Novel insect-based child nutrition: the position of the nutritional committee of the Italian society of pediatric gastroenterology, hepatology and nutrition (SIGENP).

BACKGROUND: The European Union (EU) approved the placement on European market of insect-based novel foods. Those foods were defined safe for the consumption for all European population, including children. MAIN BODY: The nutrition committee of the Italian society of Paediatric Hepatology and Nutrition (SIGENP) performed literature research to understand benefits and risk of those use of those NF for Italian children. A special attention was reserved to the European Food Safety Agency (EFSA) reports upon which those novel insect-based were approved. CONCLUSIONS: Based on the current knowledge, despite a possible ecological advantage, the group of expert suggests additional researches before pronouncing on a possible use for children diet, because of insufficient evidence on nutritional benefits and possible food allergies.

Trends and challenges in home enteral feeding methods for children with gastrointestinal disorders: an expert review on bolus feeding delivery methods.

INTRODUCTION: New evidence supports the benefits of bolus feeding for children receiving home enteral feeding (HEN). Current home methods of bolus feeding have certain limitations, particularly in mobile or restless patients. Therefore, innovative delivery methods have been introduced to provide more flexible methods of reducing feeding time and formula handling. AREAS COVERED: This manuscript presents an expert review of the updates in HEN for children and the results of an online user experience questionnaire about an innovative new cap-based bolus feeding system. A literature bibliographic search was conducted on Medline via PubMed up to September 2023 to collect relevant studies. We presented recent evidence demonstrating a dramatic increase in HEN use among children requiring EN and its benefits on patients' nutritional status and quality of life. In addition, the article examined the clinical and social benefits of bolus feeding and current challenges in delivery methods. We described the benefits of the new system and its user experience. EXPERT OPINION: The uses and indications for bolus feeding in HEN are increasing among children. However, there are still some unmet needs regarding traditional delivery methods. Innovative techniques can improve flexibility, reduce feeding time, and improve user experience and quality of life.

Pediatric Nutrition in Different Countries.

In this Special Issue, titled "Pediatric Nutrition in Different Countries", we give concise and straightforward information on the nutritional habits of children in different countries worldwide [...].

Effects of COVID-19 pandemic on pediatric tuberculosis: decrease in notification rates and increase in clinical severity.

The outbreak of COVID-19 resulted in a decrease in tuberculosis notification rates globally. We compared tuberculosis incidence rates and disease severity in children seen in our centre prior and during COVID-19 pandemic.We performed a cohort study enrolling children aged under 18 years who received a diagnosis of tuberculosis (January 1st, 2010-December 31st, 2021) at our Pediatric Infectious Diseases Unit. Disease severity was evaluated based on: the classification proposed by Wiseman et al., smear positivity, presence of symptoms at presentation, lung cavitation, extrapulmonary disease, respiratory failure and need for intensive care support. Overall, 168 children (50.6% female, median age 69 months, IQR 95.4) received a diagnosis of tuberculosis, 156 (92.8%) between 2010-2019, before COVID-19 outbreak, and 12 (7.2%) between 2020-2021, during the pandemic. The annual tuberculosis notification rate dropped by 73% in 2021 (0.38/100000, 95%CI 0.1-0.96) compared with 2019 (1.46/100000, 95%CI 0.84-2.37). Compared to the pre-pandemic period, the proportion of children classified as severe was higher in 2020-2021 (5, 41.6% vs 23, 15.7%, p = 0.006) with a higher rate of respiratory failure (2, 16.7%, vs 4, 2.6%, p = 0.01) and an increased need for intensive care support (1, 8.3% vs 1, 0.6%, p = 0.01).   Conclusion: During COVID-19 pandemic we observed a reduction in tuberculosis notification rate in pediatric population and a significant increase in disease severity. This scenario may be the consequence of a delay in diagnosis and an underreporting of cases, rather than the effect of a reduced transmission of tuberculosis. Children reached health-care services only in the need of urgent medical attention. What is Known: • COVID-19 pandemic had a huge impact on national health care systems, resulting in a reduction of access to medical care. What is New: • In Campania Region, Italy, a low tuberculosis incidence country, we witnessed a 75% reduction in tuberculosis notification rate during pandemic. In parallel we demonstrated a significant increase in disease severity, suggesting that the reduction in notification rate may be attributed to an underreporting of cases and consequential diagnostic delay, rather than a reduced transmission of infection.

Pitfalls and Risks of "New Eating Disorders": Let the Expert Speak!

