Category Archives: Δημοσιευμένες εργασίες

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Serum Activin A as Brain Injury Biomarker in the First Three Days of Life. A Prospective Case—Control Longitudinal Study in Human Premature Neonates

Dimitra Metallinou, Grigorios Karampas, Eleftheria Lazarou, Nikoletta Iacovidou, Panagiota Pervanidou, Katerina Lykeridou, George Mastorakos, Demetrios Rizos

Abstract

Disruption of normal intrauterine brain development is a significant consequence of premature birth and may lead to serious complications, such as neonatal brain injury (NBI). This prospective case-control longitudinal study aimed at determining the levels and prognostic value of serum activin A during the first three days of life in human premature neonates which later developed NBI. It was conducted in a single tertiary hospital and eligible participants were live-born premature (<34 weeks) neonates. Each case (n = 29) developed NBI in the form of an intraventricular haemorrhage, or periventricular leukomalacia, and was matched according to birth weight and gestational age to one neonate with normal head ultrasound scans. Serum activin A levels in both groups showed a stable concentration during the first three days of life as no difference was observed within the two groups from the first to the third day. Neonates diagnosed with NBI had significantly higher activin A levels during the first two days of life compared to control neonates and its levels correlated to the severity of NBI during the second and third day of life. Although serum activin A on the second day was the best predictor for neonates at risk to develop NBI, the overall predictive value was marginally fair (area under the ROC-curve 69.2%). Activin A, in combination with other biomarkers, may provide the first clinically useful panel for the early detection of premature neonates at high risk of NBI.

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Endometrial Injury and Fertility Increase in Patients with Recurrent Failed Assisted Reproduction Attempts

Athanasios Chasiotis, Antonios Makrygiannakis, Sophia Kalantaridou, Nikolaos Vrachnis

Abstract

The aim of this systematic review is the collection and presentation of all scientific data to date, regarding the effectiveness of the intrauterine injury in cases of repeated failed attempts of conception, through in vitro fertilization. A systematic review of studies evaluating the association between intrauterine injury and increased fertility in women with recurrent failed IVF attempts was performed, in the databases Medline, PubMed, Embase, Google Scholar and Cochrane Central Registry, with regard to information about the fertility potential of these women. The data of the studies analyzed in the present study, indicate that there is a significant correlation between endometrial injury and increased fertility in women with repeated failed IVF attempts. Hysteroscopy with endometrial tissue damage, or the use of a suction pipette catheter during the menstrual cycle that precedes the ovarian stimulation for a subsequent IVF / ICSI, can highly improve the implantation and clinical pregnancy rates in women with failed IVF attempts. The application of local endometrial injury at the cycle preceding the ovarian stimulation for IVF/ICSI, especially during the luteal phase, seems to enhance the endometrial receptivity to the implanted fetus. The endometrial injury may induce changes in the endometrium that are thought to be able to improve the outcomes of the assisted reproduction efforts. Future RCTs are required in order to establish the integration of this therapeutic approach in ART protocols.

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Physical activity and exercise during pregnancy in Greece: A cross-sectional study

Ermioni Tsarna, Ioanna Mavrommati, Grigorios Bogdanis, Olga Triantafillidou, George Paltoglou, Panagiotis Christopoulos

Abstract

Introduction: Physical activity and exercise during pregnancy is regarded safe and beneficial in absence of pregnancy complications. The aim of this cross-sectional study is to describe physical activity of pregnant women in Greece and explore if it changes during pregnancy compared to the period before pregnancy.

Material and Methods: The study was conducted in a private maternity hospital. Women were asked to fill in an adapted questionnaire based on Pregnant Physical Activity Questionnaire; birth outcomes and anthropometric measurements of the neonate were collected by the research midwife.

Results: In our study population of 193 pregnant women, approximately half reported no or minimal physical activity during pregnancy and were less active than current guidelines’ recommendations. Gynaecologist’s opinion regarding exercise during pregnancy was conceived as positive only by a minority of women. Overall, women were less active during pregnancy than before, although they spent more time slowly walking for fun or exercise. Lastly, significant decrease was observed in all occupational activities involving slow or quick walking and lifting weights.

