Differential diagnosis between syndrome of inappropriate antidiuretic hormone secretion and cerebral/renal salt wasting syndrome in children over 1 year: proposal for a simple algorithm.

Hyponatremia, especially if acute and severe, can be a life-threatening condition. Several conditions can trigger hyponatremia. In this review, we will discuss two conditions that can determine euvolemic hyponatremia: the cerebral/renal salt wasting (CRSW) syndrome and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), including the two subtypes: reset osmostat (RO) and nephrogenic syndrome of inappropriate antidiuresis (NSIAD) and their differential diagnoses. Despite the passage of over 70 years since its first description, to date, the true etiopathogenesis of CRSW syndrome, a rare cause of hypovolemic/euvolemic hyponatremia, is almost unknown. SIADH, including RO and NSIAD, is sometimes difficult to differentiate from CRSW syndrome; in its differential diagnosis, the clinical approach based on the evaluation of the extracellular volume (ECV) was proven insufficient. We therefore suggest a simple diagnostic algorithm based on the assessment of the degree of hyponatremia, urinary osmolality, and the assessment of the fraction of urate excretion (FEUa) in conditions of hyponatremia and after serum sodium correction, to be applied in children over 1 year of life.

Twelve Months with COVID-19: What Gastroenterologists Need to Know.

Corona virus disease-19 (COVID-19) is the latest global pandemic. COVID-19 is mainly transmitted through respiratory droplets and, apart from respiratory symptoms, patients often present with gastrointestinal symptoms and liver involvement. Given the high percentage of COVID-19 patients that present with gastrointestinal symptoms (GIS), in this review, we report a practical up-to-date reference for the physician in their clinical practice with patients affected by chronic gastrointestinal (GI) diseases (inflammatory bowel disease, coeliac disease, chronic liver disease) at the time of COVID-19. First, we summarised data on the origin and pathogenetic mechanism of SARS-CoV-2. Then, we performed a literature search up to December 2020 examining clinical manifestations of GI involvement. Next, we illustrated and summarised the most recent guidelines on how to adhere to GI procedures (endoscopy, liver biopsy, faecal transplantation), maintaining social distance and how to deal with immunosuppressive treatment. Finally, we focussed on some special conditions such as faecal-oral transmission and gut microbiota. The rapid accumulation of information relating to this condition makes it particularly essential to revise the literature to take account of the most recent publications for medical consultation and patient care.

Children's heart and COVID-19: Up-to-date evidence in the form of a systematic review.

The new coronavirus disease outbreak in 2019 (COVID-19) represents a dramatic challenge for healthcare systems worldwide. As to viral tropism, lungs are not the only COVID-19 target but also the heart may be involved in a not negligible percentage of the infected patients. Myocarditis-related cardiac dysfunction and potentially life-threatening arrhythmias are the main aftermaths. A few studies showed that myocardial injury in adult patients is often linked with a fatal outcome. Conversely, scientific evidence in children is sparse, although several reports were published with the description of a cardiac involvement in COVID-19 paediatric patients. In these young subjects, a background of surgically treated congenital heart disease seems to be a predisposing factor.Conclusion: This systematic review is aimed at summarizing all COVID-19 cases with a cardiac involvement published in paediatric age and trying to explain the underlying mechanisms responsible for COVID-19-related myocardial damage.What is Known:• Coronaviruses proved to be able to jump from animals to humans.• The outbreak of COVID-19 started from China (Dec 2019) and became pandemic.What is New:• Even in childhood, COVID-19 is not without the risk of cardiac involvement.• Myocarditis, heart failure, and arrhythmias are among the possible manifestations.

Focus on neonatal and infantile onset of nephrogenic syndrome of inappropriate antidiuresis: 12 years later.

Nephrogenic syndrome of inappropriate antidiuresis (NSIAD), first described in 2005, is a rare genetic X-linked disease, presenting with hyponatremia, hyposmolarity, euvolemia, inappropriately concentrated urine, increased natriuresis, and undetectable or very low arginine-vasopressine (AVP) circulating levels. It can occur in neonates, infants, or later in life. NSIAD must be early recognized and treated to prevent severe hyponatremia, which can show a dangerous impact on neonatal outcome. In fact, it potentially leads to death or, in case of survival, neurologic sequelae. This review is an update of NSIAD 12 years after the first description, focusing on reported cases of neonatal and infantile onset. The different molecular patterns affecting the AVP receptor 2 (V2R) and determining its gain of function are reported in detail; moreover, we also provide a comparison between the different triggers involved in the development of hyponatremia, the evolution of the symptoms, and modality and efficacy of the different treatments available.

