Bambino Gesu Research Articles

Patient preferences in genetic newborn screening for rare diseases: study protocol

IntroductionRare diseases (RDs) collectively impact over 30 million people in Europe. Most individual conditions have a low prevalence which has resulted in a lack of research and expertise in this...

Double-Outlet Left Ventricle: Case Series and Systematic Review of the Literature.

Double-outlet left ventricle (DOLV) is an abnormal ventriculo-arterial connection characterized by the origin of both great arteries from the morphological left ventricle. The aim of our paper is to describe the morphological and imaging features of DOLV and to assess the prevalence of the associated malformations and their surgical outcomes. METHODS From 2011 to 2022, we retrospectively reviewed the electronic case records of patients diagnosed with DOLV at the Bambino Gesu Children's Hospital. A systematic search was developed in MEDLINE, Web of Science, and EMBASE databases to identify reports assessing the morphology and outcomes of DOLV between 1975 and 2023. RESULTS: Over a median follow-up of 9.9 years (IQR 7.8-11.7 y), four cases of DOLV were identified at our institution. Two patients were diagnosed with (S,D,D) DOLV subaortic VSD and pulmonary stenosis (PS): one patient had (S,D,D) DOLV with doubly committed VSD and hypoplastic right ventricle, and another patient had (S,D,L) DOLV with subaortic VSD and PS (malposition type). Pulmonary stenosis was the most commonly associated lesion (75%). LITERATURE REVIEW: After systematic evaluation, a total of 12 reports fulfilled the eligibility criteria and were included in our analysis. PS or right ventricular outflow tract obstruction was the most commonly associated lesion (69%, 95% CI 62-76%). The most common locations of VSD were subaortic (pooled prevalence: 75%, 95% CI 68-81), subpulmonary (15%, 95% CI 10-21), and doubly committed (7%, 95% CI 4-12). The position of the great arteries showed that d-transposition of the aorta was present in 128 cases (59% 95% CI 42-74), and l-transposition was present in 77 cases (35%, 95% CI 29-43).

Food allergy: new therapeutic options open deeper questions

aPediatric Hospital Bambino Gesù IRCCS bNational Hospital Organization Sagamihara National Hospital, Italy Correspondence to Alessandro Fiocchi, MD, Bambino Gesu Pediatric Hospital: Ospedale Pediatrico Bambino Gesu, Rome, Italy. E-mail: [email protected]

879 STUDY OF ATRIOVENTRICULAR CONDUCTION DEFECTS AND ARRHYTHMIAS IN PATIENTS WITH DILATATIVE CARDIOMIOPATHY CLINICAL PROGNOSTIC VALUE OF THE GENETIC ANALYSIS USING NEXT GENERATION SEQUENCING AT THREE YEARS

Abstract Background Dilated cardiomyopathy is one of the most common cardiomyopathies that at the onset shows a with dysfunction, commonly expressed by the reduced ejection fraction (EF) and which can lead to heart transplantation. Cardiac "laminopathies" are part of the complex set of CMD. In many cases they show a defect in myocardial electrical conduction. Mutations in the Lamina A / C genes have been associated with high arrhythmic risk and sudden cardiac death. In addition to these, there are others concerning the MYH7, TTN, MYBPC3 genes, related to the CMD phenotype and whose meaning is being defined. Objectives The project has the goal of evaluating the association of arrhythmic disorders with possible CMD phenotypes and the genetic mutations described above. Materials and Methods We studied 33 out of 100 patients screened for CMD on voluntary availability, suffering from different forms without significant coronary lesions. All of them underwent diagnostic-instrumental checks (ECG, Holter Ecg, echocardiogram and enzymatic profile) and followed for a minimum period of 18 months. At the same time at the ordinary check -up, genetic analyses were carried out through the NGS study of a panel of genes related to CMD in collaboration between the AOU G. Martino di Messina and the Bambino Gesu’ Hospital in Rome. Results On 33 patients undergoing a genetic study, variants of uncertain significance (VUS) were identified: variant c.2359 C> T (p.Arg787Cys) in the MYH7 gene reported in VarSome as probably pathogenetic in a symptomatic patient with endomyocardial biopsy CMD +; the variant c.54016G> T in heterozygosity in the TTN gene, in another case, which at the protein level determines the introduction of the premature stop codon not described in scientific literature and classified according to the ACMG guidelines as a probably pathogenic variant; finally pathogenic variant c.949G> A in heterozygosity in the LMNA gene, in a family with a history of sudden cardiac death with manifest CMD in some members with arrhythmias at follow up (ICD). and the presence of a second mutation; c.836G> C in heterozygosity in the MYBPC3 gene, in other members of the same family with better clinical course. Conclusions Our study shows that there are VUS associated with cases of CMD. Within these, the presence of mutations in the lamina gene seem to be more closely related to the incidence of arrhythmias. Therefore, further studies are necessary for a better definition of all possible VUS also to carry out a differential diagnosis in the broad spectrum of cardiomyopathies.

