The influence of nutritional status, lipid profile, leptin concentration and polymorphism of genes encoding leptin and neuropeptide Y on the effectiveness of immunotherapy in advanced NSCLC patients.

INTRODUCTION: Neuropeptide Y is a neurotransmitter in the nervous system and belongs to the orexigenic system that increases appetite. Its excessive secretion leads to obesity. Leptin is a pro-inflammatory adipokine (produced in adipose tissue) induced in obesity and may mediate increased antitumor immunity in obesity (including the promotion of M1 macrophages). Leptin and neuropeptide Y gene polymorphisms, causing increased leptin levels and the occurrence of obesity, and lipid profile disorders, may increase the effectiveness of immunotherapy. MATERIALS AND METHODS: In 121 patients with advanced NSCLC without mutations in the EGFR gene and rearrangements of the ALK and ROS1 genes, undergoing immunotherapy (1st and 2nd line of treatment) or chemoimmunotherapy (1st line of treatment), we assessed BMI, lipid profile, PD-L1 expression on cancer cells using the immunohistochemical method (clone SP263 antibody), leptin concentration in blood serum by ELISA, polymorphisms in the promoter region of the genes for leptin (LEP) and neuropeptide Y (NPY) by real-time PCR. RESULTS: Leptin concentration was significantly higher in obese patients than in patients with normal or low weight (p = 0.00003) and in patients with disease stabilization compared to patients with progression observed during immunotherapy (p = 0.012). Disease control occurred significantly more often in patients with the GA or AA genotype than patients with the GG genotype in the rs779039 polymorphism of the LEP gene. The median PFS in the entire study group was five months (95% CI: 3-5.5), and the median OS was 12 months (95% CI: 8-16). Median PFS was highest in patients with TPS ≥ 50% (6.5 months) and in obese patients (6.6 months). Obese patients also had a slightly longer median OS compared to other patients (23.8 vs. 13 months). The multivariate Cox logistic regression test showed that the only factor reducing the risk of progression was TPS ≥ 50% (HR = 0.6068, 95% CI: 0.4001-0.9204, p = 0, 0187), and the only factor reducing the risk of death was high leptin concentration (HR = 0.6743, 95% CI: 0.4243-1.0715, p = 0.0953). CONCLUSION: Assessment of nutritional status, serum leptin concentration and polymorphisms in the LEP gene may be of additional importance in predicting the effectiveness of immunotherapy and chemoimmunotherapy in patients with advanced NSCLC.

The influence of plasma sPD-L1 concentration on the effectiveness of immunotherapy in advanced NSCLC patients.

INTRODUCTION: PD-L1 (Programmed Cell Death Ligand 1) is currently the only recognised marker of response to immunotherapy with anti-PD-1 or anti-PD-L1 antibodies in patients with advanced non-small cell lung cancer (NSCLC). However, this marker is not perfect. Soluble PD-L1 (sPD-L1) may be a novel predictor of immunotherapy efficacy in NSCLC patients. MATERIAL AND METHODS: We enrolled 120 patients (median age 68 ± 6.81 years, 70 males and 50 females) with locally advanced (stage IIIB; 10 patients) or advanced (stage IV; 110 patients) NSCLC. PD-L1 expression in tumour cells was assessed by immunohistochemistry (IHC) in 117 (97.5%) patients. The soluble PD-L1 concentration in plasma samples was measured using enzyme-linked immunosorbent assay (ELISA). The response to immunotherapy, progression-free survival (PFS), and overall survival (OS), calculated from the start of immunotherapy, were assessed in 119 patients. RESULTS: Patients with disease control had significantly lower (p = 0.0006) concentrations of sPD-L1 in blood plasma than patients with progression during the first months of immunotherapy or chemoimmunotherapy Patients with ≥ 6 month progression-free survival had a significantly higher (p = 0.013) percentage of tumor cells with PD-L1 expression than patients with shorter PFS. Patients with ≥ 6 months OS had significantly lower (p = 0.0142) plasma sPD-L1 concentrations than those with shorter overall survival. The median PFS was significantly higher in patients with low sPD-L1 concentrations than in those with high concentrations of this protein (5.8 vs. 2.5 months, HR = 0.6021, p = 0.0156). Similarly, patients with low sPD-L1 levels had a significantly higher median overall survival than those with sPD-L1 levels above the median (16.5 vs. 7 months, HR = 0.5354, p = 0.0071). There was no significant correlation between the percentage of tumour cells expressing PD-L1 and the concentration of sPD-L1 in the blood plasma. CONCLUSION: High sPD-L1 concentration is a negative predictor of immunotherapy efficacy in patients with NSCLC. It is worthwhile to determine sPD-L1 concentration to predict the risk of resistance to anti-PD-1 or anti-PD-L1 antibodies with greater certainty.

