Ο ρόλος της τεχνικής χαρτών με αυτόματη οργάνωση (self organizing map) στη λήψη θεραπευτικής απόφασης ενδοεπιθηλιακών αλλοιώσεων τραχήλου μήτρας

Σήμερα, υπάρχουν πολυάριθμες τεχνικές που ανιχνεύουν HPV DNA ή mRNA και θεωρούνται είτε ανταγωνιστικές είτε επικουρικές ως προς το τεστ Παπανικολάου για τον έλεγχο των κολποτραχηλικών επιχρισμάτων. Ωστόσο, καμία τεχνική δεν είναι τέλεια, επειδή η αύξηση της ευαισθησίας συνεπάγεται ταυτόχρονη μείωση της ειδικότητας. Για την επίλυση αυτού του προβλήματος έχουν εφαρμοστεί στο παρελθόν διάφορες τεχνικές που χρησιμοποιούν αποτελέσματα από πολλές εξετάσεις ταυτόχρονα, όπως δέντρα ταξινόμησης και παλινδρόμησης (Classification and Regression Trees – CARTs) και εποπτευόμενα τεχνητά νευρωνικά δίκτυα. Σε αυτή την εργασία χρησιμοποιήθηκαν 1258 περιπτώσεις με αποτελέσματα από τεστ Παπανικολάου, HPV DNA, HPV mRNA και p16, προκειμένου να αξιολογηθούν οι επιδόσεις του αυτο-οργανούμενου χάρτη (Self Organizing Map – SOM). Το SOM είναι ένα τεχνητό νευρωνικό δίκτυο που παρουσιάζει σημαντικά πλεονεκτήματα σε σχέση με τις άλλες μεθοδολογίες, καθώς δεν είναι επιβλεπόμενο (δηλαδή δεν χρειάζεται να γνωρίζουμε σε ποια ομάδα ανήκουν τα περιστατικά κατά την εκπαίδευσή του), μπορεί να διαχειριστεί ελλιπή δεδομένα (κάτι πολύ συνηθισμένο σε πραγματικές μελέτες) και παράγει τοπογραφικούς χάρτες (έτσι, με εύκολο τρόπο γίνονται συσχετίσεις των σημαντικών παραμέτρων στη διάγνωση). Τα αποτελέσματα της εφαρμογής της τεχνικής αυτής ήταν ενθαρρυντικά και οδήγησαν σε πολύ υψηλή ευαισθησία και ειδικότητα στη διάκριση των αλλοιώσεων <CIN2 από ≥CIN2, όπως αυτές αξιολογήθηκαν με ιστολογική εξέταση (όπου ήταν εφικτό). Επιπλέον, οι παραγόμενοι χάρτες μπορούν να βοηθήσουν στον εντοπισμό των σημαντικών δοκιμασιών (tests) για τη διάκριση μεταξύ περιστατικών <CIN2 από ≥CIN2.Nowadays, numerous techniques detecting HPV DNA or mRNA, are viewed as competitors or ancillary techniques to test Papanicolaou. However, no technique is perfect, because sensitivity increases at the cost of specificity. Various methods have been applied to resolve this issue, by using many examination results, such as classification and regression trees and supervised artificial neural networks. In this study, 1258 cases with results from test Pap, HPV DNA, HPV mRNA and p16, were used to evaluate the performance of the Self Organizing Map (SOM), an artificial neural network having three advantages: it is unsupervised, it can tolerate missing data and produces topographical maps. The results of the SOM application were encouraging and leaded to very high sensitivity and specificity for the discrimination of <CIN2 from ≥CIN2 lesions, as these were evaluated histologically (wherever that was possible). Additionally, the produced maps can be helpful in order to detect the important tests for such discrimination

Cytokine soluble receptors in perinatal and early neonatal life.

BACKGROUND: In contrast to cellular receptors, soluble receptors do not enhance the cellular activation because they do not have transmembranic and cytoplasmic parts, acting thereby as endogenous regulatory mechanisms against systemic functions of cytokines. AIM: To measure serum concentrations of the soluble interleukin-2 receptor (sIL2R), soluble interleukin-4 receptor (sIL4R), soluble interleukin-6 receptor (sIL6R), and soluble tumor necrosis factor-alpha receptor I and soluble tumor necrosis factor-alpha receptor II, during the perinatal and early neonatal period, in order to evaluate their role in activation of immune response in labor and the first days postpartum. METHODS: Soluble receptor serum concentrations were determined by enzyme-linked immunosorbent assay, in 45 healthy, full-termed neonates during the first and fifth days after birth, in 25 of their mothers (MS), in 25 samples of umbilical cords (UC) and in 25 healthy adult donors age-matched with the mothers (controls). RESULTS: Soluble receptor serum concentrations showed considerable changes during labor and early neonatal life, being significantly higher both in MS (except sIL6R) and in neonatal sample UC, first and fifth days after birth, compared with controls (p<0.0001). Neonatal serum sIL2R and sIL6R increased significantly from birth to the fifth day, while the remaining receptors showed a rapid increase in the first day (p<0.0001), declining significantly thereafter (p<0.0001). CONCLUSION: Our findings suggest that the elevated concentrations of all studied soluble cytokine receptors reflect the activation of immune response, and represent also regulatory protective mechanisms for mother and fetus-neonate against the systemic function of cytokines during labor and early neonatal life

