Natural antibodies targeting LPS in pleural effusions of various etiologies.

Respiratory infection, cancer, and heart failure can cause abnormal accumulation of fluid in the pleural cavity. The immune responses within the cavity are orchestrated by leucocytes that reside in the serosal-associated lymphoid tissue. Natural antibodies (NAbs) are abundant in the serum (S) having a major role in systemic and mucosal immunity; however, their occurrence in pleural fluid (PF) remains an open question. Our aim herein was to detect and measure the levels of NAbs (IgM, IgG, IgA) targeting lipopolysaccharides (LPS) in both the pleural fluid and the serum of 78 patients with pleural effusions (PEs) of various etiologies. The values of anti-LPS NAb activity were extracted through a normalization step regarding the total IgM, IgG, and IgA levels, all determined by in-house ELISA. In addition, the ratios of PF/S values were analyzed further with other critical biochemical parameters from pleural fluids. Anti-LPS NAbs of all Ig classes were detected in most of the samples, while a significant increase of anti-LPS activity was observed in infectious and noninfectious compared with malignant PEs. Multivariate linear regression confirmed a negative correlation of IgM and IgA anti-LPS PF/S ratio with malignancy. Moreover, anti-LPS NAbs PF/S measurements led to increased positive and negative predictive power in ROC curves generated for the discrimination between benign and malignant PEs. Our results highlight the role of anti-LPS NAbs in the pleural cavity and demonstrate the potential translational impact that should be further explored.NEW & NOTEWORTHY Here we describe the detection and quantification of natural antibodies (NAbs) in the human pleural cavity. We show for the first time that IgM, IgG, and IgA anti-LPS natural antibodies are detected and measured in pleural effusions of infectious, noninfectious, and malignant etiologies and provide clinical correlates to demonstrate the translational impact of our findings.

2-Deoxy-glucose ameliorates the peritoneal mesothelial and endothelial barrier function perturbation occurring due to Peritoneal Dialysis fluids exposure.

Peritoneal dialysis (PD) and prolonged exposure to PD fluids (PDF) induce peritoneal membrane (PM) fibrosis and hypervascularity, leading to functional PM degeneration. 2-deoxy-glucose (2-DG) has shown potential as PM antifibrotic by inhibiting hyper-glycolysis induced mesothelial-to-mesenchymal transition (MMT). We investigated whether administration of 2-DG with several PDF affects the permeability of mesothelial and endothelial barrier of the PM. The antifibrotic effect of 2-DG was confirmed by the gel contraction assay with embedded mesothelial (MeT-5A) or endothelial (EA.hy926) cells cultured in Dianeal® 2.5 % (CPDF), BicaVera® 2.3 % (BPDF), Balance® 2.3 % (LPDF) with/without 2-DG addition (0.2 mM), and qPCR for αSMA, CDH2 genes. Moreover, 2-DG effect was tested on the permeability of monolayers of mesothelial and endothelial cells by monitoring the transmembrane resistance (RTM), FITC-dextran (10, 70 kDa) diffusion and mRNA expression levels of CLDN-1 to -5, ZO1, SGLT1, and SGLT2 genes. Contractility of MeT-5A cells in CPDF/2-DG was decreased, accompanied by αSMA (0.17 ± 0.03) and CDH2 (2.92 ± 0.29) gene expression fold changes. Changes in αSMA, CDH2 were found in EA.hy926 cells, though αSMA also decreased under LPDF/2-DG incubation (0.42 ± 0.02). Overall, 2-DG mitigated the PDF-induced alterations in mesothelial and endothelial barrier function as shown by RTM, dextran transport and expression levels of the CLDN-1 to -5, ZO1, and SGLT2. Thus, supplementation of PDF with 2-DG not only reduces MMT but also improves functional permeability characteristics of the PM mesothelial and endothelial barrier.

Asbestos ban policies and mesothelioma mortality in Greece.

