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Cardiopulmonary Exercise Testing (CPET) is a standardized, non-invasive procedure assessing pulmonary, cardiovascular, hematopoietic, and skeletal muscle functions during a symptom-limited test. Few studies have examined whether CPET is of prognostic value in Systemic Sclerosis (SSc), a disease characterized by highly increased cardiorespiratory morbidity and mortality. To examine the prognostic value of CPET in SSc patients without baseline pulmonary hypertension (PH). Sixty-two consecutive SSc patients underwent CPET, Pulmonary Function Tests (PFTs) and echocardiography at baseline. Four patients with Right Ventricular Systolic Pressure ≥ 40 mmHg, were excluded. Participants repeated PFTs approximately every 3 years. At the end of the follow-up period [median (IQR): 9.79 (2.78) years] patient vital status was recorded. Cox Regression analysis was used to identify predictors of deterioration of PFTs and 10-year survival. Median (IQR) age of 58 patients (90% women) at baseline was 54.0 (15.0) years, whereas 10-year survival was 88%. Baseline respiratory Oxygen uptake (VO2max) predicted PFT deterioration, defined either as a decline in FVC ≥ 10% or a combined decline in FVC 5%-9% plus DLCO ≥ 15%, during follow-up, after correction for age, gender and smoking status (HR: 0.874, 95%CI: 0.779–0.979, p = 0.021). In addition, lower baseline VO2max (HR = 0.861, 95%CI:0.739–1.003, p = 0.054) and DLCO (HR = 0.957, 95%CI: 0.910–1.006 p = 0.088), as well as male gender (HR = 5.68, 95%CI: 1.090–29.610 p = 0.039) and older age (HR = 1.069, 95%CI: 0.990–1.154, p = 0.086) were associated, after adjustment, with an increased risk for death. In the absence of baseline PH, CPET indices may predict pulmonary function deterioration and death in SSc patients during a nearly 10-year follow-up period.

Introduction Several epidemiological studies have demonstrated that Obstructive Sleep Apnea (OSA) is a highly prevalent disorder in the general population and increases over time all over the world. The high prevalence is in part due to increasing rates of obesity. However, estimates of OSA prevalence in Southern Europe are generally lacking. Aim The aim of our study was to predict the risk of OSA in the general population of Cyprus, the southeast part of Europe, by using a dedicated questionnaire like STOP-Bang. Subjects and method We screened 5736 sample housing units for eligible adults and a total population of 4118 eligible responders completed the STOP-Bang questionnaire. Participants were all adults, age 18 + residing in Cyprus. The sample was stratified according to the last demographic report (2016) by district, rural or urban area, gender and age and the estimated sample size needed was 2000. Our survey was conducted by Computer Aided Telephone Interviewing (CATI) method. The question about Neck Circumference was removed from the final evaluation due to the uncertainty of most of the participants and the risk of bias. Results From a total of 4118 participants (2252 males – 54.7%, 1862 females – 45.3%), with 46.6% over 50 years old, 2641 (64.1%) were at low risk for OSA (0–2 positive answers), 1200 (29.1%) at intermediate risk (3–4 positive answers) and 277 (6.7%) at high risk (≥5 positive answers). In sum, 29.9% responded positively for snoring, 39.3% for feeling tired or sleepy during the day, 12.3% for observed apnea during sleep, and 24.6% for having or being treated for hypertension. Class II and III obesity with Body Mass Index (BMI) > 35 kgr/m2 was observed in 192 subjects (4.7%). In the subpopulation of obese participants (BMI>30 kg/m2), intermediate to high risk of OSA was present in 45%, whereas in obesity class II and III the percentage reached almost 90%. Conclusions Our survey yielded that the prevalence of intermediate to high risk for OSA was 50% in males and 18% in females, in the general population of Cyprus. These findings were similar to previously reported high OSA prevalence worldwide, considering the fact that a single questionnaire is only a screening tool and cannot alone diagnose sleep apnea.

Frangiskos Frangopoulos,1 Ivi Nicolaou,1 Savvas Zannetos,2 Nicholas-Tiberio Economou,3 Tonia Adamide III,1 Andreas Georgiou,1 Pantelis Theodoros Nikolaidis,4 Thomas Rosemann,5 Beat Knechtle,5 Georgia Trakada3 1Respiratory Department, Nicosia General Hospital, Nicosia, Cyprus; 2Health Economics and Statistics, Neapolis University, Paphos, Cyprus; 3Division of Pulmonology, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra Hospital, Athens, Greece; 4School of Health and Caring Sciences, University of West Attica, Athens, Greece; 5Institute of Primary Care, University of Zurich, Zurich, SwitzerlandCorrespondence: Georgia TrakadaDepartment of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra Hospital, Vas Sofias 80, Athens, 11528, GreeceTel +30 210 3381488Fax +30 213 2162889Email gtrakada@hotmail.comIntroduction: Circadian rhythm sleep-wake disorder (CRSWD) is an often-misdiagnosed group of sleep disturbances with limited data concerning diagnostic and therapeutic algorithms in the general population. Therefore, reported prevalence varies in the literature due to different case definitions, methodological, and environmental factors.Objectives: The purpose of our cross-sectional study was to estimate the prevalence of CRSWD in the general population of Cyprus and to suggest clinical parameters for the assessment of atypical sleep schedules. The estimation was carried out by introducing normal preset sleep time limits, according to the imposed local environment and by administering well-established questionnaires for symptoms and consequence dysfunction, as objective evaluation tools.Methods: In a nationwide epidemiological survey, 4118 Cypriot adult participants, selected and stratified to represent the general population, were interviewed on sleep habits and complaints by computer-assisted telephone interviewing (CATI). In the second stage, 250 adults were randomly selected from the initial representative sample, for a CRSWD assessment. According to the proposed diagnostic criteria, patients were interviewed about sleepiness and/or insomnia, and daytime dysfunction (fatigue, anxiety, and depression). They were also assessed by a weekly sleep diary for sleep schedules. Finally, all participants underwent a Type III Sleep Study, to rule out obstructive sleep apnea.Results: From 195 enrolled participants (response rate 78%), 25 individuals (12.8%) met the criteria for CRSWD. The two most prevalent disorders were delayed sleep-wake phase disorder (DSWPD) (10pts, 5.1%) and shift work sleep disorder (SWD) (13, 6.7%). Less prevalent disorders included irregular sleep-wake rhythm disorder (ISWRD) (1, 0.5%) and advanced sleep-wake phase disorder (ASWPD) (1, 0.5%).Conclusions: According to our data, CRSWDs are common in the general population of Cyprus, especially DSWPD and SWD. Affected individuals usually suffer from sleep deprivation and complain about insomnia, sleepiness and depression.Keywords: circadian sleep wake phase disorders, prevalence, sleep deprivation, guidelines

This chapter summarizes the current knowledge about the impact of pharmacotherapy on sleep and sleep disorders in the pediatric population. Poor sleep quality and/or quantity in children, especially in the presence of sleep disorders, is associated with deficits in neurodevelopment, cognition, and behavior. However, clear guidelines regarding pediatric sleep pharmacotherapy are lacking.