Morphokinetic parameters of early embryo development via time lapse monitoring and their effect on embryo selection and ICSI outcomes: a prospective cohort study

PURPOSE: To compare the outcomes of embryos selected via time lapse monitoring (TLM) versus those selected with conventional methods of selection in subfertile women undergoing ICSI. METHODS: The study population (239 women) was classified into two groups, based on the monitoring method used: Group 1 (TLM) and Group 2 (conventional monitoring). Groups were compared according to the clinical and ICSI cycle characteristics and reproductive outcomes, while transfers were performed at day 2 or 3. Subgroup analyses were performed, in women of both groups according to age and clinical parameters, and in embryos of Group 1 based on their cellular events. RESULTS: There was a statistically significant difference between the two study groups with regard to the outcome parameters, favoring Group 1 and especially in women &gt;40 years of age. No differences were found in subgroup analyses in participants of both groups, regarding the stimulation protocol used, number of the oocytes retrieved and type of subfertility, while in Group 1 the percentages of "in range" cellular events were higher in certain divisions in ages 35-40, non-smokers, and the GnRH-agonist group, and in embryos that resulted in pregnancy. CONCLUSION: Morphokinetic parameters of early embryo development via TLM are related to the characteristics of subfertile patients and associated with ICSI outcomes

Maternal plasma levels of oxytocin during physiological childbirth - a systematic review with implications for uterine contractions and central actions of oxytocin

Oxytocin is a key hormone in childbirth, and synthetic oxytocin is widely administered to induce or speed labour. Due to lack of synthetized knowledge, we conducted a systematic review of maternal plasma levels of oxytocin during physiological childbirth, and in response to infusions of synthetic oxytocin, if reported in the included studies. An a priori protocol was designed and a systematic search was conducted in PubMed, CINAHL, and PsycINFO in October 2015. Search hits were screened on title and abstract after duplicates were removed (n = 4039), 69 articles were examined in full-text and 20 papers met inclusion criteria. As the articles differed in design and methodology used for analysis of oxytocin levels, a narrative synthesis was created and the material was categorised according to effects. Basal levels of oxytocin increased 3-4-fold during pregnancy. Pulses of oxytocin occurred with increasing frequency, duration, and amplitude, from late pregnancy through labour, reaching a maximum of 3 pulses/10 min towards the end of labour. There was a maximal 3- to 4-fold rise in oxytocin at birth. Oxytocin pulses also occurred in the third stage of labour associated with placental expulsion. Oxytocin peaks during labour did not correlate in time with individual uterine contractions, suggesting additional mechanisms in the control of contractions. Oxytocin levels were also raised in the cerebrospinal fluid during labour, indicating that oxytocin is released into the brain, as well as into the circulation. Oxytocin released into the brain induces beneficial adaptive effects during birth and postpartum. Oxytocin levels following infusion of synthetic oxytocin up to 10 mU/min were similar to oxytocin levels in physiological labour. Oxytocin levels doubled in response to doubling of the rate of infusion of synthetic oxytocin. Plasma oxytocin levels increase gradually during pregnancy, and during the first and second stages of labour, with increasing size and frequency of pulses of oxytocin. A large pulse of oxytocin occurs with birth. Oxytocin in the circulation stimulates uterine contractions and oxytocin released within the brain influences maternal physiology and behaviour during birth. Oxytocin given as an infusion does not cross into the mother's brain because of the blood brain barrier and does not influence brain function in the same way as oxytocin during normal labour does

Which method is best for the induction of labour?: A systematic review, network meta-analysis and cost-effectiveness analysis

