Publications by authors named "Vassilios Fanos"

268 Publications

When a Neonate Is Born, So Is a Microbiota.

Life (Basel) 2021 Feb 16;11(2). Epub 2021 Feb 16.

Clinical and Experimental Medicine Department, Section of Pediatrics, University of Pisa, Via Roma, 55, 56126 Pisa PI, Italy.

In recent years, the role of human microbiota as a short- and long-term health promoter and modulator has been affirmed and progressively strengthened. In the course of one's life, each subject is colonized by a great number of bacteria, which constitute its specific and individual microbiota. Human bacterial colonization starts during fetal life, in opposition to the previous paradigm of the "sterile womb". Placenta, amniotic fluid, cord blood and fetal tissues each have their own specific microbiota, influenced by maternal health and habits and having a decisive influence on pregnancy outcome and offspring outcome. The maternal microbiota, especially that colonizing the genital system, starts to influence the outcome of pregnancy already before conception, modulating fertility and the success rate of fertilization, even in the case of assisted reproduction techniques. During the perinatal period, neonatal microbiota seems influenced by delivery mode, drug administration and many other conditions. Special attention must be reserved for early neonatal nutrition, because breastfeeding allows the transmission of a specific and unique lactobiome able to modulate and positively affect the neonatal gut microbiota. Our narrative review aims to investigate the currently identified pre- and peri-natal factors influencing neonatal microbiota, before conception, during pregnancy, pre- and post-delivery, since the early microbiota influences the whole life of each subject.
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http://dx.doi.org/10.3390/life11020148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920069PMC
February 2021

Genital anomalies in newborns.

J Perinatol 2021 Mar 1. Epub 2021 Mar 1.

Neonatal Intensive Care Unit, Azienda Ospedaliero-Universitaria di Cagliari, Cagliari, Italy.

Examination of genitalia should be an essential part of newborn assessment. Early detection of congenital disorders is essential to begin appropriate medical or surgical therapy and to prevent complications that could profoundly affect a child's life. The present review aims to describe the main genital anomalies in infants and provide images in order to help the physician in current clinical practice.
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http://dx.doi.org/10.1038/s41372-021-00991-1DOI Listing
March 2021

COVID-19 and developmental origins of health and disease.

Early Hum Dev 2021 04 26;155:105322. Epub 2021 Jan 26.

Department of Surgery, Neonatal Intensive Care Unit, University of Cagliari, Cagliari, Italy; Neonatal Intensive Care Unit, AOU, Cagliari, Cagliari, Italy.

From the moment of the identification of SARS-CoV-2 as an etiological agent of the severe clinical pictures of pneumonia that were being slowly observed all over the world, numerous studies have been conducted to increase the knowledge about what was an unknown virus until then. The efforts were mainly aimed to acquire epidemiological, microbiological, pathogenetic, clinical, diagnostic, therapeutic and preventive information in order to increase the available weapons to fight an infection which was rapidly taking on the characteristics of the pandemic. Given the topicality of the problem, not everything has yet been fully understood and clarified, especially in the maternal-fetal‑neonatal field, where we are beginning to question what could be the outcomes of newborn babies born to mothers who contracted SARS-CoV-2 infection during pregnancy. Thus, the aim of this review is to analyze the long-term outcomes of this infection that could affect the offspring, regardless of a possible maternal-fetal transmission, focusing on, above all, the role of maternal immune activation and the expression of the Angiotensin-converting enzyme 2 (ACE2) in particular at the placental level.
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http://dx.doi.org/10.1016/j.earlhumdev.2021.105322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837628PMC
April 2021

A review of current knowledge on Pollution, Cigarette Smoking and COVID-19 diffusion and their relationship with inflammation.

Acta Biomed 2020 10 21;91(4):e2020148. Epub 2020 Oct 21.

Neonatal Intensive Care Unit, AOU Cagliari, Italy.

Coronavirus disease (COVID-19) is an infectious disease caused by the newly discovered coronavirus, Sars-Cov-2. This infection can cause mild to very severe respiratory and systemic illness mainly related with a cytokine storm. The epidemiology of COVID-19 is under continuous evolution, and studies are ongoing aiming at identifying the possible factors facilitating the diffusion of this infection. It is documented that air pollution and smoking are a leading cause of human morbidity and mortality globally, and can increase the risk of many diseases, including respiratory diseases. Overall, a linear relationship between exposure to atmospheric pollutants and diffusion of the Sars-Cov2 virus seems to exist. However, this correlation, cannot be regarded as a cause-effect relationship.  The available data show that air pollution is responsible for inflammation and hyper-activation of innate immunity that are associated with the worst outcomes of covid-19 but do not allow to conclude that atmospheric particulate is responsible for increased contagion. As to smoking, nicotine activation of nicotinic receptors leads to enhanced protease activation, apoptosis and inflammatory signaling through the same pathways (Renin-angiotensin system (RAS) and angiotensin-converting enzyme 2 (ACE2)) used by the virus increasing the inflammatory/destructive action of the virus itself. The increase in non-communicable diseases and of chronic inflammatory diseases is in line with environmental pollution, related climate changes, and with an augmented susceptibility to infectious diseases with increased contagiousness and morbidity. Restrictive measures to limit environmental pollution are needed worldwide as this represents a threat for human health.
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http://dx.doi.org/10.23750/abm.v91i4.10263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927491PMC
October 2020