Excessive daytime sleepiness (EDS) is a symptom of obstructive sleep apnea (OSA) that resolves under treatment with continuous positive airway pressure (CPAP). In some patients, sleepiness persists despite CPAP treatment. We retrospectively analyzed data on subjective residual EDS, assessed as an Epworth Sleepiness Scale score (ESS) >10, in patients from the European Sleep Apnea Database (n = 4,853, mean age +/- SD 54.8 +/- 11.8 years, 26.1% females), at baseline and at the first visit (median follow-up: 5 months, interquartile range 3-13). An ESS > 10 occurred in 56% of patients at baseline and in 28.2% of patients at follow-up. Residual EDS was analyzed in 2,190 patients (age: 55.1 +/- 12.0 years, 26.1% females) with sleep monitoring data (median follow-up: 3 months, interquartile range 1-15). Sleep studies during CPAP use were obtained in 58% of these patients; EDS was reported by 47.2% of patients at baseline and by 30.3% at follow-up. Residual OSA, defined as an apnea-hypopnea index >10/h, and insufficient CPAP adherence, defined as nightly use 10 at the first follow-up visit was associated directly with ESS at baseline and inversely with duration of follow-up, and CPAP use (R-2 of themodel: 0.417). EDS showed heterogeneity in different European countries both at baseline and at the first follow-up visit, suggesting modulation by cultural and lifestyle factors. In conclusion, residual EDS in CPAP-treated OSA occurred in approximately one in four patients at follow-up; its prevalence was highest (40%) in the first 3 months of treatment and subsequently decreased. The finding of residual EDS in a significant percentage of optimally treated OSA patients suggests that wake-promoting agents may be useful, but their indication should be evaluated after at least 3 months of treatment., European Respiratory Society; ResMed; Philips; Bayer Pharmaceuticals; MIAI @ Grenoble Alpes [ANR19P3IA0003], The ESADA study is a Clinical Research Collaboration funded by the European Respiratory Society and by grants from ResMed, Philips and Bayer Pharmaceuticals. JP and SB are partly supported by MIAI @ Grenoble Alpes (ANR19P3IA0003) . The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.

Introduction: Little information exists in the general population whether clinical presentation phenotypes of obstructive sleep apnea (OSA) differ in terms of sleep quality and comorbidities.Aim: The purpose of our study was to assess possible differences between symptomatic and asymptomatic OSA patients concerning syndrome's severity, patients' sleep quality, and comorbidities.Subjects and methods: First, in a nationwide, stratified, epidemiological survey, 4,118 Cypriot adult participants were interviewed about sleep habits and complaints. In the second stage of the survey, 264 randomly selected adults underwent a type III sleep study for possible OSA. Additionally, they completed the Greek version of Pittsburgh Sleep Quality Index (Gr-PSQI), Epworth Sleepiness Scale (ESS), Athens Insomnia Scale (AIS), and Hospital Anxiety and Depression Scale (HADS).Results: From 264 enrolled participants, 155 individuals (40 females and 115 males) were first diagnosed with OSA. Among these 155 patients, 34% had ESS ≥ 10 and 49% AIS ≥ 6. One or both symptoms present categorized the individual as symptomatic (60%) and neither major symptom as asymptomatic (40%). There were no significant statistical differences (SSDs) between the two groups (symptomatic–asymptomatic) with regard to anthropometrics [age or gender; neck, abdomen, and hip circumferences; and body mass index (BMI)]. The two groups had no differences in OSA severity—as expressed by apnea–hypopnea index (AHI), oxygen desaturation index (ODI), and mean oxyhemoglobin saturation (SaO2)—and in cardiometabolic comorbidities. Symptomatic patients expressed anxiety and depression more often than asymptomatics (p < 0.001) and had poorer subjective sleep quality (Gr-PSQI, p < 0.001). According to PSQI questionnaire, there were no SSDs regarding hours in bed and the use of sleep medications, but there were significant differences in the subjective perception of sleep quality (p < 0.001), sleep efficiency (p < 0.001), duration of sleep (p = 0.001), sleep latency (p = 0.007), daytime dysfunction (p < 0.001), and finally sleep disturbances (p < 0.001).Conclusion: According to our data, OSA patients reporting insomnia-like symptoms and/or sleepiness do not represent a more severe phenotype, by the classic definition of OSA, but their subjective sleep quality is compromised, causing a vicious cycle of anxiety or depression.

Obstructive sleep apnea (OSA) is a chronic and prevalent disorder, strongly associated with cardiovascular disease (CVD). The apnea-hypopnea index (AHI), or respiratory event index (REI), and the oxygen desaturation index (ODI) are the clinical metrics of sleep apnea in terms of diagnosis and severity. However, AHI, or REI, does not quantify OSA-related hypoxemia and poorly predicts the consequences of sleep apnea in cardiometabolic diseases. Moreover, it is unclear whether ODI correlates with CVD in OSA. Our study aimed to examine the possible associations between respiratory sleep indices and CVD in OSA, in a non-clinic-based population in Cyprus. We screened 344 subjects of a stratified, total sample of 4118 eligible responders. All participants were adults (age 18+), residing in Cyprus. Each patient answered with a detailed clinical history in terms of CVD. A type III sleep test was performed on 282 subjects (81.97%). OSA (REI &ge, 15) was diagnosed in 92 patients (32.62%, Group A). REI &lt, 15 was observed in the remaining 190 subjects (67.37%, Group B). In OSA group A, 40 individuals (43%) reported hypertension, 17 (18.5%) arrhythmias, 10 (11%) heart failure, 9 (9.8%) ischemic heart disease and 2 (2%) previous stroke, versus 46 (24%), 21 (11%), 7 (3.7%), 12 (6.3%) and 6 (3%), in Group B, respectively. Hypertension correlated with REI (p = 0.001), ODI (p = 0.003) and mean SaO2 (p &lt, 0.001). Arrhythmias correlated with mean SaO2 (p = 0.001) and time spent under 90% oxygen saturation (p = 0.040). Heart failure correlated with REI (p = 0.043), especially in the supine position (0.036). No statistically significant correlations were observed between ischemic heart disease or stroke and REI, ODI and mean SaO2. The pathogenesis underlying CVD in OSA is variable. According to our data, hypertension correlated with REI, ODI and mean SaO2. Arrhythmias correlated only with hypoxemia (mean SaO2), whereas heart failure correlated only with REI, especially in the supine position.

Background Aim: The aim of this study was to examine the sleep characteristics of children and explore associations with various socio-demographic factors in an area of Greece characterized by cultural diversity. Methods: A questionnaire about children's sleep habits had been distributed to parents of children who visited the pediatric outpatient clinic of University General Hospital of Alexandroupolis for a medical examination and to get a health certificate for participation in sports activities. Children with chronic health conditions were excluded. Results: In the study, 449 children (27.1% belonging to minorities) were included, aged 7.6 ± 2.9 years. Most of them (81.7%) slept after 10 p.m., with a mean nocturnal sleep duration of 9.4 ± 1.2 h. The most commonly reported disturbance was snoring (26.2%). Age and high educational level of the mother were both important determinants for sleeping late [OR 1.139 (1.033–1.255); p = 0.009 and OR 1.086 (1.004–1.175); p = 0.040, respectively]. The latter was also associated with an absence of any reported sleep disorder in children [OR 0.934 (0.877–0.994); p = 0.031]. A longer sleep duration was reported among Roma children (p = 0.022), which was more overt in girls (mean sleep duration 10.4 ± 1.6 h). In the Roma group also, the prevalence of sleep disorders was higher. Conclusion: Age progression and maternal educational level, along with cultural background, seem to be correlated with variations in the sleep characteristics of children in a culturally diverse population in Greece.

