Development and validation of serum bilirubin nomogram to predict the absence of risk for severe hyperbilirubinaemia before discharge: a prospective, multicenter study

Early discharge of healthy late preterm and full term newborn infants has become common practice because of the current social and economic necessities. Severe jaundice, and even kernicterus, has developed in some term infants discharged early. This study was designed to elaborate a percentile-based hour specific total serum bilirubin (TSB) nomogram and to assess its ability to predict the absence of risk for subsequent non physiologic severe hyperbilirubinaemia before discharge

The Changing Landscape of Neonatal Diabetes Mellitus in Italy Between 2003 and 2022

Context In the last decade the Sanger method of DNA sequencing has been replaced by next-generation sequencing (NGS). NGS is valuable in conditions characterized by high genetic heterogeneity such as neonatal diabetes mellitus (NDM).Objective To compare results of genetic analysis of patients with NDM and congenital severe insulin resistance (c.SIR) identified in Italy in 2003-2012 (Sanger) vs 2013-2022 (NGS).Methods We reviewed clinical and genetic records of 104 cases with diabetes onset before 6 months of age (NDM + c.SIR) of the Italian dataset.Results Fifty-five patients (50 NDM + 5 c.SIR) were identified during 2003-2012 and 49 (46 NDM + 3 c.SIR) in 2013-2022. Twenty-year incidence was 1:103 340 (NDM) and 1:1 240 082 (c.SIR) live births. Frequent NDM/c.SIR genetic defects (KCNJ11, INS, ABCC8, 6q24, INSR) were detected in 41 and 34 probands during 2003-2012 and 2013-2022, respectively. We identified a pathogenic variant in rare genes in a single proband (GATA4) (1/42 or 2.4%) during 2003-2012 and in 8 infants (RFX6, PDX1, GATA6, HNF1B, FOXP3, IL2RA, LRBA, BSCL2) during 2013-2022 (8/42 or 19%, P = .034 vs 2003-2012). Notably, among rare genes 5 were recessive. Swift and accurate genetic diagnosis led to appropriate treatment: patients with autoimmune NDM (FOXP3, IL2RA, LRBA) were subjected to bone marrow transplant; patients with pancreas agenesis/hypoplasia (RFX6, PDX1) were supplemented with pancreatic enzymes, and the individual with lipodystrophy caused by BSCL2 was started on metreleptin.Conclusion NGS substantially improved diagnosis and precision therapy of monogenic forms of neonatal diabetes and c.SIR in Italy

The Silent Epidemic of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Children and Adolescents in Italy During the COVID-19 Pandemic in 2020

To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019

Deep structure of Pyrenees range (SW Europe) imaged by joint inversion of gravity and teleseismic delay time

International audienceWe present a new model of the lithosphere and asthenosphere structure down to 300 km depth beneath the Pyrenees from the joint inversion of recent gravity and teleseismic data. Unlike previous studies, crustal correction was not applied on teleseismic data in order (i) to preserve the consistency between gravity data, which are mainly sensitive to the density structure of the crust lithosphere, and traveltime data, and (ii) to avoid the introduction of biases resulting from crustal reductions. The density model down to 100 km depth is preferentially used here to discuss the lithospheric structure of the Pyrenees, whereas the asthenospheric structure from 100 to 300 km depth is discussed from our velocity model. The absence of a high density anomaly in our model between 30 and 100 km depth (except the Labourd density anomaly) in the northern part of the Pyrenees seems to preclude eclogitization of the subducted Iberian crust at the scale of the entire Pyrenean range. Local eclogitization of the deep Pyrenean crust beneath the western part of the Axial Zone (west of Andorra) associated with the positive central density anomaly is proposed. The Pyrenean lithosphere in density and velocity models appears segmented from east to west. No clear relation between the along-strike segmentation and mapped major faults is visible in our models. The Pyrenees’ lithosphere segments are associated with different seismicity pattern in the Pyrenees suggesting a possible relation between the deep structure of the Pyrenees and its seismicity in the upper crust. The concentration of earthquakes localized just straight up the central density anomaly can reflect the subsidence and/or delamination of an eclogitized Pyrenean deep root. The velocity model in the asthenosphere is similar to previous studies. The absence of a high-velocity anomaly in the upper mantle and transition zone (i.e. 125 to 225 km depth) seems to preclude the presence of a detached oceanic lithosphere beneath the European lithosphere

p66Shc gene has a pro-apoptotic role in human cell lines and it is activated by a p53-independent pathway

p66Shc protein has been proposed to be an indispensable factor for p53-dependent, mitochondria-mediated apoptosis in mice. Here, we show that p66Shc plays a pro-apoptotic role also in cell lines of human origin such as SaOs-2 and HeLa, where p53 is either absent or inactivated, thus, suggesting that p66Shc pro-apoptotic role is independent from the presence of a functional form of p53. The active form of p66Shc is phosphorylated in Serine 36. We confirm the importance of Serine 36 phosphorylation for p66Shc pro-apoptotic role, and our results suggest that the kinase involved in this process is activated independently from p53. © 2006 Elsevier Inc. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The Utility and Safety of a Continuous Glucose Monitoring System (CGMS) in Asphyxiated Neonates during Therapeutic Hypothermia

