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BACKGROUND: The major burden of acute gastroenteritis (AGE) in childhood is related to its high frequency and the large number of hospitalizations, medical consultations, tests and drug prescriptions. The adherence to evidence-based recommendations for AGE management in European countries is unknown. The purpose of the study was to compare hospital medical interventions for children admitted for AGE with recommendations reported in the European Societies of Pediatric Gastroenterology, Hepatology and Nutrition and Pediatric Infectious Diseases guidelines. METHODS: A multicenter prospective study was conducted in 31 Italian hospitals. Data on children were collected through an online clinical reporting form and compared with European Societies of Pediatric Gastroenterology, Hepatology and Nutrition and Pediatric Infectious Diseases guidelines for AGE. The main outcomes were the inappropriate hospital admissions and the percentage of compliance to the guidelines (full >90%, partial >80% compliance) based on the number and type of violations to evidence-based recommendations. RESULTS: Six-hundred and twelve children (53.6% male, mean age 22.8 ± 15.4 months) hospitalized for AGE were enrolled. Many hospital admissions (346/602, 57.5%) were inappropriate. Once admitted, 20.6% (126/612) of children were managed in full compliance with the guidelines and 44.7% (274/612) were managed in partial compliance. The most common violations were requests for microbiologic tests (404; 35.8%), diet changes (310; 27.6%) and the prescription of non-recommended probiotics (161; 14.2%), antibiotics (103; 9.2%) and antidiarrheal drugs (7; 0.6%). CONCLUSIONS: Inappropriate hospital admissions and medical interventions are still common in the management of children with AGE in Italy. Implementation of guidelines recommendations is needed to improve quality of care

Although linkage studies strongly suggest that proopiomelanocortin (POMC) alterations could play a role in the genetic predisposition to obesity, systematic POMC mutational analysis did not completely confirm this hypothesis.To verify the presence of mutations of the POMC coding region in Italian children with very early onset obesity.Eighty seven unrelated Italian obese children and adolescents were studied. Mean age at obesity onset was 4.7+/-2.5 y. The POMC gene coding region was screened using single-strand conformation polymorphism (SSCP) analysis. Bi-directional automatic sequencing of PCR products was performed for all individuals who showed an aberrant SSCP pattern.Three new mutations have been identified in the heterozygous state in three patients: (a) G3834C, resulting in the substitution of Ser with Thr at codon 7 within the POMC signal peptide; (b) C3840T, resulting in the substitution of Ser with Leu at codon 9 of the pre-proopiomelanocortin signal peptide; and (c) C7406G, producing the substitution of Arg with Gly at codon 236 within the beta-endorphin peptide. A polymorphism consisting of a 9 bp insertion, AGC AGC CGC, between position 6997 and 6998 has been found at the heterozygous state in nine patients. They showed leptin levels adjusted for BMI, gender and pubertal stage significantly higher than obese subjects homozyous for the POMC wild-type allele.Mutations in codons 7 and 9 of the signal peptide may alter the translocation of the pre-proopiomelanocortin into the endoplasmic reticulum and, therefore, can be implicated in obesity. Although further studies are required, the polymorphism between position 6997 and 6998 may represent one of the genetic variations that explain the linkage between obesity and POMC. International Journal of Obesity (2001) 25, 61-67

Background When the permeability of the glomerular filtration barrier increases, leading to proteinuria, nephrotic syndrome (NS) occurs. First episodes or relapses of NS can be concurrent with acute gastroenteritis (AGE) infections. This condition can cause further deterioration of the hypovolemic state, as intravascular water is lost through both AGE-related vomiting/diarrhea and NS-related fluid shifting into the interstitium. In this case report, we wish to raise the issues about the difficult management of children presenting with both NS and AGE. Case Report We report two cases characterized by concurrence of NS and AGE. Despite our intervention, case #1 required dialysis, whereas in the case #2 we restored the patient's liquid homeostasis. Why Should an Emergency Physician Be Aware of This? No guidelines helping general physicians in the management of children presenting with both NS and AGE are available in the literature. However, it is common for these patients to seek the first line of treatment at emergency departments. In these patients, restoring the liquid homeostasis is a challenge, but some key points can help the physicians with first-line management: 1) carefully evaluate the signs of hypovolemia (edematous state can be misleading); 2) bear in mind that—in hypovolemic, severely hypoalbuminemic (serum albumin levelsÂ

