Ofeleein i mi Vlaptin-Volume II: Immunity Following Infection or mRNA Vaccination, Drug Therapies and Non-Pharmacological Management at Post-Two Years SARS-CoV-2 Pandemic.

The persistence of the coronavirus disease 2019 (COVID-19) pandemic has triggered research into limiting transmission, morbidity and mortality, thus warranting a comprehensive approach to guide balanced healthcare policies with respect to people's physical and mental health. The mainstay priority during COVID-19 is to achieve widespread immunity, which could be established through natural contact or vaccination. Deep knowledge of the immune response combined with recent specific data indicates the potential inferiority of induced immunity against infection. Moreover, the prevention of transmission has been founded on general non-pharmacological measures of protection, albeit debate exists considering their efficacy and, among other issues, their socio-psychological burden. The second line of defense is engaged after infection and is supported by a plethora of studied agents, such as antibiotics, steroids and non-steroid anti-inflammatory drugs, antiviral medications and other biological agents that have been proposed, though variability in terms of benefits and adverse events has not allowed distinct solutions, albeit certain treatments might have a role in prevention and/or treatment of the disease. This narrative review summarizes the existing literature on the advantages and weaknesses of current COVID-19 management measures, thus underlining the necessity of acting based on the classical principle of "ofeleein i mi vlaptin", that is, to help or not to harm

Does COVID-19 Vaccination Warrant the Classical Principle " ofelein i mi vlaptin"?

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic warrants an imperative necessity for effective and safe vaccination, to restrain Coronavirus disease 2019 (COVID-19) including transmissibility, morbidity, and mortality. In this regard, intensive medical and biological research leading to the development of an arsenal of vaccines, albeit incomplete preconditioned evaluation, due to emergency. The subsequent scientific gap raises some concerns in the medical community and the general public. More specifically, the accelerated vaccine development downgraded the value of necessary pre-clinical studies to elicit medium- and long-term beneficial or harmful consequences. Previous experience and pathophysiological background of coronaviruses' infections and vaccine technologies, combined with the global vaccines' application, underlined the obligation of a cautious and qualitative approach, to illuminate potential vaccination-related adverse events. Moreover, the high SARS-CoV-2 mutation potential and the already aggregated genetical alterations provoke a rational vagueness and uncertainty concerning vaccines' efficacy against dominant strains and the respective clinical immunity. This review critically summarizes existing evidence and queries regarding SARS-CoV-2 vaccines, to motivate scientists' and clinicians' interest for an optimal, individualized, and holistic management of this unprecedented pandemic

Neonatal Sepsis and Hemostasis

Neonatal sepsis is considered critical for a significant increase in neonatal morbidity and mortality among hospitalized neonates. Neonatal sepsis, in most cases, coexists with coagulopathy, which can prove to be life-threatening. Complex molecular and cellular systems are involved in the cross-talk between inflammation and hemostasis during sepsis. Disturbances in the regulating systems of the vascular endothelium, and platelet–endothelial and platelet–neutrophil interactions play a pivotal role in both inflammation and coagulation. This complex process is poorly understood in neonates. In addition to the developmental maturation of hemostasis and the immune response in neonatal sepsis, a cellular model of hemostasis during sepsis should be taken into account. This review focused on the molecular and cellular mechanisms underlying inflammation and hemostasis during neonatal sepsis, taking the developmental immune response and developmental hemostasis into account in order to provide future diagnostic approaches to be applied in everyday clinical settings. Regarding the diagnostic modalities, we briefly provide the limitations of the currently used conventional coagulation assays, focusing on viscoelastic tests and platelet flow cytometry

Haemostasis assessment in septic neonates by using thromboelastometry and flow cytometry