Lung cancer is still underdiagnosed mainly due to lack of symptoms. Most patients are diagnosed in a late stage where unfortunately only systematic therapy can be applied. Fortunately in the last five years several novel therapies and combinations have emerged. However; in certain situations local therapeutics modalities have to be applied in order to solve emergency problems as in the case that we will present. Convex-EBUS probe was used along with a novel method of ventilation which keeps PCO2 concentration satisfyingly low. Keywords: Lung cancer, Interventional pulmonology, Ventilation, EBUS

Endobronchial ultrasound endoscopy is a state of the art diagnostic endoscopic procedure for the thorax. Firstly it was designed mainly for the staging of lung cancer and of course for the diagnosis of suspicious findings in large central airways. The main limitation of the equipment is the diameter of the instrument and therefore it can only be guided through large airways. However; the diameter of the working channel also provides a large tissue sample nowadays with the 19G biopsy needle. We will provide our experience with the 22G needle of the endobronchial convex-probe in several medical situations of the thorax.

Introduction: Lung cancer is still the leading cause of cancer among cancer patients. Although there are novel therapies as second line treatment for NSCLC, there is an issue for elderly patients. Patients and Methods: We collected retrospectively data from 60 patients >75 years of age. Thirty of these patients received nab-paclitaxel and first line treatment and were compared to thirty patients that received only best supportive care. Results: The median life of patients at the date of disease progression, although increased by the administration of the drug (92 days versus 70) was not confirmed statistically significantly (Mann-Whitney test: W = 280, p = 0.138). The administration of drug seems to keep stable the biological condition of patients (McNemar's test: χ2 = 0.033, p = 0.99). Patients with chemotherapy the death rate was increased by 50% as compared to those with best supportive care (12 vs 8), the median life until the unfortunate event surpassed statistically significantly the latter (150 days of life as compared to 108, Mann-Whitney test: W = 57.5, p = 0.045). Discussion: Nab-paclitaxel as a monotherapy could be considered as a first line treatment option for patients > 75 years of age without any previous cardiological medical history when compared to best supportive care.

Background: Despite the proof of principle that gene therapy can cure various monogenic diseases, limited clinical progress has been noted for gene therapy of the respiratory system. Certain anatomic features of the lungs, along with the suboptimal gene delivery vehicles utilized up to now, have significantly delayed successful clinical practice. Thus, the need for additional improvements towards safety and efficacy of the procedure is indispensable. Objective: The objective of this work was to review the progress and limitations of gene therapy in the treatment of lung disease with a focus on monogenic disease, chronic obstructive pulmonary disease and asthma and to present studies that provide a proof of principle that it works in different model systems and in patients. Method: A thorough search was performed on the aforementioned topic using Pubmed in order to identify relevant manuscripts. Several gene therapy studies for monogenic disorders affecting other organs or systems were also taken into consideration. Results: A hundred and thirty one papers were included. Inclusion criteria regarded novel gene transfer technologies of the past decade, as well as publications outlining the pitfalls that precluded earlier successful implementation of gene therapy for pulmonary diseases. Conclusion: Current gene transfer protocols and vector design require additional amelioration. The rapidly evolving and much promising technology of CRISPR/Cas9 might possibly overcome the hurdles posed to date for effective implementation of gene therapy and become the basis for the onset of new clinical trials.

Targeted therapies are on the market for the past five years and recently pembrolizumab was approved as first line treatment for patients with PD-L1 >50%. We present three cases of patients which had epidermal growth factor receptor positive expression and programmed death-ligand 1 (PD-L1), PD-L1 >50% overexpression.

Background and aim: Obstructive sleep apnea (OSA) is an independent risk factor for dyslipidemia. The current study examined the effects of positive airway pressure (PAP) treatment on lipid status in the European Sleep Apnea Database (ESADA). Methods: The prospective cohort study enrolled 1564 OSA subjects (74% male, mean age 54 ± 11y, body mass index (BMI) 32.7 ± 6.6 kg/m2 and apnea-hypopnea index (AHI) 40.3 ± 24.4 n/h) undergoing PAP therapy for at least three months (mean 377.6 ± 419.5 days). Baseline and follow-up total cholesterol (TC) from nine centers were analyzed. Repeated measures and logistic regression tests (adjusted for age, sex, weight changes, lipid lowering medication, PAP compliance, and treatment duration) were used to compare changes in TC concentration. Incident risk for a coronary heart disease event (CHD) was used to compute a Framingham CHD risk score (estimated from age, BMI, blood pressure, and TC). Results: Adjusted means of TC decreased from 194.2 mg/dl to 189.3 mg/dl during follow-up (p = 0.019). A clinically significant (10%) reduction of TC at PAP follow-up was observed in 422 patients (27%). Duration of PAP therapy was identified as independent predictor for TC reduction, which implies an approximately 10% risk reduction for incident CHD events (from 26.7% to 24.1% in men and from 11.2% to 10.1% in women, p < 0.001 respectively). Conclusion: This observational study demonstrates a reduction of TC after long-term PAP treatment. The close association between TC concentration and cardiovascular (CV) mortality suggests that identification and treatment of OSA may have a beneficial effect on overall CV risk due to this mechanism. This possibility needs to be evaluated in prospective randomized studies. © 2020 Elsevier B.V., ResMed Foundation European Respiratory Society, ERS European Respiratory Society, ERS European Respiratory Society, ERS, The ESADA network has received support from the European Union COST action B26 and the European Respiratory Society (ERS) funded Clinical Research Collaboration (CRC). Unrestricted seeding grants from the ResMed Foundation and the Philips Respironics Foundation for establishment of the database in 2007 and 2011 are gratefully acknowledged. The ESADA network has a scientific collaboration with Bayer AG., Nonfinancial support was provided by the European Sleep Research Society (ESRS) and the European Respiratory Society (ERS) in terms of logistics for communication, meetings and data presentations for the ESADA collaborators., Dr. Verbraecken reports grants and personal fees from ResMed, Bioprojet, Jazz Pharmaceutics; personal fees from Philips, Sanofi, Agfa-Gevaert, grants from AirLiquide; personal fees from Springer, Westfalen Medical, SomnoMed, Vivisol, Total Care, Medidis, Fisher & Paykel, Wave Medical, OSG, Mediq Tefa, NightBalance, Heinen & Löwenstein, AstraZen, Accuramed, Bekaert Deslee Academy and UCB Pharma, outside the submitted work. Dr. Hedner reports grants from ResMed, Philips Respironics, and the European Respiratory Society all related to maintenance of database on behalf of the ESADA group during the conduct of the study. Dr. Grote reports grants from Bayer, Resmed, Respironics/Philips, and from the European Respiratory Society during the conduct of the study; non-financial support and other from Itamar Medical, Resmed, Philips, and Astra Zeneca, outside the submitted work. In addition, Dr. Grote has a patent on sleep apnea therapy licensed. The remaining co-authors have no conflict of interest to declare.