Home Monitoring of Asthma Exacerbations in Children and Adults With Use of an AI-Aided Stethoscope.

PURPOSE: The advent of new medical devices allows patients with asthma to self-monitor at home, providing a more complete picture of their disease than occasional in-person clinic visits. This raises a pertinent question: which devices and parameters perform best in exacerbation detection? METHODS: A total of 149 patients with asthma (90 children, 59 adults) participated in a 6-month observational study. Participants (or parents) regularly (daily for the first 2 weeks and weekly for the next 5.5 months, with increased frequency during exacerbations) performed self-examinations using 3 devices: an artificial intelligence (AI)-aided home stethoscope (providing wheezes, rhonchi, and coarse and fine crackles intensity; respiratory and heart rate; and inspiration-to-expiration ratio), a peripheral capillary oxygen saturation (SpO2) meter, and a peak expiratory flow (PEF) meter and filled out a health state survey. The resulting 6,029 examinations were evaluated by physicians for the presence of exacerbations. For each registered parameter, a machine learning model was trained, and the area under the receiver operating characteristic curve (AUC) was calculated to assess its utility in exacerbation detection. RESULTS: The best single-parameter discriminators of exacerbations were wheezes intensity for young children (AUC 84% [95% CI, 82%-85%]), rhonchi intensity for older children (AUC 81% [95% CI, 79%-84%]), and survey answers for adults (AUC 92% [95% CI, 89%-95%]). The greatest efficacy (in terms of AUC) was observed for a combination of several parameters. CONCLUSIONS: The AI-aided home stethoscope provides reliable information on asthma exacerbations. The parameters provided are effective for children, especially those younger than 5 years of age. The introduction of this tool to the health care system might enhance asthma exacerbation detection substantially and make remote monitoring of patients easier.

Systemic Sclerosis and Serum Content of Transforming Growth Factor.

Systemic sclerosis is a connective tissue disease characterized by tissue fibrosis leading to interstitial lung disease. Transforming growth factor-ß (TGF-ß) has been of interest as a potential diagnostic marker and also as a drug target in systemic sclerosis. The aim of this study was to assess the serum content of TGF-ß1 in patients with systemic sclerosis and to assess its potential role in tissue fibrosis. The study included 30 patients, 5 men and 25 women, of the mean age of 46.9 ± 12.8 years, diagnosed with systemic sclerosis. The control group consisted of 19 women of the mean age of 28.4 ± 7.8 years, diagnosed with primary Raynaud's disease. TGF-ß1 serum levels were measured, chest imaging examinations were performed, and fibrotic tissue changes were assessed using the modified Rodnan Skin Score. We found that the mean serum TGF-ß1 content in patients with systemic sclerosis was 598.7 ± 242.6 pg/mL, whereas it was 568.4 ± 322.2 pg/mL in the control group (p = 0.378). We also failed to substantiate any significant relationship between TGF-ß1 serum levels and the severity of pulmonary and skin fibrosis in systemic sclerosis. In conclusion, systemic sclerosis does not seem a disease that would be accompanied by a specific enhancement of serum TGF-ß1. Thus, this cytokine is rather unlikely to play an essential role in the development and course of the disease, nor can it be considered diagnostic or prognostic marker.

