Use and Efficacy of I-Gel in Complicated Intubations in Newborn Infants: A Review of Case Reports in the Literature.

INTRODUCTION: Current guidelines for neonatal resuscitation suggest the use of a laryngeal mask when ventilation with both facemask and endotracheal tube has failed in newborns weighing >2000 g or delivered ≥ 34 weeks of gestation age. Paediatric I-gel® is one of the latest supraglottic airway management devices suitable for children and newborns. I-gel® use was effective in guaranteeing adequate ventilation in patients with anatomic abnormalities in case of respiratory impairment or during surgical procedures after the induction of anaesthesia. OBJECTIVE: The purpose of our review was to evaluate the use and efficacy of I-gel® in case of complicated intubations. METHODS: In July 2023, two authors of this paper independently conducted searches of the MEDLINE, Web of Science, and Scopus databases without imposing any time constraints or other restrictions. Three case reports were included, each describing the use of I-gel® device in difficult intubations in newborns with anatomical abnormalities. RESULTS: No difficulties were reported in the insertion of the device, which was placed even by inexperienced clinicians. CONCLUSION: The data collected highlighted the possibility of using I-gel® not only as a rescue device after attempted and failed endotracheal placement but also as a first choice in selected patients. Studies on larger cohorts would be needed. Further research involving larger patient cohorts of multicentre NICUs is necessary to confirm the use of laryngeal masks in neonates weighing less than 2000 grams.

Long-term benefits of exclusive human milk diet in small for gestational age neonates: a systematic review of the literature.

Evidence about feeding practices' consequences in small for gestational age newborns is not well established because they are less likely to initiate and continue breastfeeding than other newborns. Our aim was to study current knowledge about the benefits of exclusive human milk diet after 2 years of age in small for gestational age newborns. A systematic review of the literature was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline criteria. Pubmed and Scopus were searched for studies published from databases inception until June 2, 2023. Included articles were analysed and synthesised. Risk of bias and level of evidence assessments were performed. They were enrolled small for gestational age newborns fed by breastfeeding, breast milk or donor milk. The systematic review included 9 articles which were related to 4 health domains: neurodevelopment, cardiovascular, somatic growth and bone mineralization and atopy. Extracted data support a beneficial effect of breastfeeding on these outcomes. Better quality of evidence and longer follow-up are needed.

Umbilical cord stump medication with a topical dermo protective powder compared to dry care in healthy full-term and near-term newborns: a two-center prospective cohort study.

BACKGROUND: Proper umbilical cord stump care during the first days of life (both in hospital and at home) should not be overlooked to prevent possible complications (e.g., purulent discharge, granulomas, or periumbilical erythema or omphalitis). Despite the known benefits of its correct execution, the care of umbilical cord stump remains controversial, and many different approaches are described. The World Health Organization suggests the use of dry cord stump care (easy and economic technique) in developed countries, but in many cases in the real life various topical antiseptics are used in combination with dry cord stump. The extracts of Arnica Montana (AM) have been reported to possess antibacterial, anti-inflammatory, antifungal, and immunomodulatory activities, very useful in the management of cord stump in full term infants. METHODS: In our study we evaluated the efficacy of a powder containing AM (study group- GrA) versus dry cord stump (control group-GrB) in a population of healthy newborn >35 weeks of gestational age (GA). RESULTS: Three hundred twenty-six neonates (mean GA 39±1 in both groups and body weight 3200 g and 3400±448 g respectively in GrA and GrB) were enrolled in two standard neonatal care units (163 neonates in GrA and 163 in GrB). At T1 (48 hours after discharge) GrA showed significantly reduced incidence of mild complications in toto, in particular a lower rate of wet umbilical cord stump). No differences between the two groups at T2 (1 week after discharge). CONCLUSIONS: The use of a natural topical dermo-protective powder containing AM reduces the risk of minor complications, both nurse and parental workload in the first days after discharge, but does not have an impact on cord detachment and other complications in neonates >35 weeks GA.

Analysis of the Fecal Metabolomic Profile in Breast vs. Different Formula Milk Feeding in Late Preterm Infants.

