Varicella-zoster virus infections in immunocompromised patients - a single centre 6-years analysis

Background: Infection with varicella-zoster virus (VZV) contemporaneously with malignant disease or immunosuppression represents a particular challenge and requires individualized decisions and treatment. Although the increasing use of varicella-vaccines in the general population and rapid initiation of VZVimmunoglobulins and acyclovir in case of exposure has been beneficial for some patients, immunocompromised individuals are still at risk for unfavourable courses. Methods: In this single center, 6-year analysis we review incidence, hospitalization and complication rates of VZVinfections in our center and compare them to published data. Furthermore, we report three instructive cases. Results: Hospitalization rate of referred children with VZV-infections was 45%, among these 17% with malignancies and 9% under immunosuppressive therapy. Rate of complications was not elevated in these two high-risk cohorts, but one ALL-patient died due to VZV-related complications. We report one 4-year old boy with initial diagnosis of acute lymphoblastic leukemia who showed a rapidly fatal outcome of his simultaneous varicella-infection, one 1.8-year old boy with an identical situation but a mild course of his disease, and an 8.5-year old boy with a steroiddependent nephrotic syndrome. This boy developed severe hepatic involvement during his varicella-infection but responded to immediate withdrawl of steroids and administration of acyclovir plus single-dose cidofovir after nonresponse to acyclovir after 48 h. Conclusion: Our data show that patients with malignant diseases or immunosuppressive therapy should be hospitalized and treated immediately with antiviral agents. Despite these measures the course of VZV-infections can be highly variable in these patients. We discuss aids to individual decision-making for these difficult situations

The frequency of new-onset type 1 diabetes in pediatric population during the COVID-19 pandemic

Πολλές προηγούμενες μελέτες έχουν δείξει ότι η πανδημία CΟVID-19 έχει επηρεάσει τη συχνότητα εμφάνισης διαβήτη τύπου 1 και/ή διαβητικής κετοξέωσης στον παιδιατρικό πληθυσμό. Αυτή η μελέτη στοχεύει να διερευνήσει εάν η λοίμωξη από τον SARS-CoV-2 έχει οδηγήσει σε αύξηση της διαβητικής κετοξέωσης και/ή του διαβήτη τύπου 1 μεταξύ παιδιών και εφήβων, καθώς και να επισημάνει πιθανούς παράγοντες που μπορεί να συνέβαλαν σε αυτήν την αύξηση. Μέσα από τις βάσεις δεδομένων Scopus και PubMed αναζητήθηκαν μελέτες που διερευνούν τη συχνότητα εμφάνισης DKA και νεοεμφανιζόμενου διαβήτη τύπου 1 σε παιδιατρικούς ασθενείς κατά τη διάρκεια της πανδημίας COVID-19 σε σχέση με την περίοδο προ της πανδημίας.Background Several previous studies suggest that the Covid-19 pandemic has affected the incidence of new-onset type 1 Diabetes and/or diabetic ketoacidosis in the pediatric population. This study aims to investigate whether SARS-CoV-2 infection has led to an increase in DKA and/or T1D among children and adolescents but also to highlight possible factors that may have contributed to this rise. Methods Scopus and PubMed were broadly searched for studies investigating the incidence of DKA and new-onset type 1 diabetes among pediatric patients between the COVID‐19 pre‐pandemic and pandemic periods. Results This systematic review included 40 studies from different countries worldwide and findings revealed a significant increase in new‐onset T1D rate and DKA diagnoses among the pediatric population during the Covid-19 years compared to the prior-to-COVID-19 period. Conclusions The increase in the incidence of pediatric new‐onset T1D and DKA diagnosis worldwide during the COVID‐19 pandemic could be related to a delay in the presentation and the diagnosis of T1D and also to a lack of awareness of typical DKA or T1D symptoms. Considering the potential correlation between Sars-CoV-2 infection and the development of T1DM, long-term follow-up studies are required to investigate a possible link between the COVID-19 pandemic and the incidence of T1D