COPD Course and Comorbidities: Are There Gender Differences?

The prevalence of chronic obstructive pulmonary disease (COPD) has increased more rapidly in women than in men during the past two decades. Clinical presentation, comorbidities and prognosis may differ between genders and may influence management decisions. The influence of gender on COPD expression has not been clearly explained to date. Thus, the aim of this study was to evaluate significant differences between women and men suffering from COPD, regarding clinical presentation, pulmonary function test results, comorbidities, and prognosis. We prospectively recruited 470 patients with stable COPD with a history of smoking (152 women, 318 men, mean age 65.5 ± 8.8 vs. 66.6 ± 9.4 years, respectively). Comorbidities and exacerbations were recorded. Spirometry, body plethysmography, carbon monoxide diffusing capacity and 6-min walk tests were performed. The BODE prognostic score was also calculated. We found that women smoked less in comparison to men (30.4 vs. 41.9 pack-years, p < 0.05), showed more exacerbations (2.5 vs. 1.7, p = 0.01), higher forced expiratory volume in 1 s (FEV1%predicted), and increased residual volume/total lung capacity (RV/%TLC), but they had the same intensity of dyspnea. Women showed fewer comorbidities, on average, per patient (5.4 vs. 6.4, p = 0.002), but had a higher prevalence of at least seven comorbidities per patient (48.7% of women vs. 33.0% of men, p < 0.05). Women also had a significantly worse prognosis (4.6 vs. 3.1 BODE score, p < 0.05) that correlated with the number of comorbidities (r = 0.33, p < 0.01). In conclusion, this study strongly supports the existence of different gender phenotypes in COPD, especially regarding exacerbations, comorbidities, and prognosis. The gender difference may indicate a need for a targeted assessment and management of COPD in women and men.

Body Composition, Anthropometric Indices and Hydration Status of Obstructive Sleep Apnea Patients: Can Cachexia Coexist with Obesity?

The aim of this study was to elucidate body composition, anthropometric indices, and hydration status in obstructive sleep apnea (OSA) patients, taking into account different disease stages, gender, and the possibility of the presence of cachexia. There were 98 OSA patients and 23 control subjects enrolled into the study. All study participants underwent polysomnography examination. Body mass index (BMI), fat mass index (FMI), fat free mass, muscle mass, body cell mass, total body water, and extracellular and intracellular water were evaluated. The neck, abdominal, and waist circumference was measured. We found that overweight and obesity were present in 96% of patients. Cachexia was present in one OSA individual with comorbidities. Apnea-hypopnea index correlated with the neck and waist circumference, and with BMI in OSA patients. All muscle indices and water contents above outlined were significantly higher in severe OSA compared with control subjects. BMI, FMI, neck circumference, and extracellular water were greater in a subset of severe OSA compared with a moderate OSA stage. The female OSA patients had a higher FMI than that present in males at a comparable BMI. We conclude that the most body composition indices differed significantly between severe OSA patients and control subjects. A higher FMI in females at a comparable BMI could be due to a discordance between BMI and FMI. Cachexia occurs rarely in OSA and seems to coexist with comorbidities.

Application of plasma circulating microRNA-448, 506, 4316, and 4478 analysis for non-invasive diagnosis of lung cancer.

Aberrant expression of microRNAs (miRNAs) in cancer patients compared to healthy people as well as possibility of detection of these molecules in blood samples make them potential biomarkers of various cancers. In the present study, we investigated the potential role of four miRNAs as lung cancer (LC) biomarkers: miRNA-448, 506, 4316, and 4478. Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) technique, we assessed expression of studied miRNAs in plasma samples of 90 lung cancer patients and 85 healthy individuals. Receiver operating curves (ROC) with area under the curve (AUC) were used to assess accuracy of studied miRNAs for distinguishing LC patients from healthy individuals. The miRNA-448 and 4478 were significantly overexpressed in lung cancer patients compared to healthy people and these two molecules were qualified for further analysis. Combination ROC analysis of both biomarkers reached 90 % of sensitivity and 76.3 % of specificity (AUC = 0.896) for distinguishing operable (stage IA-IIB) non-small cell lung cancer (NSCLC) patients from healthy subjects. Our results suggest that the examination of miRNAs could be considered as potential lung cancer, non-invasive biomarkers.