804 WOLF PARKINSON WHITE SYNDROME OR ASYMPTOMATIC VENTRICULAR PRE-EXITATION IN CHILDREN: EVALUATION OF ELECTROPHYSIOLOGICAL PROPERTIES CHANGES IN TWO DIFFERENT TIMING

Abstract Background In patients with Wolf Parkinson White (WPW) syndrome or asymptomatic ventricular pre-excitation (VP), electrophysiologic study (EPS) is recommended to assess and to stratify the risk of life - threatening arrhythmias and SCD. However, little information exist on the timing of EPS study. In particular, the electrophysiological properties variations of accessory pathway (AP) in patients with asymptomatic or symptomatic VP remain to be defined. Recently, the evolution of electrophysiological data was observed in a cohort of patients by including children and adults, although a transcatheter ablation (TCA) was performed during the evaluation among the two EPS. According to our knowledge, no study exists related to the changes over time in the conductive properties of an atrioventricular accessory pathway (AP) and arrhythmic vulnerability in the pediatric - young adult population. Aims The aim of our study was to investigate the evolution of clinical and electrophysiological datas of the manifest PV (intermittent or persistent), the arrhythmic vulnerability and any modifications in the features of AP anterograde conduction in symptomatic or asymptomatic children, examined on two separate timing, at least 2 years apart from one EPS to the next. Method This is a retrospective monocentric observational study performed at Bambino Gesu` Children's Hospital, Rome, Italy. Between January 2011 and July 2022, we enrolled forty-four children and young adults (32 male, mean age 10 years± 2,42) with manifest ventricular preexcitation underwent, as our standard management, at two electrophysiolgical studies (EPS, transesophageal and/or endocavitary), both at rest and during adrenergic stress (exercise testing or isoproterenol infusion) in two different timing (T0 and T1) within a minimal interval of 2 year. No transchateter ablation was performed between two EPS. Clinical and electrophysiological data were collected and compared. Results We observed a significant modification in atrioventricular accessory pathway conductive properties from T0 to T1 in basal study. In particular, at the baseline, preAVA value and 1/1 conduction VA time were respectively 306,59±43 and 292,61±61,7 and significatively decreased on occasion of second EPS evalutation (T1) (respectively to 279,51±41 with p 0,004 and 267,13±51,6, with p 0,003). Furthermore, an ARVT were induced in 14 patients in T1 respect 9 patient in T0 (p<0,03) and AF in 16 patients in T1 respect 7 patients in T0 (p 0,24). This results were not confirmed on adrenergic test during EPS evaluation. We also reported a clinically but not statistically relevant reduction of SPERRI time evaluated during EPS with stress test from T0 to T1 (from 251,44±47,9 to 206,9±36,7; p= 0,18). Conclusion There were significant and clinically rilevant changes of electrophysiological datas in young patients with symptomatic and asymptomatic VP underwent two EPS in two different timing. Therefore, in our opinion, a systematic evaluation with repeated EPS should be considered in this population.

Tandem high-dose 131I-MIBG therapy supported by dosimetry in pediatric patients with relapsed-refractory high-risk neuroblastoma: the Bambino Gesu' Children's Hospital experience.

131I-meta-iodobenzylguanidine (131I-MIBG) combined with myeloablative chemotherapy represents an effective treatment in children affected by relapsed/refractory neuroblastoma (NBL) for disease palliation and in improving progression-free survival. The aim of our study is to evaluate the feasibility, safety and efficacy of tandem 131I-MIBG followed by high-dose chemotherapy with Melphalan. Thirteen patients (age range: 3-17 years) affected by relapsed/refractory NB, previously treated according to standard procedures, were included in the study. Each treatment cycle included two administrations of 131I-MIBG (with a dosimetric approach) followed by a single dose of Melphalan with peripheral blood stem cell rescue. At the end of the treatment, ten patients experienced grade 4 neutropenia, two grade 3 and one patient grade 2, three patients presented febrile neutropenia and all needed RBC and platelets transfusions; one patient presented grade 4 mucositis, four grade 3 and one patient grade 2 mucositis. One patient showed progressive disease, eight patients showed stable disease and four patients showed partial response. High-dose 131I-MIBG therapy combined with chemotherapy represent a well-tolerated and effective modality of treatment in heavily pretreated patients affected by relapsed/refractory NBL. However, further studies, including a wider cohort of patients, are needed.

