Early effect of NTBC on renal tubular dysfunction in hereditary tyrosinemia type 1.

BACKGROUND: Hereditary tyrosinemia type 1 (HT1) is characterized by severe progressive liver disease and renal tubular dysfunction. NTBC therapy has revolutionized the management of HT1 but its effect on renal tubular function has so far been poorly investigated. The aim of this study was to describe the early effect of NTBC on renal tubular disease in patients with HT1. METHODS: Five HT1 patients (age between 5 and 53 months) with different types of presentation were evaluated before and during the first 2 weeks of therapy with NTBC in a retrospective case analysis for phosphate metabolism and renal tubular function. RESULTS: Before starting NTBC therapy, all children manifested signs of renal dysfunction which included hypophosphatemia, acidosis, reduced phosphate reabsorption, aminoaciduria, glycosuria (Fanconi syndrome), and variable degree of proteinuria. Some patients also presented increased urinary calcium/creatinine ratio and raised fractional excretion of sodium. Starting of NTBC therapy resulted in the rapid normalization of plasma phosphate within one week from its initiation in majority of patients and in all patients during the second week of therapy. TmP/GFR normalized in 48h, while the other markers of renal dysfunction showed an improving trend over 2 weeks. CONCLUSIONS: NTBC is an efficient treatment for renal tubular dysfunction in HT1, allowing the return to normal function within a few weeks. Its early effect on renal tubular cells appeared to be very rapid, particularly in normalizing plasma phosphate and TmP/GFR. In our series of patients, the TmP/GFR resulted as the most reliable index of tubular function.

Children who develop type 1 diabetes early in life show low levels of carnitine and amino acids at birth: does this finding shed light on the etiopathogenesis of the disease?

BACKGROUND: Children and adolescents with overt type 1 diabetes (T1D) have been found to show an altered carnitine profile. This pattern has not previously been analyzed in neonates before onset of the disease. MATERIALS AND METHODS: Fifty children who developed T1D during the first 6 years of life, born and living in the Tuscany and Umbria Regions of Italy, were identified and 200 controls were recruited into the study. All newborns were subjected to extended neonatal screening by mass spectrometry at 48-72 h of life. Four controls for each of the 50 index cases were taken randomly and blinded in the same analytical batch. The panel used for neonatal screening consists of 13 amino acids, free carnitine, 33 acyl-carnitines and 21 ratios. All Guthrie cards are analyzed within 2 days of collection. RESULTS: Total and free carnitine were found to be significantly lower in neonates who later developed T1D compared with controls. Moreover, the concentrations of the acyl-carnitines - acetyl-L-carnitine (C2), proprionylcarnitine (C3), 3-hydroxyisovalerylcarnitine (C5OH), miristoylcarnitine (C4), palmitoylcarnitine (C16) and stearoylcarnitine (C18) - were also significantly low in the cases vs controls. Furthermore, total amino-acid concentrations, expressed as the algebraic sum of all amino acids tested, showed a trend toward lower levels in cases vs controls. CONCLUSIONS: We found that carnitine and amino-acid deficit may be evident before the clinical appearance of T1D, possibly from birth. The evaluation of these metabolites in the neonatal period of children human leukocyte antigen genetically at 'risk' to develop T1D, could represent an additional tool for the prediction of T1D and could also offer the possibility to design new strategies for the primary prevention of the disease from birth.

[PedsQL™ 4.0 Generic Core Infant Scales Parents Report for infants (ages 13-24 months). Linguistic validation from original US English version to Italian version]. / PedsQL™ 4.0 Generic Core Infant Scales Parents Report versione per i genitori di bambini in eta prescolare (eta 13-24 mesi): validazione linguistica della versione italiana.

