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Despite the implementation of preventive measures to counteract the obesity epidemics, the prevalence of childhood obesity is still alarming all over the world. Childhood obesity is the most common risk factor for both cardiovascular and metabolic diseases. In fact, an earlier onset of obesity can cause a greater risk of adiposity tracking across the lifespan and consequently a longer exposure to cardiometabolic risk factors. Accumulating evidence provided by prospective and intervention studies demonstrated the link between pediatric obesity and selected subclinical signs of cardiovascular damage (atherosclerosis and left ventricular hypertrophy), or fatal and not fatal cardiovascular events as early as 40 years of age.The numerous guidelines and scientific documents published in the last years demonstrate the relevance of assessing cardiometabolic risk factors in children and adolescents with OB.This Position paper, released by experts of the "Childhood Obesity study group" within the Italian Society for Pediatric Endocrinology and Diabetology, aims to review the assessment of cardiometabolic risk factors and comorbidities in children and adolescents with OW/OB on the light of the most recent scientific evidence.The main recommendations are: (a) early detection of comorbidities, including hypertension, dyslipidemia, prediabetes/type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, polycystic ovary syndrome, inactivity, obstructive sleep apnea and decline in kidney function; (b) weight loss treatment, which is associated with a reduction of all cardiometabolic risk factors; (c) specific treatment of comorbidities, through lifestyle modifications or pharmacological treatment added to lifestyle for suitable individuals; d). monitoring comorbidities for mitigating future morbidity and mortality., (© 2024. The Author(s).)

Background: Psychopathological disorders are often comorbid diagnosis in eating disorders (EDs). We aimed to assess the presence of psychopathological traits and symptoms associated with EDs in an Italian high school adolescent population., Methods: A sample of high school adolescents was enrolled, and demographic and clinical data were collected. Two self-report questionnaires, the Eating Disorder Inventory-3 (EDI-3) and the Questionnaire for the Assessment of Psychopathology in Adolescence (Q-PAD), were administered., Results: 548 adolescents (333 F/215 M; 16.89 ± 0.85 years) were included. Symptoms associated with EDs of clinical or high clinical concern were prevalent in a range of individuals, with percentages varying from 26.82% for body dissatisfaction to 51.83% for Interoceptive Deficits. The findings from the Q-PAD assessment indicated the presence of psychological distress, leading to discomfort or challenging situations requiring potential intervention in a percentage of adolescents ranging from 2.93% for psychosocial risks to 23.77% for anxiety. These percentages showed differences between genders (F > M, p < 0.001). Our study also highlighted an association between symptoms of EDs and lifestyle factors within families. We observed correlations between Q-PAD measures and EDI-3 scores, including a positive correlation between Q-PAD and EDI-3 body dissatisfaction (r = 0.7), Q-PAD interpersonal conflicts and EDI-3 interpersonal problems (r = 0.6) and a negative correlation between Q-PAD self-esteem and well-being and EDI-3 ineffectiveness Composite (r=-0.7)., Conclusions: a substantial prevalence of ED symptoms and psychological distress among high school adolescents were recorded. These conditions are interrelated, suggesting the importance of addressing them comprehensively. Early detection is essential to improve treatment outcomes and to implement preventive strategies., (© 2024. The Author(s).)

Background: The COVID-19 pandemic has accelerated the integration of digital technologies in the healthcare sector. Telemedicine has notably emerged as a significant tool, offering a range of benefits. However, various barriers, such as healthcare professionals' insufficient technological skills and competencies, can hinder its effective implementation. Scholars have examined the readiness of future physicians, with some studies exploring their readiness before or during the COVID-19 crisis. There is, however, a noteable gap in the literature concerning the post-pandemic period. This study aims to identify gaps in current medical education programs by examining two primary aspects: (1) technical readiness (encompassing general and health-related digital competencies) and (2) behavioural readiness, which includes prior experiences and future intentions related to telemedicine education and implementation among medical students and residents., Methods: A cross-sectional study was conducted using a web-based questionnaire administered to medical students and residents at a major Northern Italian university. The survey responses were analyzed to ascertain whether their distributions varied across demographic variables such as gender and level of education., Results: The most commonly owned technologies were laptops and smartphones, with smartphones perceived as the easiest to use, while desktop computers presented more challenges. Approximately 38% of respondents expressed apprehension about applying digital health information in decision-making processes. There was a significant lack of both personal and academic experience, with only 16% of students and residents having used telemedicine in a university setting. Despite this, 83% of participants expressed a desire for training in telemedicine, and 81% were open to experimenting with it during their academic journey. Moreover, 76% of respondents expressed interest in incorporating telemedicine into their future clinical practice., Conclusions: This study highlights the need for medical students and residents to receive specific education in digital health and telemedicine. Introducing curricula and courses in this domain is critical to addressing the challenges of digital healthcare., (© 2024. The Author(s).)

