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Objective: Blood bicarbonate concentration plays an important role for obstructive sleep apnea (OSA) patients to maintain acid-base balance. We investigated the association between arterial standard bicarbonate ([HCO3-]) and nocturnal hypoxia as well as comorbid hypertension in OSA.Methods: A cross-sectional analysis of 3329 patients in the European Sleep Apnea Database (ESADA) was performed. Arterial blood gas analysis and lung function test were performed in conjunction with polysomnographic sleep studies. The 4% oxygen desaturation index (ODI), mean and minimum oxygen saturation (SpO2), and percentage of time with SpO2 below 90% (T90%) were used to reflect nocturnal hypoxic burden. Arterial hypertension was defined as a physician diagnosis of hypertension with ongoing antihypertensive medication. Hypertensive patients with SBP/DBP below or above 140/90 mmHg were classified as controlled-, uncontrolled hypertension, respectively.Results: The [HCO3-] level was normal in most patients (average 24.0 +/- 2.5 mmol/L). ODI, T90% increased whereas mean and minimum SpO2 decreased across [HCO3-] tertiles (ANOVA, p = 0.030

Obstructive sleep apnea (OSA) is a common but largely undiagnosed clinical condition, which is turning into a serious public health issue. Of note is that its prevalence is gradually increasing in parallel with the obesity and type 2 diabetes mellitus (T2DM) epidemics. The aim of this article is to comprehensively review the literature in order to evaluate the cardiovascular (CV) risk among patients with OSA and prediabetes or T2DM. OSA seems to be an independent risk factor for the development as well as the progression of T2DM, whereas it is associated with T2DM-related macrovascular and microvascular complications. OSA may also act as a potential risk factor for the presentation and development of CV disease, such as hypertension, coronary artery disease, heart failure, pulmonary hypertension, atrial fibrillation and other cardiac arrythmias, as well as stroke. OSA and T2DM also share common pathophysiological mechanisms leading to atherosclerosis. Considering that the coexistence of OSA and T2DM is an independent and cumulative risk factor for CV mortality, more so than the two diseases separately, clinicians and healthcare professionals should be aware of and screen for OSA in patients with T2DM. Notably, targeted therapy for both conditions seems to substantially improve CV prognosis.

Various hormones and neuropeptides implicated in energy metabolism also regulate sleep cycles and wakefulness and promote adequate and restorative sleep [...]

This is a case description of a patient with previously diagnosed rapid eye movement sleep behavior disorder (RBD) and nocturnal enuresis, who complained about a “peculiar sound” while sleeping and, occasionally, while awake during intensive exercise, for the last three months. A home audio recording, which his wife obtained while he was sleeping, showed a high-pitched sound identified as stridor. Full video polysomnography revealed no apneas or hypopneas. The flow-volume loop yielded an inspiratory plateau, indicating variable extrathoracic obstruction. The upper and lower respiratory system computed tomography did not show any anomalies or mechanical lesions (e.g., masses and scars). Fiberoptic laryngoscopy revealed an abnormal activity of the vocal cord abductor during quiet breathing and inspiration in a supine position, leading to partial obstruction. A positive dopamine transporter scan and the coexistence of stridor, RBD, and nocturnal enuresis were diagnostic for multiple system atrophy. The patient was treated with continuous positive airway pressure as a symptomatic therapy for stridor and levodopa.

Objective: In 2010, a questionnaire-based study on obstructive sleep apnea (OSA) management in Europe identified differences regarding reimbursement, sleep specialist qualification, and titration procedures. Now, 10 years later, a follow-up study was conducted as part of the ESADA (European Sleep Apnea Database) network to explore the development of OSA management over time.Methods: The 2010 questionnaire including questions on sleep diagnostic, reimbursement, treatment, and certification was updated with questions on telemedicine and distributed to European Sleep Centers to reflect European OSA management practice.Results: 26 countries (36 sleep centers) participated, representing 20 ESADA and 6 non-ESADA countries. All 21 countries from the 2010 survey participated. In 2010, OSA diagnostic procedures were performed mainly by specialized physicians (86%), whereas now mainly by certified sleep specialists and specialized physicians (69%). Treatment and titration procedures are currently quite homogenous, with a strong trend towards more Autotitrating Positive Airway Pressure treatment (in hospital 73%, at home 62%). From 2010 to 2020, home sleep apnea testing use increased (76%-89%) and polysomnography as sole diagnostic procedure decreased (24%-12%). Availability of a sleep specialist qualification increased (52%-65%) as well as the number of certified polysomnography scorers (certified physicians: 36%-79%; certified technicians: 20%-62%). Telemedicine, not surveyed in 2010, is now in 2020 used in diagnostics (8%), treatment (50%), and follow-up (73%). Conclusion: In the past decade, formal qualification of sleep center personnel increased, OSA diagnostic and treatment procedures shifted towards a more automatic approach, and telemedicine became more prominent.(c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with a high incidence of arterial and venous thrombotic complications. However, thromboembolic events in unusual sites such as limb and visceral arterial ischemia are reported rarely in the literature. Herein, we describe a rare case of a patient with severe coronavirus disease 2019 (COVID-19) infection who experienced severe abdominal pain during the hospitalization and presented simultaneously renal artery, splenic artery and vein as well as aortic thrombi despite prophylactic antithrombotic treatment. Information about his follow-up post discharge is also provided. This case report raises significant clinical implications regarding the correct dose of antithrombotic treatment during the acute phase of the severe COVID-19 infection and highlights the need for incessant vigilance in order to detect thrombosis at unusual sites as a possible diagnosis when severe abdominal pain is present in severe COVID-19 patients.