Human milk is the gold standard for infant nutrition, but when it is not available or insufficient to satisfy the needs of the infant, formula milk is proposed as an effective substitute. A prospective observational cohort study was conducted on late preterm infants fed with breast and two different formula milks. On this basis, they were divided into three groups: group FMPB (fed with formula + postbiotic), group FM (fed with standard formula), and group BM (breastfed). Stool samples for a metabolomic study were collected at T0 (5-7 days after birth), T1 (30 days of life), and T2 (90 days of life), giving rise to 74 samples analyzed via liquid chromatography coupled with high-resolution mass spectrometry. The T0, T1, and T2 LC-MS raw data were processed for Partial Least Square Discriminant Analysis (PLS-DA), followed by a statistical analysis. This preliminary study highlighted a good overlapping between the fecal metabolome of breast and substitute feeding systems, confirming the efficacy of the formula preparations as breast milk substitutes. Moreover, several similarities were also detected between the FMPB and BM metabolome, highlighting that the addition of a postbiotic to standard formula milk could be more effective and considered a better alternative to breast milk.

Vitamin K insufficiency and the prophylaxis strategy in term healthy infants: A multicentre study.

BACKGROUND/AIM: Late vitamin K deficiency bleeding (VKDB) during early infancy is a serious problem worldwide. Vitamin K (VK) deficiency commonly occurs in newborns who are exclusively breastfed. Protein Induced by VK Absence (PIVKA-II) has been identified as an early indicator of subclinical VK deficiency in neonates, surpassing prothrombin time. To assess PIVKA-II levels at 48 h, 1 and 3 months of age in full-term newborns who were exclusively breastfed and received varying VKDB prophylaxis regimens. METHODS: A prospective observational study was conducted in four hospitals, enrolling 105 newborns. PIVKA-II levels were measured using a sandwich-type enzyme-linked immunosorbent assay. RESULTS: At 48 h of age, there was no significant difference in PIVKA-II concentrations between newborns who received intramuscular administration of 1 mg of phylloquinone (VK1) and those who received oral administration of 2 mg of VK1 at birth. At 1 and 3 months of life, infants who received any supplementation regimen between 2 and 14 weeks exhibited significantly lower PIVKA-II concentrations compared to infants who received only 1 mg of intramuscular VK1 at birth. The prophylaxis involving a dose of 1 mg of intramuscular VK1 at birth followed by oral administration of 150 µg/day of VK1 from the 2nd to the 14th week of life showed the lowest PIVKA-II blood concentrations. CONCLUSIONS: Oral supplementation of VK1 after discharge significantly reduced PIVKA-II concentrations in exclusively breastfed term infants. These findings suggest the importance of oral VK1 supplementation in exclusively breastfed infants during their first 3 months of life to avoid the risk of VK insufficiency.

Molecular mechanisms of oxidative stress-related neonatal jaundice.

Oxidative stress is a pathological condition characterized by an overload of oxidant products, named free radicals, which are not well counteracted by antioxidant systems. Free radicals induce oxidative damage to many body organs and systems. In neonatal red blood cells, free-radical mediated-oxidative stress leads to eryptosis, a suicidal death process of erythrocytes consequent to alteration of cell integrity. Neonatal red blood cells are targets and at the same time generators of free radicals through the Fenton and Haber-Weiss reactions. Enhanced eryptosis in case of oxidative stress damage may cause anemia if the increased loss of erythrocytes is not enough compensated by enhanced new erythrocytes synthesis. The oxidative disruption of the red cells may cause unconjugated idiopathic hyperbilirubinemia in neonates. High levels of bilirubin are recognized to be dangerous for the central nervous system in newborns, however, many studies have highlighted the antioxidant function of bilirubin. Recently, it has been suggested that physiologic concentration of bilirubin correlates with higher antioxidant status while high pathological bilirubin levels are associated with pro-oxidants effects. The aim of this educational review is to provide an updated understanding of the molecular mechanisms underlying erythrocyte oxidant injury and its reversal in neonatal idiopathic hyperbilirubinemia.

Results and lessons learned from the sbv IMPROVER metagenomics diagnostics for inflammatory bowel disease challenge.