Purpose: Recently, mutations of makorin RING-finger protein 3 (MKRN3) have been described in familial central precocious puberty. Serum levels of this protein decline before the pubertal onset in healthy girls and boys. The aim of the study is to investigate MKRN3 circulating levels in patients with central precocious puberty. Methods: We performed an observational cross-sectional study. We enrolled 17 patients with central precocious puberty aged 7 years (range: 2–8 years) and breast development onset

Background: Mutations in the imprinted gene MKRN3 have been described as a common genetic cause of idiopathic central precocious puberty (CPP), in particular in familial cases. However, the exact prevalence of mutations is unknown. Single nucleotide polymorphisms in 2 other imprinted genes, DLK1 and KCNK9, have been associated with age at menarche. We investigated the prevalence of mutations in MKRN3, DLK1, and KCNK9 genes in a cohort of girls with idiopathic CPP. Methods: MKRN3, DLK1, and KCNK9 coding regions were sequenced in 60 girls with idiopathic CPP (familial in 23 cases). Results: Three mutations, including a new one, in MKRN3 were found in 2 familial cases (c.1229G>A; p.Cys410Ter and c.477_485del; p.Pro160Cysfs*14) (8.7%) and in 1 sporadic case (c.982C>T; p.Arg328Cys) (2.8%). We did not find rare variants in DLK1 and KCNK9 genes. Conclusions: (1) The prevalence of MKRN3 mutations in our cohort was similar to that reported in the literature in sporadic cases but lower than previously described in familial ones. This could be due to different inheritance patterns of families studied; (2) we expanded the phenotype of MKRN3 defects describing 3 more patients with MKRN3 mutations; and (3) point mutations in DLK1 and KCNK9 at least do not seem to be a common cause of CPP in girls.

Aims: We aimed at evaluating a standard multiplex ligation-dependent probe amplification (MLPA) probe set for the detection of aneuploidy to diagnose Turner syndrome (TS). We first fixed an MLPA ratio cutoff able to detect all cases of TS in a pilot TS group. We then tested this value on a second group of TS patients and a short-stature population to measure specificity and sensitivity. Methods: 15 TS patients with X mosaicism or X structural abnormalities (Pilot TS Group), 45 TS karyotype-assessed patients (TS Group), and 74 prepubertal female patients with apparent idiopathic short stature (Short-Stature Group) were enrolled. All subjects underwent MLPA and karyotype analysis. In the TS and Short-Stature Groups, MLPA testing was performed in blind. Results: The choice of an MLPA threshold ratio of 0.76 for at least 1 probe allowed us to detect all TS cases, including mosaicisms. Sensitivity and specificity were 100% (CI 95%, 0.92-1) and 88.89% (CI 95%, 0.79-0.94), respectively. The positive predictive value was 88.5%, and the negative predictive value was 100%. MLPA detected the presence of Y chromosome material in 2 patients. Conclusion: MLPA is an accurate and inexpensive tool to screen for TS in girls with short stature. A customized MLPA kit may be useful for the screening of an even larger population.

Context: Studies examining vitamin D levels in association with childhood obesity usually do not consider the effect of insulin on vitamin D–binding protein and do not calculate the unbound, bioavailable vitamin D. Objective: This study aimed to evaluate in a group of children 1) the concentrations of both total 25-hydroxyvitamin D and bioavailable fraction, and 2) the potential role of insulin resistance in modulating the concentrations of bioavailable vitamin D. Design, Setting, and Patients or Other Participants: This was a cross-sectional study at a University Pediatric Department in which 63 obese children and 21 lean controls were enrolled. Main Outcome Measures: Total 25-hydroxyvitamin D and vitamin D–binding protein were measured, twosingle-nucleotide polymorphisms in the coding region of the vitaminD–binding protein (rs4588 and rs7041) were studied, and the vitamin D bioavailable fraction was calculated. Results: Obese children showed total 25-hydroxyvitamin D levels lower compared with nonobese children (21.36.7 ng/mL vs 29.611.7 ng/mL; P.0004). Bioavailable 25-hydroxyvitaminDlevels were not different among the two groups (3.1 1.6 ng/mL vs 2.6 1.2 ng/mL; P .05). Insulinresistant children showed higher bioavailable levels of 25-hydroxyvitamin D compared with noninsulin- resistant children (3.4 1.4 ng/mL vs 2.0 0.9 ng/mL; P .013) and an inverse correlation between insulin resistance and vitamin D–binding protein was found (r: 0.40; P .024). Conclusions: Obese children present levels of bioavailable 25-hydroxyvitamin D similar to those of normal-weight children due to reduced concentration of vitamin D–binding protein. The insulin resistance could play a role in this reduced concentrati

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. Electronic supplementary material The online version of this article (10.1186/s13052-018-0525-6) contains supplementary material, which is available to authorized users.