Since the post-pandemic period, there has been an increase in the incidence of eating disorders (EADs) and a lowering of the age of onset. In addition to the 'classic' forms, there has also been an increase in new forms of EADs. This article proposes a brief review of the literature concerning mainly two of these new disorders: atypical anorexia and avoidant/restrictive food intake disorder. In addition, a brief overview is proposed of the most frequently raised questions that clinicians may face when dealing with EADs. The answers are provided by doctors from the Federico II University of Naples, who additionally offer the most common red flags on the topic derived from long clinical experience. This article is proposed to be a brief operational guide for all clinicians working in the pediatric area in order to provide diagnostic clues and useful elements to refer patients to specialists for a correct and multidisciplinary treatment.

IFALD in children: What's new? A narrative review.

Intestinal failure-associated liver disease (IFALD) is a progressive liver disease complicating intestinal failure (IF). It is a preventable and reversible condition, but at the same time, a potential cause of liver cirrhosis and an indication to combined or non-combined liver and small bowel transplantation. The diagnostic criteria are not yet standardized, so that its prevalence varies widely in the literature. Pathophysiology seems to be multifactorial, related to different aspects of intestinal failure and not only to the long-term parenteral nutrition treatment. The survival rates of children with IF have increased, so that the main problems today are preventing complications and ensuring a good quality of life. IFALD is one of the most important factors that limit long-term survival of patients with IF. For this reason, more and more interest is developing around it and the number of published articles is increasing rapidly. The purpose of this narrative review was to focus on the main aspects of the etiology, pathophysiology, management, prevention, and treatment of IFALD, based on what has been published mainly in the last 10 years. Controversies and current research gaps will be highlighted with the aim to pave the way for new project and high-quality clinical trials.

Seronegative Villous Atrophy in Children: Clinical and Immunohistochemical Features.

OBJECTIVES: Villous atrophy (VA) is not pathognomonic of celiac disease (CD). We aimed at reporting distribution, clinical, and immunohistochemical features of seronegative VA (SNVA) in a pediatric population. METHODS: We retrospectively collected data from patients who underwent intestinal biopsies between 2010 and 2017 and showed VA without serum CD-associated autoantibodies. Marsh-Oberhuber grading was used. Density of intraepithelial lymphocytes (IELs) expressing CD3 or TCRγδ+ receptor and of lamina propria CD25+ cells was assessed by immunohistochemistry. Intestinal deposits of anti-tissue tranglutaminase2 (anti-TG2) were also investigated by double immunofluorescence. RESULTS: Over a 7-year period, 64 out of 1282 patients with VA had negative serum CD serology. Diagnoses were: inflammatory bowel diseases (IBD) (21/64), Gastro-Esophageal Reflux Disease (GERD) (12/64), food allergy (8/64), infections (7/64, of which 3 HIV infections), immune deficiency (3/64), short bowel syndrome (3/64), congenital diarrhea (2/64), other/inconclusive diagnosis (8/64). Forty-four, 15, and 5 showed Marsh 3a, 3b, and 3c lesion, respectively. The latter category included 2 patients with Crohn disease, 2 with immunodeficiencies, 1 with lymphohistiocytosis. In 41/46 (89%) patients, mononuclear CD25+ cells were above the cut-off, indicating mucosal inflammation but only 18/46 (39%) had IELs and TCRγδ + IELs above limits of normality. In 10 of 46 (22%) patients, a positive immunofluorescence indicated the presence of anti-TG2 mucosal antibodies. CONCLUSIONS: SNVA is not rare representing up to 5% of the cases of VA. Most patients have a Marsh 3a lesion. Immunohistochemical analysis may be helpful in excluding CD, whereas the finding of mucosal anti-TG2, particularly with a weak staining, shows no absolute specificity for CD.

Novel ACTG2 variants disclose allelic heterogeneity and bi-allelic inheritance in pediatric chronic intestinal pseudo-obstruction.

Variants in the ACTG2 gene, encoding a protein crucial for correct enteric muscle contraction, have been found in patients affected with chronic intestinal pseudo-obstruction, either congenital or late-onset visceral myopathy, and megacystis-microcolon-intestinal hypoperistalsis syndrome. Here we report about ten pediatric and one adult patients, from nine families, carrying ACTG2 variants: four show novel still unpublished missense variants, including one that is apparently transmitted according to a recessive mode of inheritance. Four of the remaining five probands carry variants affecting arginine residues, that have already been associated with a severe phenotype. A de novo occurrence of the variants could be confirmed in six of these families. Since a genotype-phenotype correlation is affected by extrinsic factors, such as, diagnosis delay, quality of clinical management, and intra-familial variability, we have undertaken 3D molecular modeling to get further insights into the effects of the variants here described. The present findings and further ACTG2 testing of patients presenting with intestinal pseudo-obstruction, will improve our understanding of visceral myopathies, including implications in the prognosis and genetic counseling of this set of severe disorders.