Neonatal sepsis is frequently accompanied by coagulopathy and thrombocytopenia attributed to the cross-link between inflammation and coagulation. However, sepsis-induced coagulopathy and platelet function in septic preterm neonates remain to be elucidated. In addition, there is no robust evidence for a causal relationship between thrombocytopenia and bleeding in preterm neonates with sepsis. This single-center prospective cohort study aimed to assess sepsis-induced coagulopathy and platelet function in preterm neonates during sepsis. We included twenty eight preterm neonates with sepsis and studied in comparison to thirty healthy counterparts. Coagulation was assessed using conventional coagulation tests (CCTs) and rotational thromboelastometry (ROTEM). Platelet function was evaluated by flow cytometry. The study was conducted at 3-time points, at first, at second to third, and at fith to seventh day of sepsis, respectively. Compared with healthy controls, neonates with Gram-positive sepsis present in ROTEM a hypercoagulable state; a higher maximum clot firmness and higher amplitudes of intrinsic rotational thromboelastometry, extrinsic rotational thromboelastometry and rotational thromboelastometry assay for fibrin formation. Conversely, CCTs exhibited hypocoagulation. Thrombocytopenia in preterm neonates with Gram-positive sepsis is not associated with an increased bleeding risk. In Gram-positive sepsis, platelets display increased glycoprotein (GP) surface receptors’ expression and reduced activation. A higher expression of platelets GP and improved degranulation capacity were recorded in patients in higher gestational age groups of above thirty two weeks of gestation. Platelet GPIb expression is age-dependent in healthy neonates. Neonates with Gram-negative sepsis compared with those of Gram-positive sepsis displayed hypocoagulable state with reduced values in the relevant ROTEM assays and similarly reduced platelet GP expression and degranulation. Thrombocytopenia in preterm neonates with Gram-negative sepsis is associated with increased bleeding risk. Conventional coagulation tests showed hypocoagulable state in all patients compared with their healthy counterparts. Neonatal Gram-positive sepsis is characterized by a progressive hypercoagulation along with increased GP expression, reduced platelet activation, and thrombocytopenia without bleeding. Platelet GP expression and degranulation capacity are age-dependent among neonates with sepsis. Platelet GP expression is age-dependent among healthy counterparts. Hypocoagulable profile, thrombocytopenia along with platelet impairment and bleeding are observed in patients with gram negative sepsis and disseminated intravascular coagulation. Conventional coagulation tests present low sensitivity in discrimination of hypercoagulability.Η νεογνική σήψη συχνά επιπλέκεται με διαταραχές της αιμόστασης και θρομβοπενία, τα οποία αποδίδονται στην αλληλεπίδραση της φλεγμονής και του ενεργοποιημένου πηκτικού μηχανισμού. Ωστόσο, οι διαταραχές της αιμόστασης και της λειτουργικότητας των αιμοπεταλίων που επάγονται από τη σήψη σε πρόωρα νεογνά δεν έχουν επαρκώς μελετηθεί. Επιπλέον, δεν υπάρχει επαρκής τεκμηρίωση της αιτιολογικής συσχέτισης θρομβοπενίας και αιμορραγικής διάθεσης σε πρόωρα νεογνά κατά τη διάρκεια νεογνικής σήψης. Σκοπός αυτής της μονοκεντρικής, προοπτικής μελέτης παρατήρησης είναι η εκτίμηση των διαταραχών της αιμόστασης και της λειτουργικότητας των αιμοπεταλίων σε πρόωρα νεογνά κατά τη διάρκεια σήψης. Συμπεριλήφθηκαν είκοσι οκτώ πρόωρα νεογνά με σήψη και μελετήθηκαν συγκριτικά με τριάντα αντίστοιχα υγιή νεογνά. Ο πηκτικός μηχανισμός εκτιμήθηκε με συμβατικό έλεγχο πήξης και θρομβοελαστομετρία. Η λειτουργικότητα των αιμοπεταλίων εκτιμήθηκε με κυτταρομετρία ροής. Η μελέτη διεξήχθη σε τρείς χρονικές στιγμές, στο πρώτο, δεύτερο με τρίτο και στο πέμπτο με έβδομο εικοσιτετράωρο της σήψης αντίστοιχα. Συγκριτικά με τα υγιή νεογνά, είκοσι πέντε νεογνά με σήψη από Gram θετικά βακτήρια εμφάνισαν στη θρομβοελαστομετρία υπερπηκτικότητα με υψηλότερες τιμές μέγιστης σταθερότητας θρόμβου και εύρους θρόμβου στην έκθεση του ενδογενούς, εξωγενούς και του ινωδογόνου αντίστοιχα. Κατά τη διάρκεια της σήψης από Gram θετικά βακτήρια τα αιμοπετάλια των ασθενών παρουσιάζουν αυξημένη έκφραση των επιφανειακών γλυκοπρωτεινικών υποδοχέων και μειωμένη αποκοκκίωση. Αυξημένη έκφραση των υποδοχέων και βελτιωμένη ικανότητα αποκοκκίωσης εμφανίζουν τα αιμοπετάλια σε ασθενείς με διάρκεια κύησης μεγαλύτερη των τριάντα δύο εβδομάδων. Η θρομβοπενία στα πρόωρα νεογνά με σήψη από Gram θετικά βακτήρια δεν σχετίζεται με αυξημένο κίνδυνο αιμορραγίας. Συγκριτικά με τη σήψη από Gram θετικά βακτήρια, τα τρία νεογνά με σήψη από Gram αρνητικά βακτήρια εμφάνισαν υποπηκτικότητα στη θρομβοελαστομετρία στις αντίστοιχες εκθέσεις με μειωμένες τιμές των αντίστοιχων παραμέτρων και μειωμένη έκφραση υποδοχέων και μειωμένη αποκοκκίωση των αιμοπεταλίων. Η θρομβοπενία στα πρόωρα νεογνά με Gram αρνητική σήψη σχετίζεται με αυξημένο κίνδυνο αιμορραγίας. Στην εκτίμηση με τις συμβατικές μεθόδους όλα τα νεογνά εμφάνισαν υποπηκτικότητα συγκριτικά με τα υγιή. Στα υγιή πρόωρα νεογνά η έκφραση των GPIb υποδοχέων αυξάνει με την αύξηση της διάρκειας κύησης. Συμπερασματικά, η σήψη από Gram θετικά βακτήρια στα πρόωρα νεογνά χαρακτηρίζεται από προοδευτικά αυξανόμενη υπερπηκτικότητα, αυξανόμενη ικανότητα προσκόλλησης αλλά μειωμένη ικανότητα ενεργοποίησης των αιμοπεταλίων και θρομβοπενία χωρίς αιμορραγική διάθεση. Η σήψη από Gram αρνητικά βακτήρια στα πρόωρα νεογνά χαρακτηρίζεται από υποπηκτικότητα, μειωμένη λειτουργικότητα των αιμοπεταλίων και θρομβοπενία με αυξημένο κίνδυνο αιμορραγίας. Η λειτουργικότητα των αιμοπεταλίων βελτιώνεται με την αύξηση της διάρκειας κύησης σε ασθενή και υγιή πρόωρα νεογνά. Ο συμβατικός έλεγχος πήξης παρουσιάζει χαμηλή ευαισθησία στην ανάδειξη καταστάσεων υπερπηκτικότητας

