Iatrogenic Migration of an Impacted Pharyngeal Foreign Body of the Hypopharynx to the Prevertebral Space

Impaction of foreign bodies in the upper aerodigestive tract is commonly encountered in ENT practice. The present paper describes an iatrogenic complication with migration of an impacted foreign body (chicken bone) of the hypopharynx into the prevertebral space, after unsuccessful attempt of endoscopic removal. The foreign body was visualized with cervical CT scan lying extraluminally between the major vessels of the neck. An open surgical procedure with neck exploration was necessary for the definite treatment

Η εξέλιξη του νομικού πλαισίου για τις πλημμύρες στον Ελληνικό χώρο

Το νερό (επιστημονική ορολογία με την αρχαία ονομασία ύδωρ) θεωρείται ένα πολύτιμο αγαθό πρώτης ύλης του κόσμου, απαραίτητο συστατικό για τη δημιουργία της ζωής και την ανάπτυξη του ανθρώπινου περιβάλλοντος και πολιτισμού. Οι φυσικές ατμοσφαιρικές διεργασίες ως τμήμα του υδρολογικού κύκλου όμως μπορούν να προκαλέσουν υδρομετεωρολογικές καταστροφές όπως είναι μεταξύ άλλων και οι καταστρεπτικές πλημμύρες. Οι πλημμύρες είναι η πιο συχνή και δαπανηρή φυσική καταστροφή παγκοσμίως. Αποτελούν ένα σημαντικό ζήτημα για την ασφάλεια του πληθυσμού καθώς σχετίζονται με σημαντικό τμήμα του συνόλου των ανθρώπινων απωλειών και των οικονομικών επιπτώσεων. Εκτός από τα σημαντικά ποσοστά που κατέχουν ανάμεσα στους υπόλοιπους τύπους φυσικών καταστροφών, οι πλημμύρες καταγράφουν σημαντικά απόλυτα μεγέθη, από πλευράς κόστους, θυμάτων και επηρεασθέντος πληθυσμού, τα οποία καταδεικνύουν την εξαιρετική σημασία τους. Η αύξηση της πληθυσμιακής πυκνότητας και η επέκταση των ανθρώπινων δραστηριοτήτων σε περιοχές υψηλού κινδύνου, οδηγούν σε αύξηση των καταγραφόμενων πλημμυρικών φαινόμενων. Πρόσφατα, καταστρεπτικά φαινόμενα όπως η πλημμύρα της Μάνδρας το Νοέμβριο του 2017, απέδειξαν πέραν πάσης αμφιβολίας, τη σημασία και μελέτη των φαινόμενων και τη λήψη μέτρων για τη μείωση του κινδύνου. Οι δράσεις μείωσης του κινδύνου από πλημμύρες μπορεί να είναι δομικού (π.χ. τεχνικά έργα), μη δομικού (π.χ. εκτίμηση κινδύνου και σχέδια) ή και θεσμικού χαρακτήρα (αποφάσεις, νόμοι οριοθέτησης ζωνών κινδύνου, συστήματα έγκαιρης ειδοποίησης). Η δημιουργία και η εξέλιξη ενός εθνικού νομοθετικού πλαισίου για την στρατηγική διαχείριση των υδάτων και την αντιμετώπιση ζητημάτων, απόρροιας των πλημμυρών, είχε καταστεί αναγκαία στο παρελθόν και αποδείχθηκε χρήσιμο υπόβαθρο για την εφαρμογή της Οδηγίας 2007/60. Το νομικό αυτό πλαίσιο και η εξέλιξή του θεωρείται ότι αντανακλά την οργανωτική ωριμότητα της κοινωνίας μας και των ινστιτούτων της πολιτείας, μας απέναντι στο πρόβλημα των πλημμυρών. Η καινοτομία της ευρωπαϊκής Οδηγίας που διέπεται από την αρχή της αλληλεγγύης, έγκειται στην «Λεκάνη Απορροής Ποταμού» ως βασική συγκεντρωτική μονάδα αξιολόγησης και μελέτης και διαχειριστικής δράσης από κινδύνους πλημμύρας. Η εναρμόνιση της Οδηγίας στο εθνικό δίκαιο, έγινε με την Κοινή Υπουργική Απόφαση (ΚΥΑ)31822/1542Ε103/2010 η οποία χάραξε την πολιτική για τα σχέδια διαχείρισης κινδύνων πλημμύρας, με τη συμβολή των διοικητικών δομών σε κεντρικό και περιφερειακό επίπεδο. Το χρονοδιάγραμμα όμως της εγχώριας παραγωγής νομοθετικών πράξεων σχετικών με τις πλημμύρες καθώς και τα αποτελέσματα αυτών, παραμένει εν πολλοίς αχαρτογράφητο πεδίο. Το γεγονός αυτό έχει οδηγήσει στην απουσία μιας ικανοποιητικής αποτύπωσης των ρυθμιστικών κανόνων και των ενεργειών που προέκυψαν κατά καιρούς από την πολιτική βούληση και τις κοινωνικές συμμορφώσεις, με άξονα την προστασία των ανθρώπων και την ασφάλεια των φυσικών και ανθρωπογενών συστημάτων. Η παρούσα διατριβή έχει ως στόχο, την καταγραφή της γένεσης και εξέλιξης του νομικού πλαισίου, τόσο σε εθνικό όσο και σε Ευρωπαϊκό επίπεδο καθώς και την διερεύνηση της συμβολής των σχετικών αποφάσεων, στο πρόβλημα των πλημμυρών στον Ελληνικό χώρο.Water (scientific terminology with the ancient water designation) is considered to be a valuable commodity of the world, an essential ingredient for creating life and developing the human environment and culture. However, natural atmospheric processes as part of the hydrological cycle can cause hydrometeorological disasters such as destructive floods. Floods are the most common and costly natural disaster worldwide. They are an important issue for the safety of the population as they relate to a significant part of all human losses and economic impacts. In addition to the significant percentages among other types of natural disasters, floods record significant absolute cost sizes for victims and affected populations, which demonstrate their exceptional importance. Increasing population density and expanding human activities in high risk areas, lead to an increase in recorded floods. Recent catastrophic floods in Mandra (Novemder 2017) have proved that new measures and initiatives are imperative to reduce flood risk. Flood risk mitigation actions may be structural (e.g. technical works), structural (e.g. floods risk estimation plans) or institutional (decisions, risk zoning, establishment of early warning systems etc). The creation and development of a national legislative framework for strategic water management and tackling flood-related issues has become necessary in the past and has proven to be a useful basis for the implementation of Directive 2007/60. The innovation of the European Directive governed by the principle of solidarity lies in the River Basin as a key aggregate unit of assessment and study and management action against flood risks. The harmonization of the Directive into national law was made by Joint Ministerial Decision (JMC) 31822 / 1542E103 / 2010 which established the policy for flood risk management plans with the contribution of the administrative structures at central and regional level. However, the timetable for domestic production of flood-related legislation, and the results of these, remains largely uncharted. As a result, there is a lack of satisfactory reflection of regulatory rules and actions that have emerged from time to time from political will and social compliance, with a view to protecting people and the security of natural and man-made systems. The aim of this dissertation is to record the generation and evolution of the legal framework both at national and European level and to investigate the contribution of the relevant decisions to the flood problem in Greece