Moving on: How to switch young people with chronic intestinal failure from pediatric to adult care. a position statement by italian society of gastroenterology and hepatology and nutrition (SIGENP) and italian society of artificial nutrition and metabolism (SINPE).

In 2019 the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and the Italian Society of Artificial Nutrition and Metabolism (SINPE) created a joint panel of experts with the aim of preparing an official statement on transition in Chronic Intestinal Failure (CIF). The transition from pediatric to adult care has a key role in managing all chronic diseases and in optimizing the compliance to care. Thus SIGENP and SINPE, in light of the growing number of patients with IF who need long-term Parenteral Nutrition (PN) and multidisciplinary rehabilitation programs throughout adulthood, shared a common protocol to provide an accurate and timely process of transition from pediatric to adult centers for CIF. The main objectives of the transition process for CIF can be summarized as the so-called "acronym of the 5 M": 1)Motivate independent choices which are characteristics of the adult world; 2)Move towards adult goals (e.g. self-management of his pathology and sexual issues); 3)Maintain the habitual mode of care; 4) Minimize the difficulties involved in the transition process and 5)Modulate the length of the transition so as to fully share with the adult's team the children's peculiarities.

Increasing Tuberculosis Rates and Association With Migration in Children Living in Campania Region, Southern Italy: A 10-Year Cohort Study.

BACKGROUND: Italy is classified as a low tuberculosis (TB) incidence country (rate 6.5/100,000 inhabitants). However, the Campania Region Pediatric Reference Centre (CRRC) observed an increase in TB, contemporarily with a rise in migration.Our aim was to investigate trends in TB notification rates, association with migration, and changes in clinical outcomes of children living in Campania. METHODS: We conducted a prospective cohort study (January 1, 2009-December 31, 2018), including children <18 years who received diagnosis of TB at the CRRC. Yearly crude TB incidence rates and relative confidence interval (95% CI) were calculated. Two main outcome measures were considered: loss to follow-up and poor clinical outcome, including prolonged or second-line treatment, sequelae, or death. RESULTS: Overall 146 children (52.1% male; median age, 50 months; interquartile range, 96.33) received a diagnosis of TB. TB incidence rates increased from 0.44 cases (95% CI: 0.16-0.97) per 100,000 inhabitants <18 years of age in 2009 to 1.84 cases (95% CI: 1.15-2.79) in 2018 (P < 0.05) and linearly correlated with the rate of migrants (R = 0.9272; P < 0.0001). Ziehl-Neelsen-positive children had an increased likelihood of poor clinical outcomes (odds ratio, 4.83; 95% CI: 1.28-18.2; P = 0.020). Compared with Italians, foreign children showed a lower likelihood of cure without sequelae (49.3% versus 67.9%; P < 0.001; odds ratio, 0.45; 95% CI: 0.23-0.89; P = 0.02). They accounted for all fatal cases and loss to follow-up. CONCLUSION: Pediatric TB rate in Campania increased in the last 10 years in association with the increase in migration. Emphasizing national TB rates may disregard important differences in local infection trends and limit medical awareness about TB. Foreign children may need tailored management programs.

To Wean or Not to Wean: The Role of Autologous Reconstructive Surgery in the Natural History of Pediatric Short Bowel Syndrome on Behalf of Italian Society for Gastroenterology, Hepatology and Nutrition (SIGENP).

Pediatric Short Bowel Syndrome (SBS) can require prolonged parenteral nutrition (PN). Over the years, SBS management has been implemented by autologous gastrointestinal reconstructive surgery (AGIR). The primary objective of the present review was to assess the effect of AGIR on weaning off PN. We also evaluated how AGIR impacts survival, the need for transplantation (Tx) and the development of liver disease (LD). We conducted a systematic literature search to identify studies published from January 1999 to the present and 947 patients were identified. PN alone was weakly associated with higher probability of weaning from PN (OR = 1.1, p = 0.03) and of surviving (OR = 1.05, p = 0.01). Adjusting for age, the probability of weaning off PN but of not surviving remained significantly associated with PN alone (OR = 1.08, p = 0.03). Finally, adjusting for age and primary diagnosis (gastroschisis), any association was lost. The prevalence of TX and LD did not differ by groups. In conclusion, in view of the low benefit in terms of intestinal adaptation and of the not negligible rate of complications (20%), a careful selection of candidates for AGIR should be required. Bowel dilation associated with failure of advancing EN and poor growth, should be criteria to refer for AGIR.

