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Cystic fibrosis (CF)-related diabetes mellitus is an unusual complication in very young pediatric patients with CF. It is generally associated with more severe clinical manifestations of CF. In this report, we describe a case of diabetes and CF starting in infancy. The patient manifested a form of intermittent diabetes without fasting hyperglycemia, which was exacerbated by steroid treatment during pulmonary disease and occasionally required insulin therapy. Insulin responses to oral and intravenous glucose challenge were low. The clinical and radiological status was stable during the 9-yr follow-up. Our patient demonstrates that diabetes may not only represent a complication of CF, as previously maintained, but can also be a co-morbid condition proceeding along with the exocrine disease. The early occurrence of hyperglycemia in this case may highlight an impairment of beta-cell function, which might be genetically determined. Careful monitoring of the glucose profile and of beta-cell function is indicated in patients with CF to avoid late recognition of diabetes. [ABSTRACT FROM AUTHOR]

Background: Acute liver failure (ALF) may be the first and most dramatic presentation of Wilson's disease (WD). ALF due to WD (WD-ALF) is difficult to distinguish from other causes of liver disease and is a clear indication for liver transplantation. There is no firm recommendation on specific and supportive medical treatment for this condition., Aim: To critically evaluate the diagnostic and therapeutic management of WD-ALF patients in order to improve their survival with native liver., Methods: A retrospective analysis of patients with WD-ALF was conducted in two pediatric liver units from 2018 to 2023., Results: During the study period, 16 children (9 males) received a diagnosis of WD and 2 of them presented with ALF. The first was successfully treated with an unconventional combination of low doses of D-penicillamine and zinc plus steroids, and survived without liver transplant. The second, exclusively treated with supportive therapy, needed a hepatotransplant to overcome ALF., Conclusion: Successful treatment of 1 WD-ALF patient with low-dose D-penicillamine and zinc plus steroids may provide new perspectives for management of this condition, which is currently only treated with liver transplantation., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Alagille syndrome (ALGS) is a rare autosomal dominant genetic disease caused by pathogenic variants in two genes: Jagged Canonical Notch Ligand 1 ( JAG1 ) and Notch Receptor 2 ( NOTCH2 ). It is characterized by phenotypic variability and incomplete penetrance with multiorgan clinical signs., Methods: Using Next Generation Sequencing (NGS), we analyzed a panel of liver-disease-related genes in a population of 230 patients with cholestasis and hepatopathies. For the rare variants, bioinformatics predictions and pathogenicity classification were performed., Results: We identified eleven rare NOTCH2 variants in 10 patients, two variants being present in the same patient. Ten variants had never been described before in the literature. It was possible to classify only two null variants as pathogenic, whereas the most of variants were missense (8 out of 11) and were classified as uncertain significance variants (USVs). Among patients with ALGS suspicion, two carried null variants, two carried variants predicted to be pathogenic by bioinformatics, one carried a synonymous variant and variants in glycosylation-related genes, and two carried variants predicted as benign in the PEST domain., Conclusions: Our results increased the knowledge about NOTCH2 variants and the related phenotype, allowing us to improve the genetic diagnosis of ALGS.