Italian Cystic Fibrosis Registry (ICFR). Report 2017-2018

Italian Cystic Fibrosis Registry (ICFR). Report 2017-2018

Determinants of Precocious B-Cell Aging in European Adolescents Living With Perinatally Acquired HIV-1 After Over 10 Years of Suppressive Therapy

Background: Despite a successful antiretroviral therapy (ART), adolescence living with perinatally acquired HIV (PHIV) experience B-cells dysfunction, including loss of vaccine-induced immunological memory and higher risk of developing B-cells associated tumors. In this context, perinatally HIV infected children (PHIV) deserve particular attention, given their life-long exposure to chronic immune activation. Methods: Here, we studied 40 PHIV who started treatment by 2nd year of life and maintain virological suppression for 13.5 years, with 5/40 patients experiencing transient elevation of the HIV-1 load in the plasma (Spike). We applied a multi-omics approach including immunological B and T cell phenotype, plasma proteomics analysis and serum level of anti-measles antibodies as functional correlates of vaccine-induced immunity. Findings: Elevated levels of aging B-cells (T-bet+CD11c+) were associated with later start of treatment, detectable cell-associated HIV-1 RNA, Spikes, higher frequency of exhausted T-cells (PD-1+, LAG3+, TIGIT+). The proteomic analysis revealed that subjects with expansion of aging B-cells and exhausted T-cells had enrichment of proteins involved in immune inflammation and complement activation pathways. Signs of precocious aging were associated with a reduced capacity to maintain virological memory against measles vaccination. Interpretation: To our knowledge, this is the first study focusing on precocious B-cell aging and dysfunctionality in PHIV with long-term virological suppression. We identified clinical, viral, cellular and plasma soluble markers associated with B-cells aging. Our results pave the way to further define risk of disease progression or lymphoproliferative disorders in PHIV. Funding Information: PENTA-ID Foundation (http://penta-id.org/); NIH; CFAR. Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: This is a multi-center study which include the following institutions: Bambino Gesu Children’s Hospital (OPBG, Rome, Italy), University of Padua (Padova, Italy), University Hospital 12 de Octubre (Madrid, Spain), Hospital Gregorio Maranon (Madrid, Spain), Imperial College Healthcare NHS Trust (London, UK), Great Ormond Street Hospital (London, UK), Brighton and Sussex University Hospitals (Brighton, UK). Each recruiting sites received approval by local ethic committees (Foster, Dominguez-Rodriguez et al. 2020). Study participants or their legal guardians gave written informed consent in accordance with the Declaration of Helsinki.

First Total Posterior Craniopagus Twins in Central African Republic: Two Years Challenge of Management

Introduction: Countries with limited resources have real difficulties in separating craniopagus twins. Separation surgery cannot be considered there due to lack of technological conditions and appropriate means. Objective: To show the benefits of an Italian-Central African humanitarian collaboration, after two years follow-up, aiming to improve the first childhood years of craniopagus twins, born in the Central African Republic and separated in Rome. Case Report: The two female conjoined craniopagus twin, born at term on June 29, 2018 in Mbata located about 96 km from Bangui (CAR), were referred to the neonatology unit of the CHUPB on their 3rd day of life. The mother was 31-year-old, gravida 4 and para 5. Prenatal cares were quantitatively and qualitatively poorly followed. The diagnosis of posterior conjoined craniopagus twins associated with early neonatal infection was retained. After seven days of antibiotics and regression of infectious symptoms, the newborns were kept in the neonatology unit for a closer follow-up, pending the completion of administrative procedures for a medical evacuation as part of the international humanitarian activities of the Pediatric Hospital of the Holy Seat in collaboration with the Pediatric Teaching Hospital in Bangui. Finally, the twins were transferred to the Bambino Gesu Hospital in Rome on September 10, 2018 where the 3D images confirmed the total posterior fusion. Between May 2019 and June 2020 thirty hours of interventions allowed a step-by-step separation of the twins, with a gradual rerouting of the shared blood supply, remodeling and re-creating a skin to cover the skull bones. No postoperative complications were recorded; the twins recovered satisfactorily after 6 months of separation and are awaiting discharge at their origin country where the CHUPB team will continue monitoring. Conclusion: The successful separation of total posterior craniopagus twins remains historically scarce and the guarantee of success has been based on detailed and well planned surgical management.

