[Show abstract][Hide abstract] ABSTRACT: Invasive diseases (ID) caused by Streptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae (H. influenzae), and Neisseria meningitidis are a major public health problem worldwide. Comprehensive data on the burden of bacteremia and ID in Italy, including data based on molecular techniques, are needed.
We conducted a prospective, multi-centre, hospital-based study (GSK study identifier: 111334) to assess the burden of bacteremia and ID among children less than five years old with a fever of 39 °C or greater. Study participation involved a single medical examination, collection of blood for polymerase chain reaction (PCR) and blood culture, and collection of an oropharyngeal swab for colonization analysis by PCR.
Between May 2008 and June 2009, 4536 patients were screened, 944 were selected and 920 were enrolled in the study. There were 225 clinical diagnoses of ID, 9.8 % (22) of which were bacteremic. A diagnosis of sepsis was made for 38 cases, 5.3 % (2) of which were bacteremic. Among the 629 non-ID diagnoses, 1.6 % (10) were bacteremic. Among the 34 bacteremic cases, the most common diagnoses were community-acquired pneumonia (15/34), pleural effusion (4/34) and meningitis (4/34). S. pneumoniae was the most frequently detected bacteria among bacteremic cases (29/34) followed by H. influenzae (3/34). Ninety percent (27/30) of bacteremic patients with oropharyngeal swab results were colonized with the studied bacterial pathogens compared to 46.1 % (402/872) of non-bacteremic cases (p < 0.001). PCV7 (7-valent pneumococcal conjugate vaccine) vaccination was reported for 55.9 % (19/34) of bacteremic cases. S. pneumoniae serotypes were non-vaccine serotypes in children who had been vaccinated. Mean duration of hospitalization was longer for bacteremic cases versus non-bacteremic cases (13.6 versus 5.8 days).
These results confirm that S. pneumoniae is one of the pathogens frequently responsible for invasive disease.
Full-text · Article · Dec 2015 · Italian Journal of Pediatrics
[Show abstract][Hide abstract] ABSTRACT: Aim:
To compare invasive (iNAVA) and non-invasive (nivNAVA) neurally adjusted ventilatory assist in infants, respect to gas exchange, breathing pattern, respiratory drive, infant- ventilator interaction and synchrony, vital parameters and required sedation.
10 consecutive intubated term infants admitted for respiratory failure of different etiology underwent to 2-hour not-randomized trials of iNAVA and, after extubation, nivNAVA, the latter with unchanged ventilator settings and with air-leaks compensating software. Arterialized capillary blood was sampled at the end of each trial. We computed: 1) the minimum (EAdimin) and peak (EAdipeak) values of the diaphragm electrical activity; 2) ventilator (RRmec) and own patients' (RRneu) respiratory rates; 3) inspiratory (delayTR-insp) and expiratory trigger delays (delayTR-exp) and the time of synchrony between patient's effort and ventilator assistance (Timesynch/Tineu); 4) the asynchrony index. Vital parameters and required sedation were also recorded.
iNAVA and nivNAVA did not differ between in terms of gas exchange (pH (7.35 [7.31-7.41] vs. 7.36 [7.30-7.40], p=0.745), PcCO2 (38.4 [34.8-42.6] vs. 36.9 [33.9-41.6] mmHg, p=0.469) and PcO2/FiO2 (211 [168-323] vs. 214 [189-282], p=0.195), respectively). EAdimin, EAdipeak, RRmec and RRneu were similar before and after extubation. Both modes confirmed an optimal infant-ventilator interaction (i.e. delayTR-insp, delayTR-exp and Timesynch/Tineu), irrespective of the interface, and no patients showed clinical relevant asynchronies. A low requirement of sedation with fentanyl was recorded during both trials, without differences between.
We found iNAVA and nivNAVA to be characterized by similar gas exchange, breathing pattern, respiratory drive, infant-ventilator interaction and synchrony, vital parameters and required sedation.
