Publications by authors named "E Papathanasiou"

105 Publications

Blood Eosinophils as Predictor of Outcomes in patients hospitalized for COPD Exacerbations: A Prospective Observational Study.

Biomarkers 2021 03 16:1-25. Epub 2021 Mar 16.

2nd Respiratory Medicine Department, National and Kapodistrian University of Athens, Greece.

Purpose: In the present prospective multicenter observational study, we evaluated the potential role of blood eosinophils on the outcomes of patients hospitalized for COPD exacerbations.

Material And Methods: Consecutive patients >40 years with a previous COPD diagnosis were recruited. Blood eosinophils were measured on admission prior to the initiation of treatment and were evaluated in 3 groups (<50, 50-149 and ≥150 cells/μL). Patients received standard care and were followed up for a year.

Results: A total of 388 patients were included (83.5% male, mean age 72 years). Patients with higher blood eosinophils had less dyspnea (Borg scale), lower C-Reactive Protein (CRP) and higher PaO/FiO (Partial Pressure for Oxygen/Fraction of inhaled Oxygen), and were discharged earlier (median 11 vs. 9 vs. 5 days for patients with <50, 50-149 and ≥150 cells/μL, respectively). Patients with <50 cells/μL presented higher 30-day and 1-year mortality, whereas there were no differences in moderate/severe COPD exacerbations between the 3 groups. In a post-hoc analysis, treatment with inhaled corticosteroids as per physicians' decision was associated with better exacerbation prevention during follow-up in patients with ≥150 cells/μL.

Conclusions: Higher blood eosinophils were associated with better outcomes in hospitalized COPD patients, further supporting their use as a prognostic biomarker.
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http://dx.doi.org/10.1080/1354750X.2021.1903998DOI Listing
March 2021

Specialized Pro-Resolving Mediators as Potential Regulators of Inflammatory Macrophage Responses in COVID-19.

Front Immunol 2021 24;12:632238. Epub 2021 Feb 24.

Department of Pathology, Oslo University Hospital, Oslo, Norway.

The recent outbreak of SARS-CoV2 has emerged as one of the biggest pandemics of our century, with outrageous health, social and economic consequences globally. Macrophages may lay in the center of COVID-19 pathogenesis and lethality and treatment of the macrophage-induced cytokine storm has emerged as essential. Specialized pro-resolving mediators (SPMs) hold strong therapeutic potentials in the management of COVID-19 as they can regulate macrophage infiltration and cytokine production but also promote a pro-resolving macrophage phenotype. In this review, we discuss the homeostatic functions of SPMs acting directly on macrophages on various levels, towards the resolution of inflammation. Moreover, we address the molecular events that link the lipid mediators with COVID-19 severity and discuss the clinical potentials of SPMs in COVID-19 immunotherapeutics.
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http://dx.doi.org/10.3389/fimmu.2021.632238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943727PMC
March 2021

Device use errors among patients with asthma and COPD and the role of training: a real-life study.

Postgrad Med 2021 Mar 29:1-6. Epub 2021 Mar 29.

2 Respiratory Medicine Department, "Attikon" University Hospital, Athens, Greece.

: Administration of inhaled medication for asthma and COPD is often difficult and incorrect device use is associated with unfavorable outcomes. We aimed to evaluate device use errors in asthma and COPD patients and to associate incorrect use with the patient's characteristics and medical history.: Demographics and medical history were recorded. The use of each prescribed device was evaluated according to predefined steps.: 607 patients (49.9% male, median age (IQR) 63 (51, 70) years performed 663 demonstrations (56 patients were using 2 different types of devices). 51.4% were treated for asthma and 48.6% for COPD. 79.6% of demonstrations were performed using DPIs. Errors were documented on 41.2% of demonstrations and were associated with the type of device, p < 0.001. Elderly patients were less frequently using their devices correctly compared to younger patients, 50.8% vs 62.2%, respectively, p = 0.007. Correct demonstrations were more among asthmatics compared to COPD patients 63.1% vs 54.5%, p = 0.024. Incorrect use was associated with more acute exacerbations in the preceding year [median(IQR), 1(0, 2) vs 1(0, 1)], for incorrect and correct use, respectively, p < 0.001. Upon demonstration, 15.5% of patients have never been trained (i.e., undergone actual demonstrations and observation while using their device) by anyone. Errors occurred more frequently among patients who reported not to be trained compared to those who were trained, 67.0% vs 14.6%, respectively, p < 0.001. The commonest error was associated with the inspiration maneuver and accounted for the 48.3% of errors in the DPIs and 53.0% of errors in the MDIs.: Device use errors are common and associated with unfavorable outcomes. Trained patients were more likely to use the device correctly.
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http://dx.doi.org/10.1080/00325481.2021.1902188DOI Listing
March 2021

Host Modulation and Treatment of Periodontal Disease.

J Dent Res 2021 Mar 3:22034521995157. Epub 2021 Mar 3.

Center for Clinical and Translational Research, Forsyth Institute, Cambridge, MA, USA.