Objective: We aimed to investigate which clinical and metabolic factors could influence the estimated glomerular filtration rate (eGFR) levels, evaluating a large population of obese children without suspect of primary kidney disease. Design: Retrospective, cross-sectional study. Setting: Pediatric university department. Subjects: We enrolled 2,957 obese children and adolescents consecutively attending our department between January 2000 and 2017. Inclusion criteria were body mass index (BMI) > 95th percentile and eGFR > 90 mL/min/1.73 m2. Exclusion criteria were secondary forms of obesity, eGFR < 90 mL/min/1.73 m2, proteinuria/hematuria at urine dipstick, or consumption of any medication. Interventions: Weight, waist circumference, height, waist to height ratio (W/Hr), BMI-standard deviation score (SDS), pubertal stage, systolic blood pressure (SBP) and diastolic blood pressure (DBP), duration of obesity, insulin, eGFR, and homeostasis model assessment (HOMA-IR) were obtained. A general linear model was performed for a multiple variable analysis. Main Outcome Measure: The population was divided in tertiles for BMI-SDS, W/Hr, SBP- and DBP-SDS, HOMA-IR, and duration of obesity. We compared eGFR levels among these tertiles. Results: The eGFR levels significantly increased across both BMI-SDS and W/Hr tertiles. Conversely the eGFR levels significantly decreased across SBP-SDS, HOMA-IR, and duration of obesity tertiles. No significant differences in eGFR levels across DBP-SDS tertiles were detected. Pubertal patients presented significantly lower eGFR values compared with prepubertal patients. A general linear model for eGFR variance including as covariates W/Hr, HOMA-IR, duration of obesity, pubertal stage, BMI-SDS, and SBP-SDS (model R239.7%; model P < .00001) was performed. It confirmed a direct association of eGFR values with BMI-SDS and an indirect association with HOMA-IR, duration of obesity, pubertal stage, and SBP-SDS. Conclusions: We showed a positive correlation of eGFR with both BMI-SDS and a negative one with SBP-SDS, HOMA-IR, pubertal stage, and duration of obesity. The duration of obesity was the variable most significantly associated to eGFR levels.

OBJECTIVES Existing studies usually do not measure the free vitamin D in pediatric patients with inflammatory bowel disease (IBD) and not consider the effect of inflammation on vitamin D levels. The aim of our study was to evaluate the concentrations of vitamin D-binding protein (VDBP), total and free 25-hydroxyvitamin-D (25(OH)D), and to correlate these values with the disease activity markers. METHODS Newly diagnosed children with IBD and a group of healthy controls (HCs) were enrolled. VDBP and total and free 25(OH)D levels were measured by enzyme-linked immunosorbent assay and compared using the Student t test. In each patient with IBD, the activity scores of disease and the main inflammation markers were correlated to total and free 25(OH)D levels. C-reactive protein was also measured in the control group, and it was related to VDBP by a linear regression test for all the groups. RESULTS Fifty-one consecutive children were enrolled: IBD = 33, HC = 18. Levels of total 25(OH)D were higher in HC than in patients with IBD (P = 0.01). The free/total 25(OH)D ratio was, however, higher in patients with IBD compared to HC (P