Background: More than 150,000 pregnant women in England and Wales have their labour induced each year. Multiple pharmacological, mechanical and complementary methods are available to induce labour. Objective: To assess the relative effectiveness, safety and cost-effectiveness of labour induction methods and, data permitting, effects in different clinical subgroups. Methods: We carried out a systematic review using Cochrane methods. The Cochrane Pregnancy and Childbirth Group’s Trials Register was searched (March 2014). This contains over 22,000 reports of controlled trials (published from 1923 onwards) retrieved from weekly searches of OVID MEDLINE (1966 to current); Cochrane Central Register of Controlled Trials (The Cochrane Library); EMBASE (1982 to current); Cumulative Index to Nursing and Allied Health Literature (1984 to current); ClinicalTrials.gov; the World Health Organization International Clinical Trials Registry Portal; and hand-searching of relevant conference proceedings and journals. We included randomised controlled trials examining interventions to induce labour compared with placebo, no treatment or other interventions in women eligible for third-trimester induction. We included outcomes relating to efficacy, safety and acceptability to women. In addition, for the economic analysis we searched the Database of Abstracts of Reviews of Effects, and Economic Evaluations Databases, NHS Economic Evaluation Database and the Health Technology Assessment database. We carried out a network meta-analysis (NMA) using all of the available evidence, both direct and indirect, to produce estimates of the relative effects of each treatment compared with others in a network. We developed a de novo decision tree model to estimate the cost-effectiveness of various methods. The costs included were the intervention and other hospital costs incurred (price year 2012–13). We reviewed the literature to identify preference-based utilities for the health-related outcomes in the model. We calculated incremental cost-effectiveness ratios, expected costs, utilities and net benefit. We represent uncertainty in the optimal intervention using cost-effectiveness acceptability curves. Results: We identified 1190 studies; 611 were eligible for inclusion. The interventions most likely to achieve vaginal delivery (VD) within 24 hours were intravenous oxytocin with amniotomy [posterior rank 2; 95% credible intervals (CrIs) 1 to 9] and higher-dose (≥ 50 μg) vaginal misoprostol (rank 3; 95% CrI 1 to 6). Compared with placebo, several treatments reduced the odds of caesarean section, but we observed considerable uncertainty in treatment rankings. For uterine hyperstimulation, double-balloon catheter had the highest probability of being among the best three treatments, whereas vaginal misoprostol (≥ 50 μg) was most likely to increase the odds of excessive uterine activity. For other safety outcomes there were insufficient data or there was too much uncertainty to identify which treatments performed ‘best’. Few studies collected information on women’s views. Owing to incomplete reporting of the VD within 24 hours outcome, the cost-effectiveness analysis could compare only 20 interventions. The analysis suggested that most interventions have similar utility and differ mainly in cost. With a caveat of considerable uncertainty, titrated (low-dose) misoprostol solution and buccal/sublingual misoprostol had the highest likelihood of being cost-effective. Limitations: There was considerable uncertainty in findings and there were insufficient data for some planned subgroup analyses. Conclusions: Overall, misoprostol and oxytocin with amniotomy (for women with favourable cervix) is more successful than other agents in achieving VD within 24 hours. The ranking according to safety of different methods was less clear. The cost-effectiveness analysis suggested that titrated (low-dose) oral misoprostol solution resulted in the highest utility, whereas buccal/sublingual misoprostol had the lowest cost. There was a high degree of uncertainty as to the most cost-effective intervention

Application of the self organizing map in the therapeutic approach of cervical intraepithelial lesions