BACKGROUND: Malignant mesothelioma is a rare form of cancer that mostly affects the pleura and has a strong link to asbestos exposure. Greece banned the use of asbestos in 2005, however, the public was already aware of this substance in the 1980s. This research aims to present an overview of Greece's mesothelioma age-standardized mortality rates (ASMR) from 1983 to 2019 by age, gender, and geographic region and to determine whether the actions to ban asbestos impacted these rates. METHODS: Data were retrieved by the Hellenic Statistical Authority (HSA) from death certificates that mentioned mesothelioma as the cause of death from 1983 to 2019 with details on the residence, gender, and age. Statistical analysis was performed using PRISM 6.0 software, a two-way ANOVA test, Trend analysis was conducted using Joinpoint Regression Program 5.0 software. The linear and non-linear model was used to calculate the age-standardized rates of annual percentage change (APC) and its 95% confidential interval (95% CI). RESULTS: From 1983 to 2019, 850 total mesothelioma deaths were recorded, the majority of whom were males (634). A rate of 74.6% accounts for males and 25.4% for females, and the ratio of Males: Females was 3:1. Males' ASMR and the whole population's ASMR reached their highest levels in 2011 (0.93/100000person-years and 0.53/100000person-years, respectively). To look for potential changes between the first two decades of the 21st century, we compared the mean ASMR of each geographic region in Greece between two different 10-year subperiods (2000-2009 and 2010-2019). Except for Epirus, all regions of Greece had elevated regional ASMRs, particularly in those with the highest asbestos deposits. Notably, the ASMR in Epirus decreased from 0.54/100000person-years (2000-2009) to 0.31/100000person-years (2010-2019). After 2011, the ASMR for men and the general population stabilized. This stability is important since mesothelioma in men is associated with occupational asbestos exposure. The intriguing discovery of a lower ASMR in Epirus emphasizes the need to raise awareness of the condition and implement effective public health measures. CONCLUSIONS: In Greece, the annual ASMR for males and the whole population reached its highest level in 2011, which is positive and encouraging and may be a sign that the rate will stabilize during the following years. Moreover, this study showed that the actions made in the 1980s regarding public awareness and surveillance directly impacted the decrease in Epirus rates. Future research, continual awareness, information, and recording are needed to monitor the mesothelioma epidemic. The possible benefit of a mesothelioma registry and the epidemiological surveillance of asbestos-related diseases, particularly mesothelioma mortality, need to be addressed. TRIAL REGISTRATION: Not applicable.

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.

Changes in Smoking Habits in Greece During the Lockdown Measures Due to COVID-19.

INTRODUCTION: During lockdown, people are experiencing higher than usual levels of stress related to social isolation, employment, and finances that may result in lifestyle changes. Here, we aim to assess whether smoking habits changed during the lockdown measures due to coronavirus disease 2019 (COVID-19). METHODS: For the purpose of the survey, an online questionnaire was distributed from the tenth of April to the second of May 2020, among a Greek population, by using an online platform. RESULTS: Two hundred smokers/vapers participated in the present survey (62.5% women, 44% of 36-45 years, 29% of 16-55 years, 15.5% 26-35 years). The daily number of cigarettes smoked before the onset of the COVID-19 pandemic is 15.06 ± 9.84, while during the restrictive measures due to COVID-19, the daily number of cigarettes smoked is 14.52 ± 10.13 (p > 0.05). Vapers consumed an average of 0.54 ± 2.43 mL vapor per day before the COVID-19 pandemic and 0.61 ± 2.81 mL during lockdown. Males smoked more cigarettes per day before (16.31 ± 11.87) and during the lockdown (15.33 ± 12.17) versus females (14.30 ± 8.36) and 14.04 ± 8.70, respectively) (p > 0.05 for both genders). Before versus during the restrictive measures, subjects that were primary school graduates smoked more cigarettes per day (28.00 ± 9.09 and 27.50 ± 9.57, respectively), followed by subjects that were high school graduates (16.90 ± 9.33 and 15.97 ± 9.50, respectively), university graduates (14.17 ± 10.14 and 13.93 ± 10.66, respectively), postgraduates (12.96 ± 9.52 and 12.25 ± 9.90, respectively) and middle school graduates (12.89 ± 8.22 and 14.22 ± 7.93, respectively).The self-reported reason for the change in the mL vaporized and the cigarettes smoked are confinement at home (36.3%), stress about COVID-19 (34.09%), free time (20.45%), boredom (4.54%), stress about the work status (2.27%), and participation in online lucky games (2.27%). DISCUSSION: We did not observe significant differences in the daily consumption of smoke/vaping during the lockdown measures. More studies are needed to assess the long-term effects of the pandemic in smoking habits.

Investigation of the Level of Burnout in Health Care Professionals in COVID-19 Pandemic Conditions.

