Endovascular Treatment for Acute Basilar Artery Occlusion: A Fragility Index Meta-Analysis

Introduction: High-quality evidence regarding the use of endovascular treatment (EVT) in patients with acute basilar artery occlusion (BAO) has been provided by recently completed randomized controlled clinical trials (RCTs). Methods: We conducted a systematic review and meta-analysis including all available RCTs that investigated efficacy and safety of EVT in addition to best medical treatment (BMT) versus BMT alone for BAO. The random-effects model was used, while the fragility index (FI) was calculated for dichotomous outcomes of interest. Results: Four RCTs were included comprising a total of 988 patients with acute BAO (mean age: 65.6 years, 70% men, median NIHSS: 24, 39% pretreatment with intravenous thrombolysis). EVT was related to higher likelihood of good functional outcome (RR: 1.54; 95% CI: 1.16–2.05; I2 = 60%), functional independence (RR: 1.83; 95% CI: 1.08–3.08; I2 = 79%) and reduced disability at 3 months (adjusted common OR: 1.96; 95% CI: 1.26–3.05; I2 = 59%) compared to BMT alone. Despite that EVT was associated with a higher risk for symptomatic intracranial hemorrhage (RR: 7.78; 95% CI: 2.36–25.61; I2 = 0%) and any intracranial hemorrhage (RR: 2.85; 95% CI: 1.50–5.44; I2 = 16%), mortality at 3 months was lower among patients that received EVT plus BMT versus BMT alone (RR: 0.76; 95% CI: 0.65–0.89; I2 = 0%). However, sufficient robustness was not evident in any of the reported associations (FI < 10) including the overall effect regarding the primary outcome. The former associations were predominantly driven by RCTs with recruitment limited in China. Conclusions: EVT combined with BMT is associated with a higher likelihood of achieving good functional outcomes and a lower risk of death at 3 months compared to BMT alone, despite the higher risk of sICH. An individual-patient data meta-analysis is warranted to uncover and adjust for potential sources of heterogeneity and to provide further insight

Medications prescriptions in COVID-19 pregnant and lactating women: the Bergamo Teratology Information Service experience during COVID-19 outbreak in Italy

Abstract Objectives The severe acute respiratory syndrome coronavirus 2 (COVID-19) outbreak in Italy, especially in Lombardy and Bergamo city, represented probably nowadays one of the first major clusters of COVID-19 in the world. The aim of this report is to describe the activity of Bergamo Teratology Information Service (TIS) in supporting the public and health-care personnel in case of drug prescriptions in suspected/confirmed COVID-19 pregnant and lactating patients during COVID-19 outbreak in Italy. Methods All Bergamo TIS requests concerning COVID-19 pregnant and lactating women have been retrospectively evaluated from 1 March to 15 April 2020. Type of medications, drug's safety profile and compatibility with pregnancy and lactation are reported. Results Our service received information calls concerning 48 (9 pregnant, 35 lactating) patients. Among pregnant and lactating women, the requests of information were related to 16 and 60 drugs prescriptions respectively. More than half concerned drugs prescriptions during the first and second trimester (13/16) and during the first six months of lactation (37/60). Hydroxychloroquine and azithromycin were the most involved. Conclusions Hydroxychloroquine and azithromycin at dosages used for COVID-19 may be considered compatible and reasonably safe either in pregnancy and lactation. Antivirals may be considered acceptable in pregnancy. During lactation lopinavir and ritonavir probably exhibit some supportive data from literature that darunavir and cobicistat do not. Tocilizumab may be considered for COVID-19 treatment because no increased malformation rate were observed until now. However caution may be advised because human data are limited and the potential risk of embryo-fetal toxicity cannot be excluded

Consensus Panel Recommendations for the Pharmacological Management of Pregnant Women with Depressive Disorders