Conclusions: These results indicate that systematic counselling of pregnant women regarding physical activity and exercise during pregnancy will be needed to achieve optimal physical activity levels for the majority of women in Greece.

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The Role of Hypothalamic Inflammation in Diet-Induced Obesity and Its Association with Cognitive and Mood Disorders

Sofia Dionysopoulou, Evangelia Charmandari, Alexandra Bargiota, Nikolaos F Vlahos, George Mastorakos and Georgios Valsamakis

Abstract
Obesity is often associated with cognitive and mood disorders. Recent evidence suggests that obesity may cause hypothalamic inflammation. Our aim was to investigate the hypothesis that there is a causal link between obesity-induced hypothalamic inflammation and cognitive and mood disorders. Inflammation may influence hypothalamic inter-connections with regions important for cognition and mood, while it may cause dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and influence monoaminergic systems. Exercise, healthy diet, and glucagon-like peptide receptor agonists, which can reduce hypothalamic inflammation in obese models, could improve the deleterious effects on cognition and mood.

Keywords: diet; obesity; hypothalamic inflammation; cognitive disorders; mood disorders; depression; dementia

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Novel Approaches in Addressing Ovarian Insufficiency in 2019: Are We There Yet?

Konstantinos Sfakianoudis, Anna Rapani, Sokratis Grigoriadis, Dimitra Retsina, Evangelos Maziotis, Petroula Tsioulou, Polina Giannelou, Konstantinos Pantos, Michael Koutsilieris, Nikolaos Vlahos, George Mastorakos, and Mara Simopoulou

Abstract
Ovarian insufficiency is described as a multifaceted issue typically encountered in the field of assisted reproduction. The three main identified diagnoses of ovarian insufficiency include premature ovarian failure (POF), poor ovarian response (POR), and advanced maternal age (AMA). Patient heterogeneity in the era of individualized medicine drives research forward leading to the emergence of novel approaches. This plethora of innovative treatments in the service of adequately managing ovarian insufficiency is called to undertake the challenge of addressing infertile patients exploring their reproductive options. This review provides an all-inclusive presentation and critical analysis on novel treatments that have not achieved routine clinical practice status yet, but have recently emerged as promising. In light of the lack of randomized controlled trials conveying safety and efficiency, clinicians are left puzzled in addressing the “how” and “for whom” these approaches may be beneficial. From ovarian injection employing platelet-rich plasma (PRP) or stem cells to artificial gametes and ovaries, ovarian transplantation, and mitochondrial replacement therapy, this descriptive review provides insight toward assisting the practitioner in decision making regarding these cutting-edge treatments. Biological mechanisms, invasiveness levels, efficiency, as well as possible complications, the current status along with bioethical concerns are discussed in the context of identifying future optimal treatment.

Keywords
ovarian insufficiency, premature ovarian failure, poor ovarian response, stem cells, platelet rich plasma, mitochondria replacement therapy

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Implementation of the Endocrine Society clinical practice guidelines for gestational diabetes mellitus to a knowledge tool

Vasiliki M. Korvesi MD, MSc, Ioanna Chouvarda Prof, George Mastorakos Prof, Dimitrios G. Goulis Prof