Background: Oral nutritional supplements (ONSs) are crucial for supporting the nutritional needs of pediatric populations, particularly those with medical conditions or dietary deficiencies. Bioactive compounds within ONSs play a pivotal role in enhancing health outcomes by exerting various physiological effects beyond basic nutrition. However, the comprehensive understanding of these bioactives in pediatric ONSs remains elusive., Objective: This systematic narrative review aims to critically evaluate the existing literature concerning bioactive compounds present in oral nutritional supplements from a pediatric standpoint, focusing on their types, sources, bioavailability, physiological effects, and clinical implications., Methods: A systematic search was conducted across the major academic databases, including PubMed, Scopus, and Web of Science, employing predefined search terms related to oral nutritional supplements, bioactives, and pediatrics. Studies published between 2013 and 2024 were considered eligible for inclusion. Data extraction and synthesis were performed according to the PRISMA guidelines., Results: The initial search yielded 558 of articles, of which 72 met the inclusion criteria. The included studies encompassed a diverse range of bioactive compounds present in pediatric ONS formulations, including, but not limited to, vitamins, minerals, amino acids, prebiotics, probiotics, and phytonutrients. These bioactives were sourced from various natural and synthetic origins and were found to exert beneficial effects on growth, development, immune function, gastrointestinal health, cognitive function, and overall well-being in pediatric populations. However, variations in bioavailability, dosing, and clinical efficacy were noted across different compounds and formulations., Conclusions: Bioactive compounds in oral nutritional supplements offer promising avenues for addressing the unique nutritional requirements and health challenges faced by pediatric populations. However, further research is warranted to elucidate the optimal composition, dosage, and clinical applications of these bioactives in pediatric ONS formulations. A deeper understanding of these bioactive compounds and their interplay with pediatric health may pave the way for personalized and effective nutritional interventions in pediatric clinical practice.

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.

Background: Intractable diarrhea (ID) could be defined as a syndrome of severe chronic diarrhea associated with malnutrition not easily resolved by conventional management., Aims: To provide an overview on etiology and management of ID patients in Italy in the last 12 years., Methods: The members of Italian Society for Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) enrolled all ID patients seen between January 1, 2011 and December 31, 2022., Results: 69 children were enrolled (49 M, 20 F; median age at ID onset 9.5 days) from 7 tertiary care pediatric centers. Overall 62 patients had genetic diseases; 3 had infantile Inflammatory Bowel Disease and 1 autoimmune enteropathy in absence of genetic mutations; 2 undefined ID. Defects of intestinal immune-related homeostasis caused ID in 29 patients (42 %)., Conclusion: ID is a rare but challenging problem, although the potential for diagnosis has improved over time. In particular, molecular analysis allowed to identity genetic defects in 90 % of patients and to detect new genetic mutations responsible for ID. Due to both the challenging diagnosis and the treatment for many of these diseases, the close relationship between immune system and digestive tract should require a close collaboration between pediatric immunologists and gastroenterologists, to optimize epidemiologic surveillance and management of ID., Competing Interests: Conflict of interest There is no conflict of interest associated with any of the senior author or other co-authors contributed their efforts in this manuscript., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

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., (© 2023. The Author(s).)

Competing Interests: The authors report no conflicts of interest.

Competing Interests: We declare no competing interests. All authors contributed equally to this work.

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., (© 2023. The Author(s).)