Μελέτη της επίδρασης της έκθεσης στο ανακίνρα στην κλινική έκβαση της θεραπείας COVID-19 σε ασθενείς της κλινικής μελέτης φάσεως ΙΙΙ SAVE-MORE.

Στο πλαίσιο του πρωτοκόλλου της διπλά τυφλής τυχαιοποιημένης μελέτης φάσεως ΙΙΙ SAVE-MORE, 405 πάσχοντες από COVID-19 που τυχαιοποιήθηκαν στην ομάδα του Anakinra έλαβαν 100 mg φαρμάκου υποδορίως άπαξ ημερησίως για χρονικό διάστημα 7 – 10 ημερών. Παρά τη σταθερά της δόσης των 100 mg ημερησίως, κάθε ασθενής εμφάνισε διαφορετικό ρυθμό κάθαρσης του Anakinra και κατά συνέπεια εκτέθηκε σε διαφορετική ποσότητα φαρμάκου. Η διατομική μεταβλητότητα του ρυθμού απέκκρισης του Anakinra καθορίστηκε από την ταυτόχρονη επίδραση πολλών παραγόντων μεταξύ των οποίων η βαρύτητα της νόσου κατά την έναρξη της θεραπείας, αλλά και κλινικών παραμέτρων που επηρεάζουν το ρυθμό νεφρικής κάθαρσης (π.χ. φύλο, ηλικία, συννοσηρότητες κλπ.). Βασικό σκοπό της παρούσας διπλωματικής εργασίας απετέλεσε η ανάλυση της άμεσης και έμμεσης επίδρασης της κάθαρσης του φαρμάκου στην κλινική έκβαση των ασθενών και του μηχανισμού επίδρασης παραγόντων που επιδρούν στην ίδια την κάθαρση. Η κλινική έκβαση των ασεθνών εκφράστηκε ως η εμφάνιση ή όχι σοβαρής αναπνευστικής ανεπάρκειας μέχρι και την ημέρα 14 από την έναρξη του φαρμάκου μελέτης. Το εύρος των τιμών κάθαρσης του Anakinra ήταν: 5.10 (L/h) – 9,20 (L/h) (mean: 6.83 L/h, τυπική απόκλιση: 0.64). Για τους ασθενείς με υψηλότερη κάθαρση του φαρμάκου (CL/F ≥ 6.5 L/h), ο λόγος των ασθενών που εμφάνισαν SRF ως την ημέρα 14 προς αυτούς που δεν εμφάνισαν, ήταν 2.8 φορές (OR = 2.80, 95% CI: 1.50 - 5.40, p < 0.001) μεγαλύτερος από τον αντίστοιχο λόγο για τους ασθενείς με χαμηλότερη κάθαρση του φαρμάκου (CL/F < 6.5 L/h). Παράλληλα, εξετάστηκε η επίδραση διαφορετικών παραγόντων στην κάθαρση του Anakinra και στην κλινική έκβαση των ασθενών. Το φύλο, η ηλικία και οι συννοσηρότητες φάνηκε ότι επιδρούν στατιστικά σημαντικά στην κάθαρση του φαρμάκου, όμως τα δύο τελευταία δε φάνηκε να επιδρούν στατιστικά σημαντικά στην κλινική έκβαση των ασθενών. Ο έλεγχος της επίδρασης της κάθαρσης του Anakinra στην εξέλιξη της νόσου την ημέρα 7 υπέδειξε ότι για τους ασθενείς που παρουσίασαν υψηλότερη κάθαρση του Anakinra, ο λόγος εκείνων που παρουσίασαν σταθερότητα ή επιδείνωση της κλινικής τους κατάστασης την ημέρα 7 προς εκείνους που παρουσίασαν βελτίωση ήταν περίπου 1.68 φορές μεγαλύτερος (OR: 1.68, CI: 1.06 – 2.66) από τον αντίστοιχο λόγο για τους ασθενείς που παρουσίασαν χαμηλότερη κάθαρση του Anakinra. Η ανάλυση της συσχέτισης της εξέλιξης της νόσου την ημέρα 7 με την κλινική έκβαση του ασθενούς απέδειξε ότι για τους ασθενείς που εμφάνισαν σταθερή ή επιδεινωμένη εικόνα την ημέρα 7 συγκριτικά με τη baseline κλινική εικόνα τους, ο λόγος εκείνων που εμφάνισαν SRF μέχρι και την ημέρα 14 προς αυτούς που δεν εμφάνισαν, ήταν 4.95 φορές μεγαλύτερος (OR = 4.95, CI: 2.91 – 8.41, p < 0.001) από τον αντίστοιχο λόγο για τους ασθενείς που σημείωσαν βελτίωση την ημέρα 7 συγκριτικά με τη baseline κλινική εικόνα τους. Τέλος, κεντρικό εύρημα απετέλεσε ότι οι δύο παράγοντες κινδύνου α) υψηλή καθαρση του Αnakinra (CL/F ≥ 6.5 L/h) και β) απουσία βελτίωσης της κλινικής κατάστασης την ημέρα 7 συγκριτικά με τη baseline κατάσταση των ασθενών (SOFA1 – SOFA7 ≤ 0), επιδεικνύουν μηχανισμό συνεργιστικής δράσης, όταν συνυπάρχουν, ως προς το ενδεχόμενο εμφάνισης SRF την ημέρα 14.405 COVID-19 patients were randomized to the anakinra arm in the context of their participation in the double blind randomized phase III clinical trial