Effects of pharmacological primary cilium disturbance in the context of in vitro 2D and 3D malignant pleura mesothelioma.

INTRODUCTION: Primary cilium (PC) is a single non-motile antenna-like organelle composed of a microtubule core axon originating from the mother centriole of the centrosome. The PC is universal in all mammalian cells and protrudes to the extracellular environment receiving mechanochemical cues that it transmits in the cell. AIM: To investigate the role of PC in mesothelial malignancy in the context of two-dimensional (2D) and three-dimensional (3D) phenotypes. MATERIALS AND METHODS: The effect of pharmacological deciliation [using ammonium sulphate (AS) or chloral hydrate (CH)] and PC elongation [using lithium chloride (LC)] on cell viability, adhesion, and migration (2D cultures) as well as in mesothelial sphere formation, spheroid invasion and collagen gel contraction (3D cultures) was investigated in benign mesothelial MeT-5A cells and in malignant pleural mesothelioma (MPM) cell lines, M14K (epithelioid) and MSTO (biphasic), and primary malignant pleural mesothelioma cells (pMPM). RESULTS: Pharmacological deciliation or elongation of the PC significantly affected cell viability, adhesion, migration, spheroid formation, spheroid invasion and collagen gel contraction in MeT-5A, M14K, MSTO cell lines and in pMPM cells compared to controls (no drug treatment). CONCLUSIONS: Our findings indicate a pivotal role of the PC in functional phenotypes of benign mesothelial cells and MPM cells.

Serum vitamin D levels in patients with obstructive sleep apnea syndrome and level changes after continuous positive airway pressure therapy.

PURPOSE: Patients with obstructive sleep apnea syndrome (OSAS) have been found to exhibit lower serum vitamin D levels, even when the control groups are matched for confounding conditions. However, contradictory studies are also present. This study aimed to compare serum 25-hydroxyvitamin D (25(OH)D) levels between adult patients with OSAS and non-apneic controls and to evaluate the changes in 25(OH)D levels after 3 and 12 months of continuous positive airway pressure (CPAP) therapy. METHODS: The study was comprised of 30 patients with OSAS and 30 controls. Serum 25(OH)D levels were determined at baseline and after 3 and 12 months of CPAP therapy in all patients with OSAS. For analysis, patients with OSAS were divided into subgroups by adherence, with adherence defined as CPAP usage for > 4 h per night on at least 70% of nights. RESULTS: The 25(OH)D levels were not significantly different between OSAS and control groups at baseline. 25(OH)D levels did not change after 3 and 12 months of CPAP therapy. Patients who were CPAP-adherent showed less reduction in 25(OH)D levels compared with non-adherent ones (21.18 ± 9.3 vs. 12.13 ± 3.8 ng/mL, p = 0.022) after 1 year. The 25(OH)D levels were significantly correlated with higher daily CPAP usage at 3 and 12 months. Mean daily CPAP usage was a significant predictor of serum 25(OH)D levels at 12 months. CONCLUSIONS: Patients with OSAS who demonstrated good CPAP adherence showed significantly higher 25(OH)D levels after 1 year compared with those not adequately using CPAP. Long-term good CPAP adherence and highly daily CPAP usage positively affected 25(OH)D levels in patients with OSAS.

The Alonissos Study: Cross-Sectional Study of the Healthcare Access and User Satisfaction in the Community of a Non-Profit-Line Greek Island.

Healthcare access and a high quality of the provided services to healthcare users are fundamental human rights according to the Alma Ata Declaration of 1978. Although 45 years have passed since then, health inequalities still exist, not only among countries but also within populations of the same country. For example, several small Greek islands have only a small Primary Healthcare Center in order to provide healthcare services to the insular population. In the current study, we investigated the level of self-reported overall, dental and mental health status and the level of satisfaction regarding the access to and the quality of the healthcare services provided by the Primary Healthcare center of Alonissos, along with registering the requirements for transportation to the mainland in order to receive such services. In this questionnaire-based cross-sectional study, 235 inhabitants of the remote Greek island of Alonissos that accounts for nearly 9% of the population participated (115 males and 120 females). The self-reported overall health status was reported to be moderate to very poor at a percentage of 31.49%, and the results were similar for dental and self-reported mental health status. Although nearly 60% of the participants reported very good/good quality of the healthcare provision, only 37.45% reported that the access to healthcare was very good/good, while around 94% had at least one visit to the mainland in order to receive proper healthcare services. Strategies for improving access to healthcare services need to be placed in remote Greek islands like Alonissos.