Background: Despite the production of clinical practice guidelines (CPGs) in many medical areas, their use is not sufficiently adopted in clinical practice. Incorporation of CPGs in knowledge tools (KnowT) or decision support systems (DSS) for routine use can improve healthcare providers’ compliance to CPGs.
Materials and methods: Clinical practice guidelines for gestational diabetes mellitus (GDM) were searched for, collected and compared. The CPG that met prespecified criteria ([a] published by a European or American organization between 2010 and 2018, [b] being developed a systematic way and [c] having statements of “level of evidence” and “strength of recommendation”) was chosen for implementation (Endocrine Society, 2013). Its recommendations were deconstructed, re-organized and reconstructed as an algorithm (in the form of a flowchart), which was integrated into a KnowT. Content completeness and evaluation of CPG by the Guideline Implementability Appraisal tool (GLIA) were performed as well. The primary objective was the development of a clinical algorithm in the field of GDM and its integration into a KnowT. The secondary objective was to demonstrate the completeness of the CPG content and evaluate its implementability in the KnowT.
Results: Endocrine Society 2013 CPG was restructured as a flowchart, and a KnowT was constructed with the use of the “Openlabyrinth” software. The completeness of the content was confirmed, and GLIA appraisal demonstrated its implementability.
Conclusion: Endocrine Society 2013 CPG for GDM is a complete set of recommendations. Its structure makes possible the design of a clinical algorithm and its implementation into a KnowT.

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Energy deficiency, menstrual disorders and low bone mineral density in female athletes: a systematic review

Nikitas S Skarakis, George Mastorakos, Neoklis Georgopoulos & Dimitrios G Goulis

* Poster Presentation in 7th ESE Young Endocrinologists and Scientists (EYES) Meeting

Background and aim: Low energy availability (LEA) may lead to menstrual disorders and low bone mineral density, predisposing to the female athlete triad (FAT) syndrome. The primary aim of this review was to systematically investigate the impact of sports on the energy status of professional female athletes compared to sedentary, recreationally active controls, with regard to their menstrual status and bone mineral density (BMD). A secondary aim was the estimation of the combined prevalence of the components of FAT in athletes as compared with non-athletes.
Materials and methods: A systematic review was conducted from 2007 to February 2018. Inclusion and exclusion criteria of studies were established in advance of the literature search, according to the clinical inquiry and the study design.
Results: Four studies were included in this systematic review. The FAT syndrome was more prevalent in professional athletes compared with non-athletes. The same results occurred for both LEA and menstrual disorders. However, BMD and Z-scores showed high heterogeneity among the studies.
Conclusions: Both professional athletes and sedentary women are prone to LEA and subsequent menstrual disorders and low BMD or osteoporosis. Future studies are needed to examine the energy availability in elite female athletes, as well as in non-athletes.

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Μελέτη της διαφορικής έκφρασης των ισομορφών του IGF-I στο ανθρώπινο σπέρμα

Μ. Καρβούνη, Ε. Μαζιώτης, Π. Γιαννέλου, Α. Παπαδοπετράκη, Ν. Νίτσος, Κ. Πάντος, Α. Φιλίππου, Μ. Κουτσιλιέρης, Μ. Σιμοπούλου