No preview · Article · Nov 2015 · Minerva Pediatrica
[Show abstract][Hide abstract] ABSTRACT: Background:
Several association studies confirmed HMGA2 polymorphisms as the most relevant variants contributing to height variability. Animal models and deletions in humans suggest that alterations of HMGA2 might be relevant in causing short stature. Together, these observations led us to investigate the involvement of HMGA2 in Idiopathic Short Stature (ISS) through an association study and a mutation screening.
We conducted an association study (155 ISS patients and 318 normal stature controls) with three HMGA2 SNPs (SNPs rs1042725, rs7968682 and rs7968902) using a TaqMan based assay. The patients were then analyzed by direct sequencing and Multiplex Ligation Probe Assay to detect point mutations and genomic micro-rearrangements.
Considering a recessive model, an OR value >1 was observed for genotypes rs7968682 TT (OR=1.72, C.I: 1.14-2.58) and rs1042725 TT (OR=1.51, C.I: 1.00-2.28) in accordance to the effect exhibited by the single alleles in the general population. None of the patients carried possibly causative HMGA2 mutations.
Besides the already known role in determining variability in human height, HMGA2 polymorphisms also contribute to susceptibility to ISS. Moreover we here report the first mutation screening performed in ISS concluding that HMGA2 has not a significant impact on the monogenic form of ISS.Pediatric Research (2015); doi:10.1038/pr.2015.225.
No preview · Article · Nov 2015 · Pediatric Research
[Show abstract][Hide abstract] ABSTRACT: We aim to investigate vitamin D (25OHD) levels in children with or without type 1 diabetes (T1D) according to latitude and skin colour.
We compared 25OHD levels in children with T1D living in Piedmont, of Caucasian or Moroccan origin, with healthy control subjects matched for age and ethnicity. Data of resident children in Morocco, with and without T1D, were used for comparison.
Caucasian (21.4±1.5 vs 24.0±0.5 ng/ml, p<0.05) and Moroccan children with T1D (12.0±2.6 vs 17.1±1.7 ng/ml, p<0.05) living in Piedmont had lower 25OHD levels than their counterparts without diabetes. Moroccan children living in Morocco with and without T1D had similar 25OHD levels. Vitamin D deficiency was associated with T1D in Caucasian and Moroccan children living in Piedmont (OR: 1.720, CI95% 1.034--2.860, p<0.03), CONCLUSIONS: Lower vitamin D levels were associated with T1D in Piedmont. Further studies are necessary to explain a possible relationship between vitamin D and T1D.
No preview · Article · Jan 2015 · Minerva pediatrica
[Show abstract][Hide abstract] ABSTRACT: Subclinical hypothyroidism (SH) is defined as a serum TSH concentration above the statistically defined upper limit of the reference range when serum free T4 (fT4) concentration is within its reference range [1, 2]. As serum TSH concentration varies over time in healthy subjects, leading to occasional abnormal values, the measurement of serum TSH and fT4 should be repeated within 3-4 months. If elevated serum TSH concentrations are confirmed and fT4 levels are within the normal range, the diagnosis of SH is made. SH is also defined as isolated hyperthyrotropinemia, compensated hypothyroidism, preclinical hypothyroidism, mild thyroid failure, or mild hypothyroidism. The diagnosis of SH is mainly based on a biochemical evaluation because it has been observed that most patients exhibit few or no signs or symptoms of thyroid dysfunction. Many studies suggest that some patients do indeed have clinical or functional manifestations of mild thyroid failure that are more frequent than in age-matched controls .
[Show abstract][Hide abstract] ABSTRACT: This book covers the entire spectrum of thyroid diseases in childhood, focusing on the recent advances that have been achieved, from progress in basic science research through to novel or improved approaches to diagnosis and treatment. Introductory chapters discuss thyroid embryogenesis and the role of thyroid hormones in fetal development. The two contrasting forms of thyroid dysfunction, hypo- and hyperthyroidism, are then considered in depth, with particular attention to the molecular causes of congenital hypothyroidism. Among the other topics addressed are autoimmune thyroiditis, thyroid nodules, and pediatric neoplasms. The book concludes with an overview of promising therapeutic approaches, such as stem cell therapy. Each topic is treated by an eminent expert in the field, ensuring consistently high quality. Thyroid Diseases in Childhood will be an important source of information for endocrinologists, pediatricians, oncologists, and gynecologists, as well as other professionals interested in this topic.