Background: In response to the imperative need for standardized support for adolescent Gender Dysphoria (GD), the Italian Academy of Pediatrics, in collaboration with the Italian Society of Pediatrics, the Italian Society for Pediatric Endocrinology and Diabetes, Italian Society of Adolescent Medicine and Italian Society of Child and Adolescent Neuropsychiatry is drafting a position paper. The purpose of this paper is to convey the author's opinion on the topic, offering foundational information on potential aspects of gender-affirming care and emphasizing the care and protection of children and adolescents with GD., Main Body: Recognizing that adolescents may choose interventions based on their unique needs and goals and understanding that every individual within this group has a distinct trajectory, it is crucial to ensure that each one is welcomed and supported. The approach to managing individuals with GD is a multi-stage process involving a multidisciplinary team throughout all phases. Decisions regarding treatment should be reached collaboratively by healthcare professionals and the family, while considering the unique needs and circumstances of the individual and be guided by scientific evidence rather than biases or ideologies. Politicians and high court judges should address discrimination based on gender identity in legislation and support service development that aligns with the needs of young people. It is essential to establish accredited multidisciplinary centers equipped with the requisite skills and experience to effectively manage adolescents with GD, thereby ensuring the delivery of high-quality care., Conclusion: Maintaining an evidence-based approach is essential to safeguard the well-being of transgender and gender diverse adolescents., (© 2024. The Author(s).)

Background: Limited evidence exists regarding the association between COVID-19 and Long COVID manifestations in children, particularly concerning variants of concern (VOCs). We aimed to characterize a cohort of pediatric patients hospitalized with confirmed acute SARS-CoV-2 and monitor them for Long COVID symptoms. Additionally, it seeks to explore any potential correlations between VOCs and clinical symptoms., Methods: We conducted a prospective study involving children hospitalized from November 2021 to March 2023, with confirmed acute SARS-CoV-2 infection. A telephone survey was conducted at 3-6-12 months after discharge., Results: We included 167 patients (77 F/90 M). Upon hospital admission, 95.5% of patients presented as symptomatic. Regarding patients for whom it was feasible to determine the SARS-CoV-2 variant (n = 51), the Delta variant was identified in 11 children (21.6%) and Omicron variant in the remaining 40 patients (78.4%: 27.5% BA.1 variant; 15% BA.2 variant; 57.5% BA.5 variant). 19 patients (16.5%) reported experiencing at least one symptom indicative of Long COVID (weight loss 31.6%, inappetence 26.3%, chronic cough 21.1%, fatigue 21.1%, and sleep disturbances, wheezing, abdominal pain and mood disorders 15.8%). In only 4 patients with Long COVID we could identified a specific SARS-CoV-2 variant (3 Omicron: 2 BA.1 and 1 BA.2; 1 Delta)., Conclusions: this study underscores that long COVID is a significant concern in the pediatric population. Our data reinforce the importance of continuously monitoring the impact of long-COVID in infants, children, and adolescents. A follow-up following SARS-CoV-2 infection is therefore advisable, with symptom investigation tailored to the patient's age., (© 2024. The Author(s).)

Complementary and alternative medicine (CAM) consist of a broad group of restorative resources often linked to existing local cultures and established health care systems and are also increasingly used in children with some serious illnesses. In this narrative review, we examine the epidemiology of the use, efficacy, and safety of complementary and alternative medicine in pediatric oncology, neurology, and hepatology. We searched for relevant articles published in Pubmed evaluating CAM use and its efficacy in safety in children affected by oncologic, neurologic and liver diseases. CAM is used to improve the success of conventional therapies, but also to alleviate the pain, discomfort, and suffering resulting from the diseases and their treatment, which are often associated with a significant burden of adverse effects. CAM use must be evaluated in children with neurological, oncological and liver diseases., (© 2023. The Author(s).)

This Position Statement updates the different components of the therapy of obesity (lifestyle intervention, drugs, and surgery) in children and adolescents, previously reported in the consensus position statement on pediatric obesity of the Italian Society of Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics. Lifestyle intervention is the first step of treatment. In children older than 12 years, pharmacotherapy is the second step, and bariatric surgery is the third one, in selected cases. Novelties are available in the field of the medical treatment of obesity. In particular, new drugs demonstrated their efficacy and safety and have been approved in adolescents. Moreover, several randomized control trials with other drugs are in process and it is likely that some of them will become available in the future. The increase of the portfolio of treatment options for obesity in children and adolescents is promising for a more effective treatment of this disorder., (© 2023. The Author(s).)