AIM: The purpose of this research was to show the translation and linguistic validation of the PedsQL™ 4.0 Generic Core Infant Scales Parents Report for Infants (ages 13-24 months) from its original English version to Italian language. METHODS: The linguistic validation consists in three steps: a) different forward translations from the original US English instrument to Italian; this step includes the drawing of a "reconciliation" version (version 1); b) backward translations from the Italian reconciliation version to US English; c) patient testing: the second version of the questionnaire (obtained after the backward translations) has to be tested on a panel of a minimum of 5 respondents, throughout cognitive interviewing methodology, in order to obtain the final italian version of the PedsQL™ Parents Report for Infants (ages 13-24 months). In this report we summarize the third step of this process. To study the content validity, the applicability and comprehension of our questionnarie translation, we tested it through a qualitative methodology in a sample of parents whose children were hospitalized in Bambino Gesù Children's Hospital with two different kinds of interview: 4 parents responded to the questions posed through a "thinkaloud interview" and 3 parents responded to the questionnaire and to a "respondent debriefing" interview. RESULTS AND CONCLUSION: We modified the main question of each section and also one of the possible answer in order to maintain the Italian translation that appeared in others PedsQL™. We did not modify the questions of each section because respondents expressed that are clearly comprehensible and easy to understand.

Home enteral nutrition in children: a 14-year multicenter survey.

BACKGROUND/OBJECTIVES: The practice of home enteral nutrition (HEN) represents a relevant aspect of the clinical management of both malnourished children and well-nourished children unable to be fed using an oral diet. The aim of this study was to estimate in an Italian paediatric population over a 14-year period (1996-2009), the clinical relevance and results over time of HEN activity. SUBJECTS/METHODS: HEN-computerized database and medical/dietetic charts were evaluated for patients aged at start of HEN <18 years and HEN duration >1 month. RESULTS: During the study period, we recorded 757 HEN programs. HEN began at a median age of 2 years for a median duration of 8.1 months. The complication rate was 14.8%. In the second period of the survey (2003-2009), the main changes concerned the underlying diseases requiring HEN, choice of formula feeding and access route. In 2009, the estimated overall prevalence of HEN was 3.47 and the incidence 2.45 per 100 000 inhabitants from 0 to 18 years of age. CONCLUSIONS: The epidemiological data of this study demonstrate that HEN concerns a growing number of Italian children and families. Some aspects of HEN clinical management should be modified to reach the recommended standards.

Utility of a stool antigen test to detect the incidence of helicobacter pylori infection and familial and community enviromental risk factors for this infection in pediatric age.

BACKGROUND: Helicobacter pylori (Hp) infection is mainly acquired during childhood; it is recognised as a cause of gastritis and peptic ulcer and it has been classified as a group A carcinogen by World Health Organization. The exact mode of transmission is as yet, not known. Aim of our study has been to identify risk factors associated with Helicobacter pylori infection in a preschool and school population and to confirm if Hp antigen in faeces is useful as screening in epidemiological studies. METHODS: We interviewed, with questionnaire, 400 children (203 male; age range 3-10 years; mean age 6 years) of 3 different schools and stool samples were collected of all children too. 35 of 400 (8%) children underwent to upper gastrointestinal endoscopy because of a suspect of upper gastrointestinal disease. RESULTS: stool were collected from 400 school children and 35 of them shown positivity of Hp antigen test. A questionnaire about presence of nausea, vomit, recurrent abdominal pain, family size, parent's occupations and education, use of antibiotics, country of birth of child and parents, personal hygiene, breast feeding, presence of the animals was completed. 35 children with positive Hp stool antigen test and a suspicious of upper gastrointestinal disease (recurrent abdominal pain, diurnal or nocturnal abdominal pain, nausea, vomiting, iron deficiency) underwent to esophagogastroduodenoscopy (EGDS) that demonstrated antral gastritis and positive histology and urease rapid test. CONCLUSIONS: the results of this study suggest that risk factors for Hp infection are low socioeconomics factors, hygiene and living conditions and that Hp antigen in faeces is useful as screening test.

The department of psychology within a pediatric cardiac transplant unit.