Introduction: The initiative of a consensus on the topic of antidepressant and anxiolytic drug use in pregnancy is developing in an area of clinical uncertainty. Although many studies have been published in recent years, there is still a paucity of authoritative evidence-based indications useful for guiding the prescription of these drugs during pregnancy, and the data from the literature are complex and require expert judgment to draw clear conclusions. Methods: For the elaboration of the consensus, we have involved the scientific societies of the sector, namely, the Italian Society of Toxicology, the Italian Society of Neuropsychopharmacology, the Italian Society of Psychiatry, the Italian Society of Obstetrics and Gynecology, the Italian Society of Drug Addiction and the Italian Society of Addiction Pathology. An interdisciplinary team of experts from different medical specialties (toxicologists, pharmacologists, psychiatrists, gynecologists, neonatologists) was first established to identify the needs underlying the consensus. The team, in its definitive structure, includes all the representatives of the aforementioned scientific societies; the task of the team was the evaluation of the most accredited international literature as well as using the methodology of the "Nominal Group Technique" with the help of a systematic review of the literature and with various discussion meetings, to arrive at the drafting and final approval of the document. Results: The following five areas of investigation were identified: (1) The importance of management of anxiety and depressive disorders in pregnancy, identifying the risks associated with untreated maternal depression in pregnancy. (2) The assessment of the overall risk of malformations with the antidepressant and anxiolytic drugs used in pregnancy. (3) The evaluation of neonatal adaptation disorders in the offspring of pregnant antidepressant/anxiolytic-treated women. (4) The long-term outcome of infants' cognitive development or behavior after in utero exposure to antidepressant/anxiolytic medicines. (5) The evaluation of pharmacological treatment of opioid-abusing pregnant women with depressive disorders. Conclusions: Considering the state of the art, it is therefore necessary in the first instance to frame the issue of pharmacological choices in pregnant women who need treatment with antidepressant and anxiolytic drugs on the basis of data currently available in the literature. Particular attention must be paid to the evaluation of the risk/benefit ratio, understood both in terms of therapeutic benefit with respect to the potential risks of the treatment on the pregnancy and on the fetal outcome, and of the comparative risk between the treatment and the absence of treatment; in the choice prescription, the specialist needs to be aware of both the potential risks of pharmacological treatment and the equally important risks of an untreated or undertreated disorder

Use of GLP1 receptor agonists in early pregnancy and reproductive safety: a multicentre, observational, prospective cohort study based on the databases of six Teratology Information Services.

OBJECTIVES Glucagon-like peptide 1 receptor agonists (GLP1-RA) are indicated for the treatment of type 2 diabetes and more recently for weight loss. The aim of this study was to assess the risks associated with GLP1-RA exposure during early pregnancy. DESIGN This multicentre, observational prospective cohort study compared pregnancy outcomes in women exposed to GLP1-RA in early pregnancy either for diabetes or obesity treatment with those in two reference groups: (1) women with diabetes exposed to at least one non-GLP1-RA antidiabetic drug during the first trimester and (2) a reference group of overweight/obese women without diabetes, between 2009 and 2022. SETTING Data were collected from the databases of six Teratology Information Services. PARTICIPANTS This study included 168 pregnancies of women exposed to GLP1-RA during the first trimester, alongside a reference group of 156 pregnancies of women with diabetes and 163 pregnancies of overweight/obese women. RESULTS Exposure to GLP1-RA in the first trimester was not associated with a risk of major birth defects when compared with diabetes (2.6% vs 2.3%; adjusted OR, 0.98 (95% CI, 0.16 to 5.82)) or to overweight/obese (2.6% vs 3.9%; adjusted OR 0.54 (0.11 to 2.75)). For the GLP1-RA group, cumulative incidence for live births, pregnancy losses and pregnancy terminations was 59%, 23% and 18%, respectively. In the diabetes reference group, corresponding estimates were 69%, 26% and 6%, while in the overweight/obese reference group, they were 63%, 29% and 8%, respectively. Cox proportional cause-specific hazard models indicated no increased risk of pregnancy losses in the GLP1-RA versus the diabetes and the overweight/obese reference groups, in both crude and adjusted analyses. CONCLUSIONS This study offers reassurance in cases of inadvertent exposure to GLP1-RA during the first trimester of pregnancy. Due to the limited sample size, larger studies are required to validate these findings