[Show abstract][Hide abstract] ABSTRACT: Congenital hypothyroidism (CH) is a condition of thyroid hormone deficiency present at birth. According to the duration of thyroid hormone deficiency, it may be classified into permanent and transient CH. According to the anatomic location of the pathogenic defect, CH may be further classified into primary, secondary (or central), and peripheral CH. The most frequent cause of permanent primary CH is thyroid dysgenesis, which includes thyroid ectopy, agenesis, and hypoplasia. Thyroid dysgenesis is generally sporadic in occurrence, but in about 2 % of cases, mutations in genes PAX8, TTF-2, NKX2.1, and NXK2.5 may be detected. Dyshormonogenesis is the second most common cause and may be caused by mutations in genes encoding the sodium-iodide symporter, thyroperoxidase, hydrogen peroxide generation factors, thyroglobulin, iodothyronine deiodinase, and pendrin. Rare causes of CH include resistance to TSH binding or signaling, central CH, and peripheral CH caused by thyroid hormone syndrome or defects in thyroid hormone transport and metabolism.
[Show abstract][Hide abstract] ABSTRACT: Obesity in childhood is associated with the presence of complications that can undermine health immediately or in the long term. Several conditions, such as pulmonary or orthopedic complications are strictly associated with the severity of overweight, since they are directly associated to the mechanic stress of fat tissue on the airways or on the bones. Other conditions, such as metabolic or liver complications, although increasing with the extent of overweight, are associated with insulin resistance, which can be modulated by different other factors (ethnicity, genetics, fat distribution) and can occur in overweight children as well. No less important are psychological correlates, such as depression and stigma, which can seriously affect the health related quality of life. Pediatric services for the care of childhood obesity need to be able to screen overweight and obese children for the presence of physical and psychological complications, which can be still reversed by weight loss. This article provides pediatricians a comprehensive update on the main complications in obese children and adolescents and their treatment.
No preview · Article · Oct 2014 · Minerva pediatrica
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to extend to pre-school ages the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP)-2002 growth charts for height, weight and body mass index (BMI), to obtain charts (SIEDP-2006) that apply to the Italian population from 2 to 20 yr of age, taken as a whole, or separately in two geographical areas (Central-North Italy and South Italy). The charts are based on a sample of about 70,000 subjects attending infant, primary and secondary schools, between 1994 and 2004. The distribution of the sample by gender, age and geographic area was roughly similar to that of Italian school population in the last decade of the 20th century. Height and weight were measured using portable Harpenden stadiometers and properly calibrated scales, respectively. SIEDP-2006 references are presented both as centiles and as LMS curves for the calculation of SD scores, and include the extra-centiles for overweight and obesity. Large differences in BMI growth pattern emerged between the SIEDP-2006, 2000 CDC and UK90 references: in Italy, BMI is higher and its distribution is more skewed during childhood and adolescence. At the end of growth, median values of the three references are similar, but the 97th centile of 2000 CDC charts is much higher and increases more steeply than that of SIEDP-2006 charts, which on the contrary reach a plateau. SIEDP-2006 references intend to supply pediatricians with a tool that avoids the use of charts that are outdated or that refer to other populations, and thus should be suitable for adequately monitoring the growth of their patients.
No preview · Article · Jul 2014 · Journal of endocrinological investigation
[Show abstract][Hide abstract] ABSTRACT: Background
Vitamin D exerts pleiotropic effects and few studies are available in the Italian population.
Aim of our study was to evaluate vitamin D status in children living in Northern Italy.
We studied vitamin D levels in a population of 113 normal weight (NW) and 444 obese (OB) children, prepubertal and pubertal. We considered vitamin D levels >20 ng/ml as normal, but also measured percentage of children with vitamin D levels higher than a cutoff of 30 ng/ml.
