“Either of the Height or of the Depth”: Nanos Valaoritis’ De-stereotyping of the “Greeks” in the Time of Crisis

If there is anyone who has consistently de-stereotyped Greek culture, de-mythologized, de-constructed and ultimately reconstructed its imaginative potential, that person is Nanos Valaoritis who has now been turned into a cosmopolitan “cultural phenomenon.” Always “present” in the Greek scene no matter where he lived (Paris, London, Geneva, Oakland, California or Athens and Nydri), the 96-year old avant-garde Nanos Valaoritis, like a “gadfly,” kept paving the way for new ways of seeing and radical perceptions of the self, especially as dictated by his desire to re-examine the Ancients. Amidst the current crisis, Valaoritis indeed not only is “present” as a public persona, but he also has initiated long debates about the causes and effects of the crisis, especially since his open letter to the Greek Prime Minister Mr. Antonis Samaras, dated April 30, 2013, where he warned him about the dangerous effects of the increasingly appealing Neo-Nazi party Golden Dawn. Moreover, four new books of his came out of the Greek crisis from 2010 to the present: Χρίσματα (2011), Ουρανός χρώμα βανίλιας (2011), Το Πικρό καρναβάλι (2013) and Ή του ύψους ή του βάθους: Πρόσφατα άρθρα γύρω από τον πολιτισμό στην Ελλάδα της κρίσης (2013). This article pays particular attention to the last collection of articles which present Valaoritis’s systematic exploration of the image of the Greeks as standing at the extremes, “either of the height or of the depth,” throughout their long history, in an effort to “eradicate the stereotypes against the Greek nation that so unjustly is deeply tormented,” as the book itself claims. This article not only elaborates on the main points that Valaorits makes in this collection of articles, but more importantly, it contextualizes them within the frame of his overall avant-garde contribution to the Greek Letters

Genetic prediction of ICU hospitalization and mortality in COVID-19 patients using artificial neural networks

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS13). Among 381 variants in 133 patients, we identified 5 critical variants associated with severe COVID-19: rs2547438 (C3), rs2250656 (C3), rs1042580 (THBD), rs800292 (CFH) and rs414628 (CFHR1). Using age, gender and presence or absence of each variant, we developed an ANN predicting morbidity and mortality in 89.47% of the examined population. Furthermore, THBD and C3a levels were significantly increased in severe COVID-19 patients and those harbouring relevant variants. Thus, we reveal for the first time an ANN accurately predicting ICU hospitalization and death in COVID-19 patients, based on genetic variants in complement genes, age and gender. Importantly, we confirm that genetic dysregulation is associated with impaired complement phenotype.- Pfizer Pharmaceuticals(undefined