Periodontitis is the sixth-most prevalent disease in the world and the first cause for tooth loss in adults. With focus shifted to the inflammatory/immune response in the pathogenesis of periodontitis, there is a critical need to evaluate host modulatory agents. Synthetic and biological disease-modifying antirheumatic drugs are a cornerstone for the treatment of inflammatory diseases. Recent prospective cohort studies showed that synthetic disease-modifying antirheumatic drugs improved periodontal clinical parameters following nonsurgical periodontal treatment in patients with rheumatoid arthritis. Treatment with recombinant humanized monoclonal antibodies against CD20 (rituximab) and IL-6 receptor (tocilizumab), the latter also in clinical trials for the treatment of COVID-19 pneumonia, resulted in decreased periodontal inflammation and improved periodontal status. Studies on the effect of TNF-α inhibitors in patients with periodontitis yielded inconsistent results. Recent data suggest that probiotics provide anti-inflammatory clinical benefit, as do nutritional supplements, such as n-3 fatty acids, when combined with periodontal therapy. Probiotics reduce the production of proinflammatory cytokines/chemokines by suppressing NF-κB pathways and promote the accumulation of T regulatory cells. Statins, like aspirin, have been shown to exhibit anti-inflammatory and bone-preserving actions by upregulating production of Specialized Proresolving Mediators (SPMs). Currently, there is insufficient scientific support for the topical delivery of statins or bisphosphonates as adjuncts to periodontal therapy. Here, we present a critical review of the most recent host modulatory agents applied in humans and the key immune pathways that they target. Emerging evidence from novel drug candidates, including SPMs and complement inhibitors as previously studied in animal models and currently in human clinical trials, suggests future availability of adjunctive therapeutic strategies for the management of periodontitis.
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http://dx.doi.org/10.1177/0022034521995157DOI Listing
March 2021

IL-1B(3954) polymorphism and red complex bacteria increase IL-1β (GCF) levels in periodontitis.

J Periodontal Res 2021 Feb 26. Epub 2021 Feb 26.

Department of Periodontology, Tufts University School of Dental Medicine, Boston, MA, USA.

Objective: The aim of this study was to compare IL-1β levels in gingival crevicular fluid (GCF) from healthy and periodontitis sites of IL-1B(3954)-Single Nucleotide Polymorphism (SNP) positive and IL-1B(3954)-SNP negative periodontitis subjects in association with their bacterial profiles.

Background: Susceptibility to periodontitis has been associated with several risk factors, including allelic variants at multiple gene loci. Variations in the IL-1 gene cluster have been linked with increased risk for periodontitis. IL-1B(3954)-SNP has been previously associated with increased levels of IL-1β in GCF or periodontal tissues in chronic periodontitis patients, as well as higher levels of specific periodontal pathogens. There is insufficient evidence to conclude if IL-1B gene polymorphisms affect the susceptibility to periodontitis by ultimately modulating the levels of IL-1β in GCF, the subgingival microbial profile or both.

Materials And Methods: GCF, subgingival plaque, and buccal epithelial cells were collected from 32 individuals with periodontitis. GCF IL-1β levels were measured by an enzyme-linked immunosorbent assay (ELISA). Bacterial plaque samples were analyzed for 11 periodontal pathogens using polymerase chain reaction (PCR) analysis with specific primers for the 16SrRNA gene of each bacterium. IL-1B(3954)-SNP status was determined by identifying the carriers of the polymorphic T allele.

Results: A significant association was shown between IL-1B(3954)-SNP and IL-1β GCF levels (amount and concentration). The concomitant presence of two or three red complex bacterial species was associated with increased IL-1β GCF levels in periodontitis sites (site-level analysis). The concurrent presence of all three red complex periodontal pathogens and IL-1B(3954)-SNP was associated with the highest IL-1β GCF levels in periodontitis sites.

Conclusions: Our results indicate an independent association of both IL-1B(3954)-SNP and red complex bacterial species with increased IL-1β levels in GCF of periodontitis sites. A better understanding of the interaction between genetics, bacteria, and inflammation is essential to develop more effective diagnostic, prognostic, and therapeutic tools for periodontitis.
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http://dx.doi.org/10.1111/jre.12850DOI Listing
February 2021

A Novel Animal Model for Simulating Scarring After Cleft Lip Repair.

Facial Plast Surg Aesthet Med 2021 Feb 24. Epub 2021 Feb 24.

Department of Otolaryngology-Head and Neck Surgery, Tufts University School of Medicine, Boston, Massachusetts, USA.

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http://dx.doi.org/10.1089/fpsam.2020.0525DOI Listing
February 2021

Repeated delivery of chlorhexidine chips for the treatment of peri-implantitis: A multicenter, randomized, comparative clinical trial.

J Periodontol 2021 Jan 11;92(1):11-20. Epub 2020 Nov 11.

Division of Periodontology, Department of Oral Medicine Infection and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, Massachusetts, USA.

Background: Peri-implantitis is a challenging condition to manage and is frequently treated using non-surgical debridement. The local delivery of antimicrobial agents has demonstrated benefit in mild to moderate cases of peri-implantitis. This study compared the safety and efficacy of chlorhexidine gluconate 2.5 mg chip (CHX chips) as an adjunctive treatment to subgingival debridement in patients afflicted with peri-implantitis.

Methods: A multicenter, randomized, single-blind, two-arm, parallel Phase-3 study was conducted. Peri-implantitis patients with implant pocket depths (IPD) of 5-8 mm underwent subgingival implant surface debridement followed by repeated bi-weekly supragingival plaque removal and chlorhexidine chips application (ChxC group) for 12 weeks, or similar therapy but without application of ChxC (control group). All patients were followed for 24 weeks. Plaque and gingival indices were measured at every visit whereas IPD, recession, and bleeding on probing were assessed at 8, 12, 16, 24 week.

