of stable COPD in Greece.

Introduction: Chronic obstructive pulmonary disease (COPD) places a major burden on health care systems and has substantial economic effects; however, the cost of stable disease in Greece has never been thoroughly explored. The objective of the study was to estimate the annual COPD patient cost during the maintenance phase and explore the relationships between the cost and disease severity. Methods: Data were collected from 245 COPD patients (male: 231, mean age: 69.5±8.8 years) who visited the outpatient unit of University Hospital of Larissa in 2014 and 2015. Patients were classified according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, and the patients' direct cost during the maintenance phase was calculated. Results: Eleven percent of COPD patients were stage I, 48.2% were stage II, 29% were stage III, and 11.8% were stage IV. According to the GOLD groups, 23.3% of patients were grade A, 15.5% were grade B, 22.9% were grade C, and 38.4% were grade D. The mean annual direct cost for stable disease was estimated at €1,034.55 per patient, of which €222.94 corresponded to out-of-pocket payments. The annual cost ranged from €408.23 to €2,041.89 depending on GOLD stages (I-IV) and from €550.01 to €1,480.00 depending on GOLD groups (A-D). The key cost driver was pharmaceutical treatment, which reflected almost 71% of the total expenses for the management of stable disease. The mean annual per-patient cost was two to three times higher for those with advanced disease (stages III-IV) compared to those with stages I-II disease, and it doubled for "high-risk" patients (groups C-D) compared to "low-risk" patients (groups A-B). Conclusion: The cost of COPD during the maintenance phase is remarkable, with the key cost driver found to be pharmaceutical treatment and social insurance funds the key payer for treating COPD patients in Greece. The cost of stable disease is proportional to the severity of COPD, and it is doubled in patients who belong to high-risk groups.

The pharmacological cost of COPD during Greek economic crisis.

INTRODUCTION: The economic crisis in Greece has substantially affected patients with COPD. The reduction of disposable income has its consequences on patients' ability to afford their medication. The aim of the study is to evaluate the cost of treatment for patients with COPD and the influence of the financial crisis to the patients. METHODS: Data were collected from 189 patients (male: 178, mean age: 70.1±8.4) who visited the outpatient department of University Hospital of Larissa in 2014 and 2015. The pharmacological cost of treatment was calculated based on national pharmaceutical formulary prices. RESULTS: COPD patients were classified into four stages according to Global Initiative for Chronic Obstructive Lung Disease (GOLD): 7.4% were in stage I, 43.4% in stage II, 34.4% in stage III, and 14.8% in stage IV. Patients were graded as per GOLD as follows: 18% as grade A, 14.3% as B, 23.3% as C, and 44.4% as D. The annual cost of COPD maintenance treatment per patient was €952.92 (±398.01), of which €239.91 were patients' expenses. The annual treatment cost for stable disease ranged from €615.44 to €1302.03 depending on disease stages (GOLD stages I-IV) and from €715.01 to €1101.05 depending on GOLD grades (grades A-D). The cost of maintenance medication was statistically and significantly higher for patients with advanced disease (GOLD stages III-IV) and for patients at high risk (GOLD grades C-D [P=0.000]). CONCLUSION: The pharmacological cost of treatment for COPD patients seems to be considerably high, in all disease stages. As the average income is decreased, patients face difficulties to afford inhaled medication.

Clinical Significance of Circulating Osteopontin Levels in Patients With Lung Cancer and Correlation With VEGF and MMP-9.

Osteopontin (OPN) is a multifunctional cytokine involved in carcinogenesis. Serum levels of OPN, vascular endothelial growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9) were measured by ELISA in 90 lung cancer patients. OPN levels were elevated in patients compared to controls (p <.0001). Smokers, patients with worse performance status, and weight loss exhibited higher OPN levels (p =.0012,.00036, and.0003, respectively). Increased OPN levels were associated with worse survival (p =.0018). Finally, OPN levels were positively correlated with both VEGF (p =.0008) and MMP-9 (p <.0001). OPN might serve as a prognostic biomarker, and the positive correlation between OPN and both VEGF and MMP-9 could implicate new insights in tumor angiogenesis.

