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"De Luca, Daniele"
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Transplacental transmission of SARS-CoV-2 infection
2020
SARS-CoV-2 outbreak is the first pandemic of the century. SARS-CoV-2 infection is transmitted through droplets; other transmission routes are hypothesized but not confirmed. So far, it is unclear whether and how SARS-CoV-2 can be transmitted from the mother to the fetus. We demonstrate the transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise. The transmission is confirmed by comprehensive virological and pathological investigations. In detail, SARS-CoV-2 causes: (1) maternal viremia, (2) placental infection demonstrated by immunohistochemistry and very high viral load; placental inflammation, as shown by histological examination and immunohistochemistry, and (3) neonatal viremia following placental infection. The neonate is studied clinically, through imaging, and followed up. The neonate presented with neurological manifestations, similar to those described in adult patients.
Congenital infection of SARS-CoV-2 has been described, but the transmission routes remain unclear. Here, the authors report evidence of transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise.
Journal Article
Resolving cryptic species complexes in marine protists: phylogenetic haplotype networks meet global DNA metabarcoding datasets
2021
Marine protists have traditionally been assumed to be lowly diverse and cosmopolitan. Yet, several recent studies have shown that many protist species actually consist of cryptic complexes of species whose members are often restricted to particular biogeographic regions. Nonetheless, detection of cryptic species is usually hampered by sampling coverage and application of methods (e.g. phylogenetic trees) that are not well suited to identify relatively recent divergence and ongoing gene flow. In this paper, we show how these issues can be overcome by inferring phylogenetic haplotype networks from global metabarcoding datasets. We use the
Chaetoceros curvisetus
(Bacillariophyta) species complex as study case. Using two complementary metabarcoding datasets (Ocean Sampling Day and Tara Oceans), we equally resolve the cryptic complex in terms of number of inferred species. We detect new hypothetical species in both datasets. Gene flow between most of species is absent, but no barcoding gap exists. Some species have restricted distribution patterns whereas others are widely distributed. Closely related taxa occupy contrasting biogeographic regions, suggesting that geographic and ecological differentiation drive speciation. In conclusion, we show the potential of the analysis of metabarcoding data with evolutionary approaches for systematic and phylogeographic studies of marine protists.
Journal Article
Porcine versus bovine surfactant therapy for RDS in preterm neonates: pragmatic meta-analysis and review of physiopathological plausibility of the effects on extra-pulmonary outcomes
2020
Background
While porcine seems to be superior to bovine surfactants in terms of respiratory outcomes, it is unclear if a surfactant can improve extra-pulmonary outcomes in preterm neonates with respiratory distress syndrome and if there is any physiopathological/biological mechanism linking surfactant therapy to these outcomes. We aim to fill these knowledge gaps.
Methods
Systematic and pragmatic review coupled with meta-analysis of randomized controlled trials of bovine or porcine surfactants administered to treat RDS in preterm neonates; common extra-pulmonary neonatal intensive care outcomes were considered. As additional analysis, animal or human translational studies about mechanisms linking surfactant replacement to extra-pulmonary neonatal outcomes were also systematically reviewed.
Results
Porcine surfactant is associated with lower incidence of patent
ductus arteriosus
(OR:0.655; 95%CI:0.460–0.931);
p
= 0.018; 12 trials; 1472 patients); prenatal steroids (coeff.:-0.009, 95%CI:-0.03–0.009,
p
= 0.323) and gestational age (coeff.:0.079, 95%CI:-0.18–0.34,
p
= 0.554) did not influence this effect size. No significant differences were found between porcine and bovine surfactants on neonatal intensive care unit length of stay (mean difference (days):-2.977; 95%CI:-6.659–0.705;
p
= 0.113; 8 trials; 855 patients), intra-ventricular hemorrhage of any grade (OR:0.860; 95%CI:0.648–1.139);
p
= 0.293; 15 trials; 1703 patients), severe intra-ventricular hemorrhage (OR:0.852; 95%CI:0.624–1.163);
p
= 0.313; 15 trials; 1672 patients), necrotizing entero-colitis (OR:1.190; 95%CI:0.785–1.803);
p
= 0.412; 9 trials; 1097 patients) and retinopathy of prematurity (OR:0.801; 95%CI:0.480–1.337);
p
= 0.396; 10 trials; 962 patients).
Conclusions
Physiopathological mechanisms explaining the effect of surfactant have been found for patent
ductus arteriosus
only, while they are lacking for all other endpoints. Porcine surfactant is associated with lower incidence of PDA than bovine surfactants. As there are no differences in terms of other extra-pulmonary outcomes and no physiopathological plausibility, these endpoints should not be used in future trials.
Registration
PROSPERO n.
CRD42018100906
.