Uso di farmaci Antidepressivi Inbitori del Reuptake della Serotonina, di farmaci Antiepilettici e di Retinoidi in Gravidanza

After the catastrophic event of thalidome in Europe, early in the sixties, the FDA planed experimental protocols for the study of the reproduction toxicity of drugs and other substances. In this work, we begun our route from the fecundation to the normal fetal development and the principles of developmental toxicology. We reported an outline of the pathogenesis of developmental toxicity and we mentioned the sources of the teratogenic evaluation: animal experiments and epidemiologic data. Finally, we refer the follow-up interview; this interview consisted of a comprehensive list of questions with regard to maternal health during pregnancy, pregnancy outcome, delivery, and neonatal health

Estimation and spatial-temporal dispersion of radionuclides in the aquatic environment

Radionuclides as part of the natural environment affects significantly our lives due to the radiation they emit. Since the mid-20th century human activities further enrich the environment with artificial radionuclides or disrupt the existing local natural balance. The increasing demands for electric energy and the variety of applications that use radionuclides foreshadow the already growing production of nuclear fuels, retreatment of byproducts and disposal of radionuclide wastes that have as final recipient the environment, especially the aquatic. This fact, coupled with the limited scientific knowledge about the exact behavior of radionuclides in different ecosystems makes particularly important the systematic study in this scientific field.In this frame the present PhD thesis entitled “Estimation and Spatial-temporal dispersion of radionuclides in the aquatic environment” has been realized. The purpose of this study is to provide reliable data of radiological measurements in the aquatic environment, use them as radiotracers to characterize regions of interest and model the spatial and temporal dispersion of radionuclides with final objective to determine their impact on humans. In particular, an integrated methodology for radiological characterization and radionuclides’ dispersion modeling of aquatic areas has been developed in order to predict the environmental radiological impacts. The methodology, indicatively, have been implemented at Thermaikos Gulf, N Aegean Sea including background measurements of sea water and sediment, radionuclides’ dispersion simulation for 137Cs and 90Sr; and evaluation of the modeling estimations based on scientific and social criteria. Additionally, the sedimentation rates have been