Background and Aims: To investigate the incidence and the severity of COVID-19 infection in patients enrolled in the database for home parenteral nutrition (HPN) for chronic intestinal failure (CIF) of the European Society for Clinical Nutrition and Metabolism (ESPEN)., Methods: Period of observation: March 1st, 2020 March 1st, 2021., Inclusion Criteria: patients included in the database since 2015 and still receiving HPN on March 1st, 2020 as well as new patients included in the database during the period of observation. Data related to the previous 12 months and recorded on March 1st 2021: 1) occurrence of COVID-19 infection since the beginning of the pandemic (yes, no, unknown); 2) infection severity (asymptomatic; mild, no-hospitalization; moderate, hospitalization no-ICU; severe, hospitalization in ICU); 3) vaccinated against COVID-19 (yes, no, unknown); 4) patient outcome on March 1st 2021: still on HPN, weaned off HPN, deceased, lost to follow up., Results: Sixty-eight centres from 23 countries included 4680 patients. Data on COVID-19 were available for 55.1% of patients. The cumulative incidence of infection was 9.6% in the total group and ranged from 0% to 21.9% in the cohorts of individual countries. Infection severity was reported as: asymptomatic 26.7%, mild 32.0%, moderate 36.0%, severe 5.3%. Vaccination status was unknown in 62.0% of patients, non-vaccinated 25.2%, vaccinated 12.8%. Patient outcome was reported as: still on HPN 78.6%, weaned off HPN 10.6%, deceased 9.7%, lost to follow up 1.1%. A higher incidence of infection (p = 0.04), greater severity of infection (p < 0.001) and a lower vaccination percentage (p = 0.01) were observed in deceased patients. In COVID-19 infected patients, deaths due to infection accounted for 42.8% of total deaths., Conclusions: In patients on HPN for CIF, the incidence of COVID-19 infection differed greatly among countries. Although the majority of cases were reported to be asymptomatic or have mild symptoms only, COVID-19 was reported to be fatal in a significant proportion of infected patients. Lack of vaccination was associated with a higher risk of death., Competing Interests: Conflict of interest statements LP: Participation on a Data Safety Monitoring Board or Advisory Board for Takeda, Consulting fees for Takeda, Northsea, NAPO. SL: Participation on a Data Safety Monitoring Board or Advisory Board for Baxter, Takeda, NorthSea, VectivBio; Grants or contracts from any entity for Baxter, Takeda; Consulting fees for VectivBio, Takeda, Northsea; Support for attending meetings and/or travel for Takeda; Payment or honoraria for lectures for Takeda, Fresenius. PG: none. LS: none. PO: none. NW: none. RT: Royalties or licenses for Royalties for designing the Simple Evaluation of Food Intake® (SEFI®) (Knoë, le Kremlin Bicêtre, France); Consulting fees for Nestlé Health Science; Payment or honoraria for lectures for Baxter, BBraun, Fresenius-Kabi, Nutricia; Support for attending meetings for Nutricia, NHC. PS: none. LE: none. PO: none. L D’A: none. AT: none. ND: Leadership of Pediatric Nutrition Association of Thailand Society of Parenteral Enteral Nutrition of Thailand. ASZ: Payment or honoraria for lectures for Siegfried; Consulting for Takeda; Support for attending meetings for Abbott and Nestlè. MF: Payment or honoraria for lectures for Fresenius Kabi, B Braun, Baxter. GV: none. MIS: none. MT: none. ERB: none. NVC: Payment or honoraria for lectures for Takeda, Nutricia; Payment for expert testimony, Support for attending meetings and Participation on a Data Safety Monitoring Board for Takeda. AL: Consulting fees, Support for attending meetings, Participation on a Data Safety Monitoring Board or Advisory Board for Nestlè; Participation on a Data Safety Monitoring Board or Advisory Board for Takeda; Payment or honoraria for lectures for baxter. LC: none. MA: none. EO: none. AGM: none. AVG: none. VP: honoraria for lectures for Thai Otsuka Pharmaceutical Co., Ltd., Abbott Laboratories Ltd., Nestle (Thai) Ltd., Fresenius Medical Care (Thailand) Ltd., Baxter Healthcare (Thailand) Co., Ltd., Mega Lifesciences PTY Ltd., Novo Nordisk Thailand. MSM: Grants or contracts from any entity for Fresenius Kabi, Nestle, Realfood Blends, VectivBio, Rockfield, Zealand; Consulting fees, Northsea; Participation on a Data Safety Monitoring Board for EndoBarrier. M D-S: none. TV: Grants or contracts from any entity for Vectiv Bio, Takeda; Consulting fees for Vectiv Bio, Zealand Pharma, Takeda, Baxter, Hamni, NorthSea Therapeutics; Payment or honoraria for lectures for Vectiv Bio, Takeda, Baxter; Support for attending meetings for Takeda, Vectiv Bio, Zealand Pharma, Fresenius Kabi; Receipt of equipment, materials, drugs for VectivBio. ZK: Support for attending meetings for Abbott, Fresenius, Nutricia, Nestle, Takeda; Leadership for Croatian Medical Association- The President. FP: none. LM: none. LCE: Consulting fees, Payment or honoraria for lecture and Support for attending meetings for Takeda. UA: Payment or honoraria for lectures for Takeda, Baxter; Support for attending meetings and Participation on a Data Safety Monitoring for Takeda. MK: none. MMJ: none. AC: none. DW: none. GO: none. CC: none. JS: Grants or contracts from any entity and for BBraun, FreseniusKabi, Nestle; Payment or honoraria for lectures for BBraun, OlimpLabs, FreseniusKabi, Baxter, Nestle; Support for attending meetings for FreseniusKabi. FWG: none. CS: none. MBD: none. DS: none. SL: none. SK: Payment or honoraria for lectures, for Abbott, Abela Farm, Danone/Nutricia, Fresenius, GM Pharma, Nestle, Nestle Nutrition Institute, Oktal Pharma, Shire/Takeda; Non-restricted grant delivered to the hospital from BioGaia. BC: none. GM: none. MHMdC: Grants or contracts, Consulting fees, Payment or honoraria, Support for attending meetings, Participation on a Data Safety Monitoring for lectures for Takeda Pharmaceutical Brazil. EPJ: none. FJ: none. DJ: none. GL: none. AZM: none. MT: none. DZ: none. MK: Payment or honoraria for manuscript writing and educational events for Nutricia, FreseniusKabi. ASS: none. GB: none., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