Alzheimer's disease and gastrointestinal microbiota; impact of Helicobacter pylori infection involvement

Background: Alzheimer disease (AD) is a leading cause of global burden with great impact on societies. Although research is working intensively on promising therapy, the problem remains up-to-date. Among the various proposed hypotheses regarding causality and therapy, emerging evidence supports the hypothesis that gastrointestinal microbiota through the so-called 'gut-brain axis' interacts with immune system and brain and shape the balance between homeostasis and disease; the involvement of gastrointestinal microbiota in the pathophysiology of AD is less defined, even though the role of 'gut-brain axis' has been well verified for other neurodegenerative conditions.Methods: We performed a systematic review of PubMed/MEDLINE database from 1$^{st}$ January 1990 to 17$^{th}$ October 2018, to investigate the accessible literature regarding possible association between AD and gastrointestinal microbiota. Inclusion criteria were available full text in English language, original clinical papers implicating AD patients and any sort of gastrointestinal microbiota.Results: Through our query, an initial number of 241 papers has been identified. After removing duplicates and through an additional manual search, twenty-four papers met our inclusion criteria. The great majority of eligible publications supported a possible connection between AD and gastrointestinal microbiota. The most common investigated microorganism was Helicobacter pylori.Conclusion: Our own systematic review, showed a possible association between AD and gastrointestinal microbiota mainly including Helicobacter pylori, and thus further research is required for substantiation of causality as well as for the establishment of promising novel therapies

Osteomyelitis and Thrombosis in a Newborn with Group A Streptococcus Infection

Neonatal osteomyelitis (OM), although exceptionally rare, has been linked to detrimental sequel, as diagnosis in the early stages is challenging and any delay in treatment can lead to disturbance in skeletal growth. In pediatric OM the most commonly grown bacteria is Staphylococcus aureus followed by group A Streptococcus (GAS). Notwithstanding, sepsis-induced coagulopathy is a well-known entity in children and adults, still sepsis-associated thrombosis is sparsely observed. we present a case of a newborn with GAS associated OM and thrombosis. A term neonate on the 11th day of life was referred to our NICU due to right (R) lower limb edema, cyanosis and core temperature up to 39 °C. Late onset sepsis was suspected and started on vancomycin and amikacin. A colour Doppler scan showed thrombosis of the R common femoral vein. The neonate started on iv unfractionated heparin. Ampicillin was added given positive for GAS blood culture. An MRI on the 5th day of admission, showed evidence of thrombosis resolution. On the 14th day of admission, a bone Tc99 scan showed evidence of OM of R femur. Antibiotic treatment switched to amoxicillin per os. The management was restricted to anticoagulant therapy with low molecular weight heparin for 3 months and antibiotic therapy for 6 months without surgery intervention and the patient recovered and discharged at 42 days of age. Early diagnosis and treatment of neonatal osteomyelitis can prevent bone destruction. Sepsis-associated thrombosis is barely observed during osteomyelitis, yet it should be considered as an emerged case requiring prompt treatment

Acute Liver Failure: From Textbook to Emergency Room and Intensive Care Unit With Concomitant Established and Modern Novel Therapies.