A Novel, Portable MESH Nebulizer-An Alternative to Metered Dose Inhaler: Efficacy and Usability in Preschool Wheezers.

Introduction and Objectives: Wheezing episodes are the first causes of doctor's consultation in preschool age. Treatment is usually administered with a metered dose inhaler (MDI) spacer. At variance, many parents and doctors prefer to use a compressor nebulizer, which cannot be easily carried. The study is aimed at testing whether a pocket mesh nebulizer has similar efficacy and acceptability than a standard MDI device.Materials and Methods: The IPAC study was a randomized, controlled, non-inferiority trial (number: 1616/2018, Ospedale Pediatrico Bambino Gesu'—IRCCS). The study had two arms: cases, using MicroAIR U100, and controls, using MDI+spacer device. Both devices were adopted for long-term treatment and for exacerbations. Follow-up was organized with clinical visits and a daily e-diary connected to an application for mobile phone.Results: One hundred patients were enrolled. The frequency of asthmatic symptoms showed a non-inferiority for MicroAIR U100 group vs. MDI. Accordingly, no significant difference was found in the average % of days with cough, wheezing, breathlessness after exercise, days lost at school, and not-programmed visits. Considering only patients with >1 day with symptoms, no significant sdifferences were found in the number of exacerbations nor in the cumulative days with symptoms. The acceptance and usability of both devices have been favorable. However, the MDI+AeroChamber® device showed better acceptability.Conclusions: Our study shows that MicroAIR U-100, a mesh nebulizer, has similar clinical efficacy but lower acceptance and usability than an MDI plus Aerochamber® in delivering therapy in preschool wheezers. Therefore, MicroAIR U-100 might be a valuable second choice, when the delivery of medication with an MDI plus Aerochamber® is not accepted, or wrongly used by the parents.

Impact of Early Antiretroviral Therapy Initiation on HIV-Specific CD4 and CD8 T Cell Function in Perinatally Infected Children

S Rinaldi, S Pallikkuth, M Cameron. J Immunol. 2019;204(3):540–549 To evaluate whether the time of treatment initiation of anti-retroviral therapy in vertically HIV-infected children can impact host immune responses associated with HIV infection, as it has been suggested that early treatment can be associated with loss of HIV-specific immunity. The study was cross-sectional in design and included a cohort of 20 perinatally-infected children with HIV that were identified at Bambino Gesu …

Virological and Immunological Features of SARS-CoV-2 Infected Children Developing Specific and Neutralizing Antibodies

As the global COVID-19 pandemic progresses and with the school reopening, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children in order to define possible immunization strategies and reconsider pandemic control measures. We analyzed anti-SARS-CoV-2 antibodies (Ab) and their neutralizing activity (PRNT) in 42 COVID-19-infected children 7 days after symptoms onset. Individuals with specific humoral responses presented faster virus clearance, and lower viral load associated to a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2 specific CD4-CD40L+ T-cells and Spike specific B-cells were associated with the anti-SARS-CoV-2 Ab and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, with PRNT+ patients showing higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work shed lights on cellular and humoral anti-SARS-CoV-2 responses in children which may drive future vaccination trials endpoints and quarantine measures policies.Funding: This work was made possible by support from Bambino Gesù Children’s Hospital ricerca corrente 2020 to NC and ricerca corrente 2019 to PP, by PENTA and by Fondazione Cassa di Risparmio di Padova e Rovigo, Progetti di Ricerca Covid-19 (ADR participant).Conflict of Interest: The authors declare no competing interests.Ethical Approval: Local ethical committee approved the study and written informed consent was obtained from all participants or legal guardians.