Analysis of RTEL1 and PCDHGB6 promoter methylation in circulating-free DNA of lung cancer patients using liquid biopsy: A pilot study.

BACKGROUND: Analysis of epigenetic alterations such as methylation of circulating-free DNA (cf-DNA) expression significantly broadened perspectives of lung cancer (LC) screening. Moreover, methylation of tumor suppressor genes may be analyzed with non-invasive manner in patients' blood samples (liquid biopsy), what underline necessity of detailed investigation of tumor cf-DNA. MATERIAL AND METHODS: The purpose of current study was to assess methylation of RTEL1 and PCDHGB6 promoter regions in cf-DNA of 70 LC patients and 80 healthy individuals using qMSP-PCR technique. Methylation status of both genes has not been investigated in cf-DNA of LC patients before. RESULTS: PCDHGB6 promoter methylation was found in 41.4% of LC patients and in 1.3% of healthy individuals, whereas promoter of RTEL1 was found methylated in 51.4% of LC patients and in 8.8% of healthy individuals. Combined analysis of two markers improved test sensitivity up to 62.9% and specificity up to 90% with area under the curve (AUC) in receiver operating curve (ROC) of 0.755. CONCLUSIONS: The evaluation of RTEL1 and PCDHGB6 promoter methylation may be an useful tool for non-invasive diagnosis of LC in liquid biopsy.

Association of Obesity and Severe Asthma in Adults.

The incidence of obesity and asthma continues to enhance, significantly impacting global public health. Adipose tissue is an organ that secretes hormones and cytokines, causes meta-inflammation, and contributes to the intensification of bronchial hyperreactivity, oxidative stress, and consequently affects the different phenotypes of asthma in obese people. As body weight increases, the risk of severe asthma increases, as well as more frequent exacerbations requiring the use of glucocorticoids and hospitalization, which consequently leads to a deterioration of the quality of life. This review discusses the relationship between obesity and severe asthma, the underlying molecular mechanisms, changes in respiratory function tests in obese people, its impact on the occurrence of comorbidities, and consequently, a different response to conventional asthma treatment. The article also reviews research on possible future therapies for severe asthma. The manuscript is a narrative review of clinical trials in severe asthma and comorbid obesity. The articles were found in the PubMed database using the keywords asthma and obesity. Studies on severe asthma were then selected for inclusion in the article. The sections: 'The classification connected with asthma and obesity', 'Obesity-related changes in pulmonary functional tests', and 'Obesity and inflammation', include studies on subjects without asthma or non-severe asthma, which, according to the authors, familiarize the reader with the pathophysiology of obesity-related asthma.

Variant Allele Frequency Analysis of Circulating Tumor DNA as a Promising Tool in Assessing the Effectiveness of Treatment in Non-Small Cell Lung Carcinoma Patients.

Despite the different possible paths of treatment, lung cancer remains one of the leading causes of death in oncological patients. New tools guiding the therapeutic process are under scientific investigation, and one of the promising indicators of the effectiveness of therapy in patients with NSCLC is variant allele frequency (VAF) analysis. VAF is a metric characterized as the measurement of the specific variant allele proportion within a genomic locus, and it can be determined using methods based on NGS or PCR. It can be assessed using not only tissue samples but also ctDNA (circulating tumor DNA) isolated from liquid biopsy. The non-invasive characteristic of liquid biopsy enables a more frequent collection of material and increases the potential of VAF analysis in monitoring therapy. Several studies have been performed on patients with NSCLC to evaluate the possibility of VAF usage. The research carried out so far demonstrates that the evaluation of VAF dynamics may be useful in monitoring tumor progression, remission, and recurrence during or after treatment. Moreover, the use of VAF analysis appears to be beneficial in making treatment decisions. However, several issues require better understanding and standardization before VAF testing can be implemented in clinical practice. In this review, we discuss the difficulties in the application of ctDNA VAF analysis in clinical routine, discussing the diagnostic and methodological challenges in VAF measurement in liquid biopsy. We highlight the possible applications of VAF-based measurements that are under consideration in clinical trials in the monitoring of personalized treatments for patients with NSCLC.