A growing body of evidence links gut microbiota changes with inflammatory bowel disease (IBD), raising the potential benefit of exploiting metagenomics data for non-invasive IBD diagnostics. The sbv IMPROVER metagenomics diagnosis for inflammatory bowel disease challenge investigated computational metagenomics methods for discriminating IBD and nonIBD subjects. Participants in this challenge were given independent training and test metagenomics data from IBD and nonIBD subjects, which could be wither either raw read data (sub-challenge 1, SC1) or processed Taxonomy- and Function-based profiles (sub-challenge 2, SC2). A total of 81 anonymized submissions were received between September 2019 and March 2020. Most participants' predictions performed better than random predictions in classifying IBD versus nonIBD, Ulcerative Colitis (UC) versus nonIBD, and Crohn's Disease (CD) versus nonIBD. However, discrimination between UC and CD remains challenging, with the classification quality similar to the set of random predictions. We analyzed the class prediction accuracy, the metagenomics features by the teams, and computational methods used. These results will be openly shared with the scientific community to help advance IBD research and illustrate the application of a range of computational methodologies for effective metagenomic classification.

Does high fidelity neonatal resuscitation simulation increase salivary cortisol levels of health care providers?

BACKGROUND: The use of simulation-based medical education is strongly recommended to insure neonatal resuscitation skills for health caregivers. High fidelity simulation was executed to allow the evaluation of technical and non-technical skills. Salivary cortisol level was considered reliable biomarkers of adrenocortical activity and useful tool to learning assessment and stress response. METHODS: Our primary aim was to test changes in salivary cortisol levels before and after the simulation for neonatal resuscitation between high and low fidelity setting. Secondary aim was to evaluate salivary cortisol level in the participants, leader and not leader. Fifty-two health care providers were divided in ratio 1:1 into low-fidelity (LF group) and high-fidelity scenario (HF group) of neonatal resuscitation. In each group the participants assumed the role of team leader or not team leader. Salivary samples were collected from all participants 5 minutes before and after each simulation scenario by using oral swab. Analysis of difference was analyzed by Kruskal Wallis Test. RESULTS: Salivary cortisol levels were significantly higher in HF group (N.=26) than LF group (N.=26) before the performance (5.407 mmol/L vs. 3.090 mmol/L; P=0.018). In the HF group, salivary cortisol levels were significantly lower after simulation than before (P=0.007), moreover not team leader showed higher salivary cortisol levels before of the simulation than after (P=0.003). Team leaders showed higher salivary cortisol levels than not team leader after high-fidelity scenario (P=0.039). CONCLUSIONS: High-fidelity simulation scenario had a great impact on stress level, furthermore leaders showed higher salivary cortisol levels than not team leaders.

Community Detection in Protein-Protein Interaction Networks and Applications.

The ability to identify and characterize not only the protein-protein interactions but also their internal modular organization through network analysis is fundamental for understanding the mechanisms of biological processes at the molecular level. Indeed, the detection of the network communities can enhance our understanding of the molecular basis of disease pathology, and promote drug discovery and disease treatment in personalized medicine. This work gives an overview of recent computational methods for the detection of protein complexes and functional modules in protein-protein interaction networks, also providing a focus on some of its applications. We propose a systematic reformulation of frequently adopted taxonomies for these methods, also proposing new categories to keep up with the most recent research. We review the literature of the last five years (2017-2021) and provide links to existing data and software resources. Finally, we survey recent works exploiting module identification and analysis, in the context of a variety of disease processes for biomarker identification and therapeutic target detection. Our review provides the interested reader with an up-to-date and self-contained view of the existing research, with links to state-of-the-art literature and resources, as well as hints on open issues and future research directions in complex detection and its applications.

Current Concepts of Corticosteroids Use for the Prevention of Bronchopulmonary Dysplasia.