Sleep Quality, Emotion Regulation and Parenting Stress in Children with Congenital Heart Disease

The aim of this study is to evaluate parental perceptions of parent-infant bedtime interactions and quality of sleep, after hospital discharge, in a group of children diagnosed at birth with congenital heart disease (CHD), as compared with the perceptions of parents in a control group of children who were healthy at birth. More specifically, we evaluated the associations between parental stress, parental perceptions of infant emotion regulation, and infants’ bedtime and sleep routines in each of the two groups. Fifty Italian intact two-parent families (23 boys) of toddlers ageing from 11 to 36 months (M= 23.42, SD=7.10) were recruited. 20 families of CHD children group were recruited from the Department of Cardiology at the Bambino Gesu Children’s Hospital in Rome, Italy; 30 families of the healthy children group were recruited from two childcare units. Parents completed Emotion Regulation Checklist (Shields & Cicchetti, 1997), Parent-Child Sleep Interaction Scale (PSIS; Alfano et al., 2013), Parent-Stress Index-Short Form (PSI-SF; Abidin, 1990) and ad-hoc semi-structured interview on child’s sleep quality. The independent-samples t-test evidenced that parents of healthy children reported significantly higher scores on children's emotion regulation compared with the CHD group Specifically CHD children and healthy children's emotion regulation reported both by mothers (respectively CHD children’s mothers: M= 26.11, SD= 2.9; healthy children’s mothers: M= 28.85, SD= 2.71; t(37) = 3.10, p= .004) and fathers (respectively CHD children’s fathers: M=25.76, SD= 2.79; healthy children’s fathers: M= 27.37, SD= 2.02; t(31)= 2.71, p= .010). Main correlational findings showed in the CHD children’s group that parenting stress total scores were positive related to difficult parent-infant bedtime interactions both for mothers ( r =.58, p < .01) and fathers ( r = .70, p < .01). Results show significant differences in emotion regulation between the two groups. The results of this research will show to the clinicians the aspects of parent-infant bedtime interactions to be addressed in parents of children with CHD.

M19 - Does The Frequency of Enzymatic Replacement Therapy Influence Patients’ Level of Adaptive Functioning?

Background Lysosomal storage diseases (LSDs) are a group of rare inherited metabolic disorders that result from defects in lysosomal function. LSDs are generally multisystemic diseases with reduced life expectancy. Enzymatic replacement therapy (ERT) is available for some LSDs and has led to an improvement of many somatic symptoms of some metabolic disorders. To our best knowledge no study has explored the impact of ERT frequency on adaptive functioning in this unique pediatric population. We hereby present a pilot study. Methods The parents of 27 patients with LSDs, aged between six months and 16 years (mean age 9 years 4 months), were asked to complete the Vineland Adaptive Behavior Scales (VABS) Survey Form interview to measure children’s functional outcomes within four domains: communication, daily living, socialization and motor ability. Disorders present amongst the sample included MPS (N=13; I, I H-S, I H, I S, II, IV-Morquio, VI) Gaucher (N=6; types I and III) and Pompe (N=8; infantile and late onset forms). Data collection took place during patients’ visits to the Bambino Gesu Children’s Hospital in Rome (Italy) for ERT treatment. Results The total sample obtained significantly lower scores ( When considering only children with an IQ in the normal ranges (>85; N=21), no significant differences were found comparing children’s adaptive functioning by splitting the sample into high and low ERT frequency (high=once a week; low=fortnightly). However, 58% of patients undergoing ERT once a week and 43% of patients undergoing ERT fortnightly presented with scores below the normal ranges ( Discussion Despite children with good cognitive capacities who did not differ significantly on level of adaptive functioning based on high or low ERT frequency, results suggest that higher frequency of treatment was associated with a higher occurrence of scores below the normal ranges in the adaptive behavior in this sample. Investigating this tendency could be of crucial importance in understanding whether lower scores in the daily living skills domain of the VABS and, more in general, maladaptive functioning might be associated with ERT frequency. Finally, a clearer understanding of the role of treatment frequency in this population’s adaptive functioning can lead to an improvement of both patients and families’ health outcomes.