Introduction: Obstructive sleep apnea (OSA) and its cardiometabolic alterations are closely associated with visceral obesity. Patients with OSA frequently present with symptoms of depression and anxiety. Although these subjective symptoms of OSA are the result of complex biological dysregulation, it remains unclear if they have a direct effect on the dysfunction of adipose tissue.Methods: In a pilot, prospective, randomized study, we evaluated 10 recently diagnosed male patients with severe OSA by full polysomnography (PSG) and 4 male non-apneic subjects matched for age and body mass index (BMI) with abdomen adipose tissue biopsies. Subjects with diabetes/prediabetes and cardiovascular and psychiatric diseases and who are current smokers were excluded. All patients underwent anthropometric measurements and completed the following questionnaires: Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and Hospital Anxiety and Depression Scale (HADS-A and HADS-D). Fasting venous blood samples were collected on the day after PSG, between 8:00 and 9:00 a.m., after an overnight fast. Fat biopsies were performed at the same time periods and adipose tissue samples of 300 mg were obtained from abdominal fat. Fat cell size, extent of fibrosis, vascularity, leukocyte common antigen inflammatory infiltration, and tissue macrophage accumulation were microscopically evaluated.Results: The mean age of the group was 47.4 +/- 13.8 years, with mean BMI of 35.8 +/- 4.8 kg/m(2) and mean apnea-hypopnea index of 79.4 +/- 46.1 events per hour of sleep (severe OSA). HADS-A and HADS-D scores were 5.8 +/- 2.3 (3.0-8.0) and 4.7 +/- 2.3 (2.0-8.0), respectively. HADS-A score correlated positively with macrophage accumulation in fat biopsy (r = 0.82, p = 0.047), whereas ESS, FSS, and HADS-D did not. Severity of fibrosis correlated largely with waist circumference (r = -0.66, p = 0.038) and neck circumference (r = -0.790, p = 0.006). Respiratory events correlated negatively with the extent of vascularization of adipose tissue (r = -0.614, p = 0.05).Conclusions: In the preliminary results of our pilot study, we assessed that the symptoms of anxiety mainly contribute to macrophage accumulation, whereas the increased number of respiratory events reduces the extent of vascularization in visceral fat in OSA. Based on this observation, further larger studies are required to verify if anxious OSA patients are more vulnerable to the metabolic manifestations of the syndrome.

Patients with serious psychiatric diseases (major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia and psychotic disorder) often complain about sleepiness during the day, fatigue, low energy, concentration problems, and insomnia, unfortunately, many of these symptoms are also frequent in patients with Obstructive Sleep Apnea (OSA). However, existing data about the clinical appearance of OSA in Psychiatric Disease are generally missing. The aim of our study was a detailed and focused evaluation of OSA in Psychiatric Disease, in terms of symptoms, comorbidities, clinical characteristics, daytime respiratory function, and overnight polysomnography data. We examined 110 patients (56 males and 54 females) with stable Psychiatric Disease (Group A: 66 with MDD, Group B: 34 with BD, and Group C: 10 with schizophrenia). At baseline, each patient answered the STOP&ndash, Bang Questionnaire, Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and Hospital Anxiety and Depression Scale (HADS) and underwent clinical examination, oximetry, spirometry, and overnight polysomnography. Body Mass Index (BMI), neck, waist, and hip circumferences, and arterial blood pressure values were also measured. The mean age of the whole population was 55.1 &plusmn, 10.6 years. The three groups had no statistically significant difference in age, BMI, hip circumference, and systolic and diastolic arterial blood pressure. Class II and III obesity with BMI &gt, 35 kg/m2 was observed in 36 subjects (32.14%). A moderate main effect of psychiatric disease was observed in neck (p = 0.044, &eta, 2 = 0.064) and waist circumference (p = 0.021, &eta, 2 = 0.078), with the depression group showing the lowest values, and in pulmonary function (Forced Vital Capacity (FVC, %), p = 0.013, &eta, 2 = 0.084), with the psychotic group showing the lowest values. Intermediate to high risk of OSA was present in 87.37% of participants, according to the STOP&ndash, Bang Questionnaire (&ge, 3 positive answers), and 70.87% responded positively for feeling tired or sleepy during the day. An Apnea&ndash, Hypopnea Index (AHI) &ge, 15 events per hour of sleep was recorded in 72.48% of our patients. AHI was associated positively with male sex, schizophrenia, neck, and waist circumferences, STOP&ndash, Bang and ESS scores, and negatively with respiratory function. A large main effect of psychiatric medications was observed in waist circumference (p = 0.046, &eta, 2 = 0.151), FVC (%) (p = 0.027, &eta, 2 = 0.165), and in time spend with SaO2 &lt, 90% (p = 0.006, &eta, 2 = 0.211). Our study yielded that patients with Psychiatric Disease are at risk of OSA, especially men suffering from schizophrenia and psychotic disorders that complain about sleepiness and have central obesity and disturbed respiratory function. Screening for OSA is mandatory in this medical population, as psychiatric patients have significantly poorer physical health than the general population and the coexistence of the two diseases can further negatively impact several health outcomes.

In this decade a “bloom” of novel therapies has been observed for non-small cell lung cancer. We have new tools for the diagnosis of lung cancer and also we can re-biospy easier than before in different lesions and obtain tissue samples in order to investigate whether a patient can receive new targeted therapies. Immunotherapy has been well established previously for other forms of cancer, and nowadays it is also available for lung cancer. There are two immunotherapies for now nivolumab and pembrolizumab which can be administered as second line treatment, the second can also be administered as first-line if there is a programmed death-ligand 1 ≥50% expression.

Non-small cell lung cancer is still diagnosed at late stage due to the lack of early symptoms and methods of diagnostic prevention. In the past ten years several targeted therapies have been introduced or explored. Tyrosine kinase inhibitors and immunotherapy are currently considered the most effective and safe therapies in comparison to the non-specific cytotoxic agents. Regarding tyrosine kinase inhibitors the adverse effects have been fully explored, however; on the other hand for immunotherapy there are still several issues to be clarified. We report a rare case of a patient with lung cancer adenocarcinoma who developed vitiligo throughout his body after nivolumab administration.

In the past decade novel agents are on the market for non-small cell lung cancer adenocarcinoma based on pharmacogenomics. The epidermal growth factor receptor mutation, anaplastic lymphoma kinase and programmed death-ligand 1 investigation is necessary in the everyday clinical practice for the oncologic patient. Immunotherapy is nowadays the novel therapy for advanced stage non-small cell lung cancer with two agents nivolumab and pembrolizumab. In the current case series we will present adverse effects from our centers and comment on the treatment and follow-up of the patients.

This is a case description of two patients with bipolar affective disorder, who presented complications, possibly due to underlying, undiagnosed obstructive sleep apnea syndrome (OSAS), during anesthesia for electroconvulsive therapy (ECT). The first patient, just after receiving the second ECT, developed tachypnea with spasm of the upper airways and severe oxygen desaturation He was intubated and transferred to the medical intensive care unit where he was extubated 15 h later. The second patient, just after the eighth ECT, developed tachycardia and severe hypertension. He was transferred to the recovery room where he received oxygen therapy via nasal cannula and amlodipine. Both patients in the diagnostic polysomnographic tests which followed revealed a moderate to high apnea – hypopnea index (AHI) and distortion of sleep architecture. These cases highlight the need to assess for OSAS patients who receive ECT, especially if they exhibit peri-anesthesia complications.