Background: Lymphomatoid papulosis (LyP) is a rare condition in pediatrics; LyP histological type D has been reported in only 7 children. The differential diagnosis of LyP in the spectrum of lymphoid proliferation remains controversial., Case Presentation: A 6-year-old boy presented to Emergency Department with a 3-week history of an erythematous papulo-vesicular itchy eruption over the submandibular regions, trunk and extremities. History, symptoms and laboratory tests were unremarkable. SARS-CoV-2 antigen was negative. The clinical suspicion of pityriasis lichenoides et varioliformis acuta (PLEVA) was posed, and topical steroids were introduced. One week after, he returned with an extensive painful scaly papulo-erythematous rash, with some ulcerated and necrotic lesions, and fever; therefore the child was hospitalized. Biochemical results were within reference limits, except for high level of C-reactive protein, aspartate aminotransferase, alanine transaminase and bilirubin. Due to a persistently high fever, systemic corticosteroid treatment was administered, with a good clinical response and an improvement of the skin lesions. Anti-PVB-19 Immunoglobulin M was detected. Elevated levels of IL-6, IL-10 and IFN-γ were also recorded. Five days post-admission, most of the lesions had cleared, and the child was discharged. Methotrexate was started, with a positive response. At skin biopsy a "PLEVA-like" pattern was apparent, with a dense, wedge shaped lymphoid infiltrate featuring epidermotropism and morphologically comprising pleomorphic and blastic cells. The pattern of infiltration was highlighted by immunohistochemical stains, which prove the process to feature a CD8+/CD30 + phenotype, the latter being intense on larger cells, with antigenic loss. Polymerase chain reaction for T-cell receptor gamma (TCRG) chain clonality assessment documented a monoclonal peak. A diagnosis of LyP type D was favored., Conclusion: The reported case encompasses most of the critical features of two separated entities-PLEVA and LyP-thus providing further support to the concept of them representing declinations within a sole spectrum of disease. Studying the role of infectious agents as trigger potential in lymphoproliferative cutaneous disorders and detecting novel markers of disease, such as cytokines, could have a crucial impact on pathogenic disease mechanisms and perspective therapies., (© 2022. The Author(s).)

Background: The causes of an early onset of puberty are still not clearly defined and may vary from subject to subject. In girls, even if 90% of early puberty is idiopathic, magnetic resonance imaging (MRI) of the brain is performed to exclude secondary causes of precocious puberty, in particular pathological lesions as hypothalamic tumours (hamartoma). In some cases, other intracranial lesions are considered as incidental findings. Aim of the study is evaluating the prevalence of abnormal intracranial lesions detected by brain magnetic resonance imaging MRI with particular focus on the prevalence of pineal gland cysts in the diagnostic work-up of girls with central precocious puberty (CPP) as onset before 8 years and central early puberty (CEP) as onset before 10 years., Material and Methods: MRI data of girls referred from January 2010 to December 2015 to the Pediatric Endocrinology Unit of University of Pavia for early onset of breast development were collected., Results: We collected 123 MRI data of girls referred to the Pediatric Endocrinology Unit of University of Pavia for early onset of breast development in the study period. Out of them, 25 (20.3%) had cerebral abnormalities and 15 (12.2%) had pineal gland cysts. No significant differences were noted in auxological, ultrasound and hormonal parameters at diagnosis among girls with or without pineal cysts. Patients have been observed for at least three years after the discontinuation of therapy. None of our patients had an unfavorable evolution., Conclusions: Although pineal cysts seem to be not involved in the onset of puberty, the relevance of the finding remains controversial. Our study wants to provide further insight into the incidence of pineal cysts in pubertal advances. Of note, pineal cysts are often asymptomatic and do not evolve over time., (© 2022. The Author(s).)

Background: Multisystem inflammatory syndrome in children (MIS-C) is a novel condition temporally associated with SARS-CoV2 infection. Cardiovascular involvement is mainly evident as acute myocardial dysfunction in MIS-C. The aim of this study was to describe the cardiac dysfunction in patients with MIS-C, defining the role of severity in the clinical presentations and outcomes in a single cohort of pediatric patients., Methods: A single-center retrospective study on patients diagnosed with MIS-C, according to the Center for Disease Control and Prevention (CDC) definition, and referred to Vittore Buzzi Children's Hospital in Milan from November 2020 to February 2021. Patients were managed according to a local approved protocol. According to the admission cardiac left ventricular ejection fraction (LVEF), the patients were divided into group A (LVEF < 45%) and group B (LVEF ≥45%). Pre-existing, clinical, and laboratory factors were assessed for evaluating outcomes at discharge., Results: Thirty-two patients were considered. Cardiac manifestations of MIS-C were reported in 26 patients (81%). Group A included 10 patients (9 M/1F, aged 13 years [IQR 5-15]), and group B included 22 patients (15 M/7 M, aged 9 years [IQR 7-13]). Significant differences were noted among clinical presentations (shock, diarrhea, intensive care unit admission), laboratory markers (leucocytes, neutrophils, and protein C-reactive), and cardiac markers (troponin T and N-terminal pro B-type Natriuretic Peptide) between the groups, with higher compromission in Group A. We found electrocardiogram anomalies in 14 patients (44%) and rhythm alterations in 3 patients (9%), without differences between groups. Mitral regurgitation and coronary involvement were more prevalent in group A. Total length of hospital stay and cardiac recovery time were not statistically different between groups. A recovery of cardiac functioning was reached in all patients., Conclusion: Despite significant differences in clinical presentations and need for intensive care, all of the MIS-C patients with significant cardiac involvement in this study completely recovered. This suggests that the heart is an involved organ and did not influence prognosis if properly treated and supported in the acute phase., (© 2021. The Author(s).)