Autism Spectrum Disorder from the Womb to Adulthood: Suggestions for a Paradigm Shift.

J Pers Med 2021 Jan 25;11(2). Epub 2021 Jan 25.

Neonatal Intensive Care Unit, Department of Surgical Sciences, Puericulture Institute and Neonatal Section, Azienda Ospedaliera Universitaria, 09100 Cagliari, Italy.

The wide spectrum of unique needs and strengths of Autism Spectrum Disorders (ASD) is a challenge for the worldwide healthcare system. With the plethora of information from research, a common thread is required to conceptualize an exhaustive pathogenetic paradigm. The epidemiological and clinical findings in ASD cannot be explained by the traditional linear genetic model, hence the need to move towards a more fluid conception, integrating genetics, environment, and epigenetics as a whole. The embryo-fetal period and the first two years of life (the so-called 'First 1000 Days') are the crucial time window for neurodevelopment. In particular, the interplay and the vicious loop between immune activation, gut dysbiosis, and mitochondrial impairment/oxidative stress significantly affects neurodevelopment during pregnancy and undermines the health of ASD people throughout life. Consequently, the most effective intervention in ASD is expected by primary prevention aimed at pregnancy and at early control of the main effector molecular pathways. We will reason here on a comprehensive and exhaustive pathogenetic paradigm in ASD, viewed not just as a theoretical issue, but as a tool to provide suggestions for effective preventive strategies and personalized, dynamic (from womb to adulthood), systemic, and interdisciplinary healthcare approach.
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http://dx.doi.org/10.3390/jpm11020070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912683PMC
January 2021

Overview of CAPICE-Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe-an EU Marie Skłodowska-Curie International Training Network.

Eur Child Adolesc Psychiatry 2021 Jan 20. Epub 2021 Jan 20.

Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

The Roadmap for Mental Health and Wellbeing Research in Europe (ROAMER) identified child and adolescent mental illness as a priority area for research. CAPICE (Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe) is a European Union (EU) funded training network aimed at investigating the causes of individual differences in common childhood and adolescent psychopathology, especially depression, anxiety, and attention deficit hyperactivity disorder. CAPICE brings together eight birth and childhood cohorts as well as other cohorts from the EArly Genetics and Life course Epidemiology (EAGLE) consortium, including twin cohorts, with unique longitudinal data on environmental exposures and mental health problems, and genetic data on participants. Here we describe the objectives, summarize the methodological approaches and initial results, and present the dissemination strategy of the CAPICE network. Besides identifying genetic and epigenetic variants associated with these phenotypes, analyses have been performed to shed light on the role of genetic factors and the interplay with the environment in influencing the persistence of symptoms across the lifespan. Data harmonization and building an advanced data catalogue are also part of the work plan. Findings will be disseminated to non-academic parties, in close collaboration with the Global Alliance of Mental Illness Advocacy Networks-Europe (GAMIAN-Europe).
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http://dx.doi.org/10.1007/s00787-020-01713-2DOI Listing
January 2021

COVID-19 and hepatic damage: what we know? A systematic review.

Panminerva Med 2021 Jan 20. Epub 2021 Jan 20.

Neonatal Intensive Care Unit, University of Cagliari, Cagliari, Italy.

Since the end of 2019, a new disease outbreak has been spreading worldwide, after starting from Wuhan, China. The viral pathogen responsible for the disease was named as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), and for the illness the acronym COVID-19 was coined (COronaVIrus Disease 2019). Viral pathogenesis, epidemiology, and clinics are still somewhat obscure, when occurring during childhood the most. This systematic review aims at evaluating the features of liver involvement and damage in course of COVID-19. An insight into what is known as to COVID-19 and hepatic damage in adulthood as well as paediatric age was given. All the most relevant papers up to 15/10/2020 were identified and discussed. Establishing whether liver damage is due to a direct viral action or host immune system inflammatory reaction or consequence of the administered drugs or secondary to another organ failure (for example the heart) is difficult. What is sure is the fact that liver function should be checked at the time of admission to hospital and during hospitalization. If hepatic markers are altered, a specific therapy to protect liver is needed.
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http://dx.doi.org/10.23736/S0031-0808.21.04239-7DOI Listing
January 2021

Urinary metabolome of infants with colic treated with Lactobacillus reuteri DSM 17938: a pilot randomized trial.