deduced by applying radiochonology methods and the radiological mapping of the seabed has also been performed for different characteristic aquatic environments. On the whole, the experimental measurements provide resent data in regions of interest at the NE Mediterranean.The thesis consists on seven chapters including the theoretical (Chapters 1 and 2), methodological (Chapters 2 and 4) and experimental (Chapters 5 and 6) part, concluding with an additional chapter of main findings and perspectives (Chapter 7).Τα ραδιονουκλίδια αποτελούν μέρος του φυσικού περιβάλλοντος και η ακτινοβολία που εκπέμπουν επηρεάζει σημαντικά τη ζωή μας. Οι ανθρωπογενείς δραστηριότητες από τα μέσα του 20ου αιώνα εμπλουτίζουν επιπλέον το περιβάλλον με τεχνητά ραδιονουκλίδια ή διαταράσσουν την κατά τόπους υπάρχουσα φυσική ισορροπία. Οι διαρκώς αυξανόμενες απαιτήσεις για κατανάλωση ενέργειας και η πληθώρα εφαρμογών που χρησιμοποιούν ραδιονουκλίδια, προοιωνίζουν την ήδη αυξανόμενη παραγωγή πυρηνικών καυσίμων, παραπροϊόντων χρήσης ραδιονουκλιδίων αλλά και αποβλήτων που έχουν σαν τελικό αποδέκτη το περιβάλλον, κυρίως το υδάτινο. Το γεγονός αυτό σε συνδυασμό με την περιορισμένη επιστημονική γνώση για την ακριβή συμπεριφορά των ραδιονουκλιδίων στα διάφορα οικοσυστήματα καθιστούν ιδιαίτερα σημαντική την συστηματική τους μελέτη.Σκοπός της παρούσας διατριβής είναι η παροχή αξιόπιστων δεδομένων ραδιολογικών μετρήσεων στο υδάτινο περιβάλλον, η αξιοποίησή τους ως ραδιοϊχνηθετών για τον χαρακτηρισμό περιοχών και η χωροχρονική μοντελοποίηση της ραδιενεργού διασποράς με άμεσο στόχο τον προσδιορισμό της επίδρασής τους στον άνθρωπο. Συγκεκριμένα, αναπτύχθηκε ολοκληρωμένη μεθοδολογία ραδιολογικού χαρακτηρισμού υδάτινων περιοχών και μοντελοποίησης της χωροχρονικής διασποράς ραδιονουκλιδίων με σκοπό την πρόβλεψη των ραδιολογικών επιπτώσεων. Η μεθοδολογία υλοποιήθηκε ενδεικτικά στο Θερμαϊκό Κόλπο περιλαμβάνοντας μετρήσεις υποβάθρου (νερό και ίζημα), ανάπτυξη ραδιολογικού προτύπου και αξιολόγηση των αποτελεσμάτων της μοντελοποίησης με βάση επιστημονικά και κοινωνικά κριτήρια, ενώ παράλληλα προσδιορίστηκε και ο ρυθμός ιζηματογένεσης σε υδάτινα περιβάλλοντα με διαφορετικά χαρακτηριστικά εφαρμόζοντας μεθόδους ραδιοχρονολόγησης. Σε κάθε περίπτωση, οι πειραματικές μετρήσεις στο σύνολό τους παρέχουν σύγχρονα ποιοτικά δεδομένα σε περιοχές ενδιαφέροντος στη ΒΑ Μεσόγειο. Η διατριβή είναι διαρθρωμένη σε επτά κεφάλαια αποτελούμενη από το θεωρητικό (1ο και 2ο Κεφάλαιο), το μεθοδολογικό (3ο και 4ο Κεφάλαιο) και το πειραματικό (5ο και 6ο Κεφάλαιο) μέρος, ενώ η διατριβή ολοκληρώνεται με ένα επιπλέον κεφάλαιο σύνοψης των συμπερασμάτων και συζήτησης των προοπτικών (7ο Κεφάλαιο)