Nowadays, numerous techniques detecting HPV DNA or mRNA, are viewed as competitors or ancillary techniques to test Papanicolaou. However, no technique is perfect, because sensitivity increases at the cost of specificity. Various methods have been applied to resolve this issue, by using many examination results, such as classification and regression trees and supervised artificial neural networks. In this study, 1258 cases with results from test Pap, HPV DNA, HPV mRNA and p16, were used to evaluate the performance of the Self Organizing Map (SOM), an artificial neural network having three advantages: it is unsupervised, it can tolerate missing data and produces topographical maps. The results of the SOM application were encouraging and leaded to very high sensitivity and specificity for the discrimination of <CIN2 from ≥CIN2 lesions, as these were evaluated histologically (wherever that was possible). Additionally, the produced maps can be helpful in order to detect the important tests for such discrimination.Σήμερα, υπάρχουν πολυάριθμες τεχνικές που ανιχνεύουν HPV DNA ή mRNA και θεωρούνται είτε ανταγωνιστικές είτε επικουρικές ως προς το τεστ Παπανικολάου για τον έλεγχο των κολποτραχηλικών επιχρισμάτων. Ωστόσο, καμία τεχνική δεν είναι τέλεια, επειδή η αύξηση της ευαισθησίας συνεπάγεται ταυτόχρονη μείωση της ειδικότητας. Για την επίλυση αυτού του προβλήματος έχουν εφαρμοστεί στο παρελθόν διάφορες τεχνικές που χρησιμοποιούν αποτελέσματα από πολλές εξετάσεις ταυτόχρονα, όπως δέντρα ταξινόμησης και παλινδρόμησης (Classification and Regression Trees – CARTs) και εποπτευόμενα τεχνητά νευρωνικά δίκτυα. Σε αυτή την εργασία χρησιμοποιήθηκαν 1258 περιπτώσεις με αποτελέσματα από τεστ Παπανικολάου, HPV DNA, HPV mRNA και p16, προκειμένου να αξιολογηθούν οι επιδόσεις του αυτο-οργανούμενου χάρτη (Self Organizing Map – SOM). Το SOM είναι ένα τεχνητό νευρωνικό δίκτυο που παρουσιάζει σημαντικά πλεονεκτήματα σε σχέση με τις άλλες μεθοδολογίες, καθώς δεν είναι επιβλεπόμενο (δηλαδή δεν χρειάζεται να γνωρίζουμε σε ποια ομάδα ανήκουν τα περιστατικά κατά την εκπαίδευσή του), μπορεί να διαχειριστεί ελλιπή δεδομένα (κάτι πολύ συνηθισμένο σε πραγματικές μελέτες) και παράγει τοπογραφικούς χάρτες (έτσι, με εύκολο τρόπο γίνονται συσχετίσεις των σημαντικών παραμέτρων στη διάγνωση). Τα αποτελέσματα της εφαρμογής της τεχνικής αυτής ήταν ενθαρρυντικά και οδήγησαν σε πολύ υψηλή ευαισθησία και ειδικότητα στη διάκριση των αλλοιώσεων <CIN2 από ≥CIN2, όπως αυτές αξιολογήθηκαν με ιστολογική εξέταση (όπου ήταν εφικτό). Επιπλέον, οι παραγόμενοι χάρτες μπορούν να βοηθήσουν στον εντοπισμό των σημαντικών δοκιμασιών (tests) για τη διάκριση μεταξύ περιστατικών <CIN2 από ≥CIN2

The role of inhibin-A, P-selectin and E-selectin in hypertensive disorders of pregnancy