NS-15NEUROSURGICAL MANAGEMENT OF TECTAL GLIOMAS

NS-15. NEUROSURGICAL MANAGEMENT OF TECTAL GLIOMAS Andrea Carai1, Antonio Marrazzo2, Vito Andrea dell’Anna2, Alessandro De Benedictis1, Raffaella Messina1, Franco Randi1, Giovanna Stefania Colafati3, Antonella Cacchione2, Evelina Miele2, Angela Mastronuzzi2, and Carlo Efisio Marras1; Department of Neurosciences and Neurorehabilitation, Neurosurgery Unit, Bambino Gesu Children’s Hospital, Rome, Italy; Department of Hematology and Oncology, Bambino Gesu Children’s Hospital, Rome, Italy; Department of Imaging, Neuroradiology Unit, Rome, Italy Tectal gliomas are a rare entity mostly showing an indolent clinical course. However, in some cases progression of disease prompts medical treatment. We report a series of 12 consecutive patients diagnosed with tectal glioma at the Bambino Gesu Children’s Hospital from 2012 to 2016. Diagnosis was made according to typical radiological features. Mean follow-up was 43 months (4 to 75 months). Symptoms at onset were macrocrania and full fontanelle in congenital cases and headache, vomiting, ataxia, postural instability, short term memory and attention difficulties in older children, suggesting a strong role of hydrocephalus. Mean age at diagnosis was 8 years and girls were three times more frequent than boys. Hydrocephalus was present at the timeof the diagnosis virtually inall cases (10/11). In three caseshydrocephalus was congenital but diagnosis of tectal glioma was made 8 years later in one case, due to limited access to MRI imaging at the time of hydrocephalus treatment. Hydrocephalus was treated by endoscopic ventriculostomy in all patients presenting after 2008. We had a major complication in one girl, suffering acute intracranial hypertension with severe outcome 20 months after diagnosis presumably from unexpected ventriculostomy closure. After that, we propose routine positioning of a Rickham ventricular access device in all children with hydrocephalus secondary to tectal gliomas. Three children showed progression of their tectal lesion or gaze disturbances prompting stereotactic needle biopsy to obtain histological diagnosis and start oncological treatment. Surgical resection was never indicated, as large esophytic lesions were not observed in our series. Neuro-Oncology 18:iii127–iii134, 2016. doi:10.1093/neuonc/now078.15 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Urgent Need of New Mood-Stabilizers: The Promising Results of Memantine

Giulia Serra1,2, Francesca Demontis3 and Gino Serra4* 1Clinical and Research fellow, Child Neuropsychiatry, Department of Neuroscience, I.R.C.C.S. Children Hospital Bambino Gesu, Rome, Italy. 2NESMOS Department, Sant'Andrea Hospital, Sapienza University, Rome Italy 3International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont (MA), USA 4Dipartimento di Scienze Biomediche, University of Sassari, Italy

L'esperienza di uno specializzando

Located in the central plateau area of Tanzania in East Africa, St Gaspar's Hospital was founded in 1968 by the Society of the Precious Blood Catholic Missionaries. Elevated to referral hospital at a regional level, with an approved capacity of 320 beds, it provides residential consultancy services in general medicine, surgery, obstetrics, gynecology and pediatrics for more than 100,000 people. In 2013, a cooperation agreement between the “Bambino Gesu” Children's Hospital (OPBG) and St Gaspar's has been established for the creation of a “Clinical and Surgical Pediatric Centre”. That led to the complete renovation of the Pediatric Ward, the construction of a new operating theatre and the installation of a telemedicine system for remote medical diagnosis and consultation. In this setting, a periodic turnover of clinical and surgical missions is guaranteed in order to form the local healthcare providers and improve the quality of assistance. From 2014, the Residency School in Pediatrics of the University of Rome “La Sapienza”, in agreement with OPBG, allows its residents to spend a 3-month period of work at the St Gaspar's Hospital's Pediatric Ward. Under the supervision of a local tutor, residents are involved in clinical activities including: morning work round with 90 to 150 patients visited per day; evaluation and management of new admissions for malaria, typhoid fever, meningitis, gastroenteritis, severe malnutrition and local herbs intoxication; weekly mobile clinic service, for antenatal visits, vaccinations and health education programs in rural areas around the hospital. Residents are also engaged in research activities and training courses for local health workers. One year has passed from when I decided to join the OPBG project but memories and feelings of those days are still vivid in my mind. From the sorrow for the premature deaths that you know easily preventable in developed countries to the joy for the smile of the baby you manage to treat and send back home. In the end, what you receive from this kind of experience is so much more than what you give and that is why I am certain to say, “I want to do it again”.