Pulmonary embolism is a common clinical entity related to high mortality. About 200,000 to 300,000 patients die every year due to pulmonary embolism. The purpose of this article is to describe a case of a patient who on the second postoperative day after undergoing thromboembolectomy of the left femoral artery, manifested a massive pulmonary embolism. Due to cardiorespiratory collapse a combined treatment via extracorporeal life support (ECLS) and parallel catheter thrombolysis was decided and performed. By cardiorespiratory improvement and final stabilization the patient was successfully weaned from ECLS and the system was successfully removed. After a reasonable postoperative time the patient was dismissed in good overall condition. Keywords: Pulmonary embolism, Extracorporeal membrane oxygenation, Thrombolysis, Catheter thrombolysis

European-Respiratory-Society (ERS) International Congress -- SEP 28-OCT 02, 2019 -- Madrid, SPAIN, Riha, Renata/0000-0001-8983-9985, WOS: 000507372405424, [No abstract available], European Respiratory Soc

Supplemental Digital Content is available in the text., Rationale: Cardiac involvement and hypotension dominate the prognosis of light-chain amyloidosis (AL). Evidence suggests that there is also peripheral vascular involvement in AL but its prognostic significance is unknown. Objective: To evaluate vascular dysfunction in patients with AL as a potential future area of intervention, we assessed the prognostic utility of flow-mediated dilatation (FMD), a marker of vascular reactivity, which is augmented under conditions of hypotension and autonomic dysfunction. Methods and Results: We prospectively evaluated 115 newly diagnosed untreated AL patients in whom FMD was measured. FMD in AL patients was significantly higher than age-, sex- and risk factors–matched controls (4.0% versus 2.32%; P=0.006) and comparable with control groups at lower cardiovascular risk (P>0.1). Amyloidosis patients presented increased plasma and exhaled markers of the NO pathway while their FMD significantly correlated with augmented sustained vasodilatation after sympathetic stimulation. Increased FMD (≥4.5%) was associated with early mortality (hazard ratio, 4.36; 95% CI, 1.41–13.5; P=0.010) and worse survival (hazard ratio, 2.11; 95% CI, 1.17–3.82; P=0.013), even after adjustment for Mayo stage, nerve involvement and low systolic blood pressure. This finding was confirmed in a temporal validation AL cohort (n=55; hazard ratio, 4.2; 95% CI, 1.45–12.3; P=0.008). FMD provided significant reclassification value over the best prognostic model (continuous Net Reclassification Index, 0.61; P=0.001). Finally, better hematologic response was associated with lower posttreatment FMD. Conclusions: FMD is relatively increased in AL and independently associated with inferior survival with substantial reclassification value. Reactive vasodilation merits further investigation as a novel risk biomarker in AL.Visual Overview: An online visual overview is available for this article.

European-Respiratory-Society (ERS) International Congress -- SEP 28-OCT 02, 2019 -- Madrid, SPAIN, WOS: 000507372402165, [No abstract available], European Respiratory Soc

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with multiple systemic manifestations and comorbidities, which contribute independently to its total morbidity and mortality. Pulmonary rehabilitation is an evidence-based intervention that is indicated for COPD patients who remain symptomatic, despite optimal pharmacological therapy. Although it is well documented in pure COPD, the role of pulmonary rehabilitation is uncertain in coexisting comorbidities. The aim of the present study was to clarify the effect of a pulmonary rehabilitation program in COPD patients with concomitant comorbidities.Methods: Thirty two patients with COPD were evaluated before and after a comprehensive pulmonary rehabilitation program, in terms of dyspnea, quality of life (QOL), pulmonary function tests and exercise capacity. The patients were also divided into two groups, according to the presence or the absence of comorbidities. Patients with none or only one comorbidity (Group 1, n = 11) were compared to those who had two or more comorbidities (Group 2, n = 21).Results: All patients significantly improved in dyspnea, as expressed by modified Medical Research Council scale and the COPD assessment Test (p < 0.001), QOL as assessed by the St. George respiratory questionnaire (p < 0.001) and exercise tolerance in six minute walking test (p < 0.001). Peak oxygen uptake relatively increased and body mass decreased in Group 1 compared to Group 2 (p < 0.05).Conclusion: Pulmonary rehabilitation in COPD seems to be beneficial for all patients, independently of the presence, the number or the nature of their comorbidities. Thus, the presence of comorbidities must not represent an exclusion criterion for patients that are referred to pulmonary rehabilitation programs.Trial Registration: Current controlled trials ISRCTN14648515 Retrospectively registered 15 February 2018.

Objective/Background: The Clinical Global Impression scale (CGI) reflects the clinician's assessment of the disease impact on patient's global functioning. We assessed predictors of CGI scale rating in patients with obstructive sleep apnea (OSA). Patients/Methods: Consecutive patients with suspected OSA (n = 7581) were identified in the European Sleep Apnea Database (ESADA). Anthropometrics, comorbidities, apnea severity obtained by polygraphy or polysomnography, and daytime sleepiness [Epworth Sleepiness Scale (ESS)] were assessed. The CGI 7-point scale was completed at the end of the diagnostic process (CGI-severity, ie, CGI-S) and, in a sub-population, at treatment follow-up (CGI-Improvement). Results: CGI-S was rated mild to moderate in 44% of patients. CGI rating at any given apnea intensity was worse in women than in men (p < 0.01). Patients undergoing polygraphy (n = 5075) were more frequently rated as severely ill compared to those studied with polysomnography (19.0% vs 13.0%, p < 0.001). In patients aged

Background: Due to the severity of the primary disease in patients with lung cancer, quality of life (QoL) is often overlooked. Factors that form QoL should be taken in consideration when planning the appropriate treatment and determining therapy targets, because of the increasing frequency of bone metastasis leading to high levels of pain. Purpose of this study is to assess quality of life in patients with lung cancer, before and after treatment combined with zoledronic acid. Methods and Materials: QoL was assessed in 80 patients (49 males-31 females), of which 45 developed bone metastasis. Prior and post treatment (with co administration of zoledronic acid) seven reliable scales: Pittsburgh Sleep Quality index (PSQI), Epworth Sleeping Scale (ess), Dyspnea Scale (ds), Fatigue Severity Scale (FSS), Brief Pain Inventory (BPI), Fact-G scale for sleep quality and EQ-5D for general health condition. Results: Statistically positive correlations were verified between PSQI-DS, PSQI-FSS, BPI-ESS, DS-FSS, DS-BPI and BPI-FSS (p Conclusions: Significant improvement was apparent when zoledronic acid was co administered in any treatment in patients with lung cancer. Sleep quality, fatigue and pain parameters also improved, with no positive impact on the symptoms of dyspnea.

Lung cancer is still diagnosed at a late stage in most lung cancer patients. Regarding Non-small Cell lung cancer there are novel therapies such as; tyrosine kinase inhibitors and immunotherapy. Currently we have two immunotherapies that can be used either as first-line treatment or second line treatment; pembrolizumab and nivolumab. A third one is being investigated as a combination of immunotherapy; ipilimumab. Aerosol treatment has been investigated for many diseases not only for the lung, but also for systematic diseases. The design of cups was found the most significant factor in producing significant effects. The comparison of cups reveals the design J as the most capable of reducing the droplets at a minimum size of mass median aerodynamic diameter (MMAD) MMAD=1.99. Drug effect comes second in sequence (F=62.04) showing that nivolumab is the most drastic preparation at low particle sizes (1.89), two drugs share an intermediate particle diameter (pembrolizumab and ipilimumab). In total drugs demonstrate a decreasing droplet size: Ipilimumab>Pembrolizumab> Nivolumab.