Minerva Pediatr 2021 Jan 13. Epub 2021 Jan 13.

Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.

Background: Lactobacillus reuteri DSM 17938 is the only probiotic recommended for treatment of colicky infants, but its mechanism of action is not clear. The study aim was to examine urinary metabolomic fingerprint of colicky breastfed infants before and after 1 month of orally administered Lactobacillus reuteri DSM 17938 or placebo.

Methods: This randomized, blinded, placebo-controlled clinical trial was carried out with a well-documented probiotic. Thirty-two infants were enrolled, 16 in the probiotic group and 16 in the placebo group. Urine samples were collected from each subject before starting supplementation and at the end of the study period. Metabolomic profiles were obtained using a gas chromatography/mass spectrometry instrument. Subsequently, to compare groups before and after probiotic supplementation, univariate and multivariate statistical analysis were performed.

Results: In the L. reuteri treated group all metabolites for all class of nutrients (sugars, amino acids, carboxylic acids) resulted more abundant after the study period. The comparison with a control group (placebo treated), confirmed this effect on urines.

Conclusions: The metabolomic analysis of urine samples from infants treated with L. reuteri DSM 17938 allowed to detect some interesting features related to the effect of this treatment on urinary metabolome. To validate the results, a test on a larger cohort is required.
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http://dx.doi.org/10.23736/S0026-4946.20.06128-9DOI Listing
January 2021

Why Is Antibiotic Treatment Rarely Performed in COVID-19-Positive Children Admitted in Pediatric Intensive Care Units?

JAMA Pediatr 2021 04;175(4):431-432

Neonatal Intensive Care Unit, Department of Surgical Sciences, AOU and University of Cagliari, Monserrato, Italy.

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http://dx.doi.org/10.1001/jamapediatrics.2020.5348DOI Listing
April 2021

Early Urinary Metabolomics in Patent Ductus Arteriosus Anticipates the Fate: Preliminary Data.

Front Pediatr 2020 21;8:613749. Epub 2020 Dec 21.

Neonatal Intensive Care Unit, Department of Surgical Sciences, Azienda Ospedaliero-Universitaria and University of Cagliari, Cagliari, Italy.

In premature neonates, the persistence of hemodynamically significant ductus arteriosus (hsPDA) can be associated with short- and long-term consequences, impairing their outcome. The correct strategy of management for such condition is under debate, especially regarding contraindications and/or side effects. In recent years, metabolomics was applied to several perinatal, pediatric, and adult conditions to investigate potential biomarkers of disease, which have become useful for early diagnosis and/or therapeutic management. The main purpose of our exploratory study was to asses, through H-NMR metabolomics analysis of urinary samples at birth, possible metabolic pathways differentiating, with a significant predictive power, those preterm neonates who will subsequently develop hsPDA and neonates of comparable gestational age (GA) who will undergo spontaneous ductal closure or the persistence of an irrelevant PDA (no-hsPDA). Moreover, we investigated potential prenatal or perinatal clinical factors potentially influencing the development of hsPDA. We enrolled = 35 preterm neonates with GA between 24 and 32 weeks; urinary samples were collected within the first 12 h of life. Patients were closely monitored regarding intensive care, respiratory support, fluid balance and administered drugs; an echocardiogram was performed at 48-72 h. Our results reported a significant correlation between lower GA at birth and the development of hsPDA. Moreover, neonates with GA ≤ 30w developing hsPDA were characterized by lower Apgar scores at 1' and 5', higher rates of perinatal asphyxia, higher need of delivery room resuscitation and subsequent surfactant administration. Interestingly, metabolomics analysis at birth detected a clear separation between the H-NMR urinary spectra of subjects GA ≤ 30w not developing hsPDA ( = 19) and those of subjects born at GA ≤ 30w in which hsPDA was confirmed at 48-72 h of life ( = 5). This is the first study applying metabolomics to investigate the PDA condition. Although preliminary and conducted on a limited sample, our results reveal that metabolomics could be a promising tool in the early identification of hsPDA, potentially superior to the clinical or laboratory predictive tools explored to date and even to the clinical observations and correlations in our sample, through the detection of specific urinary metabolites.
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http://dx.doi.org/10.3389/fped.2020.613749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779766PMC
December 2020

The child with medical complexity.

Ital J Pediatr 2021 Jan 6;47(1). Epub 2021 Jan 6.

Università degli Studi di Cagliari, Cagliari, Italy.