SAVEMORE. These patients received daily one subcutaneous injection containing 100 mg of anakinra for 7 – 10 days (depending on how many days they were hospitalized). Even if all patients received the same daily dose of study drug, i.e. 100 mg, anakinra clearance appeared to be different among different patients. As a result, each patient was exposed to different amount of study drug. Multiple factors, such as disease severity at the timepoint of start of study treatment and clinical covariates which affect renal excretion rate (i.e. gender, age, commorbidities, etc.) contributed to intersubject variability of anakinra clearance. It is important that the mechanism of this interaction is investigated more. This bachelor thesis aims to primarily assess if the clearance of anakinra exhibited statistically significant effect on the clinical outcome of the patients treated with that, and if yes in which manner and secondarily to examine the contribution of the covariates that affected renal excretion of anakinra to the clinical outcome. Clinical outcome was expressed as the event of appearance of severe respiratory failure (SRF) or the absence of it until Day 14 after the start of treatment with the study drug. Clearance of anakinra values ranged between 5.10 (L/h) – 9,20 (L/h) (mean: 6.83 L/h, SD: 0.64). For patients with a higher clearance of anakinra (CL/F ≥ 6.5 L/h), the ratio of patients who presented with SRF until Day 14 to patients who did not was 2.8 times greater (OR = 2.80, 95% CI: 1.50 - 5.40, p < 0.001) to the same ratio for the patients with a lower clearance of anakinra (CL/F < 6.5 L/h). 9 Effect of various factors to both anakinra clearance and clinical outcome was studied too. It seems that gender, age and commorbidities may affect anakinra clearance but they were not statistically significantly correlated to clinical outcome. When anakinra clearance effect on disease progress on Day 7 was examined, it was shown that for the patients with higher excretion rate, the ratio of patients that did not appear with improved clinical condition on Day 7 to those who appeared with clinical improvement on Day 7 was 1.68 times greater (OR: 1.68, CI: 1.06 – 2.66) than the same ratio for the patients with lower anakinra clearance. Correlation analysis between progress disease on Day 7 and clinical outcome on Day 14 indicated that for patients who were not clinically improved on Day 7 the ratio of patients who presented with SRF until Day 14 to those who did not is 4.95 times greater (OR = 4.95, CI: 2.91 – 8.41, p < 0.001) than the same ratio for the patients who were indeed clinically improved on Day 7. Clinical improvement comparatively to baseline state was expressed as a positive difference of SOFA scores for the Days 1 and 7 (SOFA1 – SOFA7 ≤ 0) Finally, an interesting finding that was extracted by the statistical analyses was that the two risk factors, that is to say higher anakinra clearance (CL/F ≥ 6.5 L/h) and absence of clinical improvement on Day 7, exhibit a possible synergistic effect to the event of SRF appearance until Day 14. This statement was supported by the finding that for the patients who were exposed to both risk factors, i.e. higher anakinra clearance (CL/F ≥ 6.5 L/h) and absence of clinical improvement on Day 7, the ratio of patients who presented with SRF until Day 14 to those who did not was 8.06 times greater than the same ratio for the patients who were not exposed to any of these two conditions.