209th ENMC International Workshop: Outcome Measures and Clinical Trial Readiness in Spinal Muscular Atrophy 7–9 November 2014, Heemskerk, The Netherlands

209th ENMC International Workshop: Outcome Measures and Clinical Trial Readiness in Spinal Muscular Atrophy 7–9 November 2014, Heemskerk, The Netherlands Richard Finkel *, Enrico Bertini , Francesco Muntoni , Eugenio Mercuri d on behalf of the ENMC SMA Workshop Study Group 1 a Nemours Children’s Hospital, Orlando, USA b UCL Institute of Child Health, Dubowitz Neuromuscular Centre, London, UK c Bambino Gesu Children’s Research Hospital, Rome, Italy d Pediatric Neurology Unit, Catholic University, Rome, Italy Received 2 March 2015

A single-centre, tertiary-care, Italian registry of celiac disease: Incidence and clinical presentation

s / Digestive and Liver Disease 46 (2014) e85–e127 e95 4.5±0.6pg/ml, mean FT4 1.2± .4 ng/dl. TSH levels were above cutoff laboratory range in 10% of our population and the 2 patients (0.2%) of the whole population presented TSH≥10 UI/ml. We found a significant positive correlation between TSH levels and BMI z-score (rho=0.121, p=0.001), even after adjustment for age and sex (r=0.117, p=0.001); a positive correlation was also observed between FT3 and BMI z-score (rho=0.161, p<0.001), but not for Ft4 (p=0.787). TSH and FT3 were also positively associated with Waist to Height ratio (WtHr, rho=0.114, p=0.002 and rho=0.095, p=0.011 respectively). No correlation was found between thyroid functionality and: Homa index, z-score of blood pressure and hepatic steatosis. Conclusions: Our data suggest a relationship between obesity and serum TSH and FT3 levels. In particular, WtHr, marker of visceral fat, is directly related to TSH levels. It is not clear whether thyroid alteration are cause or consequence of fat excess, but metabolic active visceral fat could have a role. http://dx.doi.org/10.1016/j.dld.2014.07.078 A SINGLE-CENTRE, TERTIARY-CARE, ITALIAN REGISTRY OF CELIAC DISEASE: INCIDENCE AND CLINICAL PRESENTATION Valentina Giorgio ∗, Maria Rita Sartorelli, Claudia Della Corte, Donatella Comparcola, Daniela Liccardo, Arianna Alterio, Valerio Nobili, Francesca Ferretti Malattie EpatoMetaboliche, Ospedale Pediatrico “Bambino Gesu”, Roma, Italy Objectives: The aim of this study was to assess clinical pattern and the incidence of celiac disease (CD) currently diagnosed in children living in Rome, describing a single-Italian-center experience. Methods: A prospective, single-center registry of new cases of CD in children under 18 years was conducted from 1 January 2011 to 1 June2013. The variables studiedwere: age at diagnosis, gender, breast feeding, clinical symptoms, associated diseases, IgA serum levels, CD serology, histological lesions, and HLA DQ2/QQ8. The crude incidence rate of CD was calculated as new cases per 1000 live births. Results: 800 new cases of CD were included (39% males). The median age at diagnosis was 8 years (range 0.9–18). 483/800 (60%) were breast fed≥2months, with amean breast feeding duration of 15.2±11.4months. Mean age at first gluten exposurewas 6.4±2.2 months. Regarding clinical presentation 68.9% showed classical symptoms, 27.1% were non-classical, and 4% were asymptomatic. Among atypical symptoms, celiac crises was present and seen in 3% of all children. 96.7% were positive for IgA endomysial antibodies, 97.3% were positive for IgA anti-transglutaminase type 2 antibodies. IgA selective deficiency was seen in 4% children. 85,6% performed duodenal biopsy. Villous atrophy was observed in 91% and increased intraepithelial lymphocytes with crypt hyperplasia in 10.3%. 3 children (0.37%) were diagnosed with CD after cutaneous biopsy for dermatitis herpetiformis. The HLA phenotype was performed in 200 children (25%) and was: DQ2: 84.5%, DQ2/DQ8: 5.5% and DQ8: 10%. The incidence rate was 7.08 cases of CD per 1000 live births. Conclusions: InRome, themost frequent clinicalpresentationof CD in the pediatric age is the classical form. The observed incidence of CD in children ismuchhigher than the current CD incidence rates observed in other countries. A multicenter study on larger series would be needed to verify this increasing incidence. http://dx.doi.org/10.1016/j.dld.2014.07.079 EVALUATION OF VITAMIN D STATUS IN A PEDIATRIC POPULATION OF SOUTHERN ITALY Donatella De Giovanni1,∗, Irene Rutigliano1, Clementina Calabrese1, Giovanna Nardella1, Maria Pia Falcone1, Angelo Guida1, Antonio Longo2, Massimo Pettoello-Mantovani1, Angelo Campanozzi1 1 Clinica Pediatrica, Universita’ di Foggia, Foggia, Italy 2 U.O. Pediatria, Ospedali Riuniti di Foggia, Foggia,