68.2 % of NW children showed normal levels of vitamin D, while 31.8 % showed a clear vitamin D deficiency. Only 28.3 % showed vitamin D levels higher than 30 ng/ml. Obese children showed 55.6 % of subjects with normal levels of vitamin D and 44.4 % of subjects a status of vitamin D deficiency. Only the 18.9 % showed vitamin D levels higher than 30 ng/ml. Mean vitamin D levels in NW children (27.3 ± 1.2 ng/ml) were higher than in OB children (21.8 ± 0.6 ng/ml). No differences have been found between prepubertal and pubertal children in terms of vitamin D levels.
Our paediatric population demonstrates a low percentage of vitamin D sufficiency. In particular, obese children show only 19 % of subjects with normal levels while almost half of this population shows a clear deficiency. Further studies are needed to support these results and to evaluate the possible metabolic consequences.
Full-text · Article · Jun 2014 · Journal of endocrinological investigation
[Show abstract][Hide abstract] ABSTRACT: Mutations affecting exon3 splicing are the main cause of autosomal dominant isolated GH deficiency (IGHDII) by increasing the level of exon 3-skipped mRNA encoding the functionally inactive dominant-negative 17.5-kDa isoform. The exons and introns of the gene encoding GH (GH1) were screened for the presence of mutations in 103 sporadic IGHD cases. Four different variations within exon 3 were identified in three patients. One carried c.261C>T (p.Pro87Pro) and c.272A>T (p.Glu91Val), the second c.255G>A (p.Pro85Pro) and c.261 C>T and the third c.246G>C (p.Glu82Asp). All the variants were likely generated by gene conversion from an homologous gene in the GH1 cluster. In silico analysis predicted that positions c.255 and c.272 were included within two putative novel Exon Splicing Enhancers (ESEs). Their effect on splicing was confirmed in vitro. Constructs bearing these two variants induced consistently higher levels both of transcript and protein corresponding to the 17.5 kDa isoform. When c.255 and c.272 were combined in cis with the c.261 variant, as in our patients, their effect was weaker. In conclusion we identified two variations, c.255G>A and c.272A>T, located in two novel putative ESEs and affecting GH1 splicing in vitro by increasing the production of alternatively spliced isoforms. The amount of aberrant isoforms is further regulated by the presence in cis of the c.261 variant. Thus our results evidenced novel putative splicing regulatory elements within exon 3 confirming the crucial role of this exon in mRNA processing.
[Show abstract][Hide abstract] ABSTRACT: The craniopharyngioma is a benign intracranial nonglial tumor derived from a malformation of the embryonic tissue. Represents approximately 6-9% of brain tumors in children. It grows close to the optic nerve, hypothalamus and pituitary. The most frequent histological variety in children is adamantinomatous. The initial symptoms of intracranial hypertension is headache and nausea, followed by visual disturbances, impaired hormonal changes such as the secretion of GH, gonadotropins, TSH and ACTH and central diabetes insipidus. We present the clinical case of MD, 5yrs at age, which shows signs of intracranial hypertension syndrome: neuroradiological findings raise the diagnosis of adamantinomatous craniopharyngioma for which the child underwent to sub-total surgical removal of the lesion and radiosurgery treatment. During the disease develops visual impairment, and secondary diabetes insipidus, hypothyroidism hipocotisolism that takes therapy with desmopressin (Minirin), Cortone acetate and L-tiroxine. For the failure of previous therapies, the child has performed chemotherapy with cisplatin (30 mg/sqm/day) and Etoposide (150 mg/mq/day). A year after the end of the last cycle of chemotherapy was detected new progression of the lesion with the appearance of worsening headache and vomiting in the upright position. TC notes the expansion of the third ventricle and the patient undergoes surgery craniotomy. This clinical case underlines the difficulties in treatment of recurrent craniopharyngioma in situations where the anatomical location do not permit aggressive radical surgery. Anyway, new studies are needed to evaluate the effectiveness of systemic chemotherapy as a method of experimental treatment that could reduce the progression of disease.
No preview · Article · Dec 2013 · Minerva pediatrica
[Show abstract][Hide abstract] ABSTRACT: Aim:
The aim of this paper was to know and analyze information, attitudes and behaviors related with transformations occurring in men when they become fathers.