Children with medical complexity represent a big challenge for the physicians, their families and the society as well. Although there is no clear definition of this type of patients, they are affected by a chronic, often very severe condition for their whole life. They also represent a huge cost for the health care system due to their needs of continuous assistance.In this review we summarized the definitions of child with medical complexity. Then we illustrated the strategies to treat and take care of these children in order to look at them not as a burden or a cost but as an opportunity to growth and improve as clinicians and to improve the society, to give them the best life they can live.We also wanted to give voice to the physicians, the parents and the children themselves to really show and understand what are their experiences and their feelings in dealing with their conditions. We concluded with the description of one example of children with medical complexity: prematurity. We discussed the progresses in their treatment so far in order to illustrate what is the future of pediatrics. Since it has been more and more acknowledged that every child with medical complexity is unique, the future of pediatric is to organize an individualized approach and to "see things with the eye of a child".
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http://dx.doi.org/10.1186/s13052-020-00935-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788740PMC
January 2021

Insights on Kawasaki disease and multisystem inflammatory syndrome; relationship with COVID-19 infection.

Minerva Pediatr 2020 Dec 11. Epub 2020 Dec 11.

University College of Dublin, Mater Misericordiae University Hospital, Dublin, Republic of Ireland -

At the beginning of coronavirus disease 2019 (COVID-19) children seemed to be less affected and with milder symptoms than adults. Afterward, however, a warning was released regarding the possible association between COVID-19 and Kawasaki disease (KD) or Kawasaki-like disease. Thereafter, labels of Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS) in Europe and Multisystem Inflammatory Syndrome in Children (MIS-C) in the USA were coined to refer to this new disease entity. The reality is that PIMS-TS/MIS-C resembles certain KD complications such as toxic shock syndrome and macrophage activation syndrome than to classic KD. PIMS-TS/MIS-C and KD share the viral origin (however just supposed for KD) and consequent dysregulated innate immune system inflammatory reaction. PIMS-TS/MISC symptoms occur about 2-4 weeks after the onset of COVID-19 or having been exposed to somebody positive for COVID-19, rather than in the acute phase of the infection. Clinically PIMS-TS/MIS-C affects older children than KD and presents more often with gastrointestinal symptoms, shock, and multi-organ dysfunction. myocarditis is more common in PIMS-TS/MIS-C than coronary artery aneurysms formation seen in KD. There are also differences in laboratory tests and immunology responses in KD and PIMS-TS/MIS-C. Thus PIMS-TS/MIS-C seems to be a new and multifaceted entity, distinct from KD, notwithstanding some common features in both. The dysregulated innate immune system reaction is responsible for PIMS-TS/MIS-C onset and outcome. A multidisciplinary approach, involving paediatric intensivists, paediatric cardiologists, infectious disease specialists, immunologists, and rheumatologists, is needed for the treatment of these children.
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http://dx.doi.org/10.23736/S0026-4946.20.06140-XDOI Listing
December 2020

The Urine Metabolome of Young Autistic Children Correlates with Their Clinical Profile Severity.

Metabolites 2020 Nov 23;10(11). Epub 2020 Nov 23.

Child Neurology and Psychiatry Unit, System Medicine Department, Tor Vergata University Hospital of Rome, 00133 Rome, Italy.

Autism diagnosis is moving from the identification of common inherited genetic variants to a systems biology approach. The aims of the study were to explore metabolic perturbations in autism, to investigate whether the severity of autism core symptoms may be associated with specific metabolic signatures; and to examine whether the urine metabolome discriminates severe from mild-to-moderate restricted, repetitive, and stereotyped behaviors. We enrolled 57 children aged 2-11 years; thirty-one with idiopathic autism and twenty-six neurotypical (NT), matched for age and ethnicity. The urine metabolome was investigated by gas chromatography-mass spectrometry (GC-MS). The urinary metabolome of autistic children was largely distinguishable from that of NT children; food selectivity induced further significant metabolic differences. Severe autism spectrum disorder core deficits were marked by high levels of metabolites resulting from diet, gut dysbiosis, oxidative stress, tryptophan metabolism, mitochondrial dysfunction. The hierarchical clustering algorithm generated two metabolic clusters in autistic children: 85-90% of children with mild-to-moderate abnormal behaviors fell in cluster II. Our results open up new perspectives for the more general understanding of the correlation between the clinical phenotype of autistic children and their urine metabolome. Adipic acid, palmitic acid, and 3-(3-hydroxyphenyl)-3-hydroxypropanoic acid can be proposed as candidate biomarkers of autism severity.
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http://dx.doi.org/10.3390/metabo10110476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700197PMC
November 2020

Human microbiome and allergy.