MicroRNA-126 selected with broad-spectrum analysis of microRNAs - a new predictive factor for the effectiveness of immunotherapy or chemoimmunotherapy in advanced NSCLC patients?

Introduction: Expression of PD-L1 on cancer cells is the only validated predictive factor for immunotherapy in NSCLC (Non-Small Cell Lung Cancer) patients. However, on this basis, it is difficult to predict the occurrence of resistance to immune checkpoint inhibitors (ICIs). MicroRNAs are widely studied as biomarkers of cancers. Our study was designed to determine whether microRNAs can be sensitive predictive factors in the qualification of NSCLC patients to first-line immunotherapy or chemoimmunotherapy. Material and methods: The two-stage research on validation group (n=20) and study group (n=35) of patients with advanced NSCLC was conducted. Analysis of microRNAs expression by qPCR in plasma collected prior to the start of immunotherapy (pembrolizumab) or chemoimmunotherapy (combination of pembrolizumab with chemotherapy) was made. Broad-spectrum analysis of microRNAs expression was used in the studied group. Three microRNAs selected in that group as important for the effectiveness of ICIs were then examined in the validation group. Results: In the studied group, significantly higher expression of miRNA-126-3p, miR-144-3p and miR-146-5p was observed in patients with long PFS compared to those with short PFS. In the validation group, low miRNA-126 expression indicated lower median progression-free survival and overall survival (2.3 vs. 5.0 months and 5.2 vs 11.2, respectively). These patients had a significantly higher risk of progression (HR= 2.92, 95% CI: 1.01 to 8.40, p=0.04) and death (HR=3.64, 95% CI: 1.22 to 10.84, p=0.02). Conclusion: Our study showed that the expression of miR-126 in blood plasma may be a predictive factor for the effectiveness of first-line immunotherapy or chemoimmunotherapy in advanced NSCLC patients.

Deep learning algorithm for visual quality assessment of the spirograms.

Objective. The quality of spirometry manoeuvres is crucial for correctly interpreting the values of spirometry parameters. A fundamental guideline for proper quality assessment is the American Thoracic Society and European Respiratory Society (ATS/ERS) Standards for spirometry, updated in 2019, which describe several start-of-test and end-of-test criteria which can be assessed automatically. However, the spirometry standards also require a visual evaluation of the spirometry curve to determine the spirograms' acceptability or usability. In this study, we present an automatic algorithm based on a convolutional neural network (CNN) for quality assessment of the spirometry curves as an alternative to manual verification performed by specialists.Approach. The algorithm for automatic assessment of spirometry measurements was created using a set of randomly selected 1998 spirograms which met all quantitative criteria defined by ATS/ERS Standards. Each spirogram was annotated as 'confirm' (remaining acceptable or usable status) or 'reject' (change the status to unacceptable) by four pulmonologists, separately for FEV1 and FVC parameters. The database was split into a training (80%) and test set (20%) for developing the CNN classification algorithm. The algorithm was optimised using a cross-validation method.Main results. The accuracy, sensitivity and specificity obtained for the algorithm were 92.6%, 93.1% and 90.0% for FEV1 and 94.1%, 95.6% and 88.3% for FVC, respectively.Significance.The algorithm provides an opportunity to significantly improve the quality of spirometry tests, especially during unsupervised spirometry. It can also serve as an additional tool in clinical trials to quickly assess the quality of a large group of tests.