The coronavirus disease 2019 (COVID-19) pandemic has led to high levels of stress and anxiety for health care professionals. The purpose of this study was to investigate the burnout of health care professionals in COVID-19 pandemic conditions. Quantitative research was performed, and the Copenhagen Burnout Inventory was used to study burnout. The research sample consisted of 360 health care professionals. Health professionals have been found to have fairly high levels of personal burnout, work burnout, and burnout associated with patient interactions. It has also been found that women and health professionals working in department for patients with COVID-19 have significantly greater burnout. However, it was found that age, marital status, years of service, specialty, non-basic degree, and whether they or a first-degree relative had COVID-19 were not correlated to burnout. Given the very high level of burnout among health professionals, it is necessary to develop appropriate strategies to reduce burnout.

Nursing Students' Computer Anxiety and Attitudes Before and During the COVID-19 Pandemic.

Purpose of this research was to investigate how the COVID-19 pandemic affected the level of computer anxiety of nursing students and also their attitude related to computer use. A cross-sectional study was conducted in two periods, one before the COVID-19 pandemic (1st period) and the second during the COVID-19 pandemic (2nd period). The research instrument consisted of three parts, a questionnaire with questions about demographic and educational characteristics such as gender and semester of study, the Computer Anxiety Rating Scale (CARS), that used to assess the nursing students' levels of computer anxiety and the Computer Attitude Scale (CAS) that used to measure nursing students' positive and negative attitudes towards computers. Data from 957 undergraduate nursing students were obtained. Specifically, in the 1st period, 370 nursing students participated (38.66%), while in the 2nd period 587 (61.34%) undergraduates participated. The anxiety of participants during COVID-19 pandemic period was reduced compared to that of participants before the COVID-19 period. Respondents during the COVID-19 pandemic have fewer negative feelings towards computers, based on their answers in contrast to the participants in the study before the COVID-19 pandemic. Computer anxiety and attitudes have change among nursing students among COVID-19 pandemic. Nursing students after the implementation of online training are reporting positive feeling towards computer use and are more confident for their ICT skills.

Neck mass and bilateral pleural effusions in a 53-year-old female.

Chylothorax indicates the accumulation of chyle in the pleural cavity. It is a rare cause of pleural effusion, especially bilaterally. In clinical practice, the presence of milky fluid in the pleural cavity raises the suspicion of chylothorax. The most common cause is trauma, iatrogenic or non, owing to thoracic duct injury, which transports chyle from the lymphatic system into the bloodstream. The case we describe is of a 53-year-old female who was referred to our hospital with bilateral pleural effusions and a left supraclavicular mass. From the diagnostic studies, the nontraumatic causes of chylothorax were excluded. The potential diagnosis was traumatic chylothorax, a diagnosis of exclusion, as it appeared after muscle stretch and receded with a fat-free diet and repose without any relapse.

Multifocal Tuberculosis Verrucosa Cutis: Case Report and Review of the Literature.

Cutaneous tuberculosis (TB) is still a major public health problem worldwide. Tuberculosis verrucosa cutis (TBVC) is a cutaneous form of exogenous TB caused by exogenous reinfection in previously sensitized individuals. TBVC typically presents as a unifocal condition. Multifocal cutaneous lesions without any other tubercular foci are extremely rare in exogenous TB and few cases are reported in the literature. We describe the first case of multifocal TBVC in an 81-year-old Greek man. In total, 14 cases of multifocal TBVC have been reported in the literature (8 males and 6 females), with mean age 47.64 years (SD = 20.75) and mean time to diagnosis of 9.69 years (SD = 15.31). Most cases (11/12) responded rapidly to treatment, implying the accuracy of diagnosis, while no one was reported to be immunocompromised. Finally, in 10 cases (71.4%), history of skin microtrauma was reported (related either to daily life habits or to professional praxis), confirming it as the main risk factor. The tuberculin skin test was positive in 10 cases and tissue culture for mycobacteria was negative in all cases. TBVC can present with multiple lesions, even in countries where TB prevalence is not high, especially in patients with history of skin abrasions. Prompt specialist assessment can expedite the establishment of diagnosis.

Prediction and enrichment analyses of the Homo sapiens-Drosophila melanogaster COPD-related orthologs: potential for modeling of human COPD genomic responses with the fruit fly.