Results: A total of 290 patients were included: 146 in the ChxC group and 144 in the control. At 24 weeks, a significant reduction in IPD (P = 0.01) was measured in the ChxC group (1.76 ± 1.13 mm) compared with the control group (1.54 ± 1.13 mm). IPD reduction of ≥2 mm was found in 59% and 47.2% of the implants in the ChxC and control groups, respectively (P = 0.03). Changes in gingival recession (0.29 ± 0.68 mm versus 0.15 ± 0.55 mm, P = 0.015) and relative attachment gain (1.47 ± 1.32 mm and 1.39 ± 1.27 mm, P = 0.0017) were significantly larger in the ChxC group. Patients in the ChxC group that were < 65 years exhibited significantly better responses (P < 0.02); likewise, non-smokers had similarly better response (P < 0.02). Both protocols were well tolerated, and no severe treatment-related adverse events were recorded throughout the study.

Conclusions: Patients with peri-implantitis that were treated with an intensive treatment protocol of bi-weekly supragingival plaque removal and local application of chlorhexidine chips had greater mean IPD reduction and greater percentile of sites with IPD reduction of ≥2 mm as compared with bi-weekly supra-gingival plaque removal.
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http://dx.doi.org/10.1002/JPER.20-0353DOI Listing
January 2021

Neurophysiological and Genetic Findings in Patients With Juvenile Myoclonic Epilepsy.

Front Integr Neurosci 2020 20;14:45. Epub 2020 Aug 20.

Cyprus School of Molecular Medicine, Nicosia, Cyprus.

Objective: Transcranial magnetic stimulation (TMS), a non-invasive procedure, stimulates the cortex evaluating the central motor pathways. The response is called motor evoked potential (MEP). Polyphasia results when the response crosses the baseline more than twice (zero crossing). Recent research shows MEP polyphasia in patients with generalized genetic epilepsy (GGE) and their first-degree relatives compared with controls. Juvenile Myoclonic Epilepsy (JME), a GGE type, is not well studied regarding polyphasia. In our study, we assessed polyphasia appearance probability with TMS in JME patients, their healthy first-degree relatives and controls. Two genetic approaches were applied to uncover genetic association with polyphasia.

Methods: 20 JME patients, 23 first-degree relatives and 30 controls underwent TMS, obtaining 10-15 MEPs per participant. We evaluated MEP mean number of phases, proportion of MEP trials displaying polyphasia for each subject and variability between groups. Participants underwent whole exome sequencing (WES) via trio-based analysis and two-case scenario. Extensive bioinformatics analysis was applied.

Results: We identified increased polyphasia in patients (85%) and relatives (70%) compared to controls (47%) and significantly higher mean number of zero crossings (i.e., occurrence of phases) (patients 1.49, relatives 1.46, controls 1.22; < 0.05). Trio-based analysis revealed a candidate polymorphism, p.Glu270del,in , in JME patients and their relatives presenting polyphasia. Sanger sequencing analysis in remaining participants showed no significant association. In two-case scenario, a machine learning approach was applied in variants identified from odds ratio analysis and risk prediction scores were obtained for polyphasia. The results revealed 61 variants of which none was associated with polyphasia. Risk prediction scores indeed showed lower probability for non-polyphasic subjects on having polyphasia and higher probability for polyphasic subjects on having polyphasia.

Conclusion: Polyphasia was present in JME patients and relatives in contrast to controls. Although no known clinical symptoms are linked to polyphasia this neurophysiological phenomenon is likely due to common cerebral electrophysiological abnormality. We did not discover direct association between genetic variants obtained and polyphasia. It is likely these genetic traits alone cannot provoke polyphasia, however, this predisposition combined with disturbed brain-electrical activity and tendency to generate seizures may increase the risk of developing polyphasia, mainly in patients and relatives.
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http://dx.doi.org/10.3389/fnint.2020.00045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468511PMC
August 2020

IL-1 Superfamily Members and Periodontal Diseases.

J Dent Res 2020 12 6;99(13):1425-1434. Epub 2020 Aug 6.

Department of Immunology, Tufts University School of Medicine, Boston, MA, USA.

Periodontitis is a complex, multifactorial chronic disease involving continuous interactions among bacteria, host immune/inflammatory responses, and modifying genetic and environmental factors. More than any other cytokine family, the interleukin (IL)-1 family includes key signaling molecules that trigger and perpetuate periodontal inflammation. Over the years, the IL-1 family expanded to include 11 members of cytokines, some with agonist activity (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β, and IL-36γ), receptor antagonists (IL-1Ra, IL-36Ra), and 2 anti-inflammatory cytokines (IL-37, IL-38). The IL-1 receptor antagonist (IL-1Ra) has emerged as a pivotal player in the defense against periodontitis. IL-33 primarily induces the production of Th2-associated cytokines but acts as an "alarmin" via stimulation of mast cells. The IL-36 subclass of cytokines may be important in regulating mucosal inflammation and homeostasis. IL-37 suppresses innate and acquired immune responses. IL-38 is the most recent member of the IL-1 superfamily and has anti-inflammatory properties similar to those of IL-37 but through different receptors. However, limited evidence exists regarding the role of IL-37 and IL-38 in periodontitis. Despite the development of IL-1 blocking agents, therapeutic blockade of select IL-1 family members for periodontitis has only been partially investigated in preclinical and clinical research, while the development of IL-37 and IL-38 as novel anti-inflammatory drugs has not been considered adequately. Here, we review the key properties of the IL-1 family members and provide insights into targeting or promoting select cytokines as new therapeutic agents.
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http://dx.doi.org/10.1177/0022034520945209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684837PMC
December 2020

Sirtuin 1: Endocan and Sestrin 2 in Different Biological Samples in Patients with Asthma. Does Severity Make the Difference?