Aim of the study: To report plasma concentrations of the adhesion cell molecules P-selectin and E-selectin and glicoprotein inhibin-A during pregnancy and to determine the effect of subsequent development of hypertension and preeclampsia. Material and method: 81 pregnant women were enrolled in this study; 20 of them, who sudsequently developed preeclampsia, were compared with 16 who developed gestational hypertension and 45 normotensive women with normal obstetric outcome. The determination of plasma soluble P-selectin, E-selectin and inhibin-A levels was performed using a commercial sandwich immunoassay kit. We measured the inhibin-A level, the P selectin level and the E selectin level in all 81 pregnant women. The statistical analysis followed the subsequent methodology. Firstly, the women were distinguished in two groups. a) The normotensive women with normal obstetric outcome were enrolled in the 1st group (n=45) and b) all the hypertensive women in the 2nd group (n=36). Secondly, the group of hypertensive women (n=36) was divided in two subgroups: women who developed preeclampsia were enrolled in the 1st subgroup (n=20) and women who developed gestational hypertension were enrolled in the 2nd subgroup (n=16). Results: According to the findings, inhibin-A and E-selectin concentrations did not have any statistically important difference between normotensive and hypertensive pregnant women. On the contrary, there was a significant difference in P-selectin concentration between normotensive and hypertensive pregnant women (P-selectin concentration was very low in hypertensive pregnant women). In addition, in the second stage of the statistical analysis, inhibin-A and P-selectin concentrations did not have any statistically important difference between preeclamptic and gestational hypertensive women. On the contrary, there was a significant difference in E-selectin concentration between preeclamptic and gestational hypertensive women (E-selectin concentration was very low in hypertensive pregnant women). Conclusions: P-selectin may be used as a marker for hypertensive disorders of pregnancy and E-selectin as a marker for preeclampsia.Σκοπός της μελέτης: Η μελέτη μας στοχεύει στη διερεύνηση του ρόλου της ανασταλτίνης Α (inhibin-Α), της σελεκτίνης P και της σελεκτίνης Ε στην υπερτασική νόσο της εγκυμοσύνης. Υλικό και Μέθοδος: Στη Β΄ Μαιευτική και Γυναικολογική Σχολή της Ιατρικής Σχολής του Πανεπιστημίου Αθηνών στο Αρεταίειο Νοσοκομείο και στη Γ΄ Μαιευτική και Γυναικολογική Σχολή της Ιατρικής Σχολής του Πανεπιστημίου Αθηνών στο Νοσοκομείο Αττικόν μελετήσαμε 81 έγκυες. Οι 33 γυναίκες παρακολουθήθηκαν στο Αρεταίειο Νοσοκομείο. Από αυτές 8 εμφάνισαν απλή υπέρταση κύησης, 16 προεκλαμψία και 9 είχαν φυσιολογική εγκυμοσύνη. Οι υπόλοιπες 48 έγκυες παρακολουθήθηκαν στο Νοσοκομείο Αττικόν. Οι 8 εμφάνισαν απλή υπέρταση κύησης, οι 4 προεκλαμψία και οι 36 είχαν φυσιολογική εγκυμοσύνη. Συνολικά, 20 έγκυες έπασχαν από προεκλαμψία, 16 από απλή υπέρταση της κύησης και 45 ήταν φυσιολογικές μάρτυρες. Στις έγκυες αυτές υπολογίστηκαν οι τιμές της ανασταλτίνης Α, της σελεκτίνης P και της σελεκτίνης Ε. Η στατιστική ανάλυση πραγματοποιήθηκε σε δύο φάσεις. Στην 1η φάση το υλικό χωρίστηκε σε δύο ομάδες. Την πρώτη ομάδα την αποτελούσαν οι μάρτυρες (n=45) και τη δεύτερη οι υπερτασικές έγκυες (n=36). Στη 2η φάση, η ομάδα των υπερτασικών εγκύων (n=36) χωρίστηκε σε δύο κατηγορίες : στην πρώτη συμπεριλήφθηκαν έγκυες που εμφάνισαν προεκλαμψία (n=20) και στη δεύτερη έγκυες που παρουσίασαν μόνο υπέρταση (n=16). Αποτελέσματα: Από τα δικά μας αποτελέσματα προκύπτει ότι στην 1η φάση της μελέτης η ανασταλτίνη Α και η σελεκτίνη Ε δεν παρουσιάζουν στατιστικά σημαντικές διαφορές μεταξύ των φυσιολογικών και υπερτασικών εγκύων, σε αντίθεση με τη σελεκτίνη Ρ, οι τιμές της οποίας βρέθηκαν πολύ χαμηλές στις υπερτασικές εγκύους σε σχέση με τις φυσιολογικές. Στη 2η φάση της μελέτης, η ανασταλτίνη Α και η σελεκτίνη Ρ δεν παρουσίασαν στατιστικά σημαντικές διαφορές μεταξύ των υπερτασικών και προεκλαμπτικών εγκύων. Όμως, οι τιμές της σελεκτίνης Ε βρέθηκαν πολύ χαμηλές στις υπερτασικές εγκύους και πολύ υψηλές στις προεκλαμπτικές. Συμπεράσματα: Δε διαπιστώθηκε ότι υφίσταται σημαντική διαφορά των τιμών της ανασταλτίνης Α μεταξύ των φυσιολογικών, των υπερτασικών και των προεκλαμπτικών εγκύων. Διαπιστώθηκε ότι υφίσταται στατιστικά σημαντική διαφορά των τιμών της σελεκτίνης P μεταξύ των φυσιολογικών και υπερτασικών εγκύων, με τις φυσιολογικές να παρουσιάζουν πολύ υψηλότερες τιμές (cut-off 137ng/mL), με αποτέλεσμα να καθίσταται δυνατός ο χαρακτηρισμός της σελεκτίνης P ως προγνωστικός δείκτης της υπερτασικής νόσου της εγκυμοσύνης. Διαπιστώθηκε στατιστικά σημαντική διαφορά στην τιμή της σελεκτίνης Ε μεταξύ των υπερτασικών και προεκλαμπτικών εγκύων με τις τελευταίες να παρουσιάζουν μεγαλύτερες τιμές (cut off 23,3ng/mL), με αποτέλεσμα να χαρακτηρίζεται ως προγνωστικός δείκτης της προεκλαμψίας όχι όμως της υπέρτασης της κύησης. Συνεπώς, από τους 3 δείκτες που μελετήσαμε, δηλαδή της ανασταλτίνης Α, της σελεκτίνης Ε και της σελεκτίνης P, η σελεκτίνη P μπορεί να χαρακτηριστεί ως προγνωστικός δείκτης της υπερτασικής νόσου της εγκυμοσύνης και η σελεκτίνη Ε αποκλειστικά της προεκλαμψίας