In 1979, the department of Psychology started its activity to provide psychological support to patients and their families during the course of treatment and during the follow-up period. Since 1986, a transplantation program was initiated in the cardiology and pediatric cardiac surgery departments, performing 179 cardiac, 3 heart-kidney, 18 heart-lung 14 both lung, 1 heart-lung-liver, and 1 single lung transplantation. From 1993, to September 2010 the kidney transplant program has performed. 218 cases. Since 2008, we performed (32 liver and 1 intestinal transplantations). We examined the quality of life and coping with transplantation attitudes because there is recent evidence of high levels of family anxiety and depression related to a child's poor response to the disease and compliance. Our work associated post-traumatic stress disorder (PTSD) with anxiety and with these clinical variables: gender pathology, rejection, number of drugs frequency of hospital visits, number of hospitalizations, as well as age at and time from transplantation. We examined 56 parents (25 fathers and 31 mothers) of cardiac transplant recipients. Our most relevant data demonstrated the presence of PTSD among 52% of mothers and 40% of fathers. Significant correlations were observed within the trait of anxiety. No correlations were noted between PTSD and other variables. Testing anxiety levels of parents is considered to be basic to provide psychological support to parents, encourage personal skills, and avoid PTSD symptoms.

Adherence to diet and quality of life in patients with phenylketonuria.

AIM: To investigate adherence to dietary treatment and quality of life (QoL) in patients with phenylketonuria (PKU). METHODS: In the setting of a tertiary paediatric hospital, 41 early-treated patients affected by PKU aged more than 3 years old were enrolled in a cross-sectional study. Three-days dietary assessment, QoL questionnaires for patients<18 years old (Child Health Questionnaire) and Short Form for adults were completed. RESULTS: Of 41 patients, 23 (56.1%) were considered adherent to the dietary prescriptions as their phenylalanine intake was less than prescribed. Phenylalanine intake was significantly in excess of prescribed if mothers had a lower level of education. Adherence was not correlated with age. Metabolic control was obtained in 41.5-51.2% of the patients depending on the target. QoL was reduced in children and adolescents. There was no significant correlation between adherence and QoL, except for the domains of Global Health and Family Activities (ρ=0.42 and 0.46, respectively). The overall agreement between adherence and metabolic control varied according to different targets of metabolic control (51.2-65.9%). CONCLUSIONS: It is necessary to improve the adherence to diet and the QoL in children and adolescents affected by PKU.

Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996-2003).

BACKGROUND: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. METHODS: In 1996 an IBD register of disease onset was established on a national scale. RESULTS: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohn's disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996-2003 an increase of IBD incidence from 0.89 to 1.39/10(5) inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. CONCLUSIONS: The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD.

Short antibiotic prophylaxis for bacterial infections in a neonatal intensive care unit: a randomized controlled trial.

We compared the effectiveness of a single dose and a three-day course of antibiotic prophylaxis in preventing bacterial infections in high-risk neonates. The study was a prospective, randomized controlled trial conducted in a 20-bed tertiary referral neonatal intensive care unit (NICU). A series of 130 neonates admitted consecutively to the NICU, fulfilling risk factors for infection, were assigned at random to receive intravenous antibiotic prophylaxis with ampicillin and netilmicin either in two daily doses for 72 h (three-day-administration group, 67 infants) or in a single bolus injection on admission (bolus group, 63 infants). Hospital-acquired infection, the main outcome measure, was defined as infection that developed at least 48 h after admission, and vertical infection (maternally transmitted) was considered to be present when clinical symptoms and abnormal laboratory findings became evident within 48 h of birth. Infections were considered as suspected when clinical and laboratory findings of infection were present, without positive cultures, and as confirmed when positive cultures were also present. No significant differences were found between the two groups of neonates studied in mean birth weight, gestational age or postnatal age on admission. The incidence of vertical infection was similar in the two groups (16/67, 23.9% vs. 14/63, 22.2%). Of the 130 newborns studied, 29 (22.3%) acquired at least one nosocomial infection during their NICU stay; total hospital-acquired infections, calculated as the incidence density of infection (the number of infective episodes divided by the number of days in the NICU), were less frequent among newborns who received the three-day course than the bolus (relative risk 0.69). This difference, although not statistically significant, depended on the different incidence density of confirmed nosocomial infections rather than on suspected infections (relative risk 0.59; 95% confidence interval 0.32-1.09; P=0.1). There were no significant differences between the two groups in overall mortality. A single bolus administration on admission is therefore likely to be as effective as a three-day course of antibiotic prophylaxis in preventing bacterial infection in high-risk infants admitted to an NICU.