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.

In recent years, the spectrum of possible treatments for Intestinal Failure (IF)-Short Bowel Syndrome (SBS) has been enriched by the implementation of GLP-2 analogues. In Italy, teduglutide (Ted), an analogue of GLP-2, was approved in January 2021 by the Italian Regulatory Agency for Drugs (AIFA) for IF-SBS patients ≥1 year old. According to the Agency indications, Ted can now be prescribed by regional reference centers, with costs fully charged to the National Health Service. Following pediatric-use approval in our country and in light of scarce evidence in childhood, the pediatric network for IF of the Italian Society for Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) planned to share management methods of Ted in pediatric IF. The main purpose was to identify the best candidates from a cost-effective perspective. Thus, focusing on available literature and on expert opinions, the present position statement provides consensus-based recommendations on the use of Ted for pediatric gastroenterologists and nutritionists treating children with SBS., Competing Interests: Conflict of Interest Some authors have participated as consultants on advisory boards and as speakers at Takeda-sponsored conferences, (Copyright © 2022. Published by Elsevier Ltd.)

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., (Copyright © 2022 Di Dato, Iorio and Spagnuolo.)

Background: The European Society for Clinical Nutrition and Metabolism database for chronic intestinal failure (CIF) was analyzed to investigate factors associated with nutritional status and the intravenous supplementation (IVS) dependency in children. Methods: Data collected: demographics, CIF mechanism, home parenteral nutrition program, z-scores of weight-for-age (WFA), length or height-for-age (LFA/HFA), and body mass index-for-age (BMI-FA). IVS dependency was calculated as the ratio of daily total IVS energy over estimated resting energy expenditure (%IVSE/REE). Results: Five hundred and fifty-eight patients were included, 57.2% of whom were male. CIF mechanisms at age 1−4 and 14−18 years, respectively: SBS 63.3%, 37.9%; dysmotility or mucosal disease: 36.7%, 62.1%. One-third had WFA and/or LFA/HFA z-scores < −2. One-third had %IVSE/REE > 125%. Multivariate analysis showed that mechanism of CIF was associated with WFA and/or LFA/HFA z-scores (negatively with mucosal disease) and %IVSE/REE (higher for dysmotility and lower in SBS with colon in continuity), while z-scores were negatively associated with %IVSE/REE. Conclusions: The main mechanism of CIF at young age was short bowel syndrome (SBS), whereas most patients facing adulthood had intestinal dysmotility or mucosal disease. One-third were underweight or stunted and had high IVS dependency. Considering that IVS dependency was associated with both CIF mechanisms and nutritional status, IVS dependency is suggested as a potential marker for CIF severity in children.