The significant similarities in airway epithelial cells between mammals and the fruit fly Drosophila melanogaster have rendered the latter an important model organism for studies of chronic inflammatory lung diseases. Focusing on the chronic obstructive pulmonary disease (COPD), we here mapped human gene orthologs associated with this disease in D. melanogaster to identify functionally equivalent genes for immediate, further screening with the fruit fly model. The DIOPT-DIST tool was accessed for the prediction of the COPD-associated orthologs between humans and Drosophila. Enrichment analyses with respect to pathways of the retrieved functional homologs were performed using the ToppFun and FlyMine tools, identifying 73 unique human genes as well as 438 fruit fly genes. The ToppFun analysis verified that the human gene list is associated with COPD phenotypes. Furthermore, the FlyMine investigation highlighted that the Drosophila genes are functionally connected mainly with the "ABC-family proteins mediated transport" and the "ß-catenin-independent WNT signaling pathway." These results suggest an evolutionarily conserved role toward responses to inhaled toxicants and CO2 in both species. We reason that the predicted orthologous genes should be further studied in the Drosophila models of cigarette smoke-induced COPD.

Integrated Deadenylase Genetic Association Network and Transcriptome Analysis in Thoracic Carcinomas.

The poly(A) tail at the 3' end of mRNAs determines their stability, translational efficiency, and fate. The shortening of the poly(A) tail, and its efficient removal, triggers the degradation of mRNAs, thus, regulating gene expression. The process is catalyzed by a family of enzymes, known as deadenylases. As the dysregulation of gene expression is a hallmark of cancer, understanding the role of deadenylases has gained additional interest. Herein, the genetic association network shows that CNOT6 and CNOT7 are the most prevalent and most interconnected nodes in the equilibrated diagram. Subsequent silencing and transcriptomic analysis identifies transcripts possibly regulated by specific deadenylases. Furthermore, several gene ontologies are enriched by common deregulated genes. Given the potential concerted action and overlapping functions of deadenylases, we examined the effect of silencing a deadenylase on the remaining ones. Our results suggest that specific deadenylases target unique subsets of mRNAs, whilst at the same time, multiple deadenylases may affect the same mRNAs with overlapping functions.

Pathophysiological Aspects of Aging in Venous Thromboembolism: An Update.

The aim of this review is to highlight all the factors that associate venous thromboembolism (VTE) with aging. Elderly people are characterized by a higher incidence of thrombosis taking into account the co-existing comorbidities, complications and fatality that arise. Based on the Virchow triad, pathophysiological aspects of venous stasis, endothelium injury and hypercoagulability in elderly people (≥65 years) are described in detail. More precisely, venous wall structure, nitric oxide (NO) and endothelin-1 expression are impaired in this age group. Furthermore, an increase in high-molecular-weight kininogen (HMWK), prekallikrein, factors V, VII, VIII, IX and XI, clot lysis time (CLT) and von Willebrand factor (vWF) is observed. Age-dependent platelet dysfunction and changes in anticoagulant factors are also illustrated. A "low-grade inflammation stage" is delineated as a possible risk factor for thrombosis in the elderly. Consequently, clinical implications for frail elderly people related to diagnosis, treatment, bleeding danger and VTE recurrence emerge. We conclude that aging is an acquired thrombotic factor closely related to pathophysiological changes.

Bilateral Deep Vein Thrombosis and Pulmonary Embolism Due to Right Common Iliac Artery Aneurysm with a Contained Rupture.

Venous thromboembolism (comprising deep venous thrombosis and/or pulmonary embolism) is a common disease, often of multifactorial cause. Focal iliac artery aneurysms are relatively rare, and only a few reports exist in the literature describing patients with venous thromboembolism resulting from venous floe disruption due to iliac artery aneurysm. Thus, we report a case of a 65-year-old male presenting with pulmonary embolism and bilateral deep vein thrombosis associated with a contained rupture of the right common iliac artery aneurysm.

Obesity as a Risk Factor for Venous Thromboembolism Recurrence: A Systematic Review.

Background and Objectives: Venous thromboembolism (VTE) encompasses Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE). The duration of anticoagulant therapy following a VTE event partly relies on the risk of recurrent VTE which depends on the clinical setting where VTE occurred and the VTE risk factors present. Obesity is considered a minor risk factor and studies in the literature have provided conflicting results on whether obesity influences the development of recurrences. The aim of the present study is to assess the effect of obesity on VTE recurrence in patients that suffered from a previous VTE event. Materials and Methods: We conducted systematic research for English language studies in Medline, Scopus and ProQuest databases in order to identify publications that assess the risk of VTE recurrence in obesity. Inclusion criteria were: 1. Diagnosis of VTE, 2. Definition of obesity as a body mass index ≥30 kg/m2, 3. Report of the risk of obesity on VTE recurrence, 4. Adult human population. We did not include case reports, review studies or studies that assessed other forms of thrombosis and/or used other definitions of obesity. We used the Newcastle-Ottawa scale to address the quality of the studies. Results: Twenty studies were included in the analysis, of which 11 where prospective cohort studies, 6 were retrospective cohort studies, 1 was a cross-sectional study, and 2 were post-hoc analysis of randomized clinical trials. Obesity was significantly associated with recurrences in 9 studies and in 3 of them the association was significant only in females. Conclusions: There is heterogeneity between the studies both in their design and results, therefore the effect of obesity on VTE recurrence cannot be adequately estimated. Future randomized clinical studies with appropriately selected population are needed in order to streamline the effect of obesity on VTE recurrence.