Fetal programming of neuropsychiatric disorders.

Starting from the Developmental Origins of Health and Disease (DOHaD) hypotheses proposed by David Barker, namely fetal programming, in the past years, there is a growing evidence of the major role played by epigenetic factors during the intrauterine life and the perinatal period. Furthermore, it has been assessed that these factors can affect the health status in infancy and even in adulthood. In this review, we focus our attention on the fetal programming of the brain, analyzing the most recent literature concerning the epigenetic factors that can influence the development of neuropsychiatric disorders such as bipolar disorders, major depressive disorders, and schizophrenia. The perinatal epigenetic factors have been divided in two main groups: maternal factors and fetal factors. The maternal factors include diet, smoking, alcoholism, hypertension, malnutrition, trace elements, stress, diabetes, substance abuse, and exposure to environmental toxicants, while the fetal factors include hypoxia/asphyxia, placental insufficiency, prematurity, low birth weight, drugs administered to the mother or to the baby, and all factors causing intrauterine growth restriction. A better comprehension of the possible mechanisms underlying the pathogenesis of these diseases may help researchers and clinicians develop new diagnostic tools and treatments to offer these patients a tailored medical treatment strategy to improve their quality of life. Birth Defects Research (Part C) 108:207-223, 2016. © 2016 Wiley Periodicals, Inc.

Metabolomic Studies in Inborn Errors of Metabolism: Last Years and Future Perspectives.

The inborn errors of metabolism (IEMs or Inherited Metabolic Disorders) are a heterogeneous group of diseases caused by a deficit of some specific metabolic pathways. IEMs may present with multiple overlapping symptoms, sometimes difficult delayed diagnosis and postponed therapies. Additionally, many IEMs are not covered in newborn screening and the diagnostic profiling in the metabolic laboratory is indispensable to reach a correct diagnosis. In recent years, Metabolomics helped to obtain a better understanding of pathogenesis and pathophysiology of IEMs, by validating diagnostic biomarkers, discovering new specific metabolic patterns and new IEMs itself. The expansion of Metabolomics in clinical biochemistry and laboratory medicine has brought these approaches in clinical practice as part of newborn screenings, as an exam for differential diagnosis between IEMs, and evaluation of metabolites in follow up as markers of severity or therapies efficacy. Lastly, several research groups are trying to profile metabolomics data in platforms to have a holistic vision of the metabolic, proteomic and genomic pathways of every single patient. In 2018 this team has made a review of literature to understand the value of Metabolomics in IEMs. Our review offers an update on use and perspectives of metabolomics in IEMs, with an overview of the studies available from 2018 to 2022.

Relationship between pregnancy and coronavirus: what we know.

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.

What to Expect from COVID-19 and from COVID-19 Vaccine for Expecting or Lactating Women.

Recent studies identified pregnancy as a high-risk condition for the development of maternal-fetal complications in the case of the SARS-CoV-2 infection. Therefore, the scientific community is now considering pregnant women a "fragile" category that should be vaccinated with high priority. The number of pregnant women undergoing hospitalization since summer 2021, including Intensive Care Unit admission, is growing, as well as the risk of preterm birth. Evidence from both animals and humans suggest that, similarly to other vaccines routinely administered in pregnancy, COVID-19 vaccines are not crossing the placenta, do not increase the risk of miscarriage, preterm birth, stillbirth, the birth of small gestational age neonates, as well as the risk of congenital abnormalities. To date, the World Health Organization and scientific literature are promoting and encouraging the vaccination of all pregnant and lactating women. The aim of our narrative review is to present the available literature regarding this issue with the aim to provide appropriate answers to the most frequent requests, doubts, and fears that have led many expecting and lactating women not to become vaccinated during this pandemic period.

Inflammatory Bowel Disease and COVID-19: How Microbiomics and Metabolomics Depict Two Sides of the Same Coin.