A potential role for VEGF in the diagnostic approach of pleural effusions.

BACKGROUND: Vascular endothelial growth factor (VEGF) may play a role in pleural fluid formation, as it represents a potent inducer of capillary permeability. We aimed to investigate the diagnostic utility of VEGF levels in pleural fluid and serum in patients with pleural effusions with initially negative diagnostic work up. METHODS: Seventy-one patients with exudative lymphocytic pleural effusions undiagnosed after initial diagnostic work up were enrolled in this prospective study and their clinical course was followed up to 24 months. VEGF levels were measured in serum and pleural fluid by using immunoenzymometric assay. RESULTS: During the follow up period, in 43 patients the pleural effusion was eventually attributed to malignancy while in the rest 28 patients it was due to non-malignant causes (benign and unknown origin). Patients with malignancy had significantly higher VEGF levels in pleural fluid compared to patients with non-malignant effusions (1,506 vs. 588 pg/dL, P=0.0001), while no statistically significant difference was found in the VEGF serum levels between the two groups. CONCLUSIONS: Pleural VEGF levels may be helpful in identifying malignant pleural effusion (MPE) in patients with negative diagnostic work up at the initial assessment and help in selecting patients for more invasive procedures.

Assessment of Bone Mineral Density in Male Patients with Chronic Obstructive Pulmonary Disease by DXA and Quantitative Computed Tomography.

The purpose of this study is to identify the prevalence of osteoporosis in male patients with chronic obstructive pulmonary disease (COPD) by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and to compare the diagnostic abilities of the above methods. Thirty-seven male patients with established COPD were examined with DXA and standard QCT in lumbar spine, including L1, L2, and L3 vertebrae. T-scores and bone mineral density values were calculated by DXA and QCT method, respectively. Comparative assessment of the findings was performed and statistical analysis was applied. QCT measurements found more COPD patients with impaired bone mineral density compared to DXA, namely, 13 (35.1%) versus 12 (32.4%) patients with osteopenia and 16 (43.2%) versus 9 (16.2%) patients with osteoporosis (p = 0.04). More vertebrae were found with osteoporosis by QCT compared to DXA (p = 0.03). The prevalence of osteoporosis among male patients with COPD is increased and DXA may underestimate this risk. QCT measurements have an improved discriminating ability to identify low BMD compared to DXA measurements because QCT is able to overcome diagnostic pitfalls including aortic calcifications and degenerative spinal osteophytes.

Sestrin-2 is significantly increased in malignant pleural effusions due to lung cancer and is potentially secreted by pleural mesothelial cells.

OBJECTIVES: Sestrin-2 (Sesn2) belongs to a family of highly conserved antioxidant proteins that were discovered as p53-inducible proteins and inhibits cell growth and proliferation. Our aim was to assess the levels of Sesn2 in malignant pleural effusions of lung cancer patients compared to benign pleural effusions. DESIGN AND METHODS: We enrolled 73 patients (55/males and 18/females) diagnosed with pleural effusion (PE). PEs were grouped as 44 malignant pleural effusions (MPEs; lung cancer) and 29 benign (BPE; 7 congestive heart failure, 9 tuberculosis, 13 parapneumonic). Pleural fluid (PF) Sesn2 levels were determined by enzyme-linked immunosorbent assay (ELISA) kit. Standard biochemical PF analysis was also performed and Sesn2 levels were correlated with PF lactate dehydrogenase (LDH), protein, cell counts and age. RESULTS: Sesn2 was detected in 24/44 patients with MPEs and in 3/29 patients with BPEs (p=0.0001). The mean value (mean±SEM) of Sesn2 in patients with MPEs was 0.54±0.22ng/mL while in BPEs it was 0.12±0.04ng/mL (p=0.0004). In MPEs Sesn2 pleural fluid levels did not correlate with PF LDH and cell counts (p=0.89 and p=0.64 respectively). CONCLUSIONS: Our study shows that Sesn2 is significantly increased in MPEs compared to BPEs. Moreover, the lack of correlation of Sesn2 levels with PF cell counts and PF LDH suggests that it is potentially secreted by pleural mesothelial cells.