Estimation and Spatial-temporal dispersion of radionuclides in the aquatic environment

389 σ.Τα ραδιονουκλίδια αποτελούν μέρος του φυσικού περιβάλλοντος και η ακτινοβολία που εκπέμπουν επηρεάζει σημαντικά τη ζωή μας. Οι ανθρωπογενείς δραστηριότητες από τα μέσα του 20ου αιώνα εμπλουτίζουν επιπλέον το περιβάλλον με τεχνητά ραδιονουκλίδια ή διαταράσσουν την κατά τόπους υπάρχουσα φυσική ισορροπία. Οι διαρκώς αυξανόμενες απαιτήσεις για κατανάλωση ενέργειας και η πληθώρα εφαρμογών που χρησιμοποιούν ραδιονουκλίδια, προοιωνίζουν την ήδη αυξανόμενη παραγωγή πυρηνικών καυσίμων, παραπροϊόντων χρήσης ραδιονουκλιδίων αλλά και αποβλήτων που έχουν σαν τελικό αποδέκτη το περιβάλλον, κυρίως το υδάτινο. Το γεγονός αυτό σε συνδυασμό με την περιορισμένη επιστημονική γνώση για την ακριβή συμπεριφορά των ραδιονουκλιδίων στα διάφορα οικοσυστήματα καθιστούν ιδιαίτερα σημαντική την συστηματική τους μελέτη. Σκοπός της παρούσας διατριβής είναι η παροχή αξιόπιστων δεδομένων ραδιολογικών μετρήσεων στο υδάτινο περιβάλλον, η αξιοποίησή τους ως ραδιοϊχνηθετών για τον χαρακτηρισμό περιοχών και η χωροχρονική μοντελοποίηση της ραδιενεργού διασποράς με άμεσο στόχο τον προσδιορισμό της επίδρασής τους στον άνθρωπο. Συγκεκριμένα, αναπτύχθηκε ολοκληρωμένη μεθοδολογία ραδιολογικού χαρακτηρισμού υδάτινων περιοχών και μοντελοποίησης της χωροχρονικής διασποράς ραδιονουκλιδίων με σκοπό την πρόβλεψη των ραδιολογικών επιπτώσεων. Η μεθοδολογία υλοποιήθηκε ενδεικτικά στο Θερμαϊκό Κόλπο περιλαμβάνοντας μετρήσεις υποβάθρου (νερό και ίζημα), ανάπτυξη ραδιολογικού προτύπου και αξιολόγηση των αποτελεσμάτων της μοντελοποίησης με βάση επιστημονικά και κοινωνικά κριτήρια, ενώ παράλληλα προσδιορίστηκε και ο ρυθμός ιζηματογένεσης σε υδάτινα περιβάλλοντα με διαφορετικά χαρακτηριστικά εφαρμόζοντας μεθόδους ραδιοχρονολόγησης. Σε κάθε περίπτωση, οι πειραματικές μετρήσεις στο σύνολό τους παρέχουν σύγχρονα ποιοτικά δεδομένα σε περιοχές ενδιαφέροντος στη ΒΑ Μεσόγειο. Η διατριβή είναι διαρθρωμένη σε επτά κεφάλαια αποτελούμενη από το θεωρητικό (1ο και 2ο Κεφάλαιο), το μεθοδολογικό (3ο και 4ο Κεφάλαιο) και το πειραματικό (5ο και 6ο Κεφάλαιο) μέρος, ενώ η διατριβή ολοκληρώνεται με ένα επιπλέον κεφάλαιο σύνοψης των συμπερασμάτων και συζήτησης των προοπτικών (7ο Κεφάλαιο).Radionuclides as part of the natural environment affects significantly our lives due to the radiation they emit. Since the mid-20th century human activities further enrich the environment with artificial radionuclides or disrupt the existing local natural balance. The increasing demands for electric energy and the variety of applications that use radionuclides foreshadow the already growing production of nuclear fuels, retreatment of byproducts and disposal of radionuclide wastes that have as final recipient the environment, especially the aquatic. This fact, coupled with the limited scientific knowledge about the exact behavior of radionuclides in different ecosystems makes particularly important the systematic study in this scientific field. In this frame the present PhD thesis entitled “Estimation and Spatial-temporal dispersion of radionuclides in the aquatic environment” has been realized. The purpose of this study is to provide reliable data of radiological measurements in the aquatic environment, use them as radiotracers to characterize regions of interest and model the spatial and temporal dispersion of radionuclides with final objective to determine their impact on humans. In particular, an integrated methodology for radiological characterization and radionuclides’ dispersion modeling of aquatic areas has been developed in order to predict the environmental radiological impacts. The methodology, indicatively, have been implemented at Thermaikos Gulf, N Aegean Sea including background measurements of sea water and sediment, radionuclides’ dispersion simulation for 137Cs and 90Sr; and evaluation of the modeling estimations based on scientific and social criteria. Additionally, the sedimentation rates have been deduced by applying radiochonology methods and the radiological mapping of the seabed has also been performed for different characteristic aquatic environments. On the whole, the experimental measurements provide resent data in regions of interest at the NE Mediterranean. The thesis consists on seven chapters including the theoretical (Chapters 1 and 2), methodological (Chapters 2 and 4) and experimental (Chapters 5 and 6) part, concluding with an additional chapter of main findings and perspectives (Chapter 7):Γεώργιος Δ. Ελευθερίο

Radiological assessment of hydrological characteristics of the submarine groundwater spring in Stoupa (NE Messenia, Peloponnese)