The integrity of the gastrointestinal tract structure and function is seriously compromised by two pathological conditions sharing, at least in part, several pathogenetic mechanisms: inflammatory bowel diseases (IBD) and coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. IBD and COVID-19 are marked by gut inflammation, intestinal barrier breakdown, resulting in mucosal hyperpermeability, gut bacterial overgrowth, and dysbiosis together with perturbations in microbial and human metabolic pathways originating changes in the blood and fecal metabolome. This review compared the most relevant metabolic and microbial alterations reported from the literature in patients with IBD with those in patients with COVID-19. In both diseases, gut dysbiosis is marked by the prevalence of pro-inflammatory bacterial species and the shortfall of anti-inflammatory species; most studies reported the decrease in Firmicutes, with a specific decrease in obligately anaerobic producers short-chain fatty acids (SCFAs), such as Faecalibacterium prausnitzii. In addition, Escherichia coli overgrowth has been observed in IBD and COVID-19, while Akkermansia muciniphila is depleted in IBD and overexpressed in COVID-19. In patients with COVID-19, gut dysbiosis continues after the clearance of the viral RNA from the upper respiratory tract and the resolution of clinical symptoms. Finally, we presented and discussed the impact of gut dysbiosis, inflammation, oxidative stress, and increased energy demand on metabolic pathways involving key metabolites, such as tryptophan, phenylalanine, histidine, glutamine, succinate, citrate, and lipids.

COVID-19 Vaccination in Children: An Open Question.

BACKGROUND: A safe and effective vaccine represents the best way to control the COVID-19 pandemic, which has caused more than 4 million deaths to date. Several vaccines have now been approved worldwide, depending on the country. Being administered to healthy people, anti-SARS-CoV-2 vaccines must meet high safety standards, and this is even more important among the pediatric population in which the risk of developing severe disease is significantly lower than adults. However, vaccination of the pediatric population could help in reducing viral spread in the whole population. OBJECTIVE: Our narrative review analyzes and discusses the currently available literature on the advantages and disadvantages of COVID-19 vaccination in the pediatric population. METHODS: A bibliographic research was conducted through Pubmed, Read, and Scopus using COVID-19, SARS-CoV-2, immunization, antibody, COVID-19 vaccine efficacy, COVID-19 vaccine safety, children, adolescents, MIS-C, adverse effects as keywords. RESULTS: Although children are less susceptible to COVID-19 infection, they can develop serious consequences, including multi-inflammatory syndrome. However, any vaccine-related side effects should be evaluated before administering vaccination to children while ensuring complete safety. To date, adverse effects are reported in adolescents and young adults following vaccination; however, these are mostly isolated reports. CONCLUSION: Further investigation is needed to establish whether there is indeed a cause-and-effect relationship in the development of vaccine-related adverse effects. However, to date, COVID-19 vaccination is recommended for children and adolescents older than 12 years of age. However, this question is still under debate and involves ethical, political, and social issues.

Risk, Course, and Effect of SARS-CoV-2 Infection in Children and Adults with Chronic Inflammatory Bowel Diseases.

Susceptibility and disease course of COVID-19 among patients with inflammatory bowel diseases (IBD) are unclear and epidemiological data on the topic are still limited. There is some concern that patients with immuno-mediated diseases such as IBD, which are frequently treated with immunosuppressive therapies, may have an increased risk of SARS-CoV-2 infection with its related serious adverse outcomes, including intensive care unit (ICU) admission and death. Corticosteroids, immunomodulators, and biologic drugs, which are commonly prescribed to these patients, have been associated with higher rates of severe viral and bacterial infections including influenza and pneumonia. It is not known whether these drugs can be so harmful as to justify their interruption during COVID-19 infection or if, on the contrary, patients with IBD can benefit from them. As shown by recent reports, it cannot be excluded that drugs that suppress the immune system can block the characteristic cytokine storm of severe forms of COVID-19 and consequently reduce mortality. Another cause for concern is the up-regulation of angiotensin converting enzyme-2 (ACE2) receptors that has been noticed in these patients, which could facilitate the entry and replication of SARS-CoV-2. The aim of this narrative review is to clarify the susceptibility of SARS-CoV-2 infection in patients with IBD, the clinical characteristics of patients who contract the infection, and the relationship between the severity of COVID-19 and immunosuppressive treatment.

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

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.

COVID-19 and School: To Open or Not to Open, That Is the Question. The First Review on Current Knowledge.

The COVID-19 pandemic has led to an unprecedented closure of schools in terms of duration. The option of school closure, SARS-CoV-2 initially being poorly known, was influenced by the epidemiological aspects of the influenza virus. However, school closure is still under debate and seems unsupported by sure evidence of efficacy in the COVID-19 era. The aim of our narrative review is to discuss the available literature on SARS-CoV-2 spread among children and adolescents, in the school setting, trying to explain why children appear less susceptible to severe disease and less involved in viral spreading. We also tried to define the efficacy of school closure, through an overview of the effects of the choices made by the various countries, trying to identify which preventive measures could be effective for a safe reopening. Finally, we focused on the psychological aspects of such a prolonged closure for children and adolescents. SARS-CoV-2, children, COVID-19, influenza, and school were used as key words in our literature research, updated to 29 March 2021. To our knowledge, this is the first review summarizing the whole current knowledge on SARS-CoV-2 spreading among children and adolescents in the school setting, providing a worldwide overview in such a pandemic context.