Pre-existing pulmonary disease may affect treatment choices, toxicity, and survival of patients with multiple myeloma (MM). However, data on the prognostic value of pulmonary function tests (PFTs) in myeloma patients’ outcome, at the time of initial assessment of newly diagnosed patients, are scarce. Here, we prospectively performed PFTs in 121 newly diagnosed MM patients, before initiation of treatment, and we evaluated possible associations of lung function with their outcomes. Fifty-four patients (44.63%) had either obstructive or restrictive pulmonary function defects, even among those not reporting a history of lung disease. The survival was significantly worse in those with obstructive pulmonary defect (median OS 32.8 months) vs. those with restrictive (median OS 52.5 months) or normal lung function (median not reached, 3-year survival 76%) (p = 0.013), independently of other myeloma-related factors. Forced vital capacity (FVC) (lt) (p = 0.012), forced expiratory volume in 1 s (FEV1) (lt) (p = 0.018), peak expiratory flow (PEF) (lt/min) (p = 0.008), carbon monoxide diffusion capacity (DLCO) (p = 0.012), and expiratory/inspiratory pressures (Pe) (kPa) (p = 0.032)/(Pi) (kPa) (p = 0.023) were significantly associated with OS. Myeloma-related factors associated with survival included ISS stage (p = 0.008), hypercalcemia (p = 0.064), and high-risk cytogenetics (p = 0.004). In the multivariate analysis, only the presence of high-risk cytogenetics and presence of either or both PEF and DLCO

Introduction: The incidence of echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) mutation among surgically treated patients with adenocarcinoma of the lung of the Eastern European ethnicity is underreported. The aim of this trial was the determination of EML4-ALK mutation frequency in investigated population, and the evaluation of correlations between lung adenocarcinoma subtype and clinical characteristics with mutation status. Patients and methods: This was a prospective trial which included 195 patients with adenocarcinoma of the lung who underwent surgical treatment. ALK mutation screening was performed by immunohistochemistry (IHC). IHC scores of 2+ and 3+ were regarded as positive. Confirmatory FISH was performed in all IHC positive and in 2:1 ratio in negative patients. Results: Overall ALK mutation rate established by IHC was 6.2%, while FISH confirmed rate of 5.1%. The FISH confirmed ALK positivity in 7.6% Hungarians, 5.5% Serbians, and 6.6% Slovakians. Acinar subtype of adenocarcinoma of the lung was significantly (p=0.02) related to EML4-ALK positive mutation status. Most of the patients were males (56.9%), smokers (50.8%), or former smokers (28.7%) with acinar (55.4%) or solid (35.9%) adenocarcinoma of the lung. Sensitivity and specificity of IHC were 100% and 98.9% respectively. Conclusions: ALK mutation rate in surgically treated patients with adenocarcinoma of the lung was found to be 6.2% by IHC and 5.1% by FISH. Acinar subtype of the adenocarcinoma of the lung was significantly related to ALK positive mutation.

Non-small cell lung cancer adenocarcinoma in the past decade has targeted therapies as the cornerstone for therapy. In specific patients with epidermal growth factor receptor mutation have three different therapy approaches with the tyrosine kinase inhibitors: erlotinib, gefitinib and afatinib. Nowadays we can use tyrosine kinase inhibitors as second line treatment for squamous cell carcinoma. We present a case with a patient with squamous cell carcinoma receiving afatinib tyrosine kinase inhibitor who presented elbow bursitis or olecranon bursitis in both elbows.

Purpose: Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Furthermore, somatostatin (SST) receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and are overexpressed in tumors. Since, human small-cell lung cancer overexpresses somatostatin receptors (STTR), they could be legitimate targets for treating SCLC.The aim of this study was the evaluation of cytotoxicity of somatostatin in combination with several anticancer drugs in HTB-175 cell line (Small Cell Lung Cancer Cell line that expresses neuron specific enolase). Methods: Docetaxel, Paclitaxel, Carboplatin, Cisplatin, Etoposide, Gemzar, Navelbine, Fluorouracil, Farmorubicin are the chemotherapeutic drugs that we used for the combination before and after adding somatostatin in SCLC cell culture. HTB-175 cell line was purchased from ATCC LGC Standards.At indicated time-point, 48h after the combination, cell viability and apoptosis were measured with Annexin V staining by flow cytometry. Results: Flow cytometry showed that Docetaxel, Paclitaxel, Gemzar and Cisplatin induced apoptosis more when they were added before somatostatin, whereas etoposide induced apoptosis more after somatostatin treatment. Navelbine alone or in combination with somatostatin showed no differences in apoptosis. Farmorubicin showed equal toxicity in all combinations. Fluorouracil and Carboplatin induced apoptosis more when added alone in HTB-175 cell line. However, increased apoptosis was also observed when Carboplatin was administered before somatostatin in higher concentrations. Conclusion: Our results indicated that depending on the drug, somatostatin treatment before or after chemotherapeutic drugs increased apoptosis in small cell lung cancer cells. We suggest that long acting somatostatin analogues could be used as additive and maintenance therapy in combination to antineoplastic agents in SCLC patients.

Patients with Chronic Obstructive Pulmonary Disease (COPD) and / or Obstructive Sleep Apnea (OSA) often complain about sleepiness, fatigue, anxiety and depression. However, common screening questionnaires, like Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS) and Hospital Anxiety and Depression Scale (HADS) have not been previous evaluated in patients with overlap-coexisting COPD and OSA-syndrome versus patients with OSA alone. Our study compared ESS, FSS and HADS between patients with overlap syndrome and patients with OSA, before and after treatment with Continuous Positive Airways Pressure (CPAP). We examined 38 patients with coexisting COPD and OSA versus 38 patients with OSA-only and 28 subjects without respiratory disease, serving as controls. All patients underwent pulmonary function tests (PFTs), oximetry and overnight polysomnography and completed the questionnaires, before and after 3 months of CPAP therapy. The two patient groups did not differ significantly in terms of age, Body Mass Index (BMI), neck, waist and hip circumferences, and arterial blood pressure values. They also had similar comorbidities. They differed significantly, as expected, in PFTs (Forced Vital Capacity-FVC, 2.53±0.73 vs 3.08±0.85 lt, p = 0.005, Forced Expiratory Volume in 1sec-FEV1, 1.78±0.53 vs 2.60±0.73 lt/min, p

Introduction Current evidence supports an association between Obstructive Sleep Apnea Syndrome (OSAS) and insulin resistance and type 2 diabetes mellitus (DM 2). The relation between glycemic profile and severity of OSAS, in nondiabetic patients, is complex and still remains poorly understood. Aim To examine the potential correlation between sleep characteristics and glucose metabolism in nondiabetic patients, with OSAS. Materials and Methods Included were one hundred and fifty seven (157, 104 men and 53 women), with mean age 46.63±10.45years old and mean Body Mass Index (BMI) 31.47±5.8kg/m2, nondiabetic patients, recently diagnosed with OSAS, by full polysomnography. Patients were subdivided into four groups, according to their fasting plasma glucose (FPG) levels: group I: ≤75mg/dl (n=44), group II: 76-86mg/dl (n=37), group III: 87-96mg/dl (n=33) and group IV: ≥97mg/dl (n=43). Results Both, group I, with the lowest FPG and group IV, with the highest FPG were strongly associated with apnea-hypopnea index (AHI) (p=0.02), a widely accepted marker of the severity of OSAS, and with percentage of sleep time with saturation of hemoglobin with oxygen as measured by pulse oximetry (SpO2) Conclusions In conclusion, the severity of OSAS among nondiabetic patients correlates in a u-shaped relation with FPG. A compensatory, early rise in insulin secretion to maintain normal to low FPG could be an underlying mechanism that promotes the future development of DM 2, in OSAS. More studies are needed to assess whether early diagnosis and treatment of OSAS may reverse insulin resistance and prevent progress to diabetes

Background: Gender affects the clinical presentation of obstructive sleep apnea (OSA). The classic OSA symptoms, such as sleepiness, snoring, and apnea, are not so frequent in women. Objectives: To evaluate possible gender differences in questionnaires used for OSA prediction, such as the Epworth Sleepiness Scale (ESS), STOP, STOP Bang (SB), Berlin Questionnaire (BQ), Athens Insomnia Scale (AIS), and Fatigue Scale (FS). Methods: 350 males were matched with 350 women referred to a sleep clinic, according to OSA severity. All responded to the questionnaires and underwent a sleep study. Cardiovascular disease (CVD) patients were separately analyzed. Results: ESS did not differ between genders. SB was higher in males, whereas STOP, BQ, AIS, and FS were higher in females. BQ presented the highest sensitivity in both genders, whereas STOP exhibited the highest specificity in males and ESS in females. AIS and FS were more sensitive and SB more specific in females, whereas BQ was more specific in males. For severe OSA, the predictive values of SB and BQ were almost similar for both genders, however AIS and FS were higher in women. CVD patients presented higher scores, independent of gender, except for AIS, which was higher in females. Conclusion: Gender-specific evaluation of questionnaires is necessary to prevent OSA under-diagnosis.