J Clin Med 2020 Feb 9;9(2). Epub 2020 Feb 9.

2nd Department of Respiratory Medicine, Medical School of National and Kapodistrian University of Athens, "Attikon" Hospital, 12462 Athens, Greece.

Background: Sestrin 2, Endocan, and Sirtuin 1 are distinct molecules with some biologic actions associated with asthma pathophysiology. The aim of the present study was to determine the molecular level differences attributable to underlying asthma severity.

Methods: We initially recruited 85 asthmatics with a wide spectrum of severity. All of the patients were optimally treated according to current guidelines. Demographics, test results of lung function, and treatment regimes of all patients were recorded. Sestrin 2, Endocan, and Sirtuin 1 were measured in different biological samples (sputum with two processing methods and serum).

Results: A total of 60 patients (35 with severe asthma) were analyzed, since 25 patients failed to produce an adequate sample of sputum. Patients with severe asthma showed significantly higher values for Sestrin 2 [pg/mL], measured in both sputum supernatant and cell pellet, compared to those with mild to moderate asthma [9524 (5696, 12,373) vs. 7476 (4265, 9273) = 0.029, and 23,748 (15,280, 32,742) vs. 10,084 (3349, 21,784), = 0.008, respectively]. No other significant differences were observed. No significant associations were observed between biomarkers, inflammatory cells, and lung function.

Conclusion: Sestrin 2 is increased in patients with severe asthma as part of a mechanism that may modify structural alterations through the imbalance between oxidative stress and antioxidant activity.
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http://dx.doi.org/10.3390/jcm9020473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073772PMC
February 2020

Functional brain networks of patients with epilepsy exhibit pronounced multiscale periodicities, which correlate with seizure onset.

Hum Brain Mapp 2020 06 24;41(8):2059-2076. Epub 2020 Jan 24.

University of Nicosia Medical School, Nicosia, Cyprus.

Epileptic seizure detection and prediction by using noninvasive measurements such as scalp EEG signals or invasive, intracranial recordings, has been at the heart of epilepsy studies for at least three decades. To this end, the most common approach has been to consider short-length recordings (several seconds to a few minutes) around a seizure, aiming to identify significant changes that occur before or during seizures. An inherent assumption in this approach is the presence of a relatively constant EEG activity in the interictal period, which is interrupted by seizure occurrence. Here, we examine this assumption by using long-duration scalp EEG data (21-94 hr) in nine patients with epilepsy, based on which we construct functional brain networks. Our results reveal that these networks vary over time in a periodic fashion, exhibiting multiple peaks at periods ranging between 1 and 24 hr. The effects of seizure onset on the functional brain network properties were found to be considerably smaller in magnitude compared to the changes due to these inherent periodic cycles. Importantly, the properties of the identified network periodic components (instantaneous phase) were found to be strongly correlated to seizure onset, especially for the periodicities around 3 and 5 hr. These correlations were found to be largely absent between EEG signal periodicities and seizure onset, suggesting that higher specificity may be achieved by using network-based metrics. In turn, this implies that more robust seizure detection and prediction can be achieved if longer term underlying functional brain network periodic variations are taken into account.
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http://dx.doi.org/10.1002/hbm.24930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268013PMC
June 2020

Why and when to refer patients for vestibular evoked myogenic potentials: A critical review.

Clin Neurophysiol 2019 09 31;130(9):1539-1556. Epub 2019 May 31.

Department of Neurology, University Hospital Zurich, University of Zurich, Switzerland.

Cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs respectively) are now used by an increasing number of laboratories to evaluate otolith inner ear function and their pathways through the central nervous system. However, the literature is incomplete or unclear as to what information both c- and oVEMPs can add beyond what a good clinical examination can provide, and what other paramedical tests can provide also, and the present review aims to clarify what is known so far. The following review will describe what is known with regards to both c- and oVEMPs and their use. MEDLINE (accessed by PubMed, years 1994-2018) was searched with the following string: ("vestibular evoked myogenic potentials" [all fields]). Only articles published in English were evaluated. Both c- and oVEMPs are useful not only for confirming the presence of superior semicircular canal dehiscence (SSCD), but also for confirming the presence of acoustic neuromas when MRI is not available, bilateral vestibulopathies, inferior vestibular neuritis and vestibular dysfunction in inherited neuropathies. Further work is required, especially with respect to oVEMPs. The usefulness of both c- and oVEMPs goes beyond the confirmation of SSCDs, and is useful in many clinical cases.
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http://dx.doi.org/10.1016/j.clinph.2019.04.719DOI Listing
September 2019

Diagnostic accuracy of T2 biomarkers for the prediction of airway eosinophilia in treated smoking asthmatic patients with loss of asthma control.

J Allergy Clin Immunol Pract 2020 01 13;8(1):385-387.e2. Epub 2019 Jun 13.

2nd Respiratory Medicine Department, Attiko University Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2019.05.052DOI Listing
January 2020

Graph Theoretical Characteristics of EEG-Based Functional Brain Networks in Patients With Epilepsy: The Effect of Reference Choice and Volume Conduction.

Front Neurosci 2019 20;13:221. Epub 2019 Mar 20.