Background: Homozygous mutations in the transcription factor RFX6 are the cause of the Mitchell-Riley syndrome (MRS) associating neonatal diabetes, congenital digestive system, such as biliary atresia, pancreatic hypoplasia, duodenal and/or jejunal atresia, intestinal malrotation, gallbladder aplasia, cholestasis. A constitutive inactivation of RFX6 leads also to gastric heterotopia. Application of RNA-seq in human diseases may help to better understand pathogenic mechanism of diseases and to predict the risk of developing chronic disorders and personalizing their prevention and treatment. We evaluated oncogenic patterns and cancer predisposition using the transcriptomic profile in a case of MRS with neonatal diabetes, duodenal atresia, and extensive intestinal tract gastric heterotopia., Results: We signalled the interactors of RFX6 with other up and downregulated genes, that may be interested in severity of diabetic condition, in multi-organs impairment and cancer predisposition. Furthermore, several dysregulated genes are involved in biological processes that can lead to promote cancer including "Evading apoptosis" (BAD, BBC3, EGF, FGFR2, FLT3LG, HMOX1, HRAS, IFNAR2, IGF1R, IL12RB1, IL13RA1, IL15, IL2RB, IL2RG, IL6R, KEAP1, MGST1, PDGFA, PDGFRB, PIK3R3, RALB, RALGDS, RASSF1, SOS1, TGFA, TXNRD3), "Proliferation" (APC, BRAF, CCND2, CCND3, CCNE2, FGFR2, FLT3LG, FZD1, FZD6, HMOX1, HRAS, IGF1R, KEAP1, LRP6, MAPK3, MGST1, PDGFA, PDGFB, PDGFRB, RB1, SOS1, TGFA, TXNRD3, WNT10B), "Sustained angiogenesis" (BRAF, FGFR2, FLT3LG, HRAS, IGF1R, JAG1, MAPK3, NOTCH2, PDGFA, PDGFB, PDGFRB, SOS1, TGFA, TGFB1), "Genomic instability" (BAD, BBC3) and "Insensitivity to anti-growth signals" (SMAD2, TGFB1). We also inspected the signalings and their related genes in cancer, such as "PI3K signaling", "ERK signaling", "JAK-STAT signaling", "Calcium signaling", "Other RAS signaling", "WNT signaling"., Conclusions: In our MRS patient, we signaled the interactors of RFX6 with other up- and downregulated genes that may be related to severe diabetic condition, multi-organ impairment, and cancer predisposition. Notably, many dysregulated genes may lead to triggering carcinogenesis. The possibility of the patient developing cancer degeneration in heterotopic gastric mucosa and/or additional long-term tumoral sequelae is not excluded. Personalized prevention and treatment strategies should be proposed., (© 2021. The Author(s).)

Introduction: This is the report of the first official survey from the Italian Society of Pediatric Surgery (ISPS) to appraise the distribution and organization of bedside surgery in the neonatal intensive care units (NICU) in Italy., Methods: A questionnaire requesting general data, staff data and workload data of the centers was developed and sent by means of an online cloud-based software instrument to all Italian pediatric surgery Units., Results: The survey was answered by 34 (65%) out of 52 centers. NICU bedside surgery is reported in 81.8% of the pediatric surgery centers. A lower prevalence of bedside surgical practice in the NICU was reported for Southern Italy and the islands than for Northern Italy and Central Italy (Southern