Work place and prevalence of COVID-19 in a rural population in Greece.

INTRODUCTION: Coronavirus disease-19 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic, giving rise to a serious global health threat. Many countries including Greece have seen a two-wave pattern of reported cases, with a first wave in spring and a second in autumn of 2020. METHODS: A cross-sectional seroprevalence study was designed to measure the prevalence of IgG antibodies with a quantitative SARS-CoV-2 IgG lab-based serology test, chemiluminescent microparticle immunoassay, against novel coronavirus in rural areas in Greece after the second pandemic wave. The study was conducted on 29 January 2021 in a rural semi-closed area, the municipality of Deskati, prefecture of western Macedonia in Greece after the second pandemic wave. RESULTS: Sixty-nine participants were included in this study. The present study demonstrated a high prevalence of COVID-19 infection (31 of 69 total participants; 45%) and those who were working in the public sector were at higher risk of COVID-19 infection in comparison to their counterparts in private sector (p=0.05364), (relative risk 2.64; 95% confidence interval 1.001-7.086). CONCLUSION: The study presents data showing a high prevalence of herd immunity for COVID-19 in a semi-closed area in Greece. These findings might help to understand the characteristics of this second wave, the behaviour and danger of SARS-CoV-2 in rural areas in Greece and Europe generally.

In silico investigation of the viroporin E as a vaccine target against SARS-CoV-2.

Viroporins, integral viral membrane ion channel proteins, interact with host-cell proteins deregulating physiological processes and activating inflammasomes. Severity of COVID-19 might be associated with hyperinflammation, thus we aimed at the complete immunoinformatic analysis of the SARS-CoV-2 viroporin E, P0DTC4. We also identified the human proteins interacting with P0DTC4 and the enriched molecular functions of the corresponding genes. The complete sequence of P0DTC4 in FASTA format was processed in 10 databases relative to secondary and tertiary protein structure analyses and prediction of optimal vaccine epitopes. Three more databases were accessed for the retrieval and the molecular functional characterization of the P0DTC4 human interactors. The immunoinformatics analysis resulted in the identification of 4 discontinuous B-cell epitopes along with 1 linear B-cell epitope and 11 T-cell epitopes which were found to be antigenic, immunogenic, nonallergen, nontoxin, and unable to induce autoimmunity thus fulfilling prerequisites for vaccine design. The functional enrichment analysis showed that the predicted host interactors of P0DTC4 target the cellular acetylation network. Two of the identified host-cell proteins - BRD2 and BRD4 - have been shown to be promising targets for antiviral therapy. Thus, our findings have implications for COVID-19 therapy and indicate that viroporin E could serve as a promising vaccine target against SARS-CoV-2. Validation experiments are required to complement these in silico results.

HΜGB1/sRAGE levels differ significantly between transudates and exudates.

High mobility group box 1(HMGB1) protein operates as an alarmin with multiple roles in immunity and cell homeostasis. It is highly expressed in epithelial barrier sites and acts via the binding to the receptor for advanced glycation end products (RAGE). Production of HMGB1 and soluble RAGE (sRAGE), a decoy receptor for HMGB1, has been implicated in several pulmonary diseases, but both have been scarcely investigated in pleural diseases. The aim of this study was to determine the levels of HMGB1 and sRAGE in transudative, malignant and parapneumonic pleural effusions (PEs) and to investigate the effect of low and high HMGB1 pleural fluid levels on MeT-5A cell adhesion, migration and spheroid formation, in each group. HMGB1 and sRAGE levels were significantly lower and higher in transudative PEs compared to malignant and parapneumonic PEs, respectively. Patients above 65 years of age had significantly lower HMGB1 and higher sRAGE levels compared to patients below 65 years old. Furthermore, incubation of MeT-5A cells with malignant or parapneumonic PEs bearing low or high levels of HMGB1 yielded significant differential effects on MeT-5A cell adhesion, migration and spheroid formation. In all types of effusions, high HMGB1 levels correlated with more adherence compared to low HMGB1 levels. In transudative and malignant PEs high HMGB1 levels correlated with decreased migration of MeT-5A cells while in parapneumonic ones the effect was the opposite. Only samples from parapneumonic PEs high in HMGB1 achieved uniform spheroid formation. These results reveal a clinical context-dependent effect of the HMGB1/sRAGE axis in PEs.