*Ανακοίνωση στο 46ο Πανελλήνιο Ιατρικό Συνέδριο

ΣΚΟΠΟΣ: H διερεύνηση της έκφρασης των ισομορφών του ινσουλινο-μιμητικού αυξητικού παράγοντα IGF-I (IGF-1Ea, IGF-1Eb, IGF-1Ec) στο σπέρμα μεταξύ νορμοζωοσπερμικών ανδρών και εκείνων με μη φυσιολογικές παραμέτρους σπέρματος.
ΥΛΙΚΟ: Στη μελέτη συμμετείχαν 40 άνδρες ηλικίας 32-54 ετών (43,9±4,6 έτη), οι οποίοι υποβλήθηκαν σε σπερμοδιάγραμμα και κατηγοριοποιήθηκαν σε 4 ομάδες μελέτης, σύμφωνα με τη διάγνωση του σπερμοδιαγράμματος: «Νορμοζωοσπερμικούς», «Μία μη-φυσιολογική παράμετρος», «Δύο μη-φυσιολογικές παραμέτρους» και «Ολιγοασθενοτερατοζωοσπερμικούς (ΟΑΤ)». Τα δείγματα υποβλήθηκαν σε διαδικασία απομόνωσης RNA, σύνθεση cDNA και ποσοτικοποίησή του μέσω Real-time PCR, χρησιμοποιώντας ειδικούς εκκινητές για τις τρεις ισομορφές. Ταυτόχρονα, απομονώθηκε σπερματικό πλάσμα και πρωτεΐνες από τα σπερματοζωάρια και ελέγχθηκε η πρωτεϊνική έκφραση των τριών ισομορφών μέσω Western Blot. Η στατιστική ανάλυση διεξήχθη στo υπολογιστικό περιβάλλον της R.
ΑΠΟΤΕΛΕΣΜΑΤΑ: Η ανίχνευση των ισομορφών IGF-IEa και IGF-IEb δεν ήταν δυνατή σε επίπεδο mRNA και πρωτεϊνης. Αντίθετα, η ισομορφή IGF-IEc ανιχνεύθηκε σε επίπεδο mRNA και στις 4 ομάδες μελέτης, ωστόσο, τα επίπεδα ήταν χαμηλότερα στους «Νορμοζωοσπερμικούς» από τους άνδρες με «Δύο μη-φυσιολογικές παραμέτρους» (5,1±8,5, p-value=0.0117*) και τους «OAT» (2,9±2,3, p-value=0.0072*). Επιπλέον, βρέθηκε αρνητική συσχέτιση μεταξύ των επιπέδων του IGF-IEc και του ολικού αριθμού σπερματοζωαρίων (ρ=-0.3895225, p-value=0.01298), της προωθητικής (ρ=-0.4505146, pvalue=0.003532) και της ολικής κινητικότητας (ρ =-0.3790446, p-value=0.01586).
ΣΥΜΠΕΡΑΣΜΑΤΑ: Τα αποτελέσματα της μελέτης υποδηλώνουν ότι στα σπερματοζωάρια οι δράσεις του ΙGF-I εκπροσωπούνται κυρίως από την ισομορφή Ec και υπάρχει πιθανή συσχέτιση των επιπέδων της με την ανδρική υπογονιμότητα οφειλόμενη σε 2 ή περισσότερες ανωμαλίες σπερμοδιαγράμματος. Τα υψηλά επίπεδα της Ec πιθανώς επηρεάζουν αρνητικά τη σπερματογένεση και τη διαδικασία ωρίμανσης των σπερματοζωαρίων.

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The Natural History of Neuroendocrine Changes in Pediatric Posttraumatic Stress Disorder (PTSD) After Motor Vehicle Accidents: Progressive Divergence of Noradrenaline and Cortisol Concentrations Over Time

Panagiota Pervanidou, Gerasimos Kolaitis, Stella Charitaki, Christina Lazaropoulou, Ioannis Papassotiriou, Peter Hindmarsh, Chrysa Bakoula, John Tsiantis, and George P. Chrousos

Background: The hypothalamic-pituitary-adrenal axis and the catecholaminergic system are involved in the pathophysiology of posttraumatic stress disorder (PTSD). This was a prospective and longitudinal study of neuroendocrine physiology in children with PTSD following a motor vehicle accident (MVA).
Methods: Sixty children aged 7–18 were studied immediately after an MVA and 1 and 6 months later. Fasting morning plasma catecholamine and serum cortisol concentrations were measured. Salivary cortisol concentrations were measured serially five times daily to examine circadian variation in all three assessments. Values were compared between those who did (PTSD) or did not develop PTSD (non-PTSD) after the trauma and a control group at months 1 and 6.
Results: Twenty-three of the children had PTSD at the 1-month and 9 children at the 6-month evaluations. 1) Plasma noradrenaline concentrations were higher in the PTSD group than in the other two groups at both months 1 and 6 (p = .001 and p = .001, respectively). Additionally, the PTSD patients presented with significantly higher salivary cortisol concentrations at 18.00 (p = .03) and 21.00 (p = .04) at month 1.2) Eight children suffering from PTSD at both months 1 and 6 had significantly elevated plasma noradrenaline concentrations at month 6 compared with those at month 1 and at baseline and to the other two groups (within subjects: p<.001; between subjects: p=.005). The initially elevated evening salivary cortisol concentrations in this group normalized at month 6.
Conclusions: This progressive divergence of noradrenaline and cortisol concentrations over time might underlie the natural history and pathophysiology of PTSD.

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