Background: Pubertal timing is known to be influenced by interactions among various genetic, nutritional, environmental and socio-economic factors, although the ultimate mechanisms underlying the increase in pulsatile GnRH secretion at puberty have yet to be fully elucidated. The aim of our research was to verify the role of KISSR1 (previously named GPR54) and MKRN3 genes on pubertal timing., Methods: We analyzed the DNA sequence of these genes in 13 girls affected by central precocious puberty (CPP) who showed onset of puberty before 8 years of age, and in 6 girls affected by early puberty (EP) between 8 and 10 years of age., Results: Direct sequencing of the KISS1R (GPR54) gene revealed two SNPs. One SNP is a missense variant (rs 350,132) that has been previously reported in connection to CPP in Korean girls. The other variant that we found in the GPR54 gene (rs764046557) was a missense SNP located in exon 5 at position 209 of the aminoacid. We identified this variant in only one CPP patient. Automatic sequencing of MKRN3 in all patients revealed three variants in eight subjects. In 6 out of 19 (31.5%) patients (3/13 CPP patients and 3/6 EP patients) we found the synonymous variant c.663C > T (rs2239669). Another synonymous variant (rs140467331) was found in one of our CPP patients, as well as one missense variant (rs760981395) in another CPP patient., Conclusion: In conclusion, we identified sequence variations of the KISS1R and MKRN3 genes, two of the most frequent genetic causes of ICPP. Our results suggest that these variants might be inducible factors in the pathogenesis of CPP.

Background: Progressive lung involvement in Filamin A (FLNA)-related cerebral periventricular nodular heterotopia (PVNH) has been reported in a limited number of cases., Case Presentation: We report a new pathogenic FLNA gene variant (c.7391&#95;7403del; p.Val2464Alafs*5) in a male infant who developed progressive lung disease with emphysematous lesions and interstitial involvement. Following lobar resection, chronic respiratory failure ensued necessitating continuous mechanical ventilation and tracheostomy. Cerebral periventricular nodular heterotopia was also present., Conclusions: We report a novel variant of the FLNA gene, associated with a severe lung disorder and PNVH. The lung disorder led to respiratory failure during infancy and these pulmonary complications may be the first sign of this disorder. Early recognition with thoracic imaging is important to guide genetic testing, neuroimaging and to define optimal timing of potential therapies, such as lung transplant in progressive lung disease.

Background: It has been proposed that mesenchymal stromal cells (MSCs) promote tumor progression by interacting with tumor cells and other stroma cells in the complex network of the tumor microenvironment. We characterized MSCs isolated and expanded from tumor tissues of pediatric patients diagnosed with neuroblastomas (NB-MSCs) to define interactions with the tumor microenvironment., Methods: Specimens were obtained from 7 pediatric patients diagnosed with neuroblastoma (NB). Morphology, immunophenotype, differentiation capacity, proliferative growth, expression of stemness and neural differentiation markers were evaluated. Moreover, the ability of cells to modulate the immune response, i.e. inhibition of phytohemagglutinin (PHA) activated peripheral blood mononuclear cells (PBMCs) and natural killer (NK) cytotoxic function, was examined. Gene expression profiles, known to be related to tumor cell stemness, Wnt pathway activation, epithelial-mesenchymal transition (EMT) and tumor metastasis were also evaluated. Healthy donor bone marrow-derived MSCs (BM-MSC) were employed as controls., Results: NB-MSCs presented the typical MSC morphology and phenotype. They showed a proliferative capacity superimposable to BM-MSCs. Stemness marker expression (Sox2, Nanog, Oct3/4) was comparable to BM-MSCs. NB-MSC in vitro osteogenic and chondrogenic differentiation was similar to BM-MSCs, but NB-MSCs lacked adipogenic differentiation capacity. NB-MSCs reached senescence phases at a median passage of P7 (range, P5-P13). NB-MSCs exhibited greater immunosuppressive capacity on activated T lymphocytes at a 1:2 (MSC: PBMC) ratio compared with BM-MSCs (p = 0.018). NK cytotoxic activity was not influenced by co-culture, either with BM-MSCs or NB-MSCs. Flow-cytometry cell cycle analysis showed that NB-MSCs had an increased number of cells in the G0-G1 phase compared to BM-MSCs. Transcriptomic profiling results indicated that NB-MSCs were enriched with EMT genes compared to BM-MSCs., Conclusions: We characterized the biological features, the immunomodulatory capacity and the gene expression profile of NB-MSCs. The NB-MSC gene expression profile and their functional properties suggest a potential role in promoting tumor escape, invasiveness and metastatic traits of NB cancer cells. A better understanding of the complex mechanisms underlying the interactions between NB cells and NB-derived MSCs should shed new light on potential novel therapeutic approaches.

The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase.