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., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

We tested the hypothesis that a narrative approach may enhance a bio-psycho-social model (BPS) in caring for chronically ill children. Forty-eight narratives were collected from 12 children with six different medical conditions, their mothers, physicians, and nurses. By a textual analysis, narratives were classified on their predominant focus as disease (biological focus), illness (psychologic focus), or sickness (social focus). Sixty-one percent of narrative' text were classified as illness, 28% as disease and 11% as sickness. All narratives had a degree of illness focus. Narratives by patients and physicians on the one hand, and nurses' and mothers' on the other were disease focused. Narratives were also evaluated with respect to the type of medical condition: Illness was largely prevalent in all but Crohn's disease and HIV infection, the latter having a predominance of sickness most probably related to stigma. Narrative exploration proved a valuable tool for understanding and addressing the needs of children with complex conditions. Narrative approaches allow identification of the major needs of different patients according to health conditions and story tellers. In the narratives, we found a greater illness and disease focus and surprisingly a low sickness focus, except with HIV stories. Narrative medicine provides a tool to strengthen the BPS model in health care., (© 2020 Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

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.

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., Competing Interests: Declaration of Competing Interest All authors none declared., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

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.

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.

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.

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 (R 2 0.7, p < 0.0001) and tetrasialotransferrin/disialotransferrin ratio (R 2 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., Competing Interests: The authors declare no conflict of interest.

Purpose: We reported our preliminary experience using ICG fluorescence in pediatric minimally invasive surgery (MIS) with the aim to standardize indications, dose, timing, and modality of administration of ICG according to different organs., Methods: ICG technology was adopted in 46 MIS procedures performed in our unit over the last 18 months: 30 left varicocele repairs; 5 cholecystectomies in obese adolescents; 3 tumor excisions; 3 nephrectomies; 2 partial nephrectomies; 3 lymphoma excisions. ICG solution was injected intravenously in all cases except for varicocelectomy in which it was injected into the testis. The ICG injection was performed intra-operatively in all cases except for cholecystectomy in which it was injected 18 h prior to the procedure., Results: All procedures were completed laparoscopically without conversions or intra-operative complications. No adverse or allergic reactions to ICG were reported., Conclusion: Our preliminary experience showed that ICG fluorescence is a safe, useful, and versatile technique to adopt in pediatric MIS to achieve a better identification of anatomy and an easier surgical dissection or resection in challenging cases. Currently, the main indications are varicocelectomy, difficult cholecystectomy, tumor excision, nephrectomy, and partial nephrectomy. The main limitation is the needing of a special equipment to use ICG technology.

Background: This study aimed to review our 25-year experience with pediatric laparoscopic cholecystectomy (LC) to assess its long-term outcome. Materials and Methods: The records of 215 children (127 girls and 88 boys) who underwent LC for the past 25 years (1993-2018) were retrospectively reviewed. All patients had a symptomatic cholelithiasis. The cholelithiasis was idiopathic in 185 patients (86%) and secondary in 30 patients (14%). A four-trocar technique was always adopted and cystic duct and cystic artery were clipped using 10-mm clips in the first 35 cases (16.3%) and 5-mm clips in the following 180 patients (83.7%). In the last 15 cases, indocyanine green (ICG)-enhanced fluorescence was adopted intraoperatively for a better identification of the anatomy of gallbladder and biliary tree. Results: The average operative time was 69 minutes and fell down to 52 minutes after introduction of ICG fluorescence ( P  = .001). Fifteen anatomic anomalies (6.9%), involving bile duct in 5 cases and cystic artery in 10 cases, were recorded. Technical problems were reported intraoperatively in 6 cases (2.8%). We recorded 4 postoperative Clavien IIIb complications (1.9%): 1 bleeding from the cystic artery, 1 dislocation of the clips on the cystic duct, and 2 iatrogenic injuries to the main bile duct managed with choledojejunostomy in 1 case and suture of the choleducus over a stent in the second case. We also recorded 3 umbilical granulomas (1.4%) (Clavien II). Conclusions: LC is a standardized and effective procedure to perform in children. Our 25-year experience showed that major complications (Clavien IIIb) can occur even in experienced surgeons' hands. Age, weight, and preoperative cholecystitis were significantly associated with the risk of bile duct injury in our series. Considering its versatility and safety, we believe that ICG fluorescence technology may be adopted in every LC to ease the dissection and reduce the likelihood of complications.