Despite using antenatal steroids, surfactants and protective ventilation, bronchopulmonary dysplasia (BPD) affects 10-89% of preterm infants. Since lung inflammation is central to the BPD pathogenesis, postnatal systemic corticosteroids could reduce the risk of BPD onset in preterm infants, but short and long-term adverse consequences have been underlined in literature after their use (i.e., hyperglycaemia, hypertension, hypertrophic cardiomyopathy, growth failure, gastrointestinal bleeding, cerebral palsy). Alternative therapeutic strategies such as postponing corticosteroid administration, lowering the cumulative dose, giving pulse rather than continuous doses, or individualizing the dose according to the respiratory condition of the infant have been proposed to avoid their adverse effects. Dexamethasone remains the first-line drug for newborns with severe pulmonary disease beyond the second to the third week of life. Hydrocortisone administration in very preterm infants does not appear to be associated with neurotoxic effects, even if its efficacy in preventing and treating BPD has yet been clearly demonstrated. Alternative methods of corticosteroid administration seem promising. A positive effect on BPD prevention occurs when budesonide is nebulized and intratracheally instilled with a surfactant, but more data are required to establish safety and efficacy in preterm newborns. Additional studies are still needed before the chronic lung disease issue, and its related challenges can be solved.

Untangling the Context-Specificity of Essential Genes by Means of Machine Learning: A Constructive Experience.

Gene essentiality is a genetic concept crucial for a comprehensive understanding of life and evolution. In the last decade, many essential genes (EGs) have been determined using different experimental and computational approaches, and this information has been used to reduce the genomes of model organisms. A growing amount of evidence highlights that essentiality is a property that depends on the context. Because of their importance in vital biological processes, recognising context-specific EGs (csEGs) could help for identifying new potential pharmacological targets and to improve precision therapeutics. Since most of the computational procedures proposed to identify and predict EGs neglect their context-specificity, we focused on this aspect, providing a theoretical and experimental overview of the literature, data and computational methods dedicated to recognising csEGs. To this end, we adapted existing computational methods to exploit a specific context (the kidney tissue) and experimented with four different prediction methods using the labels provided by four different identification approaches. The considerations derived from the analysis of the obtained results, confirmed and validated also by further experiments for a different tissue context, provide the reader with guidance on exploiting existing tools for achieving csEGs identification and prediction.

TumorMet: A repository of tumor metabolic networks derived from context-specific Genome-Scale Metabolic Models.

Studies about the metabolic alterations during tumorigenesis have increased our knowledge of the underlying mechanisms and consequences, which are important for diagnostic and therapeutic investigations. In this scenario and in the era of systems biology, metabolic networks have become a powerful tool to unravel the complexity of the cancer metabolic machinery and the heterogeneity of this disease. Here, we present TumorMet, a repository of tumor metabolic networks extracted from context-specific Genome-Scale Metabolic Models, as a benchmark for graph machine learning algorithms and network analyses. This repository has an extended scope for use in graph classification, clustering, community detection, and graph embedding studies. Along with the data, we developed and provided Met2Graph, an R package for creating three different types of metabolic graphs, depending on the desired nodes and edges: Metabolites-, Enzymes-, and Reactions-based graphs. This package allows the easy generation of datasets for downstream analysis.

Peripheral Saturation and Perfusion Index on the First Day of Life Play a Role in Early Discharge of Healthy Term Newborns.

Introduction: Pulse oximetry screening is a safe, feasible test, effective in identifying congenital heart diseases in otherwise well-appearing newborns. Uncertainties still persist on the most effective algorithm to be used and the timing of screening. The aim of this study was to evaluate the role of the pulse oximetry screening associated with the peripheral perfusion index performed in the first 24 hours of life for the early detection of congenital heart diseases and noncongenital heart diseases in the newborns. Materials and Methods: A prospective observational cohort study was conducted. The enrollment criteria were as follows: term newborns with an APGAR score >8 at 5 minutes. The exclusion criteria were as follows: clinical signs of prenatal/perinatal asphyxia or known congenital malformations. Four parameters of pulse oximetry screening were utilized: saturation less than 90% (screening 1), saturation of less than 95% in one or both limbs (screening 2), difference of more than 3% between the limbs (screening 3), and preductal peripheral perfusion index or postductal peripheral perfusion index below 0.70 (screening 4). The likelihood ratio, sensibility, specificity, and positive and negative predictive values for identification of congenital heart diseases or noncongenital heart diseases (suspicion of perinatal infection and any respiratory diseases) were evaluated. Results: The best predictive results for minor congenital heart disease were obtained combining screening 3 and screening 4 (χ 2 (1) = 15,279; p < 0.05; OR = 57,900 (9,465-354,180)). Screening 2, screening 3, and screening 4 were predictive for noncongenital heart diseases (χ 2 (1) = 11,550; p < 0.05; OR = 65,744 (10,413-415,097)). Combined screenings 2-4 were predictive for both congenital heart disease and noncongenital heart disease (χ 2 (1) = 22,155; p < 0.05; OR = 117,685 (12,972-1067,648)). Conclusions: Combining peripheral saturation with the peripheral perfusion index in the first 24 hours of life shows a predictive role in the detection of minor congenital heart diseases and neonatal clinical conditions whose care needs attention.