Background: To evaluate the relationship between smoking and metabolic parameters in patients affected by type 1 diabetes (T1D)., Patients and Methods: We enrolled 104 children and young adults (50 females and 54 males) with T1D (aged 16.4 ± 8.6 years). The subjects were divided into three groups according to their smoking habits: no smoking (NS), passive smoking (PS), active smoking (AS). The physical examination of the participants included nutritional status assessment by anthropometry and pubertal stage according to Marshall and Tanner as well as blood pressure measurement. In all patients, metabolic blood assays including fasting blood glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured. Insulin resistance was determined by glucose disposal rate (eGDR). Physical activity was also recorded., Results: Significant differences in biochemical and functional parameters among the three groups were demonstrated, in particular for systolic (p = 0.002) and diastolic pressure (p = 0.02) and eGDR (p = 0.039). No differences in daily insulin dose (p = 0.75) and glycated hemoglobin (p = 0.39) were observed. AS group had significantly higher blood pressure (p < 0.05) and lower eGDR (p ≤ 0.001) compared to NS and PS. Significant difference was also detected between PS and NS in systolic and diastolic (p = 0.02) pressure and eGDR (p = 0.01). In a multivariable model adjusted for age, gender, BMI and physical activity, smoking habits did not maintain any independent association with metabolic parameters., Conclusion: This is the first study in a Mediterranean population, looking at tobacco smoke and cardio-metabolic factors in youth with T1D. The relationship between smoking and unfavorable metabolic profile was demonstrated. On the basis of these findings, smoking tobacco should be considered an important modifiable risk factor for young patients with diabetes mellitus, highlighting the need for intensified smoking prevention and cessation programs.

Background: The aim of our study is to evaluate if in children with highly positive serology and HLA-DQ2/DQ8 (triple test, TT) and only extra-intestinal symptoms, it is possible to omit performing an intestinal biopsy for celiac disease (CD) diagnosis, as suggested by the new European Society for Pediatric Gastroenterology, Hepatology and Nutrition ESPGHAN guidelines., Methods: In this retrospective study a total of 105 patients, suspected of having CD because of extra-intestinal symptoms and showing serum tissue transglutaminase antibody (anti-tTG) and anti-endomysial antibody (EMA) measurements and HLA genotyping, were considered for the final analysis (33 boys and 72 girls; age range 1.5-17.6 years)., Results: Histological findings confirmed diagnosis of CD in 97 (92.4%) patients. Forty-one patients (39%) showed anti-tTG >10 times normal values, positive EMA and positive HLA-DQ2/DQ8 (positive TT). All of them had a diagnosis of CD, therefore there were no false positive cases. Sixty-four patients were negative for the TT. In eight cases, CD was ruled out and these were considered true negative cases. In the remaining 56 negative TT patients, intestinal biopsy confirmed CD diagnosis and they were considered false negatives. Based on these results, specificity for the TT was 100% and sensitivity was 42.3%., Conclusions: On the basis of the present study, diagnosis of CD can be reliably performed without a duodenal biopsy in children with only extra-intestinal symptoms.

Background: To assess the clinical validity of controlled attenuation parameter (CAP) in the diagnosis of hepatic steatosis in a series of overweight or obese children by using the imperfect gold standard methodology., Methods: Consecutive children referred to our institution for auxological evaluation or obesity or minor elective surgery were prospectively enrolled. Anthropometric and biochemical parameters were recorded. Ultrasound (US) assessment of steatosis was carried out using ultrasound systems. CAP was obtained with the FibroScan 502 Touch device (Echosens, Paris, France). Pearson's or Spearman's rank correlation coefficient were used to test the association between two study variables. Optimal cutoff of CAP for detecting steatosis was 249 dB/m. The diagnostic performance of dichotomized CAP, US, body mass indexes (BMI), fatty liver index (FLI) and hepatic steatosis index (HSI) was analyzed using the imperfect gold standard methodology., Results: Three hundred five pediatric patients were enrolled. The data of both US and CAP were available for 289 children. Steatosis was detected in 50/289 (17.3%) children by US and in 77/289 (26.6%) by CAP. A moderate to good correlation was detected between CAP and BMI (r = 0.53), FLI (r = 0.55) and HSI (r = 0.56). In obese children a moderate to good correlation between CAP and insulin levels (r = 0.54) and HOMA-IR (r = 0.54) was also found. Dichotomized CAP showed a performance of 0.70 (sensitivity, 0.72 [0.64-0.79]; specificity, 0.98 [0.97-0.98], which was better than that of US (performance, 0.37; sensitivity, 0.46 [0.42-0.50]; specificity, 0.91 [0.89-0.92]), BMI (performance, 0.22; sensitivity, 0.75 [0.73-0.77]; specificity, 0.57 [0.55-0.60]) and FLI or HSI., Conclusions: For the evaluation of liver steatosis in children CAP performs better than US, which is the most widely used imaging technique for screening patients with a suspicion of liver steatosis. A cutoff value of CAP of 249 dB/m rules in liver steatosis with a very high specificity.