Pediatr Allergy Immunol 2020 11;31 Suppl 26:5-7

Neonatal Intensive Care Unit AOU, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy.

Human microbiome contributes to critical functions that impact health and disease. It influences the development of the immune system, and the pathogenesis of immunological disorders included allergy. While it is easy to understand how airway microbiome, influencing local inflammation and immune activity, could contribute to shaping asthma phenotype, it is not so obvious to understand the influence by the gut microbiome, but there is growing evidence about it. The increase of allergic disorders in western countries led to investigate the role environment is playing and how it may change our microbiome and immune system, with the hope of finding new preventive approaches for allergy.
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http://dx.doi.org/10.1111/pai.13360DOI Listing
November 2020

COVID-19 and Comorbidities: Is Inflammation the Underlying Condition in Children? A Narrative Review.

Curr Pediatr Rev 2021 ;17(1):38-44

Neonatal Intensive Care Unit, University of Cagliari, Cagliari, Italy.

This paper examines the potential link between COVID-19 and the presence of comorbidities and assesses the role of inflammation in this correlation. In COVID-19 patients, the most frequently associated diseases share a pathogenic inflammatory basis and apparently act as a risk factor in the onset of a more severe form of the disease, particularly in adulthood. However, in children, the understanding of the underlying pathogenic mechanisms is often complicated by the milder symptoms presented. A series of theories have, therefore, been put forward with a view of providing a better understanding of the role played by inflammation in this dramatic setting. All evidence available to date on this topic is discussed in this review.
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http://dx.doi.org/10.2174/1573396316666201112093920DOI Listing
January 2021

Metabolic Profile of Patients with Severe Endometriosis: a Prospective Experimental Study.

Reprod Sci 2021 Mar 10;28(3):728-735. Epub 2020 Nov 10.

Obstetrics and Gynecology, ASSL Lanusei, ATS Sardinia, Lanusei, Italy.

Endometriosis is a common disease affecting women in reproductive age. There are several hypotheses on the pathogenesis of this disease. Often, its lesions and symptoms overlap with those of many other medical and surgical conditions, causing a delay in diagnosis. Metabolomics represents a useful diagnostic tool for the study of metabolic changes during a different physiological or pathological status. We used H-NMR to explore metabolic alteration in a cohort of patients with endometriosis in order to contribute to a better understanding of the pathophysiology of the disease and to suggest new useful biomarkers. Thirty-seven patients were recruited for the metabolomic analysis: 22 patients affected by symptomatic endometriosis and 15 not affected by it. Their serum samples were collected and analyzed with H-NMR. Multivariate statistical analysis was conducted, followed by univariate and pathway analyses. Partial Least Square Discriminant Analysis (PLS-DA) was performed to determine the presence of any differences between the non-endometriosis and endometriosis samples (RX = 0.596, RY = 0.713, Q = 0.635, and p < 0.0001). β-hydroxybutyric acid and glutamine were significantly increased, whereas tryptophan was significantly decreased in the endometriosis patients. ROC curves were built to test the diagnostic power of the metabolites (β-hydroxybutyric acid: AUC = 0.85 CI = 0.71-0.99; glutamine: AUC = 0.83 CI = 0.68-0.98; tryptophan: AUC = 0.75 CI = 0.54-0.95; β-hydroxybutyric acid + glutamine + tryptophan AUC = 0.92 CI = 0.81-1). The metabolomic approach enabled the identification of several metabolic alterations occurring in women with endometriosis. These findings may provide new bases for a better understanding of the pathophysiological mechanisms of the disease and for the discovery of new biomarkers. Trial registration number NCT02337816.
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http://dx.doi.org/10.1007/s43032-020-00370-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862197PMC
March 2021

Big data in severe mental illness: the role of electronic monitoring tools and metabolomics.

Per Med 2021 Jan 30;18(1):75-90. Epub 2020 Oct 30.

Department of Surgical Sciences, Neonatal Intensive Care Unit, Neonatal Pathology & Neonatal Section, University of Cagliari, Cagliari, Italy.

There is an increasing interest in the development of effective early detection and intervention strategies in severe mental illness (SMI). Ideally, these efforts should lead to the delineation of accurate staging models of SMI enabling personalized interventions. It is plausible that big data approaches will be instrumental in describing the developmental trajectories of SMI by facilitating the incorporation of data from multiple sources, including those pertaining to the biological make-up of affected subjects. In this review, we first aimed to offer a perspective on how big data are helping the delineation of personalized approaches in SMI, and, second, to offer a quantitative synthesis of big data approaches in metabolomics of SMI. We finally described future directions of this research area.
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http://dx.doi.org/10.2217/pme-2020-0033DOI Listing
January 2021

The dark matter of microbiome: the mother-infant pair virome.