Netpro2vec: A Graph Embedding Framework for Biomedical Applications.

The ever-increasing importance of structured data in different applications, especially in the biomedical field, has driven the need for reducing its complexity through projections into a more manageable space. The latest methods for learning features on graphs focus mainly on the neighborhood of nodes and edges. Methods capable of providing a representation that looks beyond the single node neighborhood are kernel graphs. However, they produce handcrafted features unaccustomed with a generalized model. To reduce this gap, in this work we propose a neural embedding framework, based on probability distribution representations of graphs, named Netpro2vec. The goal is to look at basic node descriptions other than the degree, such as those induced by the Transition Matrix and Node Distance Distribution. Netpro2vec provides embeddings completely independent from the task and nature of the data. The framework is evaluated on synthetic and various real biomedical network datasets through a comprehensive experimental classification phase and is compared to well-known competitors.

Antioxidant Effect of Melatonin in Preterm Newborns.

INTRODUCTION: Preterm infants are at risk of free radical-mediated diseases from oxidative stress (OS) injury. Increased free radical generation has been demonstrated in preterm infants during the first seven days of life. Melatonin (MEL) is a powerful antioxidant and scavenger of free radicals. In preterm neonates, melatonin deficiency has been reported. Exogenous melatonin administration appears a promising strategy in the treatment of neonatal morbidities in which OS has a leading role. OBJECTIVE: The aim was to evaluate plasma MEL concentrations and OS biomarkers in preterm newborns after early administration of melatonin. METHODS: A prospective, randomized double-blind placebo-controlled pilot study was conducted from January 2019 to September 2020. Thirty-six preterm newborns were enrolled. Starting from the first day of life, 21 received a single dose of oral melatonin 0.5 mg/kg once a day, in the morning (MEL group); 15 newborns received an equivalent dose of placebo (placebo group). Samples of 0.2 mL of plasma were collected at 24 and 48 hours after MEL administration. Plasma concentrations of melatonin, non-protein-bound iron (NPBI), advanced oxidation protein products (AOPP), and F2-isoprostanes (F2-Isopr) were measured. Babies were clinically followed until discharge. RESULTS: At 24 and 48 hours after MEL administration, the MEL concentrations were significantly higher in the MEL group than in the placebo group (52759.30 ± 63529.09 vs. 28.57 ± 46.24 pg/mL and 279397.6 ± 516344.2 vs. 38.50 ± 44.01 pg/mL, respectively). NPBI and AOPP did not show any statistically significant differences between the groups both at 24 and 48 hours. At 48 hours, the mean blood concentrations of F2-Isopr were significantly lower in the MEL group than in the placebo group (36.48 ± 33.85 pg/mL vs.89.97 ± 52.01 pg/mL). CONCLUSIONS: Early melatonin administration in preterm newborns reduces lipid peroxidation in the first days of life showing a potential role to protect high-risk newborns. Trial Registration. This trial is registered with NCT04785183, Early Supplementation of Melatonin in Preterm Newborns: the Effects on Oxidative Stress.

Metabolomic Profile of Young Adults Born Preterm.