Randomised Clinical Trial: Calorie Restriction Regimen with Tomato Juice Supplementation Ameliorates Oxidative Stress and Preserves a Proper Immune Surveillance Modulating Mitochondrial Bioenergetics of T-Lymphocytes in Obese Children Affected by Non-Alcoholic Fatty Liver Disease (NAFLD).

Fatty liver disease is a serious complication of childhood obesity. Calorie-restricted regimen (RCR) is one of the effective therapy for this condition. Aim of the study was to evaluate the effect of lycopene-rich tomato sauce with oregano and basil extracts in obese children with fatty liver on RCR. 61 obese children with fatty liver were enrolled, 52 completed the study. A randomized cross over clinical trial was performed. Participants were assigned to RCR alone or with a supplement of lycopene-rich tomato juice for 60 days; subsequently, the groups were switched to the alternative regimen for the next 60 days. Reduction in BMI, HOMA-IR, cholesterol, triglycerides, liver size, and steatosis was more profound in tomato-supplemented group. Leptin decreased in both groups whereas adiponectin raised only after tomato supplementation. RCR is associated with the impaired engagement of T-cells glycolysis and proliferation, tomato-supplementation resulted in glycolytic metabolic activation of T-cells. Tomato juice ameliorates glucose and lipid metabolism in obese children, improve oxidative and inflammatory state and modulates the mitochondrial metabolism of T-cells contributing to a maintenance of a proper immune surveillance in children, impaired by RCR. The addition of tomato to RCR could be considered a protective and preventive support to obese child.

Case report: horse or zebra, ascites or pseudo-ascites? Care for pictural details!

BACKGROUND: Pseudo-ascites is a very rare condition in children and remains a challenging diagnosis. Targeted imaging may be helpful, but a high index of clinical suspicion is often necessary to guide the investigations, as pseudo-ascites may efficiently mimic true ascites. To date, still many cases of pseudo-ascites suffer diagnostic and therapeutic delay, and some are only diagnosed during surgical exploration. We report the case of a patient with a late laparoscopic diagnosis of pseudo-ascites. We retrospectively review our patient's imaging findings and suggest new characteristic features which may help differentiate pseudo-ascites from true ascites. CASE PRESENTATION: A 7-month-old infant was referred for a progressive abdominal distention. Physical examination and initial ultra-sonographic findings evoked free ascites. An extensive diagnostic workup was then performed and was negative for hepatic, renal, cardiac, intestinal, pancreatic, inflammatory or infectious diseases, malignancy and congenital metabolic disorders. Pseudo-ascites was evoked and dedicated ultra-sonographic and magnetic resonance studies were repeated but could not confirm this diagnosis. Symptomatic diuretic treatment with spironolactone and furosemide was then started. A temporary and limited effect was noted but, with time, repeated paracenteses were necessary as the abdominal distention progressed causing discomfort and breathing difficulty. Last, because the patient's quality of life deteriorated, a peritoneal-venous shunting was proposed; as the operation started with a diagnostic laparoscopy, a benign giant cystic mesenteric lymphangioma was identified and totally excised. The resolution of symptoms was immediate and the patient remained symptom-free throughout the subsequent observation period that lasted more than 1 year. CONCLUSIONS: Increased awareness about pseudo-ascites is necessary, as the diagnosis is often overlooked, and treatment delayed. Targeted imaging may be helpful, as some specific, although not pathognomonic, features exist which may aid in the diagnosis.

Daily Fructose Traces Intake and Liver Injury in Children with Hereditary Fructose Intolerance.