Guidelines of the Polish Respiratory Society on the Diagnosis and Treatment of Progressive Fibrosing Interstitial Lung Diseases Other than Idiopathic Pulmonary Fibrosis.

The recommendations were developed as answers to previously formulated questions concerning everyday diagnostic and therapeutic challenges. They were developed based on a review of the current literature using the GRADE methodology. The experts suggest that PF-ILD be diagnosed based on a combination of different criteria, such as the aggravation of symptoms, progression of radiological lesions, and worsening of lung function test parameters. The experts recommend a precise diagnosis of an underlying disease, with serological testing for an autoimmune disease always being included. The final diagnosis should be worked out by a multidisciplinary team (MDT). Patients with an interstitial lung disease other than IPF who do not meet the criteria for the progressive fibrosis phenotype should be monitored for progression, and those with systemic autoimmune diseases should be regularly monitored for signs of interstitial lung disease. In managing patients with interstitial lung disease associated with autoimmune diseases, an opinion of an MDT should be considered. Nintedanib rather than pirfenidon should be introduced in the event of the ineffectiveness of the therapy recommended for the treatment of the underlying disease, but in some instances, it is possible to start antifibrotic treatment without earlier immunomodulatory therapy. It is also admissible to use immunomodulatory and antifibrotic drugs simultaneously. No recommendations were made for or against termination of anti-fibrotic therapy in the case of noted progression during treatment of a PF-ILD other than IPF. The experts recommend that the same principles of non-pharmacological and palliative treatment and eligibility for lung transplantation should be applied to patients with an interstitial lung disease other than IPF with progressive fibrosis as in patients with IPF.

Artificial Intelligence Approach to the Monitoring of Respiratory Sounds in Asthmatic Patients.

Background: Effective and reliable monitoring of asthma at home is a relevant factor that may reduce the need to consult a doctor in person. Aim: We analyzed the possibility to determine intensities of pathological breath phenomena based on artificial intelligence (AI) analysis of sounds recorded during standard stethoscope auscultation. Methods: The evaluation set comprising 1,043 auscultation examinations (9,319 recordings) was collected from 899 patients. Examinations were assigned to one of four groups: asthma with and without abnormal sounds (AA and AN, respectively), no-asthma with and without abnormal sounds (NA and NN, respectively). Presence of abnormal sounds was evaluated by a panel of 3 physicians that were blinded to the AI predictions. AI was trained on an independent set of 9,847 recordings to determine intensity scores (indexes) of wheezes, rhonchi, fine and coarse crackles and their combinations: continuous phenomena (wheezes + rhonchi) and all phenomena. The pair-comparison of groups of examinations based on Area Under ROC-Curve (AUC) was used to evaluate the performance of each index in discrimination between groups. Results: Best performance in separation between AA and AN was observed with Continuous Phenomena Index (AUC 0.94) while for NN and NA. All Phenomena Index (AUC 0.91) showed the best performance. AA showed slightly higher prevalence of wheezes compared to NA. Conclusions: The results showed a high efficiency of the AI to discriminate between the asthma patients with normal and abnormal sounds, thus this approach has a great potential and can be used to monitor asthma symptoms at home.

Methylation of DROSHA and DICER as a Biomarker for the Detection of Lung Cancer.