Department of Bioengineering, McGill University, Montreal, QC, Canada.

It is well-established that both volume conduction and the choice of recording reference (montage) affect the correlation measures obtained from scalp EEG, both in the time and frequency domains. As a result, a number of correlation measures have been proposed aiming to reduce these effects. In our previous work, we have showed that scalp-EEG based functional brain networks in patients with epilepsy exhibit clear periodic patterns at different time scales and that these patterns are strongly correlated to seizure onset, particularly at shorter time scales (around 3 and 5 h), which has important clinical implications. In the present work, we use the same long-duration clinical scalp EEG data (multiple days) to investigate the extent to which the aforementioned results are affected by the choice of reference choice and correlation measure, by considering several widely used montages as well as correlation metrics that are differentially sensitive to the effects of volume conduction. Specifically, we compare two standard and commonly used linear correlation measures, cross-correlation in the time domain, and coherence in the frequency domain, with measures that account for zero-lag correlations: corrected cross-correlation, imaginary coherence, phase lag index, and weighted phase lag index. We show that the graphs constructed with corrected cross-correlation and WPLI are more stable across different choices of reference. Also, we demonstrate that all the examined correlation measures revealed similar periodic patterns in the obtained graph measures when the bipolar and common reference (Cz) montage were used. This includes circadian-related periodicities (e.g., a clear increase in connectivity during sleep periods as compared to awake periods), as well as periodicities at shorter time scales (around 3 and 5 h). On the other hand, these results were affected to a large degree when the average reference montage was used in combination with standard cross-correlation, coherence, imaginary coherence, and PLI, which is likely due to the low number of electrodes and inadequate electrode coverage of the scalp. Finally, we demonstrate that the correlation between seizure onset and the brain network periodicities is preserved when corrected cross-correlation and WPLI were used for all the examined montages. This suggests that, even in the standard clinical setting of EEG recording in epilepsy where only a limited number of scalp EEG measurements are available, graph-theoretic quantification of periodic patterns using appropriate montage, and correlation measures corrected for volume conduction provides useful insights into seizure onset.
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http://dx.doi.org/10.3389/fnins.2019.00221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436604PMC
March 2019

Standardizing the way we perform and apply vestibular evoked myogenic potentials (VEMPs).

Clin Neurophysiol Pract 2019 26;4:37-38. Epub 2019 Feb 26.

Clinical Neurophysiology Laboratory, Clinic B, The Cyprus Institute of Neurology & Genetics, 6 International Airport Avenue, P.O. Box 23462, Nicosia 1683, Cyprus.

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http://dx.doi.org/10.1016/j.cnp.2019.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411592PMC
February 2019

Vestibular evoked myogenic potentials (VEMPs) in systemic disease.

Clin Neurophysiol 2019 05 6;130(5):789-790. Epub 2019 Mar 6.

Clinical Neurophysiology Laboratory, Clinic B, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus. Electronic address:

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http://dx.doi.org/10.1016/j.clinph.2019.02.009DOI Listing
May 2019

Salivary alkaline phosphatase activity and chronological age as indicators for skeletal maturity.

Angle Orthod 2019 07 6;89(4):637-642. Epub 2019 Mar 6.

Objectives: To investigate the relationship between salivary alkaline phosphatase activity (ALP), protein concentration, and chronological age with cervical vertebral maturation stages (CVMS) as noninvasive biomarkers for skeletal maturity assessment.

Materials And Methods: This cross-sectional study included 79 subjects (48 females, 31 males; 7 to 23 years old) categorized into five CVMS based on lateral cephalographs evaluated by three examiners. ALP activity and protein concentration in unstimulated whole saliva were compared among five CVMS. The association between age and CVMS was assessed and five multinomial logistic regression models were utilized to predict CVMS based on salivary ALP activity, protein concentration, and chronological age.

Results: Salivary ALP reached the peak at early pubertal stage and then declined with a significant difference between CVMS I and CVMS II ( < .001) and between CVMS I and CVMS V ( = .004). A significant positive correlation between age and CVMS was found (r = 0.763, < .001). The models' overall correct classification rates for predicting CVMS were 32.9% using protein concentration, 35.4% using ALP activity, and 53.2% using both ALP activity and age.

Conclusions: The combination of salivary ALP activity and chronological age may provide the best CVMS prediction.
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http://dx.doi.org/10.2319/030918-197.1DOI Listing
July 2019

Peripheral neuropathies and the vestibular system: Is there a role for vestibular rehabilitation?

Clin Neurophysiol 2018 04 31;129(4):847-848. Epub 2018 Jan 31.

Clinical Neurophysiology Laboratory, Neurology Clinic B, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus. Electronic address:

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http://dx.doi.org/10.1016/j.clinph.2018.01.013DOI Listing
April 2018

Ability of using different dry powder inhalers during COPD exacerbations.

Pulm Pharmacol Ther 2018 02 19;48:211-216. Epub 2017 Dec 19.

2nd Respiratory Medicine Department, "Attikon" University Hospital, Athens Medical School, National and Kapodistrian University of Athens, Greece.

Background: Guidelines suggest that patients hospitalized for acute COPD exacerbations (AECOPD) are treated with short acting bronchodilators. Long acting bronchodilators, offer longer symptom relief but since they are usually administered via Dry Powder Inhalers (DPIs) it is considered that during AECOPD patients would not be able to achieve appropriate inspiratory flow (IF) to receive appropriate drug doses. The aim of the present study was to evaluate whether patients admitted to the hospital for AECOPD, are able to achieve the necessary IF using different DPIs.