Περιγεννητικές ψυχικές διαταραχές

Ο βασικός σκοπός αυτής της διπλωματικής εργασίας είναι να προβάλλει όσο πιο λεπτομερώς γίνεται τις ψυχικές διαταραχές που μπορεί να εμφανιστούν κατά την κύηση έως και τον πρώτο χρόνο μετά την γέννα. Είναι σημαντικό να αναφερθεί η ανάγκη για περισσότερες μελέτες και η ενημέρωση για την πρόληψη, την διάγνωση, τα συμπτώματα και την θεραπεία των περιγεννητικών ψυχικών διαταραχών, όπως αυτή αναλύεται μέσα από την διερεύνηση της συναφής βιβλιογραφίας. Μέσα από την παρούσα εργασία επιχειρείται να δοθεί έμφαση στην διαφορική διάγνωση των ψυχικών διαταραχών, καθώς ενέχουν ίδια συμπτώματα με αυτά της κύησης. Στον ψυχισμό της εγκύου επιδρούν ποικίλοι παράγοντες εκτός της κύησης, οι οποίοι παρουσιάζουν διαφορές σε κάθε περίπτωση. Η ανάλυση της αιτίας των περιγεννητικών ψυχικών διαταραχών αποδεικνύεται από την μελέτη των παραγόντων κινδύνου εμφάνισης μια ψυχικής διαταραχής, τομέας που διατηρεί κύρια θέση στην παρούσα εργασία. Επιπρόσθετα, δεν μπορεί να λείπει η σημαντικότητα μια κατάλληλης θεραπείας που εξατομικεύεται σε κάθε περίπτωση (Flynn et al., 2004). Η μετάβαση στη γονεικότητα είναι αδιάψευστα εξαιρετική στιγμή της ζωής της γυναίκας. Η γέννηση ενός παιδιού αν και κατά κύριο λόγο συνδέεται με συναισθήματα χαράς και ευτυχίας, κάποιες φορές μπορεί να φέρει στην επιφάνεια συναισθηματικές διαταραχές, που μπορεί να προκαλέσουν δυσκολίες στην μετάβαση στη γονεικότητα (O’ Hara και Swain, 1996). Τέλος, σύμφωνα με όσα αναφέρει ο Πλάτων: «είναι υψίστης σημασίας να προσέχει κανείς τις γυναίκες ιδιαίτερα κατά της διάρκεια της κύησης, ώστε να μην βρεθεί ούτε με πολλές οδύνες, ούτε με πολλά πάθη, ούτε με λύπες, αλλά να διανύει αυτή τη περίοδο, τιμώντας την, με χαρά και καλή ψυχική διάθεση» (Πλάτων νόμοι, 792 Ε).The main aim of this dissertation is to present in a thorough way the psychic dimensions of the perinatal period, especially that of the perinatal mental disorders. It seeks to highlight and stress the need for additional research and information about the symptoms, prognosis, and diagnosis as well as the approach-treatment of mental disorders that may appear during pregnancy and the postpartum period, through a review of the relevant, contemporary, international-literature. It attempts to emphasize issues of clinical and social interest that are very often being confused or overlooked, due to the common symptoms they share with pregnancy itself. It finds that the mental health of pregnant women is affected by many factors other than pregnancy itself that vary from case to case. The analysis of the factors plays a fundamental role in this study, highlighting the broad spectrum of the causes of perinatal mental disorders as well as underlining its importance during the process of identifying an appropriate personalised approach-treatment (Flynn et al., 2004) The period of maternity is undoubtedly an important aspect in the life of a woman. Pregnancy and giving birth are complex events that are accompanied by biological, social, and emotional changes. Even though in most cases they are accompanied by feelings of happiness and fulfillment, they may sometimes cause psycho-emotional issues and subsequent difficulties in adapting to parenthood (O’ Hara και Swain, 1996). To end, as Plato says: “women with child, above all others, should be cared for during their years of pregnancy, lest any of them should indulge in repeated and intense pleasures or pains, instead of cultivating, during the whole of that period, a cheerful, bright and calm demeanor” (Plato, Laws, 792E)