BACKGROUND: Hereditary fructose intolerance (HFI) is a rare genetic disorder of fructose metabolism due to aldolase B enzyme deficiency. Treatment consists of fructose, sorbitol, and sucrose (FSS)-free diet. We explore possible correlations between daily fructose traces intake and liver injury biomarkers on a long-term period, in a cohort of young patients affected by HFI. METHODS: Patients' clinical data and fructose daily intake were retrospectively collected. Correlations among fructose intake, serum alanine aminotransferase (ALT) level, carbohydrate-deficient transferrin (CDT) percentage, liver ultrasonography, genotype were analyzed. RESULTS: We included 48 patients whose mean follow-up was 10.3 ± 5.6 years and fructose intake 169 ± 145.4 mg/day. Eighteen patients had persistently high ALT level, nine had abnormal CDT profile, 45 had signs of liver steatosis. Fructose intake did not correlate with ALT level nor with steatosis severity, whereas it correlated with disialotransferrin percentage (R2 0.7, p < 0.0001) and tetrasialotransferrin/disialotransferrin ratio (R2 0.5, p = 0.0001). p.A150P homozygous patients had lower ALT values at diagnosis than p.A175D variant homozygotes cases (58 ± 55 IU/L vs. 143 ± 90 IU/L, p = 0.01). CONCLUSION: A group of HFI patients on FSS-free diet presented persistent mild hypertransaminasemia which did not correlate with fructose intake. Genotypes may influence serum liver enzyme levels. CDT profile represents a good marker to assess FSS intake.

Metabolism and Autoimmune Responses: The microRNA Connection.

Distinct metabolic pathways are known to regulate growth, differentiation, survival, and activation of immune cells by providing energy and specific biosynthetic precursors. Compelling experimental evidence demonstrates that effector T cell functions are coupled with profound changes in cellular metabolism. Importantly, the effector T cell-dependent "anti-self" response characterizing the autoimmune diseases is accompanied by significant metabolic alterations. MicroRNAs (miRNAs), evolutionary conserved small non-coding RNA molecules that affect gene expression by binding to target messenger RNAs, are now known to regulate multiple functions of effector T cells, including the strength of their activation, thus contributing to immune homeostasis. In this review, we will examine the most recent studies that describe miRNA direct involvement in the metabolic reprogramming that marks effector T cell functions. In particular, we will focus on the work showing a connection between miRNA regulatory function and the molecular network dysregulation that leads to metabolic pathway derangement in autoimmunity. Finally, we will also speculate on the possibility that the interplay between miRNAs and metabolism in T cells may help identify novel miRNA-based therapeutic strategies to treat effector T cell immunometabolic alterations in pathological conditions such as autoimmunity and chronic inflammation.

Tubercular hemoptysis in a young liver transplanted patient: Case report.

RATIONALE: Liver transplanted patients have excellent survival rates, but infectious complications are a major cause of morbidity and mortality. Diagnosis and treatment of tuberculosis (TB) in liver recipients are very challenging. Specific recommendations for anti-TB treatment in liver transplanted patients are lacking. PATIENT CONCERNS AND DIAGNOSIS: A 22-year-old male liver transplanted patient because of biliary atresia showed unexpected acute hemoptysis while he was on immunosuppressive therapy with tacrolimus and mycophenolate mofetil. Computed tomography (CT) identified a pulmonary arteriovenous malformation (PAVM) successfully treated with endovascular embolization. A post-embolization thoracic CT revealed pulmonary cavitation and miliary pattern suggesting pulmonary TB causing PAVM. TB diagnosis was confirmed by microbiological assays and genetic amplification techniques. INTERVENTION: Anti-TB 4-drug regimen was started. Following the beginning of treatment, liver enzymes increased. In order to clarify if liver cytolysis was due to hepatotoxicity or hepatic rejection linked to the reduction of immunosuppression or a worsening of pre-existing graft hepatitis, a liver biopsy was performed. A mild graft rejection was found so that tacrolimus doses were increased despite the risk of tubercular dissemination. OUTCOME: The patient completed anti-TB therapy in 8 months with resolution of TB disease and stable liver disease. LESSONS: TB management in liver transplanted patients is challenging and needs to be individualized especially if chronic graft hepatitis is present.

Type 2 Diabetes: How Much of an Autoimmune Disease?

Type 2 diabetes (T2D) is characterized by a progressive status of chronic, low-grade inflammation (LGI) that accompanies the whole trajectory of the disease, from its inception to complication development. Accumulating evidence is disclosing a long list of possible "triggers" of inflammatory responses, many of which are promoted by unhealthy lifestyle choices and advanced age. Diabetic patients show an altered number and function of immune cells, of both innate and acquired immunity. Reactive autoantibodies against islet antigens can be detected in a subpopulation of patients, while emerging data are also suggesting an altered function of specific T lymphocyte populations, including T regulatory (Treg) cells. These observations led to the hypothesis that part of the inflammatory response mounting in T2D is attributable to an autoimmune phenomenon. Here, we review recent data supporting this framework, with a specific focus on both tissue resident and circulating Treg populations. We also propose that selective interception (or expansion) of T cell subsets could be an alternative avenue to dampen inappropriate inflammatory responses without compromising immune responses.