Minerva Pediatr 2020 Oct 27. Epub 2020 Oct 27.

Neonatal Intensive Care Unit, AOU Cagliari, Cagliari, Italy.

The human virome belongs to one of the most complex ecosystems in the world, the microbiome. The virome that inhabits the intestinal niche and its dynamic variation during the first year of life had been the most investigated. Many pathogenic viruses are well known to be potentially transmitted transplacentally or during vaginal delivery to the newborn, but recent studies on healthy term pregnancies found that there was no evidence of a principal viral community. In the maternalfetal dyad, human milk has been demonstrated to be one of the earliest factors involved in the direct virome transmission. Despite the relationship between humans and viruses traces its roots back to ancient times, the mother-infant pair virome has been poorly investigated and represents currently a "dark matter" of the microbiome.
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http://dx.doi.org/10.23736/S0026-4946.20.05938-1DOI Listing
October 2020

The Docosahexanoic Acid: From the Maternal-Fetal Dyad to Early Life Toward Metabolomics.

Front Pediatr 2020 30;8:538. Epub 2020 Sep 30.

Complex Structure Neonatology Unit, Department of Public Health and Paediatric, University of Turin, Turin, Italy.

Docosahexaenoic acid (DHA) is an essential ω-3 long-chain polyunsaturated fatty acid (LCPUFA) and represents the dominant structural fatty acid in the retina and in the brain's gray matter. Due to its active participation in the development of the nervous system, DHA is one of the most studied LCPUFA and is currently considered a critical nutrient during pregnancy and breastfeeding. Increasing evidence in literature suggests that an adequate concentration of DHA is required from the fetal stage through to early life to ensure optimal neurological development. Likewise, many studies in literature demonstrated that an adequate supply of DHA during pregnancy and lactation is essential to promote proper brain development in utero and in early life. Daily supplementation of DHA in newborns has potentially stronger effects compared to maternal supplementation during pregnancy. Supplementation initiated in the second year of life in children born preterm did not result in global cognitive development improvements. Preliminary findings arising from metabolomics has reported that mother's milk and infant formula supplementation of Vitamin D associated with DHA results in a higher antioxidant and protective action, with a possible positive influence on renal function and body fat on preterm infants compared to those receiving only vitamin D. Recent applications of metabolomic studies on newborns may lead to a better understanding of the metabolic process linked to early nutrition and, subsequently, to the development of targeted and personalized nutritional strategies.
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http://dx.doi.org/10.3389/fped.2020.00538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555995PMC
September 2020

Sportomics in professional soccer players: metabolomics results during preseason.

J Sports Med Phys Fitness 2021 Feb 16;61(2):324-330. Epub 2020 Sep 16.

Department of Chemical and Geological Sciences, University of Cagliari, Monserrato, Cagliari, Italy.

Background: Sportomics is the application of metabolomics to study the metabolism shifts of individuals that practice sports or do physical exercise. This aim was reached by the analysis of low molecular weight metabolites (<1.5 kDa) present in biological fluids such as blood, saliva or urine.

Methods: In this study, authors performed a H-NMR analysis of urine from 21 professional soccer players collected at 3 different time points during the preseason preparation period before the beginning of Serie A Championship (first division) in Italy.

Results: Urine profile changed during the observational period. In particular, significant variations were observed for trimethylamine-N-oxide, dimethylamine, hippuric acid, hypoxanthine, guanidoacetic acid, 3-hydroxybutyric acid, citric acid and creatine. These modifications could be related to the diet, training and microbiota. For instance, trimethylamine-N-oxide and hippuric acid are both of dietary origins but are also related to the microbiota, while 3-hydroxy-butyric acid is associated with the type of physical exercise.

Conclusions: This is the first sportomics study ever performed on professional soccer players, according to authors' knowledge. In the future, sportomics could be applied in a tailored way to choose the best diet and training program in the single individual to obtain the best possible performances and to prevent injuries of athletes.
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http://dx.doi.org/10.23736/S0022-4707.20.11200-3DOI Listing
February 2021

Comparison of Conventional Statistical Methods with Machine Learning in Medicine: Diagnosis, Drug Development, and Treatment.

Medicina (Kaunas) 2020 Sep 8;56(9). Epub 2020 Sep 8.

Neonatal Intensive Care Unit, Department of Surgical Sciences, AOU and University of Cagliari, 09042 Cagliari, Italy.