Poly(A)-specific ribonuclease and Nocturnin in squamous cell lung cancer: prognostic value and impact on gene expression.

BACKGROUND: Lung cancer is the leading cause of cancer mortality worldwide, mainly due to late diagnosis, poor prognosis and tumor heterogeneity. Thus, the need for biomarkers that will aid classification, treatment and monitoring remains intense and challenging and depends on the better understanding of the tumor pathobiology and underlying mechanisms. The deregulation of gene expression is a hallmark of cancer and a critical parameter is the stability of mRNAs that may lead to increased oncogene and/or decreased tumor suppressor transcript and protein levels. The shortening of mRNA poly(A) tails determines mRNA stability, as it is usually the first step in mRNA degradation, and is catalyzed by deadenylases. Herein, we assess the clinical significance of deadenylases and we study their role on gene expression in squamous cell lung carcinoma (SCC). METHODS: Computational transcriptomic analysis from a publicly available microarray was performed in order to examine the expression of deadenylases in SCC patient samples. Subsequently we employed real-time PCR in clinical samples in order to validate the bioinformatics results regarding the gene expression of deadenylases. Selected deadenylases were silenced in NCI-H520 and Hep2 human cancer cell lines and the effect on gene expression was analyzed with cDNA microarrays. RESULTS: The in silico analysis revealed that the expression of several deadenylases is altered in SCC. Quantitative real-time PCR showed that four deadenylases, PARN, CNOT6, CNOT7 and NOC, are differentially expressed in our SCC clinical samples. PARN overexpression correlated with younger patient age and CNOT6 overexpression with non-metastatic tumors. Kaplan-Meier analysis suggests that increased levels of PARN and NOC correlate with significantly increased survival. Gene expression analysis upon PARN and NOC silencing in lung cancer cells revealed gene expression deregulation that was functionally enriched for gene ontologies related to cell adhesion, cell junction, muscle contraction and metabolism. CONCLUSIONS: Our results highlight the clinical significance of PARN and NOC on the survival in SCC diagnosed patients. We demonstrate that the enzymes are implicated in important phenotypes pertinent to cancer biology and provide information on their role in the regulation of gene expression in SCC. Overall, our results support an emerging role for deadenylases in SCC and contribute to the understanding of their role in cancer biology.

Pleural effusion levels of DJ-1 are increased in elderly lung cancer patients with malignant pleural effusions.

OBJECTIVES: DJ-1 is a multifunctional protein implicated in redox dependent cell fate decisions. The aim of our study was to determine the pleural fluid (PF) levels of DJ-1 in malignant pleural effusions (MPEs) secondary to lung cancer. Additionally, we opted to assess potential correlations of DJ-1 PF levels with the PF levels of superoxide dismutase-1 (SOD1) and 8-isoprostane that are known antioxidant enzymes and have been previously reported in MPEs. METHODS: Forty lung cancer patients with cytological proof of MPE were enrolled in this study. The PF levels of DJ-1, SOD1, and 8-isoprostane were measured by means of enzyme-linked immunosorbent assay. RESULTS: The median PF levels of DJ-1 were 826 ng/mL (interquartile range, IQR: 482-1010 ng/mL). DJ-1 PF levels significantly correlated with PF Cu/Zn-SOD1 and PF 8-isoprostane levels (Spearman's rho, r; r = -0.476, P = 0.002 and r = -0.264, P = 0.033, respectively), PF lactate dehydrogenase (r = -0.497, P = 0.001) and total PF cell counts (r = -0.325, P = 0.041). Finally, in patients aged over 65 the PF DJ-1 levels were significantly higher than patients aged less than 65 (875 ng/mL vs. 607 ng/mL, respectively, P = 0.037). DISCUSSION: To our knowledge, this is the first report to determine DJ-1's levels in MPEs due to lung cancer. The negative correlations between DJ-1, SOD1, and 8-isorpostane warrant further investigation regarding the altered redox regulation associated with MPEs.

Clinical significance of serum adipokines levels in lung cancer.