Introduction: Aortopulmonary collateral arteries are an uncommon variant of alternative blood supply in cases of complex congenital heart disease. Although surgery may still be the classic approach for this condition, mini-invasive endovascular occlusion has been recently attempted as an alternative less traumatic procedure. Children born to women with epilepsy are at increased risk of congenital malformations., Case Presentation: A cardiovascular malformation in a 6-year-old white boy with prenatal exposure to carbamazepine is described. At birth, he underwent atrial-ventricular septal defects repair. At 6 years of age, he was diagnosed to have an aberrant aortopulmonary artery from the descending aorta. He presented with recurrent respiratory infections and no cardiovascular signs, but there was associated right upper lobe hyperperfusion. Collateral percutaneous plug embolization was performed because of risk for cardiorespiratory infections, pulmonary hypertension and atrioventricular dilatation. The post-releasing control showed a complete occlusion of the aberrant artery. A chest radiogram and computed tomography showed normalization of vascular pattern of his right lung at 9-months follow-up. No complications and no respiratory infections in the first follow-up year were observed. A good growth gain was obtained., Conclusions: Plug embolization in an aortopulmonary collateral artery is an interesting alternative to surgery and is suitable for children with minor congenital heart disease and without severe respiratory and/or cardiovascular symptoms. Management and long-term pediatric multidisciplinary follow-up is recommended. Prenatal exposure to carbamazepine could be considered in the pathogenesis and diagnosis of the malformation.

Objective: Mesenchymal stromal cells (MSCs) expanded in vitro have been proposed as a potential therapy for congenital or acquired skin defects in pediatrics. The aim of this pre-clinical study was to investigate the effects of intradermal injections of MSC in experimental cutaneous wound repair comparing allogeneic and autologous adipose stem cells (ASCs) and autologous bone marrow-mesenchymal stromal cells (BM-MSCs)., Methods: Mesenchymal stromal cells were in vitro expanded from adipose and BM tissues of young female New Zealand rabbits. MSCs were characterized for plastic adhesion, surface markers, proliferation and differentiation capacity. When an adequate number of cells (ASCs 10 × 10(6) and BM-MSCs 3 × 10(6), because of their low rate of proliferation) was reached, two skin wounds were surgically induced in each animal. The first was topically treated with cell infusions, the second was used as a control. The intradermal inoculation included autologous or allogeneic ASCs or autologous BM-MSCs. For histological examination, animals were sacrificed and wounds were harvested after 11 and 21 days of treatment., Results: Rabbit ASCs were isolated and expanded in vitro with relative abundance, cells expressed typical surface markers (CD49e, CD90 and CD29). Topically, ASC inoculation provided more rapid wound healing than BM-MSCs and controls. Improved re-epithelization, reduced inflammatory infiltration and increased collagen deposition were observed in biopsies from wounds treated with ASCs, with the best result in the autologous setting. ASCs also improved restoration of skin architecture during wound healing., Conclusion: The use of ASCs may offer a promising solution to treat extended wounds. Pre-clinical studies are however necessary to validate the best skin regeneration technique, which could be used in pediatric surgical translational research.

Background: Acute cerebellitis (AC) is the most common neurological complication of varicella. Nevertheless, it has been scarcely studied. The objective of this study were to asses the occurrence of AC among children hospitalized for varicella and to analyze its specific clinical picture and outcome., Methods: We retrospectively reviewed the medical records of children admitted to the hospital for varicella between 1st October 2003 and 1st June 2013 and we compared our results with literature. Children were all unvaccinated for varicella., Results: In our case series, AC was found out in 48 out of 457 patients (10.5%). The highest frequency of AC was observed in children from 1 to 5 years of age (60.9%). The most characteristic symptom of AC was a broad-based gait disturbance that progressed gradually over the course of a few days (95.8%). Other common symptoms included slurred speech (37.5%), vomiting (31.25%), headache (29.16%), dysmetry (25%) and tremor (22.91%). After a long hospitalization (median of 11 days), all but one children were dismissed without invalidating sequelae., Conclusions: Data from this study may help to better address the problem of varicella cerebellar complications in hospitalized children and to monitor changes over time caused by an increase in vaccination coverage.

Objective: Bariatric surgery results in decreased food intake and a variable degree of malabsorption. Without adequate supplementation, the most common complications of this surgery are nutritional disorders. Pregnancy following surgery for obesity is a particular condition requiring strict monitoring of nutrient intake necessary for fetal development and a favourable neonatal prognosis., Patients: Malnutrition in pregnancy and congenital neural malformations are reported in three women who had previously undergone bariatric surgery (1, 5 and 18 years before pregnancy, respectively). Two patients underwent the Roux en Y bypass and one bilio-pancreatic diversion with gastroplasty. None of the three received pre-conceptional nutritional counselling. Patients 1 and 2 did not undergo postoperative nutritional surveillance; nutrient supplementation was started at 22 and 20 weeks gestation, respectively. In patient 3, supplementation was stopped at six weeks gestation., Results: Newborns 1 and 2 presented with dorsal myelomeningocele and ventricular dilation. Both underwent surgery and a ventriculo-peritoneal shunt was inserted in the first month of life. Newborn 3 had microcephaly, bilateral microphthalmia and sensorineural deafness., Conclusions: Diet and nutritional status, before and during pregnancy, play an important role in the early processes of fetal development and neonatal outcome. Women of childbearing age who have had bariatric surgery, should be encouraged to follow a well-balanced diet as part of a weight management strategy. They should be advised to take recommended maternal supplements.