OBJECTIVES The aims of this retrospective study were to describe ulcerative colitis (UC) phenotype at diagnosis and follow-up and to identify possible predictors of severe disease course. METHODS This was a retrospective, single-center study. We reviewed the charts of patients with UC diagnosed between 2 and 18 years at our referral center from January 2007 to January 2016. Laboratory and clinical features at diagnosis, such as disease extent, atypical phenotypes, extraintestinal manifestations, and therapies, and pattern changes during the follow-up, including relapse rate, disease extension, and the cumulative risk for colectomy were collected. RESULTS One hundred eleven patients were enrolled. Atypical phenotypes were identified at diagnosis in 55 out of 111 patients (49.5%). Extraintestinal manifestations were detected in 16 out of 111 (14.4%) at the diagnosis. During the follow-up 60 out of 111 (54%) patients needed to start azathioprine, 9 out of 111 (8.1%) patients started biologic therapy and 10 out of 111 (patients underwent surgery, resulting in a cumulative risk of 8% at 5 years and 16% at 10 years. Steroid refractoriness (hazard ratio: 13.9) and starting of biologic therapy (hazard ratio: 25.3) represented the best predictors for surgery. The cumulative probability of first relapse was 47% at 6 months and 63% at 1 year. Disease extension was reported in 21 out of 70 patients (30%). CONCLUSION Pediatric UC is associated with a severe phenotype and a high percentage of atypical features. Surgery rate seems to be decreased from early reports.

Summary Introduction Since standardization of the ICCS terminology, only two small case series of children with extraordinary daytime only urinary frequency (EDOUF) have been published. The aims of the present study were i) to describe a large cohort of children affected by EDOUF, to evaluate its rate among the main micturition pediatric disturbances, and to determine if there is different EDOUF onset among seasons; ii) to investigate possible associations with urodynamic abnormalities by non-invasive techniques; iii) to evaluate whether postponing micturition exercise (PME) can objectively verify the anamnestic data hinting at the EDOUF diagnosis; and iv) to determine the effect of postponing micturition at home. Material and methods We reviewed the records of all patients with EDOUF, nocturnal enuresis, and/or overactive bladder firstly examined from March 2012 to February 2016. We evaluated post-void residual and bladder wall thickness by urinary ultrasound and uroflowmetry and recorded the season in which the EDOUF started. Through the PME, the EDOUF diagnosis was confirmed if patients were able to postpone micturition reaching at least 80% of the expected bladder capacity without showing urinary incontinence. At home, we recommended postponing micturition for a maximum of 3 h if EDOUF affected the normal daily activities of both children and parents. We set a telephone interview for 3 months later. Results The clinical characteristics of the EDOUF population are shown in the Table. The EDOUF rate was 12.1%. The rate of EDOUF onset was significantly lower during the summer than in other seasons (p = 0.02) and the OR for onset of EDOUF in the summer – compared with the other seasons – was 0.37 (95% CI 0.18–0.74; p = 0.005). Eighty-five (80.2%) patients reported an intermittent trend of the EDOUF with variable periods of improvement and worsening. All the EDOUF patients had normal uroflowmetry, 1/106 had post-micturition bladder wall thickness >5 mm and one post-void residual. At the PME, 106 out of 106 (100%) patients with EDOUF were able to reach at least 80% of the EBC without showing urinary incontinence or urgency incontinence. After 3 months, in 98.1% of the patients the symptoms had disappeared or improved. Discussion and conclusions Childhood EDOUF is rather common and is generally associated with normal non-invasive urodynamic patterns. The PME allows verification of anamnestic data of EDOUF. The sole recommendation to postpone micturition for a maximum of 3 h or until the micturition postponement became stressful could be considered as a possible approach. Table . Clinical characteristics of the 106 patients with EDOUF. Age at EDOUF diagnosis, yr 6.8 ± 2.3 Female sex, no. (%) 53 (50) SBP, SDS 0.31 ± 0.7 DBP, SDS 0.17 ± 0.8 Age at continence, yr 2.3 ± 0.5 Nocturia, no. (%) 1 (0.9) Constipation, no. (%) 19 (17.4) Urgency, no. (%) 0 (0) Incontinence, no. (%) 0 (0) EBC >80% at PME, no. (%) 106 (100) Post-micturition bladder wall thickness >5 mm, no. (%) 1 (0.9) Presence of post-void residual, no. (%) 1 (0.9) a Maximum flow, mL/s 19.34 ± 10.2 Normal uroflowmetry, no. (%) 106 (100) Normal urinalysis, no. (%) 106 (100) Previous UTIs, % 2 (1.9) b Daily micturitions, no. 20.1 ± 7.2 Mean daily voided volumes (% of the EBC) 28.7 ± 9.2 Data are given as means ± SDS, unless stated otherwise. DBP, diastolic blood pressure; EBC, expected bladder capacity; EDOUF, extraordinary daytime only urinary frequency; PME, postponing micturition exercise; SBP, systolic blood pressure; SDS, standard deviation score; UTI, urinary tract infection. a Only one patient presented a post-void residual of 30 mL. b All the UTIs were not febrile.