Young systemic factors as a medicine for age-related neurodegenerative diseases

It is widely known that neurogenesis, brain function and cognition decline with aging. Increasing evidence suggests that cerebrovascular dysfunction is a major cause of cognitive impairment in the elderly but is also involved in age-related neurodegenerative diseases. Finding ways and molecules that reverse this process and ameliorate age- and disease-related cognitive impairment by targeting vascular and neurogenic deterioration would be of great therapeutic value. In Katsimpardi et al. we reported that young blood has a dual beneficial effect in the aged brain by restoring age-related decline in neurogenesis as well as inducing a striking remodeling of the aged vasculature and restoring blood flow to youthful levels. Additionally, we identified a youthful systemic factor, GDF11 that recapitulates these beneficial effects of young blood. We believe that the identification of young systemic factors that can rejuvenate the aged brain opens new roads to therapeutic intervention for neurodegenerative diseases by targeting both neural stem cells and neurogenesis as well as at the vasculature

Regulation of neurogenesis in the adult and aging brain

International audienceNeural stem cells (NSCs) represent a remarkable developmental unit, necessary for the proper functioning of neurogenesis, by retaining their plasticity to self-renew and give rise to progeny throughout life in specific regions of the adult brain. Although NSCs were thought to merely represent a stem cell type in the brain, recent advances have demonstrated the incredible complexity of NSC identity and functions. Ranging between quiescence, activation and intermediary subtypes, NSCs choose their fate through their developmental inheritance, regional positioning within the niche, as well as dynamic transcriptional and metabolic states. The plasticity of their developmental program is reflected in the tremendous changes they undergo upon external environmental cues and extrinsic manipulations, and harnessing these potentials can open new avenues to fight against brain injury, neurodegenerative and age-related diseases

Congenital cytomegalovirus infection alters olfaction prior to hearing deterioration in mice

The odorant mixtures are the subject of a patent application (EP3245944 published on November 22, 2017) by Institut Pasteur, Centre National de la Recherche Scientifique, and Assistance Publique–Hôpitaux de Paris on which F.L., P.-M.L., N.T., and S.L. are named as inventors. The remaining authors declare no competing financial interests.International audienceIn developed countries, cytomegalovirus (CMV)-infected newborns are at high risk of developing sensorineural handicaps such as hearing loss, requiring extensive follow-up. However, early prognostic tools for auditory damage in children are not yet available. In the fetus, CMV infection leads to early olfactory bulb (OB) damage, suggesting that olfaction might represent a valuable prognosis for neurological outcome of this viral infection. Here, we demonstrate that in utero CMV inoculation causes fetal infection and growth retardation in mice of both sexes. It disrupts OB normal development, leading to disproportionate OB cell layers and rapid major olfactory deficits. Olfaction is impaired as early as day 6 after birth in both sexes, long before the emergence of auditory deficits. Olfactometry in males reveals a long-lasting alteration in olfactory perception and discrimination, particularly in binary mixtures of monomolecular odorants. Although sensory inputs to the OB remain unchanged, hallmarks of autophagy are increased in the OB of 3-postnatal week-old mice, leading to local neuroinflammation and loss of neurons expressing tyrosine hydroxylase and calbindin. At the cellular level, we found CMV-infected cells and an increased number of apoptotic cells scattered throughout the OB layers, whereas cell proliferation in the neurogenic subventricular zone was decreased. These cellular observations were long-lasting, persisting up to 16 weeks after birth in both males and females and thus providing a mechanism supporting olfactory loss. Despite obvious differences in neurogenesis between human and mouse, these findings offer new strategies aimed at early detection of neurological dysfunctions caused by congenital infections.SIGNIFICANCE STATEMENT In developed countries, congenital cytomegalovirus (CMV)-infected newborns are at high risk of developing sensory handicaps such as hearing loss, thus requiring prolonged follow-up. In this study, we describe for the first time the functional impact of congenital CMV infection on the olfactory system and its associated sense of smell. We demonstrate that a mouse model of congenital CMV infection shows defects in olfactory bulb (OB) normal development and pronounced olfactory deficits affecting acuity and discrimination of odorants. These major olfactory deficits occur long before the emergence of auditory deficits through the upregulation of OB autophagy inducing local neuroinflammation and altered neuron content. Our findings provide new opportunities for designing olfactory means to monitor the possible neurological outcome during congenital CMV infection