195 σ.Εθνικό Μετσόβιο Πολυτεχνείο--Μεταπτυχιακή Εργασία. Διεπιστημονικό-Διατμηματικό Πρόγραμμα Μεταπτυχιακών Σπουδών "Φυσική και Τεχνολογικές Εφαρμογές"Το νερό είναι το επικρατέστερο συστατικό του πλανήτη και αποτελεί πηγή ζωής για τον άνθρωπο και όλα τα έμβια όντα της Γης.Πολύ σημαντικό κομμάτι του υδρολογικού κύκλου αποτελούν οι υποθαλάσσιες εκροές υπόγειων υδάτων μέσα στην θάλασσα (SGD). Πρόκειται για ένα φαινόμενο καθοριστικής σημασίας τόσο για τις παράκτιες και ηπειρωτικές περιοχές, όσο και για όλες τις ωκεάνιες και περιβαλλοντικές διαδικασίες που συνδέονται με τις κλιματολογικές συνθήκες. Στην παρούσα εργασία πραγματοποιήθηκε η ραδιολογική μελέτη της παραθαλάσσιας περιοχής της Στούπας, στην Νοτιοανατολική Μεσσηνία, με απώτερο στόχο την διερεύνηση του φαινομένου των υποθαλάσσιων εκροών με μεθόδους πυρηνικής φυσικής. Σκοπός της έρευνας ήταν ο προσδιορισμός υδρολογικών δεδομένων μέσω της ανίχνευσης ραδιοϊχνηθετών στα υπόγεια νερά και στην παράκτια θαλάσσια ζώνη της ευρύτερης περιοχής, με κύριο σημείο ενδιαφέροντος την υποθαλάσσια ανάβλυση γλυκού νερού στον όρμο της Καλογριάς. Παράλληλα έγινε προσπάθεια εφαρμογής, ελέγχου και σύγκρισης προτεινόμενων μεθόδων επιτόπιας και εργαστηριακής υποθαλάσσιας εντοπισμένης (σημειακής) φασματοσκοπίας-γ. Στην εργασία επιπλέον περιλαμβάνεται αναλυτική αναφορά στο θεωρητικό υπόβαθρο του ευρύτερου φαινομένου και των τρόπων διερεύνησης των SGD, πλήρης περιγραφή της περιοχής έρευνας, της οργανολογίας και της μεθοδολογίας των ραδιολογικών μετρήσεων και των διασκοπίσεων που πραγματοποιήθηκαν, ενώ παρατίθονται με λεπτομέρεια τα αποτελέσματα της έρευνας που αφορούν στο φαινόμενο καθεαυτό, καθώς και την ανάπτυξη νέων τεχνικών και γενικότερων πρακτικών συμπερασμάτων που απορρέουν από την όλη διαδικασία.Submarine groundwater discharges (SGD) into the sea are an integral part of the global hydrological cycle. The last decades it has been well known that SGD are a phenomenon of crucial importance for both coastal and inland areas; and responsible for many oceanic and environmental processes. Only very recently has been explored the role that applied nuclear physics can play in the field of SGD’s investigation; and is nowadays clear that the use of radiotracers as a potential mean of research, is very promising. In the present work the radiological study of the coastal area of Stoupa, Southeast Messenia, is presented, exploring the offshore groundwater discharges with nuclear spectrometry methods. The purpose of this study is to identify hydrologic data by detecting radiotracers in groundwater in the coastal marine area of the region, with main point of interest the freshwater vent at Kalogria Bay. Furthermore, new proposed techniques for in situ and laboratory underwater localized (spot) gamma spectroscopy were implemented, tested and compared with each other. In this work a detailed reference to the essential theoretical background is also included, along with the standard methods of SGD’s investigation. A full description of the research area, instrumentation and applied methodologies are also included, while are out in detail the results of the research concerning the phenomenon itself, the developed new techniques and the general conclusions arising from the experimental processes.Γεώργιος Δ. Ελευθερίο