Methods: IF was measured daily in patients admitted for AECOPD with a portable IF meter (In-Check Oral inhaler assessment kit), containing a series of adapters that simulate the resistance of 4 DPIs [Turbuhaler (T), Breezhaler/Aerolizer (B/F), Discus (A/A/D) and Handinhaler (HH)]. Dyspnea, spirometry and arterial blood gases were also recorded daily.

Results: 44 consecutive patients were included in the study. The majority of patients were able to achieve an IF over 30 L/min with all four device resistances. This minimum required IF was achieved in 90.9%, 100%, 95.5% and 81.8% of patients on admission and in 100%, 100%, 97.7%, and 95.5% of patients on discharge for T, B/F, A/A/D and HH respectively. No functional characteristic was able to predict the achievement of this minimum necessary IF.

Conclusion: Most patients hospitalized for AECOPD, are able to receive treatment with long acting bronchodilators administered via DPIs. The possible beneficial effects of such an intervention should be tested in further studies.
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http://dx.doi.org/10.1016/j.pupt.2017.12.007DOI Listing
February 2018

Exhaled breath temperature in optimally treated asthmatics: severity and underlying mechanisms.

J Breath Res 2018 02 20;12(2):026013. Epub 2018 Feb 20.

2nd Respiratory Medicine Department, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Introduction: Increased vascularity may lead to loss of heat in the airways and may modulate exhaled breath temperature (EBT). Increased EBT has been associated with uncontrolled asthma.

Aim: We wanted to determine whether the measurement of EBT in optimally treated asthmatic patients is influenced by the increased vascular permeability and whether Vascular endothelial growth factor (VEGF) is implicated in the above process. Furthermore, to assess the impact of asthma severity on EBT values. The diagnostic performance of EBT for the identification of inflammatory profiles in induced sputum was also assessed.

Methods: 88 stable asthmatic patients optimally treated for at least 6 months were studied (46 with Severe Refractory Asthma, SRA). EBT was measured with the X-halo device. All patients underwent spirometry, sputum induction for the measurement of % inflammatory cells and for the assessment of both VEGF and albumin in sputum supernatant. The airway vascular permeability index was calculated as the ratio of albumin concentrations in induced sputum and serum.

Results: EBT (°C) was significantly higher in patients with SRA compared to those with mild to moderate asthma (median IQR 34.2 [32.4-34.6] versus 31.8 [26.3-34.1], p = 0.001). EBT was significantly associated with VEGF levels in sputum supernatant, while SRA was recognized as a significant co-variate. No other significant associations were observed. Finally, in ROC analysis, the diagnostic performance of EBT for the pure eosinophilic or/and neutrophilic profile did not reach statistical significance.

Conclusion: EBT is increasing in severe asthma and is significantly modulated by VEGF levels. Despite the above results its performance for predicting cellular profiles is of limited value.
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http://dx.doi.org/10.1088/1752-7163/aa9d46DOI Listing
February 2018

Emphysematous Phenotype is Characterized by Low Blood Eosinophils: A Cross-Sectional Study.

COPD 2017 Dec 3;14(6):635-640. Epub 2017 Nov 3.

b 1st Respiratory Medicine Department , University of Athens, Sotiria Hospital , Athens Greece.

Sputum and blood eosinophils are proposed as candidate biomarkers for the identification of chronic obstructive pulmonary disease (COPD) patients at risk for exacerbation and treatment response. In this study, we evaluated the associations of eosinophils with the presence of emphysema in COPD patients. Induced sputum and blood eosinophil measurements were performed in consecutive COPD patients. Patients underwent lung function testing and high resolution computed tomography (HRCT) of the chest and the presence of emphysema was quantified. Patients with emphysematous lesions in ≥15% of the pulmonary parenchyma were considered having significant emphysema. Ninety-eight patients were included in the study. Patients with significant emphysema had lower blood eosinophil counts compared to patients without emphysema [median (IQR) 34.6 (0.0, 63.0) vs. 169.0 (110.0, 260.0) cells/µL, p < 0.001]; similar results were observed for the percentage (%) of blood eosinophils, but no difference was observed for sputum eosinophils. The differences were evident in frequent and non-frequent exacerbators and irrespective of the use of inhaled corticosteroids (ICS). Patients with significant emphysema in HRCT present lower levels of blood eosinophils and these differences were present irrespective of the frequent exacerbator history or the use of ICS. Blood eosinophils may not represent a clinically relevant biomarker in the presence of emphysema.
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http://dx.doi.org/10.1080/15412555.2017.1386644DOI Listing
December 2017

Unsupervised detection and removal of muscle artifacts from scalp EEG recordings using canonical correlation analysis, wavelets and random forests.

Clin Neurophysiol 2017 09 8;128(9):1755-1769. Epub 2017 Jul 8.

McGill University, Department of Bioengineering, 817 Sherbrooke St. W., Macdonald Engineering Building, Room 270, Montreal, QC H3A 0C3, Canada. Electronic address:

Objective: This paper proposes supervised and unsupervised algorithms for automatic muscle artifact detection and removal from long-term EEG recordings, which combine canonical correlation analysis (CCA) and wavelets with random forests (RF).