Background: Cerebral venous sinus thrombosis (CVT) is a rare and potentially life-threatening condition in the pediatric population. The clinical presentation is frequently nonspecific; thus diagnosis is often delayed or missed., Case Presentation: A previously healthy 8 month-old boy was diagnosed with meningococcal meningitis. At hospital admission, an urgent non contrast-enhanced computed tomography (CT) of the head and neck was performed with normal results. Ceftriaxone was promptly started and the clinical condition of the patient improved. However, on the 7th day of hospitalization, the child suddenly manifested irritability and lethargy. An urgent contrast-enhanced CT of the head and neck was immediately performed, revealing thrombosis of the superior sagittal, transverse and rectus sinuses. A thrombophilic evaluation was performed, revealing hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) variants (C677T and A1298C)., Conclusions: The causes of CVT may be categorized into three main groups: hypercoagulable states, conditions causing blood flow disturbances, and all causes of inflammation or infection. In this case report, we observed more than one risk factor that predisposed the patient to CVT. Consequently, even if a causative factor is detected, a thrombophilic blood evaluation should be performed. In fact, in case of a prothrombotic condition, the patient's family should be advised that prompt administration of anticoagulant is necessary in the event of situations that could lead to thrombosis. Finally, CVT may be considered a possible complication of infection even when recent imaging results are normal. A prompt CVT diagnosis is required to obtain a good outcome. Delayed diagnosis is mainly due to the rarity of the disease and physicians' unawareness of this type of complication.

Introduction: Norovirus infection with necrotizing enterocolitis has so far been reported as a specific tropism of the small bowel in premature newborns., Case Presentation: Three cases of premature newborns presenting with extensive isolated colonic ischemia due to norovirus infection are reported.Patient 1 was a Caucasian girl with a gestational age of 29+2 weeks. She had sudden onset of abdominal distension on the 30th day of life. Radiological signs of colonic pneumatosis were present 48 hours before perforation and stool analysis was positive for norovirus. On the 34th day, free air was detected on plain abdominal X-ray. At laparotomy, stenosis, necrosis and perforations involved the whole colon. The patient underwent ileostomy. A large colon resection and ileosigmoid anastomosis were done 3 months later.Patient 2 was a Caucasian boy with a gestational age of 28+3 weeks. On the 19th day, bloody stools with abdominal distension appeared. Stool analysis resulted positive for norovirus. A plain abdominal X-ray showed distended bowel loops. Antibiotic treatment was started. On the 32nd day due to the progressive deterioration of clinical conditions and the appearance of colic pneumatosis, a laparotomy was performed. Severe damage of the transverse colon and multiple areas of necrosis were found. Terminal ileostomy was performed. Six months later surgery consisted of mid-transverse colon resection as far as the splenic flexure, colocolic anastomosis and closure of ileostomy.Patient 3 was a Caucasian boy with a gestational age of 30 weeks. On the 44th day bloody-mucous stools appeared and stool analysis was positive for norovirus infection. Even with institution of antibiotic therapy clinical abdominal radiologic signs of colonic pneumatosis of the upper right quadrant were found. At the 70th day an explorative laparotomy showed dilated bowel loops and stenotic right colon and ileostomy was mandatory. Partial colectomy was later necessary and ileocolic anastomosis was performed., Conclusion: We hypothesize that norovirus infection may be responsible for severe, distinctive colonic lesions, even in premature newborn infants.

3-M syndrome is a rare autosomal recessive disorder that causes short stature, unusual facial features and skeletal abnormalities. Mutations in the CUL7, OBSL1 and CCDC8 genes could be responsible for 3-M syndrome.Here we describe the growth and evolution of dismorphic features of an Italian boy with 3-M syndrome and growth hormone deficiency (GHD) from birth until adulthood. He was born full term with a very low birth weight (2400 g=-3.36 standard deviation score, SDS) and length (40.0 cm =-6.53 SDS). At birth he presented with a broad, fleshy nose with anteverted nostrils, thick and patulous lips, a square chin, curvilinear shaped eyebrows without synophrys, short thorax and long slender bones. Then, during childhood tall vertebral bodies, hip dislocation, transverse chest groove, winged scapulae and hyperextensible joints became more evident and the diagnosis of 3-M syndrome was made; this was also confirmed by the finding of a homozygous deletion in exon 18 of the CUL7 gene, which has not been previously described.The patient also exhibited severe GHD (GH <5 ng/ml) and from the age of 18 months was treated with rhGH. Notwithstanding the early start of therapy and good compliance, his growth rate was always very low, except for the first two years of treatment and he achieved a final height of 132 cm (-6.42 SDS).