Adipokines have a significant effect on metabolism, immunoinflammatory responses as well as on carcinogenesis; therefore, we aimed at evaluating their potential predictive and prognostic significance in lung cancer. Eighty patients--mean age 62.9 ± 9.2 years--with previously untreated lung cancer (61 NSCLC and 19 SCLC) of all stages and 40 healthy individuals were enrolled in this study. Serum levels of leptin, adiponectin and ghrelin were measured using human Radioimmunoassay kits. Serum leptin levels in lung cancer patients were lower compared to control (p < 0.0001), while adiponectin and ghrelin levels were significantly increased in patients (p = 0.0003 and p = 0.0043, respectively). Additionally, the leptin/adiponectin ratio was significantly lower in the patients group compared to controls (p < 0.0001]. There was no association between serum levels of adipokines and any of the patient clinicopathological characteristics or response to therapy. Nevertheless, patients with lower values of serum leptin had shorter overall survival (p = 0.014), whereas multivariate analysis revealed leptin levels as an independent prognostic factor for survival (p = 0.024, HR 0.452, CI 95 % 0.232-0.899). These results suggest that adipokines may play a role in the pathogenesis of lung cancer, while leptin serum levels might provide useful prognostic information.

Six minute walking test and carbon monoxide diffusing capacity for non-small cell lung cancer: easy performed tests in every day practice.

BACKGROUND: Several studies have demonstrated that reduced lung function is a significant risk factor for lung cancer and increased surgical risk in patients with operable stages of lung cancer. The aim of the study was to perform pulmonary function tests and investigate which is a favorable respiratory function test for overall survival between lung cancer stages. METHODS: Lung function tests were performed to lung cancer patients with non-small cell lung cancer of stage I, II, III and IV (241 patients in total). They had the last follow-up consecutively between December 2006 and July 2008. The staging was decided according to the sixth edition of TNM classification of NSCLC. The Forced Expiratory Volume in 1sec (FEV1), Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) were measured according to American Thoracic Society/European Respiratory Society guidelines. The 6 Minute Walking Test (6MWT) was measured according to the American Thoracic Society. RESULTS: There was a significant association of the DLCO upon diagnosis and overall survival for stage II (P<0.007) and IV (P<0.003). Furthermore, there was a significant association between 6MWT and overall survival for stage III (P<0.001) and stage IV (P<0.010). CONCLUSIONS: The significance for each lung function test is different among the stages of NSCLC. DLCO and 6MWT upon admission are the most valuable prognostic factors for overall survival of NSCLC.

Differential expression of hypoxia-inducible factor 1α in non-small cell lung cancer and small cell lung cancer

OBJECTIVES: The aim of this study was to compare the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor in small cell lung cancer and subtypes of non-small cell lung cancer and examine their relationships with clinicopathologic factors, response to treatment and survival. METHODS: We examined samples obtained by bronchial endoscopic biopsy from 55 patients with inoperable lung cancer (16 with adenocarcinoma, 17 with squamous cell carcinoma, and 22 with small cell lung cancer). Hypoxiainducible factor 1α and vascular endothelial growth factor were detected using immunohistochemistry. The diagnosis, treatment, and follow-up of patients were conducted according to the standard practice. RESULTS: A significant difference (p=0.022) in hypoxia-inducible factor 1α expression was observed between nonsmall cell lung cancer (75.8% positive) and small cell lung cancer (45.5% positive). The frequency of hypoxiainducible factor 1α nuclear expression was 88.2% in squamous cell carcinoma, 62.5% in adenocarcinoma, and 45.5% in small cell lung cancer. A significant correlation was observed between hypoxia-inducible factor 1α and vascular endothelial growth factor expression (Fisher's exact test, p=0.001) when all types of lung cancer were examined, either collectively or separately. CONCLUSIONS: The expression of hypoxia-inducible factor-1α differs significantly between subtypes of lung cancer. These findings could help elucidate the biology of the different types of non-operable lung carcinomas and have implications for the design of new therapeutic approaches for lung cancer.

Health costs from hospitalization with H1N1 infection during the 2009-2010 influenza pandemic compared with non-H1N1 respiratory infections.