Obstructive sleep apnea is linked to severe health consequences such as hypertension, daytime sleepiness, and cardiovascular disease. Nearly a billion people are estimated to have obstructive sleep apnea with a substantial economic burden. However, the current diagnostic parameter of obstructive sleep apnea, the apnea-hypopnea index, correlates poorly with related comorbidities and symptoms. Obstructive sleep apnea severity is measured by counting respiratory events, while other physiologically relevant consequences are ignored. Furthermore, as the clinical methods for analysing polysomnographic signals are outdated, laborious, and expensive, most patients with obstructive sleep apnea remain undiagnosed. Therefore, more personalised diagnostic approaches are urgently needed. The Sleep Revolution, funded by the European Union's Horizon 2020 Research and Innovation Programme, aims to tackle these shortcomings by developing machine learning tools to better estimate obstructive sleep apnea severity and phenotypes. This allows for improved personalised treatment options, including increased patient participation. Also, implementing these tools will alleviate the costs and increase the availability of sleep studies by decreasing manual scoring labour. Finally, the project aims to design a digital platform that functions as a bridge between researchers, patients, and clinicians, with an electronic sleep diary, objective cognitive tests, and questionnaires in a mobile application. These ambitious goals will be achieved through extensive collaboration between 39 centres, including expertise from sleep medicine, computer science, and industry and by utilising tens of thousands of retrospectively and prospectively collected sleep recordings. With the commitment of the European Sleep Research Society and Assembly of National Sleep Societies, the Sleep Revolution has the unique possibility to create new standardised guidelines for sleep medicine.

Background: Cardiopulmonary exercise testing (CPET) has been widely used for the functional evaluation of patients with heart failure. Patients with amyloidosis and cardiac involvement typically present with heart failure with preserved or mildly reduced ejection fraction. We sought to evaluate the use of CPET parameters in patients with AL amyloidosis for the assessment of disease severity and prognosis and their association with cardiac imaging findings. Methods: A single-center prospective analysis was conducted, which included 23 consecutive ambulatory patients with AL amyloidosis with cardiac involvement, not requiring hospitalization or intravenous diuretics. Patient evaluation included CPET, laboratory testing, echocardiography and cardiac MRI. The cohort was divided according to the presence of high-risk CPET characteristics (below median peak VO2 and above median VE/VCO2). Results: Patients with AL amyloidosis and cardiac involvement (median age was 60 years (56.5% males) had median peak relative VO2 (VO2/kg) of 17.8 mL/kg/min, VE/VCO2 slope of 39.4 and circulatory power of 2362.5 mmHg⋅mL/kg/min. Peak relative VO2 gradually declined across Mayo stages (p = 0.046) and exhibited a significant inverse correlation with NT-proBNP levels (r = −0.52, p = 0.01). Among imaging parameters, peak VO2 positively correlated with global work efficiency (r = 0.61, p < 0.001), and global work index (r = 0.45, p = 0.04). The group of patients with high-risk CPET findings showed evidence of more advanced disease, such as higher NT-proBNP levels (p = 0.007), increased septal and posterior left ventricular wall thickness (p = 0.043 and p = 0.033 respectively) and decreased global work efficiency (p = 0.027) without substantial differences in cardiac MRI parameters. In this group of patients, peak VO2 and VE/VCO2 were not associated significantly with overall survival and cardiac response at one year. Conclusion: In patients with AL amyloidosis, evaluation of exercise capacity with CPET identified a group of patients with more advanced cardiac involvement. The potential of CPET as a risk stratification tool in AL amyloidosis with cardiac involvement warrants further research.