Υιοθεσία από ομόφυλα ζευγάρια. Σύγχρονα δεδομένα και αντιλήψεις

Εισαγωγή: Η υιοθεσία είναι μια νομική διαδικασία τοποθέτησης ενός παιδιού σε μια νέα οικογένεια. Τα τελευταία χρόνια παρατηρείται αλλαγή προς τη θεσμοθέτηση υιοθεσίας από ομόφυλα ζευγάρια. Σκοπός: Η παρούσα εργασία έχει σκοπό τη διερεύνηση των αλλαγών στις στάσεις και στη μορφή των νέων οικογενειών. Μεθοδολογία: Πραγματοποιήθηκε ανασκόπηση της παρούσας βιβλιογραφίας, από τον Οκτώβρη έως τον Απρίλιο 2018, στις εξής βάσεις δεδομένων : PubMed, Scopus, Cinahl και Cochrane. Αποτελέσματα: Ανευρέθηκαν 383 άρθρα από τα οποία τα 103 ήταν σχετικά με το θέμα καθώς αυτά ανταποκρίνονταν στα κριτήρια ένταξης, δηλαδή να αφορούν σε οικογένειες με ομόφυλους γονείς που υιοθετούν μαζί τουλάχιστον ένα παιδί, 118 οικογένειες ομόφυλων γονέων όπου το παιδί που αναθρέφουν μπορεί να έχει βιολογική σχέση με τον ένα γονέα και υιοθετείται από τον δεύτερο, ενώ αφορούσαν και σε μελέτες παρατήρησης και καταγραφής στάσεων απέναντι στην υιοθεσία από αυτά τα ζευγάρια. Σύμφωνα με τα υπάρχοντα στοιχεία, η απόφαση για τη δημιουργία οικογένειας φαίνεται να προέρχεται από την ανάγκη εκπλήρωσης γονικού ρόλου και την επιθυμία παροχής φροντίδας σε ένα παιδί, με θετικές και αρνητικές συνέπειες στη σχέση των γονέων, όπως συμβαίνει και στις ετερόφυλων γονέων οικογένειες. Τα παιδιά φαίνεται να αναπτύσσονται φυσιολογικά, ενώ παρατηρείται αυξανόμενη θετική στάση απέναντι στα ομόφυλα ζευγάρια. Η υιοθεσία από ομόφυλα ζευγάρια οδηγεί στη δημιουργία μιας νέας μορφής οικογένειας, που φαίνεται να είναι λειτουργική και με θετικές επιπτώσεις στην ψυχοκοινωνική ανάπτυξη του παιδιού. Σημαντικό ρόλο διαδραματίζει η θεσμοθέτηση, καθώς διευκολύνει την κοινωνική αποδοχή και περιορίζει το στιγματισμό και τον ομοφοβικό εκφοβισμό. Συμπεράσματα: Στο κέντρο του ενδιαφέροντος παραμένει το συμφέρον του παιδιού, έτσι χρειάζονται περισσότερες έρευνες σε οικογένειες ομόφυλων γονέων που μεγαλώνουν παιδιά, έρευνες με μεγαλύτερα δείγματα και τυχαιοποίηση. Απαιτείται κοινοποίηση των ερευνητικών αποτελεσμάτων και ευαισθητοποίηση της κοινωνίας, καθώς και αλλαγές στο σχολικό περιβάλλον και στις κοινωνικές υπηρεσίες που ασχολούνται με θέματα υιοθεσίας.Introduction: Adoption consists of a legal process where a child is being part of a new family. Legalization of adoption from same-sex couples is slowly emerging over the past few years. Aim: The purpose of this study is to examine possible changes in the same-sex family as well as the change in attitude of the society towards this new kind of family. Methodology: Α systematic review of English and Greek literature was performed between October to April 2018 in the following databases PubMed, Scopus, Cinahl, and Cochrane. Results: A total of 383 articles were found, 103 of which were selected because they fulfilled the predefined criteria that a same- sex couple should try to adopt, the child could have one biological parent but it must be raised in a same- sex parent family. Another aspect of the study is the attitude towards same- sex adoption. According to the available data, adopting a child is a way to parenthood and also their will to contribute t0 a child in need, with the implications of adoption for the couple whether it is a same- sex one or a different sex couple. A new kind of family is emerging, which seems to be functioning well and to have beneficial effects on adopted children. As for children, they seem to have an ensured well-being. Society seems to be changing its attitude towards same- sex adoption in a 120 positive way. Legalizing same- sex adoption is crucial to social acceptance of these families, as it seems to lower stigma and homophobic bullying Conclusions: The primary goal is to guarantee the interest of the child, so further research is needed on same- sex families that raise children, protocols that involve larger specimens and randomization use. It is crucial that research results be communicated to the public in order to raise awareness of society and take appropriate measures in the school environment and social services dealing with adoption issues to provide better treatment of such families

High versus Standard Intensity of Thromboprophylaxis in Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis

Thromboprophylaxis in hospitalized patients with COVID-19 has been associated with a survival benefit and is strongly recommended. However, the optimal dose of thromboprophylaxis remains unclear. A systematic review and meta-analysis (PubMed/EMBASE) of studies comparing high (intermediate or therapeutic dose) versus standard (prophylactic dose) intensity of thrombo-prophylaxis with regard to outcome of hospitalized patients with COVID-19 was performed. Randomized and non-randomized studies that provided adjusted effect size estimates were included. Meta-analysis of 7 studies comparing intermediate versus prophylactic dose of thromboprophylaxis (2 randomized and 5 observational, n = 2009, weighted age 61 years, males 61%, ICU 53%) revealed a pooled adjusted relative risk (RR) for death at 0.56 (95% confidence intervals (CI) 0.34, 0.92) in favor of the intermediate dose. For the same comparison arms, the pooled RR for venous thromboembolism was 0.84 (95% CI 0.54, 1.31), and for major bleeding events was 1.63 (95% CI 0.79, 3.37). Meta-analysis of 17 studies comparing therapeutic versus prophylactic dose of thromboprophylaxis (2 randomized and 15 observational, n = 7776, weighted age 64 years, males 54%, ICU 21%) revealed a pooled adjusted RR for death at 0.73 (95% CI 0.47, 1.14) for the therapeutic dose. An opposite trend was observed in the unadjusted analysis of 15 observational studies (RR 1.24 (95% CI 0.88, 1.74)). For the same comparison arms, the pooled RR for venous thromboembolism was 1.13 (95% CI 0.52, 2.48), and for major bleeding events 3.32 (95% CI 2.51, 4.40). In conclusion, intermediate compared with standard prophylactic dose of thromboprophylaxis appears to be rather safe and is associated with additional survival benefit, although most data are derived from observational retrospective analyses. Randomized studies are needed to define the optimal thromboprophylaxis in hospitalized patients with COVID-19