Mortality Among Hospitalized Patients With Pleural Effusions. A Multicenter, Observational, Prospective Study.

Background: Data regarding the prognostic significance of pleural effusion (PE) are scarce. Objective: Explore the impact of PE on mortality among hospitalized patients. Methods: Multicenter prospective observational study. Patients that underwent computed tomography (thorax and/or abdomen) and in which PE was detected, were admitted to the study. PE was classified by size on CT, anatomical distribution, diagnosis, and Light's criteria. Charlson comorbidity index (CCI), APACHE II, and SOFA score were calculated. Mortality at 1 month and 1 year were recorded. Results: Five hundred and eight subjects, mean age 78 years. Overall mortality was 22.6% at 1 month and 49.4% at 1 year. Bilateral effusions were associated with higher mortality than unilateral effusions at 1 month (32 vs. 13.3%, p = 0.005) and large effusions with higher mortality than small effusions at 1 year (66.6 vs. 43.3%, p < 0.01). On multivariate analysis age, CCI, APACHE II, SOFA score, and bilateral distribution were associated with short-term mortality, while long-term significant predictors were CCI, APACHE II, SOFA, and malignant etiology. Exudates (excluding MPE) exhibited a survival benefit at both 1 month and 1 year but due to the smaller sample, fluid characteristics were not included in the multivariate analysis. Conclusions: Pleural effusion is a marker of advanced disease. Mortality is higher within the first month in patients with PEs related to organ failure, while patients with MPE have the worst long-term outcome. Independent predictors of mortality, apart from CCI, APACHE II, and SOFA scores, are age and bilateral distribution in the short-term, and malignancy in the long-term.

Association between Interleukin-6 and vitamin D serum levels in patients with obstructive sleep apnea syndrome and impact of long-term continuous positive airway pressure therapy on biomarker levels.

OBJECTIVE: Hypoxia induces interleukin-6 (IL-6) production in obstructive sleep apnea syndrome (OSAS). Low serum 25 hydroxyvitamin D (25(OH)D) levels have been linked to OSAS susceptibility. Serum 25(OH)D levels have been negatively correlated with serum IL-6 levels in patients with chronic inflammation. No data exist to assess whether there is a correlation between 25(OH)D and IL-6 serum levels in OSAS, while the impact of continuous positive airway pressure (CPAP) therapy on IL-6 or 25(OH)D levels needs further investigation. We aimed to compare the serum 25(OH)D and IL-6 levels between OSAS patients and controls, examine a possible correlation between 25(OH)D and IL-6 levels and the changes of their concentrations after twelve months of CPAP therapy in OSAS patients. METHODS: 15 newly-diagnosed OSAS patients and 15 non-apneic controls were recruited. Serum IL-6 and 25(OH)D levels were measured in the study population at baseline and twelve months after CPAP initiation in OSAS patients. RESULTS: IL-6 levels were elevated in OSAS patients than controls and were positively and negatively correlated with body mass index (BMI) and minimum oxyhemoglobin saturation (minSpO2), respectively. Diabetes mellitus, BMI and minSpO2 independently predicted IL-6 levels. No difference was found in 25(OH)D levels between groups. No correlation between IL-6 and 25(OH)D levels was detected. Effective CPAP therapy did not impact IL-6 or 25(OH)D levels after one year in OSAS patients. CONCLUSIONS: No correlation between IL-6 and 25(OH)D levels was found. IL-6 levels were significantly elevated in OSAS patients than the controls and positively correlated with BMI, diabetes mellitus, and nocturnal hypoxemia.

Are younger COPD patients adequately vaccinated for influenza and pneumococcus?