Futurists have anticipated that novel autonomous technologies, embedded with machine learning (ML), will substantially influence healthcare. ML is focused on making predictions as accurate as possible, while traditional statistical models are aimed at inferring relationships between variables. The benefits of ML comprise flexibility and scalability compared with conventional statistical approaches, which makes it deployable for several tasks, such as diagnosis and classification, and survival predictions. However, much of ML-based analysis remains scattered, lacking a cohesive structure. There is a need to evaluate and compare the performance of well-developed conventional statistical methods and ML on patient outcomes, such as survival, response to treatment, and patient-reported outcomes (PROs). In this article, we compare the usefulness and limitations of traditional statistical methods and ML, when applied to the medical field. Traditional statistical methods seem to be more useful when the number of cases largely exceeds the number of variables under study and a priori knowledge on the topic under study is substantial such as in public health. ML could be more suited in highly innovative fields with a huge bulk of data, such as omics, radiodiagnostics, drug development, and personalized treatment. Integration of the two approaches should be preferred over a unidirectional choice of either approach.
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http://dx.doi.org/10.3390/medicina56090455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560135PMC
September 2020

The dispelled hope, but not all is lost: the magic of human breast milk.

J Matern Fetal Neonatal Med 2020 Sep 1:1-2. Epub 2020 Sep 1.

Neonatal Intensive Care Unit, Department of Surgical Sciences, AOU and University of Cagliari, Monserrato, Italy.

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http://dx.doi.org/10.1080/14767058.2020.1815701DOI Listing
September 2020

Neonatal supraventricular tachycardia and necrotizing enterocolitis: case report and literature review.

Ital J Pediatr 2020 Aug 26;46(1):117. Epub 2020 Aug 26.

Neonatal Intensive Care Unit, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy.

Background: Necrotizing enterocolitis (NEC) and supraventricular tachycardia (SVT) are serious emergencies in the neonatal period. Although these conditions are recognized as distinct pathologies, literature reports suggest that recurrent episodes of SVT may predispose patients to NEC via disturbances in mesenteric blood flow and a decrease in tissue perfusion.

Case Presentation: We present a case of a preterm infant affected by recurrent episodes of SVT who developed the initial stage of NEC on the 17th day of life. Moreover, a detailed description of all the cases described in the literature is reported.

Materials And Methods: An integrative review of the updated literature in the Medline database and PubMed and scientific books and articles was conducted. The research from October 2019 to December 2019 was searched for with MeSH and free terms (necrotizing enterocolitis, supraventricular tachycardia) and was linked by Boolean operators.

Conclusions: SVT can be considered a risk factor for the development of NEC. Therefore, clinicians should have a high level of suspicion for NEC in infants affected by SVT. This article is the first structured literature review analysing the association between SVT and NEC.
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http://dx.doi.org/10.1186/s13052-020-00876-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448440PMC
August 2020

The Human Breast Milk Metabolome in Overweight and Obese Mothers.

Front Immunol 2020 21;11:1533. Epub 2020 Jul 21.

Neonatal Intensive Care Unit, Department of Surgical Sciences, AOU and University of Cagliari, Monserrato, Italy.

Pre-pregnancy body mass index (BMI) is a major relevance factor, since maternal overweight and obesity can impair the pregnancy outcome and represent risk factors for several neonatal, childhood, and adult conditions, including excessive weight gain, cardiovascular disease, diabetes mellitus, and even behavioral disorders. Currently, breast milk (BM) composition in such category of mothers was not completely defined. In this field, metabolomics represents the ideal technology, able to detect the whole profile of low molecular weight molecules in BM. Limited information is available on human BM metabolites differences in overweight or obese compared to lean mothers. Analyzing all the metabolomics studies published on Medline in English language, this review evaluated the effects that 8 specific types of metabolites found altered by maternal overweight and obesity (nucleotide derivatives, 5-methylthioadenosine, sugar-alcohols, acylcarnitine and amino acids, polyamines, mono-and oligosaccharides, lipids) can exert on the risk of offspring obesity development and other potentially associated health outcomes and complications. However, metabolites variations in samples collected from overweight and obese mothers and the potentially correlated effects highlighted below still need further investigations and should be confirmed in future metabolomics studies on larger samples. Finally, the positive or negative influence of maternal overweight and obesity on the offspring, potentially exerted by breastfeeding, should be analyzed in close correlation with maternal age, genetic and environmental factors, including diet, and taking into account the interactions occurring between BM metabolites and lactobiome. The evaluation of all the factors affecting BM metabolites in overweight and obese mothers can lead to the comprehensive description of such biofluid and the related effects on breastfed subjects, potentially highlighting personalized needs of BM supplementation or short- and long-term prevention strategies to optimize offspring health.
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http://dx.doi.org/10.3389/fimmu.2020.01533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385070PMC
July 2020

Could the E/A ratio be included in the cardiological evaluation of the offspring of diabetic mothers? A case-control study in South Sardinia.

J Matern Fetal Neonatal Med 2020 Aug 5:1-10. Epub 2020 Aug 5.