Acute liver failure is a rare hepatic emergent situation that affects primarily young people and has often a catastrophic or even fatal outcome. Definition of acute liver failure has not reached a universal consensus and the interval between the appearance of jaundice and hepatic encephalopathy for the establishment of the acute failure is a matter of debate. Among the wide variety of causes, acetaminophen intoxication in western societies and viral hepatitis in the developing countries rank at the top of the etiology list. Identification of the clinical appearance and initial management for the stabilization of the patient are of vital significance. Further advanced therapies, that require intensive care unit, should be offered. The hallmark of treatment for selected patients can be orthotopic liver transplantation. Apart from well-established treatments, novel therapies like hepatocyte or stem cell transplantation, additional new therapeutic strategies targeting acetaminophen intoxication and/or hepatic encephalopathy are mainly experimental, and some of them do not belong, yet, to clinical practice. For clinicians, it is substantial to have the alertness to timely identify the patient and transfer them to a specialized center, where more treatment opportunities are available

Thromboelastometry in Neonates with Respiratory Distress Syndrome: A Pilot Study

Background: Although respiratory distress syndrome (RDS) constitutes a postnatal risk factor for bleeding and thromboembolic events in neonates, few studies have addressed this issue. We aimed to evaluate the hemostatic profile of neonates with RDS using rotational thromboelastometry (ROTEM). Methods: An observational study was conducted from November 2018 to November 2020 in the NICU of General Hospital of Nikaia “Aghios Panteleimon”. Preterm and term neonates with RDS hospitalized in the NICU were included and EXTEM (tissue factor-triggered extrinsic pathway), INTEM (ellagic acid activated intrinsic pathway), and FIBTEM (with platelet inhibitor cytochalasin D) assays were performed at the onset of the disease. Results: A hypocoagulable profile was noted in neonates with RDS compared to controls, expressed as significant prolongation of EXTEM CT (clotting time) and CFT (clot formation time), lower EXTEM A10 (amplitude at 10 min), MCF (maximum clot firmness), and LI60 (lysis index). Furthermore, prolongation of INTEM CFT and FIBTEM CT, and decreased INTEM and FIBTEM A10 and MCF were found in neonates with RDS. Multivariable logistic regression analysis showed that RDS is an independent factor for the recorded alterations in ROTEM variables. Conclusions: RDS is associated with a hypocoagulable profile and greater hyperfibrinolytic potential compared to healthy neonates

Thromboelastometry in Neonates with Respiratory Distress Syndrome: A Pilot Study.

BACKGROUND: Although respiratory distress syndrome (RDS) constitutes a postnatal risk factor for bleeding and thromboembolic events in neonates, few studies have addressed this issue. We aimed to evaluate the hemostatic profile of neonates with RDS using rotational thromboelastometry (ROTEM). METHODS: An observational study was conducted from November 2018 to November 2020 in the NICU of General Hospital of Nikaia "Aghios Panteleimon". Preterm and term neonates with RDS hospitalized in the NICU were included and EXTEM (tissue factor-triggered extrinsic pathway), INTEM (ellagic acid activated intrinsic pathway), and FIBTEM (with platelet inhibitor cytochalasin D) assays were performed at the onset of the disease. RESULTS: A hypocoagulable profile was noted in neonates with RDS compared to controls, expressed as significant prolongation of EXTEM CT (clotting time) and CFT (clot formation time), lower EXTEM A10 (amplitude at 10 min), MCF (maximum clot firmness), and LI60 (lysis index). Furthermore, prolongation of INTEM CFT and FIBTEM CT, and decreased INTEM and FIBTEM A10 and MCF were found in neonates with RDS. Multivariable logistic regression analysis showed that RDS is an independent factor for the recorded alterations in ROTEM variables. CONCLUSIONS: RDS is associated with a hypocoagulable profile and greater hyperfibrinolytic potential compared to healthy neonates