Influenza and pneumococcal pneumonia are major causes of increased morbidity and mortality among elderly and COPD patients. Vaccines against influenza and pneumococcus are recommended for COPD patients according to GOLD 2020 guidelines to prevent serious illnesses. Despite their high morbidity and mortality burden, the vaccination coverage rates remain far below the WHO's recommended targets. In Greece, there are insufficient data on influenza and pneumococcal immunization rates among younger COPD patients. This study investigated whether COPD patients under the age of 65 are adequately vaccinated against influenza and pneumococcus and the factors that influence vaccination rates. 1100 individuals at 22 Primary Health Centers in Central Greece participated in a two-year spirometry monitoring program. Face-to-face interviews were used to collect information regarding demographics, smoking status, comorbidities, respiratory illnesses in the previous two years, and influenza and pneumococcal vaccination coverage from all COPD patients. 117 patients aged 40-65 years old were diagnosed with COPD and 80.3% were males. Only 40.2% of them had received influenza and 32.5% pneumococcus vaccinations. Age, advanced stage of COPD, years on COPD diagnosis, respiratory infection within the previous two years, comorbidity, and smoking cessation are all positively connected with influenza and pneumococcus vaccine coverage in younger COPD patients. Gender, education level, and marital status did not affect influenza and pneumococcus vaccination rates. These vaccination rates among younger COPD patients demonstrate the need for increased awareness and knowledge about the advantages of immunizations in lowering morbidity and mortality.

The Alonissos Study: Cross-Sectional Study of the Community Respiratory Health Status in a Greek Healthcare Access Underprivileged Island.

In this study, we investigated the self-reported (questionnaire-based) prevalence of Obstructive Sleep Apnoea Syndrome (OSAS) and the prevalence of Chronic Obstructive Pulmonary Diseases (COPD) in the context of demographics and adherence to the Mediterranean diet in the general population of Alonissos, a non-profit line island in Greece (i.e., with scarce boat transportation to the mainland). In this cross-sectional study, 236 inhabitants of Alonissos participated (circa 10% of the island's population), and 115 males and 121 females were evaluated with appropriate questionnaires for OSAS, COPD, and adherence to the Mediterranean diet and subsequently underwent spirometry testing to establish COPD diagnosis. The self-reported prevalence of OSAS and COPD was 9.44% and 18.8%, respectively. However, only 8.99% of the participants were diagnosed with COPD based on their spirometry testing. Adherence to the Mediterranean Diet was moderate. The high prevalence of COPD and OSAS in this underprivileged island in terms of healthcare access highlights the need for improvements in health promotion and primary healthcare provision in non-profit line Greek islands.

Discrimination of Exudative Pleural Effusions Based on Pleural Adenosine Deaminase (ADA)-C-Reactive Protein (CRP) Levels, and Their Combination: An Observational Prospective Study.

(1) Background: Malignant (MPE), parapneumonic (PPE) and tuberculous (TPE) pleural effusions constitute common causes of pleurisy. Discriminating among them is usually challenging. C-reactive protein (CRP) and adenosine deaminase (ADA) pleural levels (p-CRP, p-ADA) have been used as differentiators in many studies showing promising results. This study aims to evaluate the diagnostic value of p-CRP, p-ADA levels and their combination among the three categories. (2) Methods: A prospective study of 100 patients with MPE (n = 59), PPE (n = 34) and TPE (n = 7) from a single centre was performed. p-CRP levels were evaluated between PPE and non-PPE and between complicated (CPPE) and non-complicated PPE. ADA levels were also measured to classify patients among MPE and non- MPE. Eventually, the combination of p-CRP and p-ADA values was used as a discrimination factor among PPE, MPE and TPE. (3) Results: ROC analysis revealed that p-CRP with a cut-off value: 4.4 mg/dL can successfully differentiate PPE (AUC = 0.998). The cut-off level of 10 mg/dL can predict CPPE with sensitivity: 63%, specificity: 71.4%, positive predictive value (PPV): 89%, and negative predictive value (NPV): 33%. Furthermore, patients with ADA levels ≤ 32 U/L were more likely to belong to the malignant group sensitivity: 93%, specificity: 78%, PPV: 85.9%, and NPV: 88.9%. Discriminant analysis showed that the combination of p-CRP and p-ADA levels can discriminate PPE, MPE and TPE in 93% of cases. (4) Conclusion: This study provides evidence that p-CRP and p-ADA levels could be possibly used in clinal practice in order to establish a diagnosis among MPE, PPE and TPE.