Methods: The proposed algorithms first perform CCA and continuous wavelet transform of the canonical components to generate a number of features which include component autocorrelation values and wavelet coefficient magnitude values. A subset of the most important features is subsequently selected using RF and labelled observations (supervised case) or synthetic data constructed from the original observations (unsupervised case). The proposed algorithms are evaluated using realistic simulation data as well as 30min epochs of non-invasive EEG recordings obtained from ten patients with epilepsy.

Results: We assessed the performance of the proposed algorithms using classification performance and goodness-of-fit values for noisy and noise-free signal windows. In the simulation study, where the ground truth was known, the proposed algorithms yielded almost perfect performance. In the case of experimental data, where expert marking was performed, the results suggest that both the supervised and unsupervised algorithm versions were able to remove artifacts without affecting noise-free channels considerably, outperforming standard CCA, independent component analysis (ICA) and Lagged Auto-Mutual Information Clustering (LAMIC).

Conclusion: The proposed algorithms achieved excellent performance for both simulation and experimental data. Importantly, for the first time to our knowledge, we were able to perform entirely unsupervised artifact removal, i.e. without using already marked noisy data segments, achieving performance that is comparable to the supervised case.

Significance: Overall, the results suggest that the proposed algorithms yield significant future potential for improving EEG signal quality in research or clinical settings without the need for marking by expert neurophysiologists, EMG signal recording and user visual inspection.
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http://dx.doi.org/10.1016/j.clinph.2017.06.247DOI Listing
September 2017

Current and Emerging Treatments for Postsurgical Cleft Lip Scarring: Effectiveness and Mechanisms.

J Dent Res 2017 Nov 26;96(12):1370-1377. Epub 2017 Jun 26.

1 Center for Clinical and Translational Research, Forsyth Institute, Cambridge, MA, USA.

Cleft lip with or without cleft palate is the most common congenital malformation of the head and the third-most common birth defect. Surgical repair of the lip is the only treatment and is usually performed during the first year of life. Hypertrophic scar (HTS) formation is a frequent postoperative complication that impairs soft tissue form, function, or movement. Multiple lip revision operations are often required throughout childhood, attempting to optimize aesthetics and function. The mechanisms guiding HTS formation are multifactorial and complex. HTS is the result of dysregulated wound healing, where excessive collagen and extracellular matrix proteins are deposited within the wound area, resulting in persistent inflammation and resultant fibrosis. Many studies support the contribution of dysregulated, exaggerated inflammation in scar formation. Fibrosis and scarring result from chronic inflammation that interrupts tissue remodeling in normal wound healing. Failure of active resolution of inflammation pathways has been implicated. The management of HTS has been challenging for clinicians, since current therapies are minimally effective. Emerging evidence that specialized proresolving mediators of inflammation accelerate wound healing by preventing chronic inflammation and allowing natural uninterrupted tissue remodeling suggests new therapeutic opportunities in the prevention and management of HTS.
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http://dx.doi.org/10.1177/0022034517717261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652856PMC
November 2017

Predictors of response to therapy with omalizumab in patients with severe allergic asthma - a real life study.

Postgrad Med 2017 Aug 28;129(6):598-604. Epub 2017 Apr 28.

a 2nd Respiratory Medicine Department, "Attikon" University Hospital, Athens Medical School , National and Kapodistrian University of Athens , Greece.

Objectives: Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE antibody, used for the treatment of severe refractory allergic asthma. However, not all patients with IgE levels within the limits of administration, respond to treatment. The aim of the present study, was to determine clinical and inflammatory characteristics that could predict response to omalizumab.

Methods: We studied retrospectively patients treated with omalizumab as per GINA guidelines in one asthma tertiary referral center. Demographic and functional characteristics, level of asthma control, fractional exhaled nitric oxide, blood and eosinophils and IgE level, induced sputum cell count, eosinophil cationic protein and Interleukin-13 in sputum supernatant were recorded. All measurements were performed before starting treatment with omalizumab. Response to treatment was evaluated according to the physician's global evaluation of treatment effectiveness. Patients were characterized as early responders when improvement was achieved within 16 weeks and as late responders when improvement was achieved between 16 and 32 weeks. Patients who did not show any improvement after 32 weeks of therapy were considered as non-responders.

Results: Forty-one patients treated with omalizumab were included in the study. 28 (68.3%) patients were characterized as responders while 13 patients (31.7%) were considered as non-responders. Among responders, 25 (89%) were early responders and 3 (n = 11%) were late responders. Responders were characterized by lower baseline FEV and FEV/FVC and higher IL-13 levels in induced sputum supernatant compared to non-responders. Late responders had higher serum IgE levels, shorter disease duration and higher number of blood eosinophils. Finally, using ROC curve analysis, the best predictors of response to omalizumab were FEV (AUC = 0.718) and IL-13 in sputum supernatant (AUC = 0.709).

Conclusion: Lower baseline FEV and higher IL-13 levels in induced sputum supernatant were predictors of response to omalizumab. Patients with higher baseline serum IgE levels, shorter disease duration and higher blood eosinophils may experience a late response and might benefit from a more prolonged treatment before being characterized as non-responders.
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http://dx.doi.org/10.1080/00325481.2017.1321945DOI Listing
August 2017

The association between serum periostin and a type 2 helper airway composite index in optimally treated asthmatics.

J Allergy Clin Immunol Pract 2017 Jul - Aug;5(4):1129-1131.e3. Epub 2017 Apr 7.

1st Respiratory Medicine Department, National and Kapodistrian University of Athens Medical School, Sotiria Chest Hospital, Athens, Greece.

