Καρκίνος του μαστού κατά την κύηση

Στην παρούσα διπλωματική εργασία εξετάζεται εκτενώς ο μαστός καθώς και οι παθήσεις αυτού, όπως ο καρκίνος. Ο μαστός είναι ένα εξαιρετικά ευαίσθητο και πολύπλοκο όργανο γι’ αυτό η δομή και η λειτουργία του μπορούν να επηρεαστούν από ενδογενείς και εξωγενείς παράγοντες, όπως το κληρονομικό ιστορικό, το περιβάλλον διαβίωσης, διατροφή και συνήθειες του ατόμου κλπ. Οι απεικονιστικές μέθοδοι σε συνδυασμό με την κλινική εξέταση, συμβάλλουν στην άμεση διάγνωση και θεραπεία της εκάστοτε πάθησης. Ανάλογα πάντα με τον βαθμό σοβαρότητας και εξέλιξης της βλάβης, επιλέγεται η κατάλληλη θεραπεία, η οποία θα είναι είτε φαρμακευτική, είτε συντηρητική είτε χειρουργική. Αναφέρονται επίσης και λύσεις για τη διατήρηση της γονιμότητας της γυναίκας πριν από οποιαδήποτε θεραπεία. Σύμφωνα με νέες μελέτες η εξέλιξη στην θεραπεία του καρκίνου μαστού είναι η ανοσοθεραπεία η οποία έχει τις λιγότερο δυνατές συνέπειες στον οργανισμό της γυναίκας καθώς και εκπληκτικά αποτελέσματα έναντι του καρκίνου. Ο συνδυασμός οποιασδήποτε πάθησης του μαστού, ιδιαίτερα του καρκίνου, με την κύηση δυσχεραίνει ακόμα περισσότερο την αντιμετώπισή του. Σε ο, τι αφορά την διάγνωση, οι εξετάσεις που μπορούν να γίνουν για την εκτίμηση της βλάβης του μαστού είναι περιορισμένες λόγω της υπάρχουσας κύησης. Ακόμα πιο περιορισμένες είναι οι επιλογές της θεραπείας λόγω ενδεχόμενης βλάβης του εμβρύου. Με τις όλο και περισσότερο εξελισσόμενες στον τομέα του καρκίνου έρευνες, πλέον η διάγνωση και η θεραπεία μπορεί να γίνει πιο εύκολα και γρήγορα χωρίς να κινδυνεύει το έμβρυο. Μην ξεχνάμε όμως ότι ο καρκίνος μαστού στην κύηση είναι μία πολύ δύσκολη κατάσταση διότι η γυναίκα εκτός από την ασθένειά της θα πρέπει να ανησυχεί και για το έμβρυό της. Για το λόγο αυτό θα πρέπει να έχει ψυχολογική στήριξη καθ’ όλη τη διάρκεια της κύησης αλλά και μετέπειτα.Regarding this dissertation, the breast is examined extensively as well as all of its diseases, such as cancer. The breast is an extremely sensitive and complicated organ that is why its structure and function can be affected by intrinsic and extrinsic factors, such as the hereditary background, the living environment, the nutrition and the daily habits of the person. All the essential tests, in combination with the clinical examination, contribute to the immediate diagnosis and the treatment of the specific disease. Suitable intervention must be chosen depending on the seriousness and the development of the damage, which is going to be either pharmaceutical, conventional or surgical. Moreover, there are some solutions referred to the preservation of woman’s fertility before any kind of treatment. According to new researches, the evolution in the cure of breast cancer is immunotherapy which has less possible effects to the organism of a woman and amazing results against cancer. The combination of any breast disease, especially the cancer one, with pregnancy makes its effectiveness even more difficult. As far as the diagnosis is concerned, the tests that can be runfor the evaluation of the damage of the breast are limited due to pregnancy. With all the more developed researches in the sector of cancer, both the diagnosis and the treatment can be done faster and easier without setting the embryo in danger. We should bear in mind though, that breast cancer throughout pregnancy is a very difficult situation to cope with, since the woman has to worry, besides her disease, about her baby as well. For this reason, she should have psychological support, not only throughout her pregnancy but after she gives birth as well

A Multimodal Approach for the Risk Prediction of Intensive Care and Mortality in Patients with COVID-19

Background: Although several studies have been launched towards the prediction of risk factors for mortality and admission in the intensive care unit (ICU) in COVID-19, none of them focuses on the development of explainable AI models to define an ICU scoring index using dynamically associated biological markers. Methods: We propose a multimodal approach which combines explainable AI models with dynamic modeling methods to shed light into the clinical features of COVID-19. Dynamic Bayesian networks were used to seek associations among cytokines across four time intervals after hospitalization. Explainable gradient boosting trees were trained to predict the risk for ICU admission and mortality towards the development of an ICU scoring index. Results: Our results highlight LDH, IL-6, IL-8, Cr, number of monocytes, lymphocyte count, TNF as risk predictors for ICU admission and survival along with LDH, age, CRP, Cr, WBC, lymphocyte count for mortality in the ICU, with prediction accuracy 0.79 and 0.81, respectively. These risk factors were combined with dynamically associated biological markers to develop an ICU scoring index with accuracy 0.9. Conclusions: to our knowledge, this is the first multimodal and explainable AI model which quantifies the risk of intensive care with accuracy up to 0.9 across multiple timepoints