Increased monocyte count and red cell distribution width as prognostic biomarkers in patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) represents a chronic lung disease with unpredictable course. METHODS: We aimed to investigate prognostic performance of complete blood count parameters in IPF. Treatment-naïve patients with IPF were retrospectively enrolled from two independent cohorts (derivation and validation) and split into subgroups (high and low) based on median baseline monocyte count and red cell distribution width (RDW). RESULTS: Overall, 489 patients (derivation cohort: 300, validation cohort: 189) were analyzed. In the derivation cohort, patients with monocyte count ≥ 0.60 K/µL had significantly lower median FVC%pred [75.0, (95% CI 71.3-76.7) vs. 80.9, (95% CI 77.5-83.1), (P = 0.01)] and DLCO%pred [47.5, (95% CI 44.3-52.3) vs. 53.0, (95% CI 48.0-56.7), (P = 0.02)] than patients with monocyte count < 0.60 K/µL. Patients with RDW ≥ 14.1% had significantly lower median FVC%pred [75.5, (95% CI 71.2-79.2) vs. 78.3, (95% CI 76.0-81.0), (P = 0.04)] and DLCO%pred [45.4, (95% CI 43.3-50.5) vs. 53.0, (95% CI 50.8-56.8), (P = 0.008)] than patients with RDW < 14.1%. Cut-off thresholds from the derivation cohort were applied to the validation cohort with similar discriminatory value, as indicated by significant differences in median DLCO%pred between patients with high vs. low monocyte count [37.8, (95% CI 35.5-41.1) vs. 45.5, (95% CI 41.9-49.4), (P < 0.001)] and RDW [37.9, (95% CI 33.4-40.7) vs. 44.4, (95% CI 41.5-48.9), (P < 0.001)]. Patients with high monocyte count and RDW of the validation cohort exhibited a trend towards lower median FVC%pred (P = 0.09) and significantly lower median FVC%pred (P = 0.001), respectively. Kaplan-Meier analysis in the derivation cohort demonstrated higher all-cause mortality in patients with high (≥ 0.60 K/µL) vs. low monocyte count (< 0.60 K/µL) [HR 2.05, (95% CI 1.19-3.53), (P = 0.01)]. CONCLUSIONS: Increased monocyte count and RDW may represent negative prognostic biomarkers in patients with IPF.

Clinical profile of severe asthmatics receiving biological treatment: see behind the scenes.

The clinical phenotyping of severe asthma could improve treatment outcomes, quality of life, morbidity, and mortality of asthma patients. The growing availability of rich clinical data could provide opportunities to address a broad range of real-world questions regarding clinical phenotyping and effective therapeutic approaches of severe asthma. Accordingly, in this Letter to the Editor, we provide data relevant to constructing the clinical profile of a Greek severe asthma patient cohort who receive biological treatment.

Cell and extracellular matrix interaction models in benign mesothelial and malignant pleural mesothelioma cells in 2D and 3D in-vitro.

Malignant pleural mesothelioma (MPM) is an aggressive tumour that grows in the pleural cavity. MPM spheroids released in the pleural fluid can form new tumour foci. Cell-cell, cell-extracellular matrix (ECM) interactions in 2D and 3D impact malignant cell behaviour during cell adhesion, migration, proliferation and epithelial-mesenchymal transition (EMT). In this study, epithelioid, biphasic and sarcomatoid MPM cell types as well as benign mesothelial cells were tested with regards to the above phenotypes. Fibronectin (FN) and homologous cell-derived extracellular matrix (hcd-ECM) treated substratum differentially affected the above phenotypes. 3D MPM spheroid invasion was higher in FN-collagen matrices in the epithelioid and biphasic cells, while 3D cell cultures of epithelioid and sarcomatoid MPM cells in FN-collagen showed a higher contractility compared to hcd-ECM-collagen. Cell aggregates demonstrated invasive behaviour in hcd-ECM matrices alone. Our results suggest that ECM and the dimensionality affect malignant cell behaviour during cell culture studies.