Obstructive sleep apnea syndrome (OSAS) is common in adult population and it is associated with increased morbidity and mortality, especially due to cardiovascular disease (CVD). Both diagnosis, based on polysomnography, and treatment with continuous positive airway pressure (CPAP), carry a potentially high cost. The present study aims to analyze the cost-effectiveness of CPAP treatment versus no treatment, in the long-term, as it examines the effect of this treatment on the incidence of CVD.A Markov model was constructed to observe the disease evolution in patients with OSAS based on published evidence. Data on treatment costs were collected from public hospitals in Greece. Within each cycle of the model, each patient may remain free of CVD, may develop CVD, may die due to a cause related to CVD, or may die from other causes. The model begins at the age of 55 years in a severe OSAS patient (apnea-hypopnea index ≥30/h) and lasts for 45 years.Within the limitation of the model, CPAP was found to be a cost-effective strategy versus no treatment, due to the reduction of the cost for the CVD treatment, when the analysis was restricted to the male population. Moreover, CPAP was found to be clinically more effective than no treatment, as it increases life expectancy in both males and females.CPAP was found to be clinically more effective therapy than no treatment in relation to CVD and a cost-effective strategy in males with severe OSAS.

Lung involvement in patients with systemic AL amyloidosis is not very common and consensus criteria require direct biopsy verification with symptoms or typical radiographic changes of diffuse interstitial lung disease. Dyspnea and other symptoms are commonly attributed to cardiac dysfunction and thus, lung dysfunction may go unrecognized while, in some series evidence suggest that lung involvement is probably more frequent than reported. No prospective comprehensive evaluation of lung function has been performed in patients with AL amyloidosis; the aim of our study was to prospectively assess lung function by performing comprehensive pulmonary function tests (PFTs) in consecutive patients with systemic AL amyloidosis. This was a non-interventional prospective study that included consecutive patients with systemic AL amyloidosis treated in the Department of Clinical Therapeutics (Athens, Greece). Patients with localized lung amyloidosis were excluded. PFTs were performed in a Master screen Body (Jaeger, Germany), according to manufacturer's instructions and standard European Respiratory Society / American Thoracic Society guidelines. We performed spirometry, lung volumes measurement, single-breath determination of carbon monoxide uptake in the lung corrected for hemoglobin (carbon monoxide diffusion capacity, DLCO) and maximal expiratory (Pe) and inspiratory (Pi) pressures measurement, in a sitting position. The patient's age, height and weight were recorded for use in the calculation of reference values. We adjusted DLCO for Hb prior to the interpretation of the maneuver in the predicted values. Smoking habits were recorded (smoker or no, pack/years, years of smoking cessation). We report on the first 84 patients with systemic AL amyloidosis that were included in the study. Median age was 63 years (range 44-84), 60% were males, median baseline dFLC was 162 mg/L, median BM infiltration was 15% (range 0-30%). Kidney involvement was present in 73%, median eGFR was 63 ml/min/1.73 m2. Heart was involved in 72% and 12%, 62%, 17% & 8% of patients were Mayo stage 1,2, 3A and 3B respectively. Liver was involved in 25%, peripheral/autonomic nerve in 21% and soft tissue in 12%. Based on imaging and/or lung biopsy, lung involvement was present in 2 (2%) patients; 48% of the patients were current or ex-smokers. Primary treatment was bortezomib-based in 89% of the patients. According to PFTs, breathing pattern was normal in 49%, restrictive in 37%, obstructive in 11% and mixed in 3%. The presence of a restrictive pattern was marginally associated with heart involvement (p=0.056) but not with Mayo stage and was more common in patients with liver (p=0.022) and soft tissue involvement (0.031) and there was no association with renal or nerve involvement or FLC levels. In univariate analysis, restrictive pattern was associated with worse survival (24 months vs not reached for obstructive and normal, p=0.015); 1-year mortality was 42% for restrictive vs 13% for obstructive and 5% for normal breathing patterns. When adjusted for Mayo stage, restrictive pattern (HR 2.63, p=0.033) and Mayo stage 3B (HR: 12, p=0.033) were independently associated with survival. Among individual PFTs indices, corrected DLCO (p=0.02), TLC% (p=0.012) and Pe% (p=0.019) were associated with survival. A DLCO In this comprehensive evaluation of lung function by PFTs we found that restrictive breathing pattern is common among patients with systemic AL, and indices of lung function are associated with prognosis independently of cardiac dysfunction. Our results point to the presence of unrecognized pulmonary involvement, despite the absence of typical imaging findings. Disclosures Kastritis: Genesis: Honoraria; Prothena: Honoraria; Takeda: Honoraria; Pfizer: Honoraria; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Gavriatopoulou:Janssen: Honoraria, Other: Travel expenses; Amgen: Honoraria; Takeda: Honoraria, Other: Travel expenses; Genesis: Honoraria, Other: Travel expenses. Terpos:Medison: Honoraria; Genesis: Honoraria, Other: Travel expenses, Research Funding; Amgen: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Celgene: Honoraria; Janssen: Honoraria, Other: Travel expenses, Research Funding. Dimopoulos:Sanofi Oncology: Research Funding.

Cyclophosphamide is considered the treatment of choice for interstitial lung disease (ILD) secondary to systemic sclerosis (SSc), albeit having a minimal effect. Although controlled evidence does not exist, mycophenolate is used increasingly in clinical practice as an alternative. We aimed to compare the long-term efficacy of these drugs. Patients from our SSc cohort who received mycophenolate for over 1 year for progressive ILD were 1:1 matched for age, gender, and baseline forced vital capacity (FVC ±3 %) with cyclophosphamide-treated patients. Changes in FVC, total lung capacity (TLC), diffusion capacity for carbon monoxide (DLCO), and high-resolution computed tomography (HRCT) scans were compared between groups. Changes in pulmonary function tests (PFTs) over at least 1 year in six unmatched control patients, who had denied mycophenolate or cyclophosphamide, also were examined. FVC, TLC, and DLCO did not change significantly in either mycophenolate (from 79.0 ± 12.5 to 80.2 ± 8.1 to 81.2 ± 11.4, from 71.5 ± 16.1 to 74.3 ± 10.8 to 71.8 ± 13.0, from 56.8 ± 12.0 to 55.2 ± 9.9 to 50.6 ± 8.5, respectively) or cyclophosphamide group (from 77.3 ± 12.5 to 79.7 ± 10.3 to 82.5 ± 12.9, from 64.7 ± 14.9 to 68.6 ± 16.0 to 66.1 ± 15.5, from 53.1 ± 14.3 to 56.4 ± 13.5 to 56.3 ± 6.7, respectively), after 1 or 2 years of treatment. PFTs also remained stable in the control group. In either the mycophenolate or cyclophosphamide groups, six patients remained stable, three improved, and one deteriorated according to the definitions of the American Thoracic Society. However, and despite the fact that patients in the cyclophosphamide group had more extended ILD at baseline, a deterioration of lung HRCT findings at 2 years was noticed after mycophenolate (from 10.0 ± 8.9 to 12.7 ± 8.2, p = 0.039) but not after cyclophosphamide. Although these results derive from patients selected for receiving at least 1 year of treatment and therefore they do not represent an intention-to-treat cohort, an eagerness to replace cyclophosphamide by mycophenolate in SSc-associated ILD treatment is not supported.