Detection of Zoonotic Gastrointestinal Pathogens in Dairy Sheep and Goats by Using FilmArray® Multiplex-PCR Technology

The objectives of this study were (a) to detect gastrointestinal pathogens in faecal samples of sheep and goats using the FilmArray® GI Panel and (b) to evaluate factors that were associated with their presence. Faecal samples from ewes or does in 70 sheep flocks and 24 goat herds in Greece were tested for the presence of 22 gastrointestinal pathogens by means of the BioFire® FilmArray® Gastrointestinal (GI) Panel. The most frequently detected pathogens were Shiga-like toxin-producing Escherichia coli stx1/stx2 (94.7% of farms), Giardia lamblia (59.6%), and Campylobacter spp. (50.0% of farms). Other pathogens detected were Cryptosporidium spp., Salmonella spp., enterotoxigenic E. coli lt/st, Yersinia enterocolitica, E. coli O157, Rotavirus A, Shigella/enteroinvasive E. coli, and Plesiomonasshigelloides. There was a difference in the prevalence of detection of pathogens between sheep and goat farms only for Salmonella spp.: 18.3% versus 0.0%, respectively. Mixed infections were detected in 76 farms (80.9% of farms), specifically 57 sheep flocks and 19 goat herds, with on average, 2.5 ± 0.1 pathogens detected per farm. The body condition score of ewes in farms, in which only one pathogen was detected in faecal samples, was significantly higher than that of ewes in farms, in which at least two pathogens were detected: 2.55 ± 0.11 versus 2.31 ± 0.04. In sheep flocks, the number of pathogens in faecal samples was significantly higher in farms with semi-extensive management. In goat herds, the number of pathogens in faecal samples was positively correlated with average precipitation and inversely correlated with temperature range in the respective locations