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.

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 (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.

Microvillous inclusion disease (MVID) typically appears with severe chronic diarrhea in the few days after birth and rapidly causes dehydration and metabolic acidosis. In this context, presenting two novel cases, we underline the crucial importance of mutation analysis for the diagnosis of this disease that may be easily misdiagnosed.

Home Artificial Nutrition (HAN) is a safe and efficacious technique that insures children's reintegration into the family, society and school. Epidemiological data on paediatric HAN in Italy are not available., Aim: to detect the prevalence and incidence of Home Parenteral Nutrition (HPN) and Home Enteral Nutrition (HEN), either via tube or mouth, in Italy in 2016., Materials and Methods: a specific form was sent to all registered SIGENP members and investigators of local HAN centres, inviting them to provide the requested centre's data and demographics, underlying diseases and HAN characteristics of the patients., Results: we recorded 3403 Italian patients on HAN aged 0 to 19 years from 22 centres: 2277 HEN, 950 Oral Nutritional Supplements (ONS) and 179 HPN programs. The prevalence of HEN (205 pts/million inhabitants) and HPN (16 pts/million inhabitants) has dramatically increased in Italy in the last 9 years. Neurodisabling conditions were the first indication for HEN by tube or mouth while HPN is mainly requested in digestive disorders., Conclusions: HAN is a widespread and rapidly growing treatment in Italy, as well as in other European countries. Awareness of its extent and characteristics helps improving HAN service and patients' quality of life.

Background: Early nutrition affects the risk of atopy and infections through modifications of intestinal microbiota. The Prebiotics in the Prevention of Atopy (PIPA) study was a 24-month randomised, double-blind, placebo-controlled trial. It aimed to evaluate the effects of a galacto-oligosaccharide/polydextrose (GOS/PDX)-formula (PF) on atopic dermatitis (AD) and common infections in infants who were born to atopic parents and to investigate the relationship among early nutrition, gut microbiota and clinical outcomes., Methods: A total of 201 and 199 infants were randomized to receive a PF and standard formula (SF), respectively; 140 infants remained on exclusive breastfeeding (BF)., Results: The cumulative incidence of AD and its intensity and duration were not statistically different among the three groups. The number of infants with at least one episode of respiratory infection (RI) and the mean number of episodes until 48 weeks of age were significantly lower in the PF group than in the SF group. The number of patients with recurrent RIs and incidence of wheezing lower RIs until 96 weeks were lower in the PF group than the SF group, but similar to the BF group. Bifidobacteria and Clostridium cluster I colonization increased over time in the PF group but decreased in the SF and BF groups. Bifidobacteria had a protective role in RIs, whereas Clostridium cluster I was associated with atopy protection., Conclusion: The early administration of PF protects against RIs and mediates a species-specific modulation of the intestinal microbiota., Trial Registration: clinicaltrial.gov Identifier: NCT02116452., Competing Interests: : A.G. has participated as a clinical investigator, and/or advisory board member, and/or consultant and/or speaker from Biocodex, Dicofarm, the Menarini Group, Malesci, Angelini, and Mead Johnson Nutrition. His institution received research grants from Mead Johnson USA, Dicofarm Italy, and Ippsen France. The study was supported by Mead Johnson, which produced the PF formula analysed in this study.