Background: Lung cancer is the leading cause of cancer-related deaths. Early diagnosis may improve the prognosis. Methods: Using quantitative methylation-specific real-time PCR (qMSP-PCR), we assessed the methylation status of two genes (in two subsequent regions according to locations in their promoter sequences) related to carcinogenesis, DICER and DROSHA, in 101 plasma samples (obtained prior to the treatment) of lung cancer patients and 45 healthy volunteers. Results: The relative level of methylation of DROSHA was significantly lower (p = 0.012 for first and p < 0.00001 for the second region) and DICER significantly higher (p = 0.029 for the first region) in cancer patients. The relative level of methylation of DROSHA was significantly (p = 0.037) higher in patients with early-stage NSCLC (IA-IIIA) and could discriminate them from healthy people with a sensitivity of 71% and specificity of 76% (AUC = 0.696, 95% CI: 0.545-0.847, p = 0.011) for the first region and with a sensitivity of 60% and specificity of 85% (AUC = 0.795, 95% CI: 0.689-0.901, p < 0.0001) for the second region. Methylation analysis of the first region of the DICER enabled the distinction of NSCLC patients from healthy individuals with a sensitivity of 96% and specificity of 60% (AUC = 0.651, 95% CI: 0.517-0.785, p = 0.027). The limitations of the study include its small sample size, preliminary nature, being an observational type of study, and the lack of functional experiments allowing for the explanation of the biologic backgrounds of the observed associations. Conclusion: The obtained results indicate that the assessment of DICER and DROSHA methylation status can potentially be used as a biomarker for the early detection of lung cancer.

Promoter polymorphisms of TOP2A and ERCC1 genes as predictive factors for chemotherapy in non-small cell lung cancer patients.

BACKGROUND: Topoisomerase 2-alpha (TOP2A) is an enzyme that controls topologic changes in DNA during transcription and replication. ERCC1 is an enzyme that takes part in DNA repair processes. The purpose of this study was to assess the predictive role of particular single nucleotide polymorphisms (SNPs) in the promoter regions of TOP2A and ERCC1 genes in non-small cell lung cancer patients (NSCLC) treated with chemotherapy. MATERIALS AND METHODS: We enrolled 113 NSCLC patients treated in the first line with platinum-based chemotherapy. Effectiveness was available for 71 patients. DNA was isolated from whole blood using the Qiamp DNA Blood Mini kit (Qiagen). We examined five SNPs: rs11615 (ERCC1), rs3212986 (ERCC1), rs13695 (TOP2A), rs34300454 (TOP2A), rs11540720 (TOP2A). Quantitative PCR using the TaqMan probe (ThermoFisher) was performed on a Eco Illumina Real-Time PCR system device (Illumina Inc). RESULTS: Patients with the A/A genotype in rs11615 of the ERCC1 gene had significantly longer median progression free survival (PFS) (8.5 months; P = .0088). Patients with the C/C genotype in rs3212986 of the ERCC1 gene had longer median PFS (7 months; P = .05). Patients with the C/C genotype in rs34300454 of TOP2A gene had significantly higher median PFS (7.5 months; P = .0029). Carriers of the C/C genotype in rs34300454 of the TOP2A gene had significantly longer median OS (15.5 months; P = .0017). Patients with the A/A genotype in rs11615 of the ERCC1 gene had significantly higher risk of neutropenia (P = .0133). CONCLUSIONS: Polymorphisms of the TOP2A and ERCC1 genes may be a predictive factor of toxicities and survival for chemotherapy in NSCLC patients.

Does nesfatin-1 influence the hypothalamic-pituitary-gonadal axis in adult males with obstructive sleep apnoea?

There is growing evidence that obstructive sleep apnoea (OSA) influences the hypothalamic-pituitary-gonadal axis (HPG axis) in men. The aim of the study was to assess the association of nesfatin-1 with HPG axis disturbances in OSA. This is a prospective study with consecutive enrolment. It comprises 72 newly diagnosed OSA patients ((AHI: apnoea-hypopnea index) 18 subjects: 5 ≤ AHI < 15; 24: 15 ≤ AHI < 30; 30: AHI ≥ 30) and a control group composed of 19 patients (AHI < 5). All patients underwent polysomnography and fasting blood collection for nesfatin-1, testosterone, luteinising hormone (LH), high-sensitivity C-reactive protein (hsCRP), aspartate transaminase (AST), alanine aminotransferase (ALT), creatinine and glucose. Groups had similar levels of LH, nesfatin-1 and testosterone (p = 0.87; p = 0.24; p = 0.08). Nesfatin-1 was not correlated to LH (p = 0.71), testosterone (p = 0.38), AHI (p = 0.34) or the oxygen desaturation index (ODI) (p = 0.69) either in the whole group, or in sub-groups. The study did not reveal any association between the HPG axis and nesfatin-1 in OSA adult males. It is possible that nesfatin-1 is not a mediator of HPG axis disturbances in adult patients with OSA.