COVID-19 and developmental origins of health and disease.

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-fetal­neonatal 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.

Thiamine as a Possible Neuroprotective Strategy in Neonatal Hypoxic-Ischemic Encephalopathy.

On the basis that similar biochemical and histological sequences of events occur in the brain during thiamine deficiency and hypoxia/ischemia related brain damage, we have planned this review to discuss the possible therapeutic role of thiamine and its derivatives in the management of neonatal hypoxic-ischemic encephalopathy (HIE). Among the many benefits, thiamine per se as antioxidant, given intravenously (IV) at high doses, defined as dosage greater than 100 mg IV daily, should counteract the damaging effects of reactive oxygen and nitrogen species in the brain, including the reaction of peroxynitrite with the tyrosine residues of the major enzymes involved in intracellular glucose metabolism, which plays a key pathophysiological role in HIE in neonates. Accordingly, it is conceivable that, in neonatal HIE, the blockade of intracellular progressive oxidative stress and the rescue of mitochondrial function mediated by thiamine and its derivatives can lead to a definite neuroprotective effect. Because therapeutic hypothermia and thiamine may both act on the latent period of HIE damage, a synergistic effect of these therapeutic strategies is likely. Thiamine treatment may be especially important in mild HIE and in areas of the world where there is limited access to expensive hypothermia equipment.

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

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.

Neonatal Congenital Central Hypoventilation Syndrome: Why We Should not Sleep on it. Literature Review of Forty-two Neonatal Onset Cases.

Congenital Central Hypoventilation Syndrome (CCHS), also referred with the expression "Ondine's Curse", is a rare genetic life-long disease resulting from the mutation of PHOX2B gene on chromosome 4p12.3. CCHS represents an autonomic nervous system disorder; its more fearsome manifestation is central hypoventilation, due to a deficient response of chemoreceptors to hypercapnia and hypoxia. Several associated symptoms can occur, such as pupillary anomalies, arrhythmias, reduced heart rate variability, esophageal dysmotility, and structural comorbidities (Hirschsprung's Disease or neural crest tumours). CCHS typical onset is during the neonatal period, but cases of delayed diagnosis have been reported; moreover, both sporadic or familial cases can occur. In preterm newborns, asphyxia and typical prematurity-related findings may overlap CCHS clinical manifestations and make it harder to formulate a correct diagnosis. The early recognition of CCHS allows appropriate management, useful to reduce immediate and long- term consequences.

The first case of neonatal priapism during hypothermia for hypoxic-ischemic encephalopathy and a literature review.

Neonatal priapism is a rare condition with only 26 described cases in literature since 1879. It is defined as a persistent penile erection occurring in the first 28 days of life, lasting at least 4 h that usually happens in the first days (from 2 to 12 days). It is a very different condition compared to the adult one because in newborns it is a relatively benign phenomenon. As a result of this paucity of described cases, classification and management are not well known by most of neonatologists and currently there are no established guidelines for its management. Most cases are idiopathic but other aetiologies are possible (polycythemia, blood transfusion and drugs). We describe our only case, which occurred during hypothermia therapy and review the literature to clarify the best choice in management of this rare entity.

Urinary 1H-NMR Metabolomics in the First Week of Life Can Anticipate BPD Diagnosis.

Despite the advancements in medical knowledge and technology, the etiopathogenesis of bronchopulmonary dysplasia (BPD) is not yet fully understood although oxidative stress seems to play a role, leading to a very demanding management of these patients by the neonatologist. In this context, metabolomics can be useful in understanding, diagnosing, and treating this illness since it is one of the newest omics science that analyzes the metabolome of an individual through the investigation of biological fluids such as urine and blood. In this study, 18 patients admitted to the Neonatal Intensive Care Unit of the Cagliari University Hospital were enrolled. Among them, 11 patients represented the control group and 7 patients subsequently developed BPD. A sample of urine was collected from each patient at 7 days of life and analyzed through 1H-NMR coupled with multivariate statistical analysis. The discriminant metabolites between the 2 groups noted were alanine, betaine, trimethylamine-N-oxide, lactate, and glycine. Utilizing metabolomics, it was possible to detect the urinary metabolomics fingerprint of neonates in the first week of life who subsequently developed BPD. Future studies are needed to confirm these promising results suggesting a possible role of microbiota and oxidative stress, and to apply this technology in clinical practice.