High versus Standard Intensity of Thromboprophylaxis in Hospitalized Patients with COVID-19: A Systematic Review and Meta-Analysis

Thromboprophylaxis in hospitalized patients with COVID-19 has been associated with a survival benefit and is strongly recommended. However, the optimal dose of thromboprophylaxis remains unclear. A systematic review and meta-analysis (PubMed/EMBASE) of studies comparing high (intermediate or therapeutic dose) versus standard (prophylactic dose) intensity of thrombo-prophylaxis with regard to outcome of hospitalized patients with COVID-19 was performed. Randomized and non-randomized studies that provided adjusted effect size estimates were included. Meta-analysis of 7 studies comparing intermediate versus prophylactic dose of thromboprophylaxis (2 randomized and 5 observational, n = 2009, weighted age 61 years, males 61%, ICU 53%) revealed a pooled adjusted relative risk (RR) for death at 0.56 (95% confidence intervals (CI) 0.34, 0.92) in favor of the intermediate dose. For the same comparison arms, the pooled RR for venous thromboembolism was 0.84 (95% CI 0.54, 1.31), and for major bleeding events was 1.63 (95% CI 0.79, 3.37). Meta-analysis of 17 studies comparing therapeutic versus prophylactic dose of thromboprophylaxis (2 randomized and 15 observational, n = 7776, weighted age 64 years, males 54%, ICU 21%) revealed a pooled adjusted RR for death at 0.73 (95% CI 0.47, 1.14) for the therapeutic dose. An opposite trend was observed in the unadjusted analysis of 15 observational studies (RR 1.24 (95% CI 0.88, 1.74)). For the same comparison arms, the pooled RR for venous thromboembolism was 1.13 (95% CI 0.52, 2.48), and for major bleeding events 3.32 (95% CI 2.51, 4.40). In conclusion, intermediate compared with standard prophylactic dose of thromboprophylaxis appears to be rather safe and is associated with additional survival benefit, although most data are derived from observational retrospective analyses. Randomized studies are needed to define the optimal thromboprophylaxis in hospitalized patients with COVID-19

mRNA expression of specific HER ligands and their association with clinical outcome in patients with metastatic breast cancer treated with trastuzumab

Prognostic and predictive biomarkers are being studied for the diagnosis and treatment of breast cancer. The present study retrospectively assessed the mRNA expression of HER family receptor ligands and of other potential prognostic biomarkers and their association with time to progression (TTP), survival and clinicopathological characteristics in patients with metastatic breast cancer (MBC) treated with trastuzumab. A total of 145 tumour tissue samples were analysed. mRNA expression analysis of the transcripts of interest was performed and the association of these markers with selected clinicopathological parameters was examined. HER2 status was centrally re-evaluated. Only 67.6% of patients were truly HER2-positive according to the central HER2 re-evaluation. Heparin binding epidermal growth factor (EGF)-like growth factor, transforming growth factor beta 1 (TGFB1) and thyroid hormone receptor alpha (THRA) mRNA expression was higher in HER2-positive patients (P=0.026, P<0.001 and P<0.001). Insulin-like growth factor binding protein 4 was correlated with retinoic acid receptor alpha, TGFB1 and THRA (rho=0.45, rho=0.60 and rho=0.45). In HER2-positive patients, high neuregulin 1 and high betacellulin were unfavourable factors for TTP [hazard ratio (HR) = 1.78, P=0.040 and HR=2.00, P=0.043, respectively]. In patients with de novo MBC, high EGF expression was associated with a non-significant prolongation of TTP (HR=0.52, P=0.080) and significantly longer survival (HR=0.40, P=0.020). The present study examined clinical and biological implications of specific genes and it was concluded that their expression has an impact on the outcome of trastuzumab-treated patients with MBC