Prematurity is a risk factor for the development of chronic adult diseases. Metabolomics can correlate the biochemical changes to a determined phenotype, obtaining real information about the state of health of a subject at that precise moment. Significative differences in the metabolomic profile of preterm newborns compared to those born at term have been already identified at birth. An observational case-control study was performed at the University Hospital of Siena. The aim was to evaluate and compare the metabolomic profiles of young adults born preterm to those born at term. Urinary samples were collected from 67 young adults (18-23 years old) born preterm (mean gestational age of 30 weeks, n = 49), and at term of pregnancy (mean gestational age of 38 weeks, n = 18). The urinary spectra of young adults born preterm was different from those born at term and resembled what was previously described at birth. The Random Forest algorithm gave the best classification (accuracy 82%) and indicated the following metabolites as responsible for the classification: citrate, CH2 creatinine, fumarate and hippurate. Urine spectra are promising tools for the early identification of neonates at risk of disease in adulthood and may provide insight into the pathogenesis and effects of fetal programming and infants' outcomes.

Management of oxygen saturation monitoring in preterm newborns in the NICU: the Italian picture.

BACKGROUND: Although many studies emphasize the importance of using oxygen saturation (SpO2) targets in the NICUs, there is a wide variability in used saturation ranges among centers. Primary aim was to draw a representative picture on how the management of oxygen monitoring is performed in the Italian NICUs. Second aim was to identify healthcare-professionals related factors associated with oxygen targeting in the preterm population. METHODS: Cross-sectional study with data collection via an electronic survey form. A questionnaire containing pre-piloted and open questions on monitoring and management of the SpO2 was administered to neonatologists across the network of the Italian Society of Neonatology. The questions focused on: the infrastructure, specific training, healthcare professionals and patients-related factors. The results of the survey were anonymously collected, summarized and analyzed. RESULTS: Out of 378 questionnaires, 93 were correctly filled. Thirty-six different SpO2 ranges were observed. Centers using written standard operating procedures on oxygen management and SpO2 monitoring maintained a correct average range of SpO2 90-95%, avoided hyperoxia and reconsidered saturation targets in relation to comorbidities. 39.8% of responders disabled alarms during neonatal care. One center used biomarkers for complete monitoring of neonatal oxygenation status. CONCLUSIONS: There is considerable variation in SpO2 targets for preterm infants in the Italian NICUs. Standard operating procedures and specific training for health care personnel are the main factors playing a role for the correct maintenance of the recommended oxygen targets in preterms.

New Strategies for Necrotizing Enterocolitis Diagnosis and Prevention in Newborns.

Necrotizing enterocolitis is one of the most frequent and severe gastrointestinal diseases that affect preterm newborns in Neonatal Intensive Care Units. It was firstly described in 1960s, but this clinical entity was not widely recognized until the advent of modern neonatal intensive care. The disease is characterized by submucosal edema, infiltration of intestinal wall by immune cells, specifically neutrophils and, in severe forms, wall necrosis that leads to intestinal perforation. Its incidence is inversely associated to birth weight and gestational age. Necrotizing enterocolitis has been responsible for high rates of morbidity and mortality (15-30%), despite improvements made in neonatal care in the last decades. The challenge is to optimize strategies for early diagnosis, define the best medical and surgical treatments and standardize preventive measures. Several biomarkers have been proposed for the early prediction of necrotizing enterocolitis onset in preterm newborns and can be useful not only for diagnostic purposes but also for prediction of disease progression and severity. The purpose of this paper is to illustrate the most recent evidence regarding the diagnosis and prevention of necrotizing enterocolitis. This manuscript contributes to clinical decision-making in preterm neonates at high risk of developing necrotizing enterocolitis.

The clinical course of SARS-CoV-2 positive neonates.

The COVID-19 pneumonia was firstly reported in Wuhan, China, in December 2019. The disease had a rapid spread all over the word becoming an international public health emergency. Limited data were available on COVID-19 positive neonates. We reviewed relevant literature to understand the clinical course of disease and transmission routes in affected neonates. The aim of the study was evaluating the clinical course and prognosis of SARS-CoV-2 positive neonates. Based on current literature, the hypothesis of vertical transmission of SARS-CoV-2, though conceivable, remains unproven. A research conducted on PubMed database from December 2019 to April 27, 2020 revealed that were reported 25 neonates affected by SARS-CoV-2. Main symptoms were fever, cough, or shortness of breath but often these neonates did not show other symptoms during length stay in hospital. No deaths occurred.