Journal Article
Empirical evidence for concerted evolution in the 18S rDNA region of the planktonic diatom genus Chaetoceros
by
Kooistra, Wiebe H. C. F.
,
Biffali, Elio
,
Piredda, Roberta
in
631/181/735
,
631/208/182
,
631/208/728
2021
Concerted evolution is a process of homogenisation of repetitive sequences within a genome through unequal crossing over and gene conversion. This homogenisation is never fully achieved because mutations always create new variants. Classically, concerted evolution has been detected as “noise” in electropherograms and these variants have been characterised through cloning and sequencing of subsamples of amplified products. However, this approach limits the number of detectable variants and provides no information about the abundance of each variant. In this study, we investigated concerted evolution by using environmental time-series metabarcoding data, single strain high-throughput sequencing (HTS) and a collection of Sanger reference barcode sequences. We used six species of the marine planktonic diatom genus
Chaetoceros
as study system. Abundance plots obtained from environmental metabarcoding and single strain HTS showed the presence of a haplotype far more abundant than all the others (the “dominant” haplotype) and identical to the reference sequences of that species obtained with Sanger sequencing. This distribution fitted best with Zipf’s law among the rank abundance/ dominance models tested. Furthermore, in each strain 99% of reads showed a similarity of 99% with the dominant haplotype, confirming the efficiency of the homogenisation mechanism of concerted evolution. We also demonstrated that minor haplotypes found in the environmental samples are not only technical artefacts, but mostly intragenomic variation generated by incomplete homogenisation. Finally, we showed that concerted evolution can be visualised inferring phylogenetic networks from environmental data. In conclusion, our study provides an important contribution to the understanding of concerted evolution and to the interpretation of DNA barcoding and metabarcoding data based on multigene family markers.
Journal Article
Synthesis and systematic review of reported neonatal SARS-CoV-2 infections
by
Vauloup-Fellous, Christelle
,
Benachi, Alexandra
,
Loi, Barbara
in
692/308/174
,
692/308/3187
,
Betacoronavirus - genetics
2020
A number of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections have been reported in neonates. Here, we aim to clarify the transmission route, clinical features and outcomes of these infections. We present a meta-analysis of 176 published cases of neonatal SARS-CoV-2 infections that were defined by at least one positive nasopharyngeal swab and/or the presence of specific IgM. We report that 70% and 30% of infections are due to environmental and vertical transmission, respectively. Our analysis shows that 55% of infected neonates developed COVID-19; the most common symptoms were fever (44%), gastrointestinal (36%), respiratory (52%) and neurological manifestations (18%), and lung imaging was abnormal in 64% of cases. A lack of mother–neonate separation from birth is associated with late SARS-CoV-2 infection (OR 4.94 (95% CI: 1.98–13.08),
p
= 0.0002; adjusted OR 6.6 (95% CI: 2.6–16),
p
< 0.0001), while breastfeeding is not (OR 0.35 (95% CI: 0.09–1.18),
p
= 0.10; adjusted OR 2.2 (95% CI: 0.7–6.5),
p
= 0.148). Our findings add to the literature on neonatal SARS-CoV-2 infections.
There are a growing number of reports of neonatal SARS-CoV-2 infections. Here, De Luca and colleagues systematically analyse 176 published cases to better understand the route of transmission, as well as the clinical features and outcomes of neonatal COVID-19.
Journal Article
Randomised al.Phase 2b trial of rhIGF-1/rhIGFBP-3 (OHB-607) for bronchopulmonary dysplasia prevention in preterm neonates: study protocol
by
Bonadies, Luca
,
Hirano, Shinya
,
Bancalari, Eduardo
in
Angiogenesis
,
Bronchopulmonary Dysplasia - prevention & control
,
Clinical Trials, Phase II as Topic
2026
IntroductionBronchopulmonary dysplasia (BPD) is the most common complication of prematurity, characterised by impaired alveolarisation and pulmonary vascular development. BPD has been associated with an increased risk of respiratory morbidity, neurodevelopmental impairment and death, intensifying a lifelong health and economic burden. The current standard of neonatal care is primarily supportive, with no approved therapies to restore lung development, promote maturation and lung growth or prevent long-term sequelae. Therefore, there is a critical unmet need for novel interventions, particularly in high-risk, extremely premature (EP) infants. In EP infants, serum insulin-like growth factor-1 (IGF-1) levels decrease rapidly and remain low for the first weeks after birth relative to the corresponding foetal levels in utero.Methods and analysisOHB-607, a recombinant human IGF-1 combined with its binding protein-3, may replenish IGF-1 during this period of deficiency and support lung and vascular maturation. OHB-607 is being investigated as a first-line therapy to prevent severe BPD in EP infants in a Phase 2b, multicentre, open-label, randomised trial. Here, we present the Phase 2b study protocol. Target enrolment is 338 EP infants. To mimic physiological IGF-1 levels in utero, OHB-607 will be administered starting within 24 hours of birth until 29+6 weeks postmenstrual age (PMA) via continuous intravenous infusion. The primary endpoint is the incidence of severe BPD, based on the modified National Institute of Child Health and Human Development criteria, or death by 36 weeks PMA. Key secondary endpoints include weaning from respiratory support at 12 months corrected age and BPD severity (Grade 2/3) by the 2019 Neonatal Research Network definition. Other secondary endpoints include other complications of prematurity, neurodevelopmental outcomes and family and infant well-being and social functioning through 24 months’ corrected age, and pharmacokinetic and dynamic impact of OHB-607 on the multisystem consequences of prematurity, and overall safety in modifying the natural history of BPD and its consequences.Ethics and disseminationFindings will be disseminated via local and international congresses and publications.Trial registration numberClinicalTrials.gov (NCT03253263), Clinicaltrialsregister.eu (EudraCT: 2018-001393-16), Euclinicaltrials.eu (EUCT: 2024-515914-41-00) and Pmda.go.jp (PMDA: jRCT2031240339).