BACKGROUND: The first positive patient with influenza A (H1N1) was recorded in March 2009 and the pandemic continued with new outbreaks throughout 2010. This study's objective was to quantify the total cost of inpatient care and identify factors associated with the increased cost of the 2009-2010 influenza A pandemic in comparison with nonviral respiratory infection. METHODS: In total, 133 positive and 103 negative H1N1 patients were included from three tertiary care hospitals during the two waves of H1N1 in 2009 and 2010. The health costs for protective equipment and pharmaceuticals and hospitalization (medications, laboratory, and diagnostic tests) were compared between H1N1 positive and negative patients. RESULTS: The objective of the study was to quantify the means of daily and total costs of inpatient care. Overall, cost was higher for H1N1 positive (€61,0117.72) than for H1N1-negative patients (€464,923.59). This was mainly due to the protection measures used and the prolonged hospitalization in intensive care units. In H1N1-negative patients, main contributors to cost included additional diagnostic tests due to concern regarding respiratory capacity and laboratory values, as well as additional radiologic and microbial culture tests. The mean duration of hospitalization was 841 days for H1N1 positive and 829 days for negative patients. CONCLUSION: Cost was higher in H1N1 patients, mainly due to the protection measures used and the increased duration of hospitalization in intensive care units. An automated system to monitor patients would be desirable to reduce cost in H1N1 influenza.

Differential expression of hypoxia-inducible factor 1α in non-small cell lung cancer and small cell lung cancer.

OBJECTIVES: The aim of this study was to compare the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor in small cell lung cancer and subtypes of non-small cell lung cancer and examine their relationships with clinicopathologic factors, response to treatment and survival. METHODS: We examined samples obtained by bronchial endoscopic biopsy from 55 patients with inoperable lung cancer (16 with adenocarcinoma, 17 with squamous cell carcinoma, and 22 with small cell lung cancer). Hypoxiainducible factor 1α and vascular endothelial growth factor were detected using immunohistochemistry. The diagnosis, treatment, and follow-up of patients were conducted according to the standard practice. RESULTS: A significant difference (p=0.022) in hypoxia-inducible factor 1α expression was observed between nonsmall cell lung cancer (75.8% positive) and small cell lung cancer (45.5% positive). The frequency of hypoxiainducible factor 1α nuclear expression was 88.2% in squamous cell carcinoma, 62.5% in adenocarcinoma, and 45.5% in small cell lung cancer. A significant correlation was observed between hypoxia-inducible factor 1α and vascular endothelial growth factor expression (Fisher's exact test, p=0.001) when all types of lung cancer were examined, either collectively or separately. CONCLUSIONS: The expression of hypoxia-inducible factor-1α differs significantly between subtypes of lung cancer. These findings could help elucidate the biology of the different types of non-operable lung carcinomas and have implications for the design of new therapeutic approaches for lung cancer.

Long-term respiratory follow-up of H1N1 infection.

BACKGROUND: The first case of 2009 pandemic influenza A (H1N1) virus infection was documented in our Hospital on 10th August 2009. METHODS AND FINDINGS: Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm the diagnosis. All patients were treated with oseltamivir from the first day of hospitalization. Upon admission 12/44 had local patchy shadowing in their chest x-ray and additionally antibiotic regimen was added to these patients as pneumonia was suspected based on clinical evidence. In total 44 patients were hospitalized 15/44 had asthma, 6/44 COPD, 5/44 leukemia. Lung function was evaluated with forced vital capacity, forced expiratory volume in 1 sec and diffused carbon monoxide upon discharge and every 3 months, until 6 months of observation was completed after discharge. The purpose of this retrospective cohort study was to evaluate whether influenza A (H1N1) had an impact on the respiratory capacity of the infected patients. CONCLUSIONS: An improvement of pulmonary function tests was observed between the first two measurements, implicating an inflammatory pathogenesis of influenza A (H1N1) to the respiratory tract. This inflammation was not associated with the severity or clinical outcome of the patients. All patients had a mild clinical course and their respiratory capacity was stable between the second and third measurement, suggesting that the duration of respiratory inflammation was two months. Early treatment with antiviral agents and vaccination represent the mainstay of management.