Paroxysmal atrioventricular block in young patients.

We describe 17 patients (8 girls, and 9 boys), aged 9.6 +/- 5.7 years, with paroxysmal atrioventricular block (PAVB), a condition rarely described in children. Holter monitoring documented the PAVB in 15 patients, and tilt test was performed in 4 patients (positive in 1). The electrocardiograph (ECG) was normal in 7 patients. Two patients had acquired and 11 patients had congenital heart disease (CHD). Syncope or presyncope were present in 7 patients. A normal ECG was significantly more frequent in symptomatic patients. Pauses were significantly longer in girls and in children <5 years. PAVB was recorded only during nocturnal hours in 6 patients and throughout the day in the others. The sinus rate decreased during PAVB in 6 patients and increased in 4 (generally younger girls with symptoms). Permanent pacemakers were implanted in 13 patients, including 7 asymptomatic patients with CHD and severe bradycardia. During follow-up (3.7 +/- 2.5 years), 1 patient developed complete AVB. Although PAVB was still present in 91% of paced patients, symptoms did not recur because pacing prevented the pauses. In conclusion, PAVB is a rare arrhythmia. Autonomic nervous system dysfunction seems to play an etiological role and permanent pacing was an effective treatment.

Interferon alpha in the treatment of chronic hepatitis C in children: a meta-analysis [correction of metanalysis].

Children with chronic hepatitis C may be ideal candidates for treatment with interferon alpha (IFNalpha) as they have liver disease at an early stage. However, adverse drug reactions need to be considered. The aim of this study was to conduct a systematic review of literature on interferon therapy of chronic hepatitis C in children, and to perform a meta-analysis of pooled data. A computerized search gave 18 articles on IFNalpha therapy in children with chronic hepatitis C; after exclusion of uncontrolled trials and of trials including patients with comorbidities, data from two studies could be pooled (48 patients). The outcomes assessed were biochemical, defined as normalization of alanine transaminase, and virologic, defined as HCV-RNA loss, both sustained at 24 months after enrollment. Results of the studies were homogenous. Risk difference was 37% (95%CI: 12.9-61) in favour of IFNalpha treated children for sustained biochemical response, and 36.8% (95%CI: 14.3-59.3) in favour of treated children for sustained HCV clearance, respectively. The differences were highly significant (P = 0.007 and P = 0.004, respectively). The histological end-point, as well as side-effects, could not be analysed, due to lack of data. This review identifies the poor methodology of the majority of the published trials. The study provides support for the efficacy of IFNalpha in improving both biochemical and virologic outcomes in chronic hepatitis C in children, but evidence is confined to these surrogate end-points.

Risk factors for nosocomial infections in a neonatal intensive-care unit.

The clinical records a years cohort of 280 newborn infants consecutively hospitalized for 48 h or more in our neonatal intensive-care unit (NICU) were reviewed. Information on the infants' conditions during the first 12h of life, and on the procedures used in the NICU, were collected. Statistical significance was tested by univariate analysis with the chi(2) test and by multivariate logistic regression analysis with the software program SPSS (Version 10). Over the one-year period reviewed, 90 hospital-acquired infections (HAIs) were contracted; 55 (19.6%) of infants had at least one infection during their stay. The overall in-hospital mortality was 7.1%, and mortality was higher in infants in whom at least one infection developed than in non-infected infants (12.7 vs. 5.8% P=0.13). Very low birthweight infants (VLBW<1,501 g) who had more severe clinical conditions on admission [clinical risk index for babies (CRIB) score >/=5] had an almost two-fold higher risk of contracting a HAI. In the multivariate regression analysis, the onset of a HAI was strongly associated with a low gestational age and the presence of an intravascular catheter. HAIs frequently complicate hospitalization in NICUs and are associated with increased mortality. Our findings also suggest that CRIB could be predictive for the risk of infection in VLBW infants.