Sodium and potassium intake in children: Relationship with age, body mass and blood pressure

s / Digestive and Liver Disease 46 (2014) e85–e127 e95 4.5±0.6pg/ml, mean FT4 1.2± .4 ng/dl. TSH levels were above cutoff laboratory range in 10% of our population and the 2 patients (0.2%) of the whole population presented TSH≥10 UI/ml. We found a significant positive correlation between TSH levels and BMI z-score (rho=0.121, p=0.001), even after adjustment for age and sex (r=0.117, p=0.001); a positive correlation was also observed between FT3 and BMI z-score (rho=0.161, p<0.001), but not for Ft4 (p=0.787). TSH and FT3 were also positively associated with Waist to Height ratio (WtHr, rho=0.114, p=0.002 and rho=0.095, p=0.011 respectively). No correlation was found between thyroid functionality and: Homa index, z-score of blood pressure and hepatic steatosis. Conclusions: Our data suggest a relationship between obesity and serum TSH and FT3 levels. In particular, WtHr, marker of visceral fat, is directly related to TSH levels. It is not clear whether thyroid alteration are cause or consequence of fat excess, but metabolic active visceral fat could have a role. http://dx.doi.org/10.1016/j.dld.2014.07.078 A SINGLE-CENTRE, TERTIARY-CARE, ITALIAN REGISTRY OF CELIAC DISEASE: INCIDENCE AND CLINICAL PRESENTATION Valentina Giorgio ∗, Maria Rita Sartorelli, Claudia Della Corte, Donatella Comparcola, Daniela Liccardo, Arianna Alterio, Valerio Nobili, Francesca Ferretti Malattie EpatoMetaboliche, Ospedale Pediatrico “Bambino Gesu”, Roma, Italy Objectives: The aim of this study was to assess clinical pattern and the incidence of celiac disease (CD) currently diagnosed in children living in Rome, describing a single-Italian-center experience. Methods: A prospective, single-center registry of new cases of CD in children under 18 years was conducted from 1 January 2011 to 1 June2013. The variables studiedwere: age at diagnosis, gender, breast feeding, clinical symptoms, associated diseases, IgA serum levels, CD serology, histological lesions, and HLA DQ2/QQ8. The crude incidence rate of CD was calculated as new cases per 1000 live births. Results: 800 new cases of CD were included (39% males). The median age at diagnosis was 8 years (range 0.9–18). 483/800 (60%) were breast fed≥2months, with amean breast feeding duration of 15.2±11.4months. Mean age at first gluten exposurewas 6.4±2.2 months. Regarding clinical presentation 68.9% showed classical symptoms, 27.1% were non-classical, and 4% were asymptomatic. Among atypical symptoms, celiac crises was present and seen in 3% of all children. 96.7% were positive for IgA endomysial antibodies, 97.3% were positive for IgA anti-transglutaminase type 2 antibodies. IgA selective deficiency was seen in 4% children. 85,6% performed duodenal biopsy. Villous atrophy was observed in 91% and increased intraepithelial lymphocytes with crypt hyperplasia in 10.3%. 3 children (0.37%) were diagnosed with CD after cutaneous biopsy for dermatitis herpetiformis. The HLA phenotype was performed in 200 children (25%) and was: DQ2: 84.5%, DQ2/DQ8: 5.5% and DQ8: 10%. The incidence rate was 7.08 cases of CD per 1000 live births. Conclusions: InRome, themost frequent clinicalpresentationof CD in the pediatric age is the classical form. The observed incidence of CD in children ismuchhigher than the current CD incidence rates observed in other countries. A multicenter study on larger series would be needed to verify this increasing incidence. http://dx.doi.org/10.1016/j.dld.2014.07.079 EVALUATION OF VITAMIN D STATUS IN A PEDIATRIC POPULATION OF SOUTHERN ITALY Donatella De Giovanni1,∗, Irene Rutigliano1, Clementina Calabrese1, Giovanna Nardella1, Maria Pia Falcone1, Angelo Guida1, Antonio Longo2, Massimo Pettoello-Mantovani1, Angelo Campanozzi1 1 Clinica Pediatrica, Universita’ di Foggia, Foggia, Italy 2 U.O. Pediatria, Ospedali Riuniti di Foggia, Foggia,