The Utility of NGS Analysis in Homologous Recombination Deficiency Tracking

Several tumor types have been efficiently treated with PARP inhibitors (PARPis), which are now approved for the treatment of ovarian, breast, prostate, and pancreatic cancers. The BRCA1/2 genes and mutations in many additional genes involved in the HR pathway may be responsible for the HRD phenomenon. The aim of the present study was to investigate the association between genomic loss of heterozygosity (gLOH) and alterations in 513 genes with targeted and immuno-oncology therapies in 406 samples using an NGS assay. In addition, the %gLOHs of 24 samples were calculated using the Affymetrix technology in order to compare the results obtained via the two methodologies. HR variations occurred in 20.93% of the malignancies, while BRCA1/2 gene alterations occurred in 5.17% of the malignancies. The %LOH was highly correlated with alterations in the BRCA1/2 genes, since 76.19% (16/21) of the BRCA1/2 positive tumors had a high %LOH value (p = 0.007). Moreover, the LOH status was highly correlated with the TP53 and KRAS statuses, but there was no association with the TMB value. Lin’s concordance correlation coefficient for the 24 samples simultaneously examined via both assays was 0.87, indicating a nearly perfect agreement. In conclusion, the addition of gLOH analysis could assist in the detection of additional patients eligible for treatment with PARPis

Isolation of Listeria ivanovii from Bulk-Tank Milk of Sheep and Goat Farms—From Clinical Work to Bioinformatics Studies: Prevalence, Association with Milk Quality, Antibiotic Susceptibility, Predictors, Whole Genome Sequence and Phylogenetic Relationships

A cross-sectional study was performed in 325 sheep and 119 goat dairy farms in Greece. Samples of bulk-tank milk were examined by standard microbiological techniques for Listeria spp. Listeria monocytogenes was isolated from one (0.3%) and Listeria ivanovii from three (0.9%) sheep farms. No associations between the isolation of L. monocytogenes or L. ivanovii and milk quality were found. No resistance to antibiotics was identified. Three variables emerged as significant predictors of isolation of the organism: the presence of pigs, low average relative humidity and a high number of ewes on the farm. The three L. ivanovii isolates were assessed in silico for identification of plasmids, prophages, antibiotic resistance genes, virulence factors, CRISPRs and CAS genes. Phylogenetic analysis using the core genome revealed that the three strains belonged to the L. ivanovii subsp. ivanovii branch and were especially close to the PAM 55 strain. All strains of the branch appeared to be very similar, with the distance between them being small

Mental health and conspirasism in health care professionals during the spring 2020 COVID-19 lockdown in Greece

Introduction: The aim of the study was to investigate mental health and conspiracy theory beliefs concerning COVID-19 among Health Care Professionals (HCPs). Material and Methods: During lockdown, an online questionnaire gathered data from 507 HCPs (432 females aged 33.86±8.63 and 75 males aged 39.09±9.54). Statistical Analysis: A post-stratification method to transform the study sample was used; descriptive statistics were calculated. Results: Anxiety and probable depression were increased 1.5-2-fold and were higher in females and nurses. Previous history of depression was the main risk factor. The rates of the believing in conspiracy theories concerning the COVID-19 were alarming with the majority of individuals (especially females) following some theory to at least some extend. Conclusions: The current paper reports high rates of depression, distress and suicidal thoughts in the HCPs during the lockdown, with a high prevalence of beliefs in conspiracy theories. Female gender and previous history of depression acted as risk factors while the belief in conspiracy theories might act as a protective factor. The results should be considered with caution due to the nature of the data (online survey on a self-selected but stratified sample

Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial

Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1 alpha/beta inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR >= 6 ng ml(-1), 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26-0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.The SAVE-MORE phase 3 study demonstrates the efficacy of anakinra, an IL-1 alpha/beta inhibitor, in patients with COVID-19 and high serum levels of soluble plasminogen activator receptor

Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial

Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1 alpha/beta inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR >= 6 ng ml(-1), 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26-0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter. The SAVE-MORE phase 3 study demonstrates the efficacy of anakinra, an IL-1 alpha/beta inhibitor, in patients with COVID-19 and high serum levels of soluble plasminogen activator receptor