Purpose: We evaluated the clinical course of patients prenatally diagnosed and enrolled early with congenital solitary functioning kidney, and identified the risk factors for renal injury. Materials and Methods: We retrospectively evaluated 322 patients with congenital solitary functioning kidney according to the inclusion criteria of 1) prenatal diagnosis of solitary kidney; 2) first evaluation at 1 to 3 months of life with confirmation of congenital solitary functioning kidney, and evaluation of possible associated congenital anomalies of the kidney and urinary tract by abdominal ultrasound, renal scintigraphy and cystography; and 3) absence of any condition potentially affecting renal function in the neonatal period as well as absence of renal injury at enrollment (1 to 3 months of life) confirmed by a normal estimated glomerular filtration rate, lack of proteinuria and hypertension. Followup of 306 patients was evaluated. Results: Median followup was 7.2 years (range 1 to 23) and 1 or more signs of renal injury were found in 12 of 306 patients (3.9%). Considering the entire population the cumulative proportion of patients free from renal injury at 17 years old was 93.7%, vs 81.3% and 95.9% for subjects with and those without congenital anomalies of the kidney and urinary tract of congenital solitary functioning kidney (p

Background:Increased thyroid stimulating hormone (TSH) serum concentration can be a marker of subclinical hypothyroidism (SCH) or transient hyperthyrotropinemia. The aim of our study was to evaluate whether high serum TSH concentrations in allergic children could represent true SCH or isolated and transient hyperthyrotropinemia.Methods:We enrolled 620 allergic children (1.11–12.8 years) consecutively attending to our department. They were classified as atopics and non-atopics on the basis of the atopy work-up and, at baseline, they were investigated for thyroid function and low-grade inflammation state. Further, TSH was evaluated after 6 (T1) and 12 (T2) months.Results:Both atopics and non-atopics showed higher SCH prevalence compared to controls (p=0.0055 and p=0.02, respectively), and a significant association between atopy and SCH (OR 10.11, 95% CI 1.36–75.12) was found. Both at T1 and T2, atopics had a significant risk of developing severe SCH compared to non-atopics (RR 1.8, 95% CI 1.39–2.34 and 1.61, 95% CI 1.21–2.14; respectively).Conclusions:Our data may suggest that hyperthyrotropinemia in atopic children could be used as a marker of true SCH.

Adiponectin (Acrp30), its high molecular weight (HMW) oligomers, and Irisin are molecules involved in several metabolic processes. To investigate if these cytokines could represent new metabolic markers, we evaluated the expression of Acrp30 and Irisin in serum of obese children from South Italy affected by different degrees of insulin resistance (IR). The anthropometric and metabolic features were evaluated in 27 obese children versus 13 age-matched controls. The expression of Acrp30, its pattern and Irisin were investigated by ELISA, western blotting and fast protein liquid chromatography. The HOMA index was significantly higher in obese children versus controls, and metabolic syndrome was more prevalent in obese children with elevated IR versus those with normal HOMA (38% vs 16%). Total Acrp30 and HMW oligomers were significantly lower in obese than in control children, and the difference was more pronounced in children with HOMA >3.4. In control and obese children, total Acrp30 and HMW oligomers were inversely related to HOMA (r-0.38, p 0.02; r-0.35, p 0.03). Irisin was significantly higher in obese than in control children, and was inversely correlated with Acrp30 and HMW (r-0.32, p 0.04; r-0.39, p 0.01). The inverse correlation of Acpr30 and HMW oligomers with HOMA indicates that Acpr30 is directly involved in IR status. Moreover, the inverse correlation between Irisin and Acrp30 and, more significantly, between Irisin and HMW oligomers suggests that the two cytokines are closely connected. The use of Acrp30, HMW oligomers and Irisin as predictive factors of IR in obese children remains to be further elucidated.