Screening and prevention of congenital toxoplasmosis: an effectiveness study in a population with a high infection rate.

OBJECTIVES: Secondary prevention of congenital toxoplasmosis has been attempted by screening pregnant women or by screening neonates. We compared the results of these two approaches, in order to evaluate the effectiveness of these strategies and of the antibiotic treatment of infected women. METHODS: A prenatal serological screening program for toxoplasmosis enrolled 8061 pregnant women; 9730 neonates were screened during the same period. RESULTS: Out of 5288 susceptible pregnancies, 188 were identified as infected by Toxoplasma gondii (35/1000). The transmission rate was 11.3%, with a higher rate for neonates exposed in the last trimester (relative risk 10.6); four neonates were affected. Out of 9730 screened neonates, four tested positive (0.4/1000) and one was affected. Out of a total of 163 exposed neonates, 12 were clinically affected. The rate of clinical sequelae was 31.6% among those infected and 7.4% among all exposed to infection; neonates born of women who had not been treated were more likely to be affected than treated neonates (odds ratio 4), but after adjustment for trimester of infection no significant association was found. CONCLUSIONS: Neonatal screening for toxoplasmosis seems to be less effective than pregnancy screening. Observational data do not support the effectiveness of treatment during pregnancy to prevent clinical disorders.

Clinical and economic outcomes of pneumonia in children: a longitudinal observational study in an Italian paediatric hospital.

RATIONALE, AIMS AND OBJECTIVES: Antibiotic prescription for acute lower respiratory infections (ALRI) in hospitalized children can have a major impact on cure and costs. We performed a longitudinal study to explore the appropriateness of prescriptions, the predictors of therapeutic patterns, and the main outcomes: readmission, length of stay (LOS) and costs. METHODS: Ninety-nine children who were inpatients of a paediatric hospital receiving antibiotic treatment for community acquired ALRI were consecutively enrolled. To calculate the costs of pneumonia treatment, we collected data on clinical presentation and resources consumption. We used multiple regression analysis to identify predictors of LOS and choice of therapy, and one-way ANOVA to evaluate cost differences among treatment groups. RESULTS: Parenteral antibiotics were administered in 64.6% of cases, whereas 35.4% received oral antibiotic therapy by itself (OAT). Switch therapy (SWT) was performed in 43.4% of cases. The most frequently prescribed antibiotic for parenteral therapy was ceftriaxone (58.3%), and for oral therapy cefprozil (58.1%). The median LOS was 3 days and the cure rate 99% (95%CI: 97-100%). SWT and OAT were significantly associated with a shorter LOS. The clinical variables were not significantly associated with SWT or OAT. The average costs per patient in the management of pneumonia were Euro 1435. SWT or OAT were associated with significant lower costs: Euro 1487 per patient (95%CI: 1395-1580) and Euro 1335 per patient (95%CI: 1233-1437), respectively. CONCLUSIONS: The hospital management of paediatric pneumonia was more influenced by the early discharge policy than by clinical variables without under-cure.

Koch's triangle in pediatric age: correlation with extra- and intracardiac parameters.

The atrioventricular node is situated in the lower atrial septum, at the apex of the Koch's triangle. The dimensions of the Koch's triangle are studied in adult humans, while no data exist about them in pediatric age. The knowledge of the dimensions of Koch's triangle in childhood is very important for safe and correct application of radiofrequency energy during transcatheter ablation. The dimensions of Koch's triangle were determined in 69 human pediatric hearts. The median age of the children was 3 months, with a range from 1 day to 14 years, 30 were female and 39 were male. Relations between body weight (extracardiac parameter) and tricuspid valve diameter (intracardiac parameter) were determined in all hearts to show morphometric modifications with growth. The distribution of body weight was not Gaussian and no correlation could be obtained between Koch's triangle dimensions and body weight. However, it was possible to identify that the mean ratio between the cathetus of the Koch's triangle corresponding to the annulus of the tricuspid valve and the tricuspid valve diameter was 0.45 +/- 0.16, with a highly significant correlation coefficient (r = 0.653, P < 0.001). Therefore, by knowing: (1) the diameter of the tricuspid valve, and (2) the constant ratio between the cathetus of the Koch's triangle and the tricuspid valve diameter, it is possible to calculate the length of the segment of the tricuspid annulus along which the transcatheter application of radiofrequency current can be applied to ablate the slow-pathway, thus reducing the risks of damage of the atrioventricular node.