Journal Article
“Playing it SAFE in the NICU” SAFE-R: a targeted diagnostic ultrasound protocol for the suddenly decompensating infant in the NICU
2022
Rapid diagnosis of sudden, unexpected, and potentially fatal complications in the neonatal intensive care unit (NICU) is essential for the initiation of prompt and life-saving management. Point-of-care ultrasound (POCUS) protocols are widely used in adult emergency situations to diagnose and guide treatment, but none has been specifically developed for the neonate. We propose a targeted diagnostic ultrasound protocol for the suddenly decompensating infant in the NICU for rapid screening for the most common life-threatening complications needing immediate attention. We integrated current knowledge on the use of POCUS for diagnosis of the most critical neonatal complications into the “SAFE-R protocol” (Sonographic Assessment of liFe-threatening Emergencies — Revised). The ultrasound algorithm was evaluated at the bedside for suitability and ease of use. Main features of SAFE-R are the use of standardized ultrasound points and a simple one-probe rule-in/rule-out approach. The flowchart is designed by order of urgency and priority is given to treatable causes. Hence, ruling out cardiac tamponade is the first step in the decision tree, followed by pneumothorax, pleural effusion, then acute critical aortic occlusion, acute abdominal complications, and severe intraventricular hemorrhage.
Conclusion
: SAFE-R is the first ultrasound algorithm specifically conceived for use in the NICU to screen for the most common urgent neonatal complications leading to sudden deterioration, thereby providing critical information within minutes. The simplified and rapid approach is designed for the neonatologist and is easy to learn and quick to perform.
What is Known:
• The fields of neonatal and pediatric critical care are undergoing a transformation with the adoption of POCUS and the recent publication of the first international guidelines on POCUS for critically ill children and neonates.
• Targeted emergency ultrasound protocols are widely used in adult emergency and critical care medicine, but specific and adapted ultrasound algorithms are lacking for the pediatric and neonatal population.
What is New:
• We propose the first targeted ultrasound protocol specifically designed for the suddenly decompensating infant in the NICU for rapid screening of the most common life-threatening complications needing immediate attention.
• The SAFE-R ultrasound algorithm integrates current knowledge on ultrasound diagnosis of the most critical neonatal complications into a simple and easy-to-perform emergency scanning protocol aimed to guide initial management and resuscitation efforts.
Journal Article
International evidence-based guidelines on Point of Care Ultrasound (POCUS) for critically ill neonates and children issued by the POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC)
by
Cortes, Rafael Gonzalez
,
Lang, Hans-Joerg
,
Tissieres, Pierre
in
Agreements
,
Cardiac function
,
Children
2020
Background
Point-of-care ultrasound (POCUS) is nowadays an essential tool in critical care. Its role seems more important in neonates and children where other monitoring techniques may be unavailable. POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) aimed to provide evidence-based clinical guidelines for the use of POCUS in critically ill neonates and children.
Methods
Creation of an international Euro-American panel of paediatric and neonatal intensivists expert in POCUS and systematic review of relevant literature. A literature search was performed, and the level of evidence was assessed according to a GRADE method. Recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLA voting method. AGREE statement was followed to prepare this document.
Results
Panellists agreed on 39 out of 41 recommendations for the use of cardiac, lung, vascular, cerebral and abdominal POCUS in critically ill neonates and children. Recommendations were mostly (28 out of 39) based on moderate quality of evidence (B and C).
Conclusions
Evidence-based guidelines for the use of POCUS in critically ill neonates and children are now available. They will be useful to optimise the use of POCUS, training programs and further research, which are urgently needed given the weak quality of evidence available.
Journal Article