The purpose of this study was to investigate the role of a fatty meal before bedtime, on sleep characteristics and blood pressure in patients with obstructive sleep apnea (OSA). Recently diagnosed, by full polysomnography (PSG), patients with OSA (n = 19) were included. These underwent PSG for additional two consecutive nights. Two hours before the PSG examination, a ham and cheese sandwich of 360 kcal was served to all patients, at first night, while a fatty meal of 1,800 kcal was served before the second PSG examination. Comparisons were performed between the last two examinations in terms of PSG data and morning and night blood pressure measurements. After the fatty meal, a significant increase was observed in total sleep time (p = 0.026) in the Apnea–Hypopnea Index (AHI) (p = 0.015), as well as in the absolute number of obstructive and central apneas (p = 0.032 and p = 0.042, respectively) compared to the previous night. Conversely, distribution of sleep stages and indices of nocturnal hypoxia (average and minimum SpO2 and sleep time with SpO2

INTRODUCTION: COPD is a disease with comorbidities, which contribute to morbidity and mortality, independently severity. AIM: Study comorbidity patterns of COPD patients, correlation between comorbidities and outcomes of pulmonary rehabilitation. METHODS: 32 patients with COPD, underwent a comprehensive pulmonary rehabilitation program, divided into two groups, according to comorbidities. Patients with none or one comorbidity (n=11) compared to those with two or more , in terms of their response to parameters: mMRC, CAT, SGRQ, 6MWT and CPET. As cardiovascular and metabolic comorbidities were the most frequent (68.8% and 53.1% respectively), we studied the outcomes of the program between two more subgroups of patients, those who presented and those who didn9t present those two comorbidities. RESULTS: The presence of comorbidity was reported (n=28, 87.5%) and more frequent were cardiovascular, metabolic, musculoskeletal, psychological, gastroenterological, cancers and sleep disorders. The outcomes of the subgroup of patients with none or one comorbidity and the subgroup of patients with two or more comorbidities did not present statistically significant difference to the following parameters: dyspnea (mMRC , CAT), quality of life (SGRQ),exercise capacity (6MWT). Only significant change was observed on Cardiopulmonary Exercise Testing, where V02MAX showed an important percentage increase of 25.7% in the subgroup of patients with none or one comorbidity compared to the subgroup of patients with two or more (p=0.024). CONCLUSIONS: Pulmonary Rehabilitation in COPD seems to benefit all the subgroups of patients, independently of the presence, the number or the nature of their comorbidities.

Obstructive sleep apnea syndrome (OSAS) is associated with obesity and insulin resistance. Visfatin is an insulin-mimicking adipokine, which is considered a link between obesity and insulin resistance. Aim of this study was to evaluate levels of plasma visfatin in patients with severe OSAS and examine their potential correlation with sleep characteristics and several biochemical parameters.Nondiabetic patients with severe OSAS (Apnea Hypopnea Index30/h, n = 32) and healthy controls (Apnea Hypopnea Index5/h, n = 12), examined with polysomnography, underwent a biochemical analysis to estimate fasting levels of visfatin, glucose, insulin, C-peptide, and lipid profile.The two groups were matched for age and body mass index (BMI). OSAS patients had significantly higher fasting insulin levels (p = 0.045), but no difference was shown in visfatin between patients and controls (p = 0.585). In OSAS patients, visfatin levels correlated positively with sleep latency (r = 0.539, p = 0.01) and triglyceride levels (r = 0.584, p = 0.036) and negatively with total sleep time, percentage of stage 2 and REM sleep, and LDL-cholesterol levels (r = -0.659 and p = 0.001; r = -0.496 and p = 0.019; r = -0.577 and p = 0.005; r = -0.804 and p = 0.003, respectively). No association was found, however, between visfatin levels and HOMA index or indices of nocturnal hypoxia.In patients with severe OSAS, visfatin levels are associated with characteristics of sleep architecture. However, there is no correlation between visfatin and insulin resistance or nocturnal hypoxia.

Background: Lung cancer is the leading cause of cancer-related deaths worldwide. 25% show neuroendocrine differentiation (typical/atypical carcinoids, large-/small-cell neuroendocrine carcinomas). Carcinoids present with long survival rates, but metastatic carcinoids correlate with decreased survival and are commonly insensitive to standard chemotherapy or radiation. Therefore, novel therapeutic strategies are urgently needed. Material and methods: 70 representative tumor specimens were used for next-generation sequencing analysis of 14 genes related to therapy response. Additionally, mRNA-expression profiles of 60 matching samples were determined for 13 selected drug targets by using the NanoString nCounter technology. Results: A number of features known to sensitize tumors for different targeted therapies could be identified, which hopefully improve the clinical management of this subgroup of lung neoplasias. In particular, EGFR expression was observed in the investigated tumors in a noteworthy manner. Additionally, MDM2 was strongly expressed in the majority of all samples whereas the expression of its physiological inhibitor, CDKN2A, was nearly absent in all low-grade tumors. TP53 showed a high frequency of variants in high-grade tumors but mutations were rare in carcinoids. Conclusion: Based on our results, therapeutic approaches with MDM2-inhibitors and monoclonal anti-EGFR antibodies may be promising in pulmonary carcinoid tumors. CA extern

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an independent risk factor for hypertension, coronary artery disease, and diabetes mellitus. Epicardial fat has been recently recognized as a new risk factor and active participant on cardiometabolic risk. The aim of this study was to assess an independent relationship between sleep apnea severity, metabolic and vascular markers, and epicardial fat, at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy.Our study group consisted of 48 patients with suspected OSAHS and no prior history of cardiovascular disease or diabetes mellitus. All patients underwent full overnight polysomnography. Thickness of epicardial and visceral adipose tissue, brachial artery flow-mediated dilation (FMD), carotid intima media thickness (cIMT), pulse wave velocity (PWV), plasma C-reactive protein (CRP) levels, fasting glucose levels, HbA1c, homeostatic model assessment of insulin resistance index (HOMA), and lipid profile were measured at baseline and after 3 months of CPAP use in patients with moderate to severe OSAHS.In OSAHS patients (Apnea-hypopnea index (AHI) ≥15/h, N = 28), epicardial fat correlated with fasting glucose (rho = 0.406, p = 0.04) and HOMA (rho = 0.525, p = 0.049) but was not associated with visceral fat (rho = 0.126, p = 0.595). Epicardial adipose tissue (EAT) (p = 0.022) increased across AHI severity along with PWV (p = 0.045) and carotid intima media thickness (IMT) (p = 0.034) while FMD (p = 0.017) decreased. Therapy with CPAP reduced both epicardial (p 0.001) and visceral fat (p = 0.001). Alterations in epicardial fat across the follow-up were associated with changes in PWV (p = 0.026) and HOMA (p = 0.037) independently of major confounders.Epicardial fat thickness was associated with OSA severity and may be an additional marker of cardiovascular risk as well as of future diabetes in these patients. CPAP therapy reduced epicardial fat, suggesting its potentially beneficial role in reducing cardiometabolic risk in OSA patients.