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

Efficacy and safety of early soluble urokinase plasminogen receptor plasma-guided anakinra treatment of COVID-19 pneumonia: a subgroup analysis of the SAVE-MORE randomised trialResearch in context

Summary: Background: The SAVE-MORE trial demonstrated that anakinra treatment in COVID-19 pneumonia with plasma soluble urokinase plasminogen activator (suPAR) levels of 6 ng/mL or more was associated with 0.36 odds for a worse outcome compared to placebo when expressed by the WHO-Clinical Progression Scale (CPS) at day 28. Herein, we report the results of subgroup analyses and long-term outcomes. Methods: This prospective, double-blind, randomised clinical trial, recruited patients with a confirmed SARS-CoV-2 infection, in need of hospitalisation, lower respiratory tract infection and plasma suPAR ≥6 ng/mL from 37 academic and community hospitals in Greece and Italy. Patients were 1:2 randomised to subcutaneous treatment with placebo or anakinra (100 mg) once daily for 10 days. Pre-defined subgroups of Charlson's comorbidity index (CCI), sex, age, level of suPAR, and time from symptom onset were analysed for the primary endpoint (overall comparison of distribution of frequencies of the scores from the WHO-CPS between treatments on day 28), by multivariable ordinal regression analysis in the intention to treat (ITT) population. This trial is registered with the EU Clinical Trials Register (2020-005828-11) and ClinicalTrials.gov (NCT04680949). Findings: Patients were enrolled between 23 December 2020 and 31 March 2021; 189 patients in the placebo arm and 405 patients in the anakinra arm were the ITT population. Multivariable analysis showed that anakinra treatment was accompanied by significantly lower odds for worse outcome compared to placebo at day 28 for all studied subgroups (CCI ≥ 2, OR: 0.34, 95% confidence intervals [CI] 0.22–0.50; CCI 9 ng/mL, OR: 0.35, 95% CI 0.19–0.66; suPAR 6–9 ng/mL, OR: 0.35, 95% CI 0.24–0.52; patients ≥65 years, OR: 0.41, 95% CI 0.25–0.66; and patients <65 years, OR: 0.29, 95% CI 0.19–0.45). The benefit was uniform, irrespective of the time from start of symptoms until the start of the study drug. At days 60 and 90, anakinra treatment had odds of 0.40 (95% CI 0.28–0.57) and 0.46 (95% CI 0.32–0.67) respectively, for a worse outcome compared to placebo. The costs of general ward stay, ICU stay, and drugs were lower with anakinra treatment. Interpretation: Anakinra represents an important therapeutic tool in the management of COVID-19 that may be administered in all subgroups of patients; benefits are maintained until day 90. Funding: Hellenic Institute for the Study of Sepsis; Swedish Orphan Biovitrum AB

Genetic prediction of ICU hospitalization and mortality in COVID-19 patients using artificial neural networks

There is an unmet need of models for early prediction of morbidity and mortality of Coronavirus disease-19 (COVID-19). We aimed to a) identify complement-related genetic variants associated with the clinical outcomes of ICU hospitalization and death, b) develop an artificial neural network (ANN) predicting these outcomes and c) validate whether complement-related variants are associated with an impaired complement phenotype. We prospectively recruited consecutive adult patients of Caucasian origin, hospitalized due to COVID-19. Through targeted next-generation sequencing, we identified variants in complement factor H/CFH, CFB, CFH-related, CFD, CD55, C3, C5, CFI, CD46, thrombomodulin/THBD, and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS13). Among 381 variants in 133 patients, we identified 5 critical variants associated with severe COVID-19: rs2547438 (C3), rs2250656 (C3), rs1042580 (THBD), rs800292 (CFH) and rs414628 (CFHR1). Using age, gender and presence or absence of each variant, we developed an ANN predicting morbidity and mortality in 89.47% of the examined population. Furthermore, THBD and C3a levels were significantly increased in severe COVID-19 patients and those harbouring relevant variants. Thus, we reveal for the first time an ANN accurately predicting ICU hospitalization and death in COVID-19 patients, based on genetic variants in complement genes, age and gender. Importantly, we confirm that genetic dysregulation is associated with impaired complement phenotype