Cytolytic T-cell response against Epstein-Barr virus in lung cancer patients and healthy subjects.

BACKGROUND: This study aimed to examine whether EBV seropositive patients with lung cancer have an altered virus-specific CTL response, as compared to age-matched healthy controls and whether any variation in this response could be attributed to senescence. METHODS: Peripheral blood mononuclear cells from lung cancer patients, age-matched and younger healthy individuals were used to measure EBV-specific CTLs after in vitro amplification with the GLCTLVAML and RYSIFFDYM peptides followed by HLA-multimer staining. RESULTS: Lung cancer patients and aged-matched controls had significantly lesser EBV-specific CTL than younger healthy individuals. Multimer positive populations from either group did not differ with respect to the percentage of multimer positive CTLs and the intensity of multimer binding. CONCLUSIONS: This study provides evidence that patients with lung cancer exhibit an EBV-specific CTL response equivalent to that of age-matched healthy counterparts. These data warrant the examination of whether young individuals have a more robust anti-tumor response, as is the case with the anti-EBV response.

Vibration response imaging: evaluation of rater agreement in healthy subjects and subjects with pneumonia.

BACKGROUND: We evaluated pulmonologists variability in the interpretation of Vibration response imaging (VRI) obtained from healthy subjects and patients hospitalized for community acquired pneumonia. METHODS: The present is a prospective study conducted in a tertiary university hospital. Twenty healthy subjects and twenty three pneumonia cases were included in this study. Six pulmonologists blindly analyzed images of normal subjects and pneumonia cases and evaluated different aspects of VRI images related to the quality of data acquisition, synchronization of the progression of breath sound distribution and agreement between the maximal energy frame (MEF) of VRI (which is the maximal geographical area of lung vibrations produced at maximal inspiration) and chest radiography. For qualitative assessment of VRI images, the raters' evaluations were analyzed by degree of consistency and agreement. RESULTS: The average value for overall identical evaluations of twelve features of the VRI image evaluation, ranged from 87% to 95% per rater (94% to 97% in control cases and from 79% to 93% per rater in pneumonia cases). Inter-rater median (IQR) agreement was 91% (82-96). The level of agreement according to VRI feature evaluated was in most cases over 80%; intra-class correlation (ICC) obtained by using a model of subject/rater for the averaged features was overall 0.86 (0.92 in normal and 0.73 in pneumonia cases). CONCLUSIONS: Our findings suggest good agreement in the interpretation of VRI data between different raters. In this respect, VRI might be helpful as a radiation free diagnostic tool for the management of pneumonia.

Naturally occurring tumor-specific CD8+ T-cell precursors in individuals with and without cancer.

Boosting pre-existing, naturally occurring cytolytic CD8(+) T-cell (CTLs) responses directed against class-I MHC-restricted peptides of tumor antigens, represents a primary goal of cancer immunotherapy. The number of pre-existing antitumor CTLs and their impaired function has been incriminated as the most likely candidates for the reduced clinical efficacy of these trials. This study was scheduled to determine possible differences in the frequency and the function of naturally occurring CTL precursors (pCTLs) against multiple peptides derived from the cancer-testis antigens MAGE-A1 and MAGE-A3, and the overexpressed antigen hTERT, in newly diagnosed lung cancer patients as compared with aged-matched healthy individuals. The cumulative frequency of circulating peptide-specific pCTLs was found significantly higher in the cancer patients, varied widely and was not affected by radiotherapy and chemotherapy. Furthermore, this frequency was greatly different between the various tumor-antigen peptides. Under the light of recent evidence provided from animal models, these results indicate that the peptide-specific pCTL frequency might represent an important determinant for the fate of cancer immunotherapy. In addition, our results show that tumor-specific pCTLs of cancer patients can present functional differences regarding their proliferative capacity, intensity of multimer staining and lytic capacity, when compared with those of healthy individuals. Hence, our findings could have an important role for the design of improved immunotherapeutic approaches for lung cancer.