Underestimation of respiratory symptoms by smokers: a thorn in chronic obstructive pulmonary disease diagnosis.

Primary care centers are ideal positions to identify chronic obstructive pulmonary disease (COPD). We determined the COPD prevalence among ever-smokers aged 40-65 years attending a 2-year program conducted in 22 Greek primary healthcare centers and made comparisons between genders, patients less than or greater than 55 years, and newly or previously diagnosed COPD patients. A total of 117 persons, after studying 1100 people, were diagnosed with previously unknown or known COPD, providing a COPD prevalence of 10.6% among the study population. In all, 7.5% of the participants were newly diagnosed with COPD. Women with COPD reported smoking less but experienced worse respiratory and depressive symptoms than men. A total of 19% of the COPD population below 55 years experienced wheezing and exacerbations more frequently than older patients. Newly diagnosed COPD patients were significantly younger, reported a significant burden of symptoms without seeking medical help. Primary health care has a crucial role in the early detection of COPD among unsuspecting smokers.

The Use of a Novel Quantitative Marker of Echogenicity of Pleural Fluid in Parapneumonic Pleural Effusions.

Background: Thoracic ultrasound is an essential tool in the daily clinical care of pleural effusions and especially parapneumonic pleural effusions (PPEs), in terms of diagnosis, management, and follow-up. Hypoechogenicity index (HI) is a quantitative marker of pleural fluid echogenicity. We aimed to examine associations of HI with pleural inflammation in patients with PPE. Methods: All patients included underwent a thoracic ultrasound with HI determination at the first day of their admission for a PPE. Thoracentesis was performed in all patients. Demographics, laboratory measurements, and clinical data were collected prospectively and recorded in all subjects. Results: Twenty-four patients with PPE were included in the study. HI was statistically significantly correlated with intensity of inflammation as suggested by pleural fluid LDH (p < 0.001, r = -0.831), pleural fluid glucose (p=0.022, r = 0.474), and pleural fluid pH (p < 0.001, r = 0.811). HI was correlated with ADA levels (p=0.005, r = -0.552). We observed a statistically significant correlation of HI with pleural fluid total cell number (p < 0.001, r = -0.657) and polymorphonuclears percentage (p=0.02, r = -0.590), as well as days to afebrile (p=0.046, r = -0.411), duration of chest tube placement (p < 0.001, r = -0.806), and days of hospitalization (p=0.013, r = -0.501). Discussion. HI presents a fast, easily applicable, objective, and quantitative marker of pleural inflammation that reliably reflects the intensity of pleural inflammation and could potentially guide therapeutic management of PPE.

Correlation of pleural effusions' grayscale sonographic parameters with fluid's analysis results.

BACKGROUND: Quantitative sonographic methods are used to assess pleural fluid's volume but no validated method exists for the measurement of the fluids' density and other qualitative values. We suggest a quantitative method, based on the pixel density of the pleural effusion's image, in order to evaluate the echogenicity of pleural effusion. METHODS: Pleural ultrasound (US) was performed in 62 patients with pleural effusion. Five consequent images of the pleural effusion were retrieved through axial view between the 9th and the 10th rib and one from the 10th rib through coronal view and converted into the high-resolution tagged image file format. The mean echo levels of all pixels of the pleural effusion and of the 10th rib were counted, and the hypoechogenicity index (HI) was calculated according to the following formula: HI = mean echo level of all pixels of the rib/mean echo levels of all pixels of pleural effusion. HI greater than 1 indicates pleural effusion's hypoechogenicity. Diagnostic thoracocentesis was performed and biochemical markers were measured. RESULTS: LDH, Cell Count, pH and Effusion Pixels (Mean) were both significantly correlated and associated with pixel ratio. Conversely, pixel ratio was not correlated with any other ultrasonography-derived parameter or biomarker. CONCLUSIONS: This study introduced HI as new index, which could demonstrate the inflammation density of pleural effusions. Moreover, when used in combination with classical biomarkers, HI might be a useful adjunct for the discrimination of pleural transudate.