The aim of the present study was to evaluate the possible correlations between sleep, physical activity, and diet in the general population of Greece during the second lockdown due to COVID-19 pandemic. A web-based questionnaire including 28 items was completed by 494 adults (age 31.5 ± 12.4 years). Half of the participants (49.8%) reported good, 44.1% moderate, and 6.1% bad quality of sleep, whereas 17.2% answered that the quality of sleep improved, 56.5% did not change, and 26.3% worsened compared to a normal week. Compared to normal, sleep duration in lockdown increased by 0.24 h (95% CI, 0.13, 0.35, p &lt, 0.001, d = 0.198). More under-weight (32.4%) and obese (34.1%) respondents reported worsened quality of sleep in lockdown compared with normal (25.6%) and overweight participants (22.7%) (p = 0.006, Cramer’s φ = 0.191). A small effect for BMI group on sleep duration was observed (p = 0.011, η2 = 0.023), where overweight and obese slept less (–0.44 h and –0.66 h, respectively) than normal weight participants. Subjects with the highest percentage of increased food consumption reported decreased sleep duration (p = 0.012) and worsened sleep quality (p = 0.003). Compared with a normal week, physical activity of a high and moderate intensity decreased for 43.0% and 37.0% of participants, did not change in 32.9% and 36.1% of participants, and increased in 24.1% 26.9%, respectively, whereas walking time decreased in 31.3%, did not change in 27.3%, and increased in 41.5% of participants. Increased high and moderate intensity physical activity was related with an improvement in sleep quality (p &lt, 0.001). Those with decreasing walking time reported the highest percentage of decreased sleep quality (p = 0.006) and worsened sleep quality (p = 0.016). In conclusion, both quality and quantity of sleep were impaired during the second lockdown and the observed changes were associated with diet and physical activity.

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

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.

The aim of this study was to determine if the lockdown measures applied due to the pandemic of Coronavirus Disease 2019 (COVID-19) affected the sleep of the general population and health professionals in six different countries (Greece, Switzerland, Austria, Germany, France, and Brazil). We used a web-based survey with a short questionnaire of 13 questions, translated into four languages (Greek, German, French, and Portuguese). The questionnaire included information about demographic and professional data, quantitative and qualitative characteristics of sleep, degree of abidance in lockdown measures, and data about illness or close contact with active confirmed cases of COVID-19. Initially, 2093 individuals participated. After exclusion of those who did not report their duration of sleep, the final sample comprised 1908 participants (Greek, n = 1271, German, n = 257, French, n = 48, Portuguese, n = 332), aged 42.6 &plusmn, 12.7 years, who were considered for further analysis. A main effect of the lockdown week on sleep duration was observed (+0.25 h, 95% confidence intervals, CI, 0.17, 0.32, p &lt, 0.001), with the total sleep time of the lockdown week being longer than that under normal conditions. A week*occupation interaction on sleep duration was demonstrated (p &lt, 0.001, &eta, 2 = 0.012). Sleep duration remained stable in health professionals (&minus, 0.18 h, 95% CI &minus, 0.36, 0.01, p = 0.063), whereas it increased in other occupations by 0.31 h (95% CI, 0.24, 0.39, 0.001). In terms of sleep quality, 15% of participants characterized their sleep as bad and 37.9% as average during the lockdown week. Almost 1 in 3 individuals (31.3%) reported worse quality of sleep during the lockdown week than under normal conditions. Sleep during the lockdown week was characterized as good by 47.1%, but only 38% of the health professionals group. In conclusion, the COVID&minus, 19 pandemic and lockdown affected sleep in different ways, depending on age, level of education, occupation, and country of residence.

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.

As the COVID-19 pandemic spreads across the globe, it will undoubtedly cross paths with long endemic infectious diseases in different areas. Interactions between SARS-CoV2 and well-known pathogens will likely give rise to unfamiliar clinical presentations, depending on complex and as yet unknown immunological interactions. We present a case of coinfection with COVI19 and visceral leishmaniasis and discuss recent reports regarding coexistence of SARS-CoV2 and Leishmania spp. to date.

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.

Guidelines for the treatment of non-small cell lung cancer adenocarcinoma positive in epidermal growth factor mutations indicate tyrosine kinase inhibitors. There are currently three tyrosine kinase inhibitors that can be used as first line treatment: gefitinib, erlotinib and afatinib. Regarding erlotinib and afatinib dosage can be modified in the case of severe adverse effects. In the case of disease relapse investigation for T790M mutation has to be made either with re-biopsy or liquid biopsy and osimertinib has to be administered when T790M is diagnosed. Based on a case series we indicate which is the best approach for T790M mutation.

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.