Neonatal Intensive Care Unit, Department of Surgical Sciences, AOU and University of Cagliari. SS, Monserrato, Italy.

Introduction: Diabetes mellitus (DM) is a chronic disease widespread in the world. Sardinia represents, together with Finland, the region with the highest incidence of type 1 DM (DM1), as well as a high prevalence of gestational DM (GDM). Despite the improvement in obstetric surveillance, perinatal and long-term adverse outcomes are still frequent in the offspring of diabetic mothers. During gestations complicated by DM, fetal heart is one of the most affected organ potentially undergoing structural heart defects or several degrees of fetal myocardium hypertrophy and impaired cardiac function.

Aim: The aim of our study was to evaluate, through echocardiographic examination, cardiac features and performance in a South Sardinian population of newborns of diabetic mothers comparing them to a group of control subjects.

Conclusions: In our sample, the E/A ratio resulted a significant marker of early diastolic dysfunction in asymptomatic neonates born by diabetic mothers, even if such result should be confirmed on larger samples.
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http://dx.doi.org/10.1080/14767058.2020.1798397DOI Listing
August 2020

Urinary Metabolomic Profile of Preterm Infants Receiving Human Milk with Either Bovine or Donkey Milk-Based Fortifiers.

Nutrients 2020 Jul 27;12(8). Epub 2020 Jul 27.

Department of Chemical and Geological Sciences, Cittadella Universitaria, University of Cagliari, 09042 Cagliari, Italy.

Fortification of human milk (HM) for preterm and very low-birth weight (VLBW) infants is a standard practice in most neonatal intensive care units. The optimal fortification strategy and the most suitable protein source for achieving better tolerance and growth rates for fortified infants are still being investigated. In a previous clinical trial, preterm and VLBW infants receiving supplementation of HM with experimental donkey milk-based fortifiers (D-HMF) showed decreased signs of feeding intolerance, including feeding interruptions, bilious gastric residuals and vomiting, with respect to infants receiving bovine milk-based fortifiers (B-HMF). In the present ancillary study, the urinary metabolome of infants fed B-HMF ( = 27) and D-HMF ( = 27) for 21 days was analyzed by H NMR spectroscopy at the beginning (T0) and at the end (T1) of the observation period. Results showed that most temporal changes in the metabolic responses were common in the two groups, providing indications of postnatal adaptation. The significantly higher excretion of galactose in D-HMF and of carnitine, choline, lysine and leucine in B-HMF at T1 were likely due to different formulations. In conclusion, isocaloric and isoproteic HM fortification may result in different metabolic patterns, as a consequence of the different quality of the nutrients provided by the fortifiers.
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http://dx.doi.org/10.3390/nu12082247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468788PMC
July 2020

Microbiota and Covid-19. Which came first, the chicken or the egg?

Clin Infect Dis 2020 Jul 10. Epub 2020 Jul 10.

Neonatal Intensive Care Unit, Department of Surgical Sciences, AOU and University of Cagliari. Monserrato. Italy.

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http://dx.doi.org/10.1093/cid/ciaa965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454432PMC
July 2020

Lactoferrin is an important factor when breastfeeding and COVID-19 are considered.

Acta Paediatr 2020 Oct 28;109(10):2139-2140. Epub 2020 Jun 28.

Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, AOU Cagliari, Cagliari, Italy.

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http://dx.doi.org/10.1111/apa.15417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323098PMC
October 2020

Coronavirus disease 2019, Kawasaki disease, and multisystem inflammatory syndrome in children.

J Pediatr 2020 09 12;224:184. Epub 2020 Jun 12.

Neonatal Intensive Care Unit, University of Cagliari, Cagliari, Italy.

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http://dx.doi.org/10.1016/j.jpeds.2020.06.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291990PMC
September 2020

Relationship between pregnancy and coronavirus: what we know.

J Matern Fetal Neonatal Med 2020 Jun 4:1-12. Epub 2020 Jun 4.

Neonatal Intensive Care Unit, AOU Cagliari, Cagliari, Italy.

The identification in China in December 2019 of a new coronavirus (SARS-CoV-2) immediately rekindled the spotlight on a problem also addressed in the past during the epidemics of SARS in 2002-2003 and MERS in 2012: the implications of a possible infection during pregnancy, both for pregnant women and for fetuses and infants. Pregnancy is characterized by some changes involving both the immune system and the pulmonary physiology, exposing the pregnant woman to a greater susceptibility to viral infections and more serious complications. The objective of this review is therefore to analyze the relationship between pregnancy and known coronaviruses, with particular reference to SARS-CoV-2.
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http://dx.doi.org/10.1080/14767058.2020.1771692DOI Listing
June 2020