Background: The present study was designed to assess the feasibility and reliability of a Continuous Glucose Monitoring System (CGMS) in a population of asphyxiated neonates during therapeutic hypothermia. Methods: This non-randomized feasibility study was conducted in the Neonatal Intensive Care Unit (NICU) facilities of Fondazione Policlinico A. Gemelli IRCSS. Infants matching the criteria for hypothermic treatment were included in this study and were connected to the CGMS (Medtronic, Northridge, CA, USA) within the first 12 h of life. Hypoglycemia was defined as a glucose value ≤ 47 mg/dL, and hyperglycemia was defined as a glucose value ≥ 180 mg/dL. Data obtained via the CGMS were compared with those obtained via a point-of-care blood glucometer (GTX). Results: The two measuring techniques were compared using the Modified Clarke Error Grid (MCEG). Sixteen infants were enrolled. The sensor had an average (standard deviation) duration of 93 (38) h. We collected 119 pairs of glycemia values (CGMVs) from the CGMS vs. GTX measurements. The CGMS detected twenty-five episodes of hypoglycemia and three episodes of hyperglycemia. All the CGMVs indicating hyperglycemia matched with the blood sample taken via the point-of-care glucometer. Conclusions: The use of a CGMS would be useful as it could detect more episodes of disglycemia than standard care. Our data show poor results in terms of the accuracy of the CGMS in this particular setting

p66shc is highly expressed in fibroblasts from centenarians

p66shc-/- mice exhibit prolonged lifespan and increased resistance to oxidative and hypoxic stress. To investigate p66shc involvement in human longevity, p66shc mRNA and protein were evaluated in fibroblasts from young people, elderly and centenarians, exposed to oxidative or hypoxic stress. Unexpectedly, centenarians showed the highest basal levels of p66shc. Oxidative stress induced p66shc in all samples. At variance, hypoxic stress caused p66shc reduction only in cells from centenarians. These changes occurred in absence of any modification of p66shc promoter methylation pattern. Intriguingly, in cells from centenarians, p66shc induction was affected by p53 codon 72 polymorphism. Thus, cells from centenarians present a peculiar regulation of p66shc, suggesting that its role in mammalian longevity is more complex than previously thought. © 2005 Elsevier Ireland Ltd. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A Machine Learning Approach for Postoperative Outcome Prediction: Surgical Data Science Application in a Thoracic Surgery Setting

The use of innovative methodologies, such as Surgical Data Science (SDS), based on artificial intelligence (AI) could prove to be useful for extracting knowledge from clinical data overcoming limitations inherent in medical registries analysis. The aim of the study is to verify if the application of an AI analysis to our database could develop a model able to predict cardiopulmonary complications in patients submitted to lung resection

Trends and Cyclic Variation in the Incidence of Childhood Type 1 Diabetes in Two Italian Regions Over 33 Years and During The Covid-19 Pandemic

Aims: There is conflicting evidence about the impact of the COVID-19 pandemic on the incidence of type 1 diabetes. Here we analyzed long-term trends in the incidence of type 1 diabetes in Italian children and adolescents from 1989 to 2019 and compared the incidence observed during the COVID-19 pandemic with that estimated from long-term data. Materials and methods: This was a population-based incidence study using longitudinal data from two diabetes registries in mainland Italy. Trends in the incidence of type 1 diabetes from 1 January 1989 through 31 December 2019 were estimated using Poisson and segmented regression models. Results: There was a significant increasing trend in the incidence of type 1 diabetes of 3.7% per year (95%CI 2.4-4.9) between 1989 and 2003, a breakpoint in 2003, and then a constant incidence until 2019 (0.5%, 95%CI -0.01-2.4). There was a significant four-year cycle in incidence over the entire study period. The rate observed in 2021 (26.7, 95%CI 23.0-30.9) was significantly higher than expected (19.5, 95%CI 17.6-21.4; p = 0.010). Conclusion: Long-term incidence analysis showed an unexpected increase in new cases of type 1 diabetes in 2021. The incidence of type 1 diabetes now needs continuous monitoring using population registries to better understand the impact of COVID-19 on new-onset type 1 diabetes in children. This article is protected by copyright. All rights reserved