[Analysis of nutritional status disorders in patients with chronic obstructive pulmonary disease]. / Analiza zaburzen stanu odzywienia u pacjentów z przewlekla obturacyjna choroba pluc.

INTRODUCTION: Among the most common extrapulmonary manifestations of COPD are nutritional status disorders. The specific loss of weight, called cachexia, characterized by loss of lean body mass in some COPD patients is observed. The aim of the study was the quantitative and qualitative analysis of COPD patients' nutritional status disturbances. MATERIAL AND METHODS: Fifty-five patients in different stages of COPD--43 males and 12 females (mean age 62.31 +/- 11.08) and 32 subjects from a control group (mean age 57.43 +/- 8.79) participated in the study. In both groups nutritional status was assessed using different indicators such as PIBW--percentage of ideal body weight, BMI--body mass index, FFMI--fat-free mass index and FMI--fat mass index. RESULTS: Malnutrition measured by PIBW, BMI, BMI percentiles, and FFMI was observed in 5.45%, 3.64%, 3.64% and 18.18% of COPD patients, respectively, and in the control group 3.12%, 0%, 3.12% and 3.12%, respectively. The BMI mean value did not differ significantly between groups. It was confirmed that cachexia assessed by FFMI occured more frequently in COPD patients than in the control group--19.05 kg/m2 vs. 20,55 kg/m2 (p = 0.04). CONCLUSIONS: 1. Nutritional status disorders pose a serious problem, which concerns about 1/5 of the COPD population. 2. It is necessary to perform quantitative analysis of nutritional status (assessment of lean and fat mass) because indicators of body mass (PIBW, BMI) are not sufficient for cachexia detection. 3. Having normal body mass does not exclude the possibility of nutritional status disorders in COPD patients.

Lung cancer in chronic obstructive pulmonary disease patients: importance of cellular senescence.

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of lung cancer, independently of smoking, although the link between these diseases remains unknown. Possible pathophysiologic mechanisms include inflammation and cellular senescence. COPD is a chronic inflammatory disease associated with secretion of numerous inflammatory mediators, many of which play a documented role in the promotion of cancer cell progression. COPD is also an age­related disease involving increased cellular senescence, an important hallmark of aging. Previous studies have confirmed the significant role of cellular senescence in the development of various tumors, including lung cancer. It is highly probable that cellular senescence contributes to carcinogenesis in COPD patients.

Garlic extract favorably modifies markers of endothelial function in obese patients -randomized double blind placebo-controlled nutritional intervention.

OBJECTIVE: Garlic exerts a range of effects relevant to human health. However, its influence on the endothelium in obese individuals remains unknown. We aimed to determine the effects of garlic extract (GE) on arterial stiffness and markers of endothelial function. METHODS: Ninety-two subjects were enrolled in this study. The participants were randomly assigned to receive 400 mg of GE or placebo daily for 3 months. The arterial stiffness index (SI) and markers of endothelial function such as high-sensitivity C-reactive protein (hsCRP), cholesterol (total, LDL, HDL), triglycerides, and plasminogen activator inhibitor 1 (PAI-1), as well as total antioxidant status (TAS) were quantified at baseline and the end of study. RESULTS: At the end of study SI (p = 0.01), hsCRP (p < 0.001, PAI-1 (p < 0.001), LDL cholesterol (p < 0.001), and TAS (p < 0.01) were reduced in the GE-supplemented group, but not in the placebo group. CONCLUSION: This randomized, double-blind, placebo-controlled trial demonstrates that supplementation with GE favorably modifies endothelial biomarkers associated with cardiovascular risk and suggests that GE can be used to suppress chronic inflammation in obese individuals.