A Multimodal Approach for the Risk Prediction of Intensive Care and Mortality in Patients with COVID-19

Background: Although several studies have been launched towards the prediction of risk factors for mortality and admission in the intensive care unit (ICU) in COVID-19, none of them focuses on the development of explainable AI models to define an ICU scoring index using dynamically associated biological markers. Methods: We propose a multimodal approach which combines explainable AI models with dynamic modeling methods to shed light into the clinical features of COVID-19. Dynamic Bayesian networks were used to seek associations among cytokines across four time intervals after hospitalization. Explainable gradient boosting trees were trained to predict the risk for ICU admission and mortality towards the development of an ICU scoring index. Results: Our results highlight LDH, IL-6, IL-8, Cr, number of monocytes, lymphocyte count, TNF as risk predictors for ICU admission and survival along with LDH, age, CRP, Cr, WBC, lymphocyte count for mortality in the ICU, with prediction accuracy 0.79 and 0.81, respectively. These risk factors were combined with dynamically associated biological markers to develop an ICU scoring index with accuracy 0.9. Conclusions: to our knowledge, this is the first multimodal and explainable AI model which quantifies the risk of intensive care with accuracy up to 0.9 across multiple timepoints

Cysteine-scanning Analysis of Helices TM8, TM9a, and TM9b and Intervening Loops in the YgfO Xanthine Permease: A CARBOXYL GROUP IS ESSENTIAL AT ASP-276

Bacterial and fungal members of the ubiquitous nucleobase-ascorbate transporter (NAT/NCS2) family use the NAT signature motif, a conserved 11-amino acid sequence between amphipathic helices TM9a and TM9b, to define function and selectivity of the purine binding site. To examine the role of flanking helices TM9a, TM9b, and TM8, we employed Cys-scanning analysis of the xanthine-specific homolog YgfO from Escherichia coli. Using a functional mutant devoid of Cys residues (C-less), each amino acid residue in sequences 259FLVVGTIYLLSVLEAVGDITATAMVSRRPIQGEEYQSRLKGGVLADGLVSVIASAV314 and 342TIAVMLVILGLFP354 including these TMs (underlined) was replaced individually with Cys, except the irreplaceable Glu-272 and Asp-304, which had been studied previously. Of 67 single Cys mutants, 55 accumulate xanthine to 35–140% of the steady state observed with C-less, five (I265C, D276C, I277C, G299C, L350C) accumulate to low levels (10–20%) and seven (T278C, A279C, T280C, A281C, G305C, G351C, P354C) show negligible expression in the membrane. Extensive mutagenesis reveals that a carboxyl group is needed at Asp-276 for high activity and that D276E differs from wild type as it recognizes 8-methylxanthine (Ki 79 μm) but fails to recognize 2-thioxanthine, 3-methylxanthine or 6-thioxanthine; bulky replacements of Ala-279 or Thr-280 and replacements of Gly-305, Gly-351, or Pro-354 impair activity or expression. Single Cys mutants V261C, A273C, G275C, and S284C are sensitive to inactivation by N-ethylmaleimide and sensitivity of G275C (IC50 15 μm) is enhanced in the presence of substrate. The data suggest that residues crucial for the transport mechanism cluster in two conserved motifs, at the cytoplasmic end of TM8 (EXXGDXXAT) and in TM9a (GXXXDG)

Patients Hospitalized for COVID-19 in the Periods of Delta and Omicron Variant Dominance in Greece: Determinants of Severity and Mortality

Background: Coronavirus disease 2019 (COVID-19) has been a pandemic since 2020, and depending on the SARS-CoV-2 mutation, different pandemic waves have been observed. The aim of this study was to compare the baseline characteristics of patients in two phases of the pandemic and evaluate possible predictors of mortality. Methods: This is a retrospective multicenter observational study that included patients with COVID-19 in 4 different centers in Greece. Patients were divided into two groups depending on the period during which they were infected during the Delta and Omicron variant predominance. Results: A total of 979 patients (433 Delta, 546 Omicron) were included in the study (median age 67 years (54, 81); 452 [46.2%] female). Compared to the Omicron period, the patients during the Delta period were younger (median age [IQR] 65 [51, 77] vs. 70 [55, 83] years, p p = 0.001), had higher procalcitonin levels (ng/mL): 0.08 [0.05, 0.17] vs. 0.06 [0.02, 0.16], p = 0.005, ferritin levels (ng/mL): 301 [159, 644] vs. 239 [128, 473], p = 0.002, C- reactive protein levels (mg/L): 40.4 [16.7, 98.5] vs. 31.8 [11.9, 81.7], p = 0.003, and lactate dehydrogenase levels (U/L): 277 [221, 375] vs. 255 [205, 329], p p p 2/FiO2 ratio on admission were identified as independent predictors of mortality for patients in the Omicron period. Conclusions: In the Omicron wave, patients were older with a higher number of comorbidities, but patients with the Delta variant had more severe disease and a longer duration of hospitalization

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population