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http://dx.doi.org/10.1016/j.jaip.2017.03.005DOI Listing
June 2019

Epileptic seizure onset correlates with long term EEG functional brain network properties.

Annu Int Conf IEEE Eng Med Biol Soc 2016 Aug;2016:2822-2825

We investigated the correlation of epileptic seizure onset times with long term EEG functional brain network properties. To do so, we constructed binary functional brain networks from long-term, multichannel electroencephalographic data recorded from nine patients with epilepsy. The corresponding network properties were quantified using the average network degree. It was found that the network degree (as well as other network properties such as the network efficiency and clustering coefficient) exhibited large fluctuations over time; however, it also exhibited specific periodic temporal structure over different time scales (1.5hr-24hr periods) that was consistent across subjects. We investigated the correlation of the phases of these network periodicities with the seizure onset by using circular statistics. The results showed that the instantaneous phases of the 3.5hr, 5.5hr, 12hr and 24hr network degree periodic components are not uniformly distributed, suggesting that functional network properties are related to seizure generation and occurrence.
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http://dx.doi.org/10.1109/EMBC.2016.7591317DOI Listing
August 2016

Letter to the Editor: Authors' Response.

J Periodontol 2017 03;88(3):239-240

Department of Periodontology, School of Dental Medicine, Tufts University, and private practice in periodontics, Athens, Greece.

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http://dx.doi.org/10.1902/jop.2017.160685DOI Listing
March 2017

Ocular vestibular evoked myogenic potentials and the importance of the bifid response.

Clin Neurophysiol 2017 01 19;128(1):260-261. Epub 2016 Nov 19.

Clinical Neurophysiology Laboratory, Clinic B, The Cyprus Institute of Neurology & Genetics, 6 International Airport Avenue, P.O. Box 23462, Nicosia 1683, Cyprus. Electronic address:

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http://dx.doi.org/10.1016/j.clinph.2016.11.011DOI Listing
January 2017

Neuroradiological, neurophysiological and molecular findings in infantile Krabbe disease: two case reports.

Balkan J Med Genet 2016 Jul 2;19(1):85-90. Epub 2016 Aug 2.

1 Pediatric Clinic, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Krabbe disease is an autosomal recessive neurodegenerative disorder due to a defect of the lysosomal enzyme β-galactocerebrosidase (β-GALC). Depending on the age of onset, the disease is classified into infantile and later-onset forms. We report neuroradiological, neurophysiological and molecular findings in two Greek patients with the infantile form of Krabbe disease. The index patients presented at the age of 3.5 and 6 months, respectively, due to developmental delay. Magnetic resonance imaging (MRI) of the first patient's brain demonstrated signs of leukodystrophy, while nerve conduction velocities (NCVs) were significantly decreased. The second patient's MRI at the age of 4 months was initially normal, but at 18 months demonstrated leukodystrophic alterations as well, whereas NCVs were also significantly delayed. In both patients, a severe decrease in β-GALC, activity supported the diagnosis of Krabbe disease, while the final diagnosis was confirmed by molecular genetic testing. Two homozygous mutations of the gene, the c.411_413delTAA [p.K139del] mutation in the first patient, and the c.749T>C [p.I250T] mutation in the second patient, were identified. At their last follow-up visit at the age of 4 and 6 years, respectively, both patients were bedridden and quadri-plegic, suffering from frequent respiratory tract infections and fed through a gastrostomy. Both mutations found in homozygosity in these two unrelated patients of Greek ancestry, could pinpoint a common origin. Genotyping of patients with Krabbe disease is important, in order to contribute to the creation of a European mutation database and to further study possible genotype-phenotype correlations of the disease.
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http://dx.doi.org/10.1515/bjmg-2016-0011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026284PMC
July 2016

SOCS-3 Regulates Alveolar Bone Loss in Experimental Periodontitis.

J Dent Res 2016 08 28;95(9):1018-25. Epub 2016 Apr 28.

Department of Applied Oral Sciences, Center for Periodontology, Forsyth Institute, Cambridge, MA, USA

The host immune response plays a key role in bacteria-induced alveolar bone resorption. Endogenous control of the magnitude and duration of inflammatory signaling is considered an important determinant of the extent of periodontal pathology. Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathways and may play a role in restraining periodontal inflammation. We hypothesized that SOCS-3 regulates alveolar bone loss in experimental periodontitis. Periodontal bone loss was induced in 16-wk-old myeloid-specific SOCS-3-knockout and wild-type (WT) C57Bl6-B.129 mice by oral inoculation 9 times with 10(9) colony-forming units of Porphyromonas gingivalis A7436 through an oral gavage model for periodontitis. Sham controls for both types of mice received vehicle without bacteria. The mice were euthanized 6 wk after the last oral inoculation. Increased bone loss was demonstrated in P. gingivalis-infected SOCS-3-knockout mice as compared with P. gingivalis-infected WT mice by direct morphologic measurements, micro-computed tomography analyses, and quantitative histology. Loss of SOCS-3 function resulted in an increased number of alveolar bone osteoclasts and increased RANKL expression after P. gingivalis infection. SOCS-3 deficiency in myeloid cells also promotes a higher P. gingivalis lipopolysaccharide-induced inflammatory response with higher secretion of IL-1β, IL-6, and KC (IL-8) by peritoneal macrophages as compared with WT controls. Our data implicate SOCS-3 as a critical negative regulator of alveolar bone loss in periodontitis.
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http://dx.doi.org/10.1177/0022034516645332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959623PMC
August 2016