A self-administered questionnaire has been given out to all men whose newborns were born in the Hospitals located into Borgosesia, Ivrea, Novara, Verbania and Vercelli (Piedmont region in north west of the Italy) in the last quarter of 2006. The questionnaire was created ad hoc and filled out on the day of discharge; results underwent statistical analyses through SPSS system.
For the duration of the research, out of 870 men who became fathers in the hospitals were involved in this study, 570 responded voluntarily to the self-administered questionnaire (65.6% of the total sample). They showed a lack of information about how to take care of their newborns and the emotional turmoil of women after delivery (58% think children are blind when they are born, 52% think it is better to breastfeed newborns at fixed times and 47% ignore that mothers can enter a depression state). Eighty-eight percent of respondents were in the delivery room to see their child's birth, 56% took a leave from job to stay with mother and child in the hospital and 58% of them report the intention to take an additional 2-3 days leave after coming home from the hospital; 27% had trouble sleeping during pregnancy and are afraid not to be good fathers for their child; 90% believe that their newborn will make them change life habits. Most of the new fathers had difficulties in sharing emotions and feelings related with their status of fathers-to-be with other men. Some of these results are significantly different in older fathers, fathers having their first child and fathers with a lesser level of education.
During pregnancy and in the first months after their child is born, fathers-to-be and new fathers must be considered a potential target for educational interventions aiming at promoting their parenting information and reinforcing their positive attitudes and beliefs related with their fathering status.
No preview · Article · Oct 2013 · Minerva pediatrica
[Show abstract][Hide abstract] ABSTRACT: Patients without spleen or with diminished splenic function are at high risk (10-50 times higher than in normal population) of developing life-threatening infections (OPSI). Mortality from OPSI is estimated at 50 to 80% of cases. More frequent causative agents are encapsulated bacteria: Streptococcus Pneumoniae, Haemophilus influenzae type b and Neisseria Meningitidis. The risk of OPSI can be reduced by immunizing patients against these pathogens and by prescribing antibiotic prophylaxis. Continuous antibiotic prophylactic for 2-5 years after splenectomy (longer periods might expose the patients to the risk of antibiotic resistance) with penicillin or amoxicillin/clavulanate acid is mandatory. Asplenic individuals should take empirical antibiotic therapy - so called "self-treatment" - and immediate medical consultation in presence of febrile illness. All patients and their parents should be carefully educated about the risk of infections in order to obtain a good long-term compliance with these recommendations.
No preview · Article · Aug 2013 · Minerva pediatrica
[Show abstract][Hide abstract] ABSTRACT: Background: TSHR is a G-protein-coupled seven transmembrane domain receptor that activates the two major signal transduction pathways: the Gαs/adenylate cyclase and the Gαq/11/phospholipase C pathways. Inactivating mutations in the TSHR gene have been demonstrated to be responsible for subclinical hypothyroidism, a disorder characterized by elevated serum TSH concentrations despite normal thyroid hormones levels. Aim: We identified in a child a nonsense mutation (W520X) in the third transmembrane domain of the TSHR that causes the lack of the C-terminus portion of the receptor. The functional significance of this variation was assessed in vitro. Material/Subject and Methods: The W520X mutation was introduced into the pSVL vector containing the wild-type sequence of TSHR gene. Wild-type and mutated vectors were expressed in CHO cells and cAMP, IP, immunofluorescence and FACS analyses were performed. Results: Transfection with pSVL-TSHR vector induced basal cAMP and IP production in the absence of TSH stimulation, indicating a constitutive activity for the TSHR. An impairment of receptor function was demonstrated by the observation that cells expressing the mutant TSHR exhibited a lower second messenger production with respect to the wild-type, despite a normal expression of the receptor at the cell surface. Conclusions: The mechanism through which the W520X mutation exerts its effect is more likely haploinsufficiency rather than a dominant-negative effect. This could explain the phenotype of our patient, who has a hormonal pattern in the range of a mild subclinical hypothyroidism, without an overt disease phenotype.
No preview · Article · Apr 2013 · Journal of endocrinological investigation