[What are the costs of pediatric cardiosurgery?]. / Quanto costa la cardiochirurgia pediatrica?

A cost analysis of patients discharged from the Department of Pediatric Cardiology and Heart Surgery of "Bambino Gesu" Children's Hospital was performed. Analysis focused on the costs and revenue from Diagnosis-Related Group 108 ("other cardiovascular procedures") during a six-month period in 1994 (n. = 76). The sample of 30 charts reviewed (MLOS 20.36 +/- 27.87 days) showed a mean cost of 30,381,000 italian lire (ITL) vs a revenue of ITL 23,545,800. The Pearson correlation coefficient between LOS and total cost was high (R = 0.85; p < 0.001). Other cases in DRG 108 (n. = 46) had an MLOS of 29.13 +/- 25.25 days and a higher cost. We emphasize the usefulness of identifying the costs for patients grouped in a specific DRG in order to establish an accurate departmental budget as well as to ensure the financial survival of referral hospitals.

Reciprocating supraventricular tachycardia in children: low rate at rest as a major factor related to propensity to syncope during exercise.

Reciprocating supraventricular tachycardia may have several clinical presentations, with symptoms often more severe during exercise or emotional stress. This study shows by using transesophageal atrial pacing, the factors related to syncope during exercise. Between May 1989 and June 1994, transesophageal atrial pacing was performed at rest and during exercise in 75 children aged > 6 years with suspected or documented episodes of paroxysmal supraventricular tachycardia. Reciprocating supraventricular tachycardia could be induced both at rest and during exercise in 22 patients (8 girls, 14 boys; mean age 10.6 +/- 2.7 years, range 7 to 15 years) with ventriculoatrial interval < 70 msec in 11 patients and > 70 msec in 11. At rest, all patients had palpitations caused by the induction of tachycardia. After conversion to sinus rhythm, when tachycardia was induced during exercise, symptoms did not change in 14 patients (group A), whereas symptoms worsened (presyncope) in eight (group B). The statistical analysis showed a significant difference of mean reciprocating supraventricular tachycardia rate at rest between the two groups (group A, 211 +/- 23 beats/min; group B, 173 +/- 33 beats/min; p = 0.0057) and reciprocating supraventricular tachycardia rate variation from rest to exercise (group A, 62 +/- 18 beats/min; group B, 105 +/- 24 beats/min; p = 0.0001). These data suggest that children with low tachycardia rate during normal activities may have syncope more frequently, independently of the tachycardia rate during exercise or emotional stress.

Vaccination against hepatitis B virus in children and adolescents in a pediatric hospital.

Vaccination against hepatitis B has become compulsory in Italy and is routinely administered in outpatient clinics of Local Health Service. In the setting of a pediatric hospital 205 children (less than 10-year-old) and 144 adolescents (10-19-year-old) have been vaccinated with anti-HBV recombinant yeast-derived vaccine (Engerix B 10 U.I. at 0.1 and 6 months in children and 20 U.I. in adolescents). Anti-HBs titers were evaluated 1 month after least dose. Geometric mean titer (GMT) was 9500 mU/I in children and 18,000 in adolescents; 99.85% of subjects had a protective anti-HBs titer (10 mU/I or more) at one month after the third dose and 89.1% had titers of 1000 mU/I or more. Only 9.7% of subjects had adverse events, mainly (75%) at the injection site, anyway of trivial importance, without any difference of sex and age. Anti-hepatitis B yeast-derived vaccine is highly immunogenic, without relevant adverse events; the hospital setting is appropriate to participate to the program of vaccination in pediatric age.