Objective: To verify in obese children whether or not the presence of i) high waist-to-height ratio (WHtR), ii) family history for type 2 diabetes (T2D) and iii) acanthosis nigricans (AN), singularly or together, might predict the occurrence of metabolic syndrome or prediabetes. Methods. 1,080 Italian obese children (567 females) were enrolled. Blood pressure, fasting plasma glucose, insulin, and lipids were measured, and oral glucose tolerance test (OGTT) was performed. The WHtR was calculated, family history for T2D was assessed, and the presence of AN was noticed. The odds ratios for showing metabolic syndrome and/or prediabetes according to the presence of these features were calculated. Results: The prevalence of metabolic syndrome was 29.2%. AN (OR1.81; p = 0.002) and WHtR higher than 0.60 (OR 2.24; p < 0.0001) were the clinical signs linked to higher risk for showing metabolic syndrome, and the odds raised significantly when these elements occurred simultaneously (OR 3.34; p < 0.0001). T2D family history (OR 2.36; p = 0.01) and WHtR higher than 0.60 (OR 2.32; p = 0.009) were the two features associated with increased odds of showing prediabetes. Conclusions: Three simple actions, i.e., looking at the patient, asking about T2D family history, and measuring WHtR, may represent a powerful tool in the hands of pediatricians to identify obese children with high cardiovascular and metabolic risk.

Factitious disorders are characterized by physical or psychological symptoms that are intentionally produced or feigned in order to assume the sick role. “Munchausen’s syndrome” is one of these disorders and often is under-recognized or only suspected after unnecessary investigations. We report the case of a 15-year-old boy who came to our notice because of reduced urine output and recurrent abdominal pain during the previous 3 months. The patient attended several emergency room visits and he had been hospitalized for 1 month in an adult internal medicine department because of “oliguria”. He had undergone several invasive investigations with normal results before the diagnosis of Munchausen’s syndrome was made. General pediatricians and practitioners should be aware that suspecting Munchausen’s syndrome in the first instance in the management of a patient showing discrepancies between reported urinary symptoms and the detectable clinical signs could avoid unnecessary and invasive exams.

Context: Obesity is associated with a low-grade inflammatory state and adipocyte (ADP) hyperplasia/hypertrophy. Obesity inhibits the “browning” of white adipose tissue. Cannabinoid receptor 2 (CB2) agonists reduce food intake and induce antiobesity effect in mice. A common missense CB2 variant, Q63R, causes CB2-reduced function. Objective: To evaluate the influence of CB2 receptor on the modulation of childhood obesity and of ADP activity and morphology. Design: CB2-Q63R variant was analyzed in obese Italian children. The effects of an inflammatory stimulus and those of drugs selectively acting on CB2 were investigated on in vitro ADPs obtained from mesenchymal stem cells of adult healthy donors or from sc adipose biopsies of adult nonobese and obese subjects. Setting: Department of Women, Child and General and Specialist Surgery of the Second University of Naples. Patients or Other Participants: A total of 501 obese Italian children (age 11 ± 2.75). Twelve healthy bone marrow donors (age 36.5 ± 15); and 17 subjects, 7 lean (age 42 ± 10) and 10 obese (age 37.8 ± 12) underwent sc adipose tissue biopsies. Main Outcome Measures: Effects of CB2 stimulation on adipokine, perilipin, and uncoupling protein-1 expression. Results: The less-functional CB2-R63 variant was significantly associated with a high z-score body mass index. CB2 blockade with AM630 reverse agonist increased inflammatory adipokine release and fat storage and reduced browning. CB2 stimulation with JWH-133 agonist reversed all of the obesity-related effects. Conclusion: CB2 receptor is a novel pharmacological target that should be considered for obesity.

BACKGROUND The N-acetyltransferase 2 ( NAT2 ) A803G polymorphism has been associated with decreased insulin sensitivity in a large adult population with the A allele associated with insulin-resistance-related traits. OBJECTIVE Evaluate the association of this polymorphism with anthropometric and metabolic parameters in obese children and adolescents. SUBJECTS A total of 748 obese children and adolescents were enrolled. METHODS Anthropometric and laboratory data were collected. During oral glucose tolerance test, the presence of a possible exaggerated plasma glucose excursion at 1 h (1HPG) or impaired glucose tolerance (IGT) was considered. Homeostasis model assessment, oral disposition index (oDI) and insulinogenic index (IDI) were calculated. Patients were genotyped for the NAT2 A803G polymorphism. RESULTS The prevalence of both IGT and elevated-1HPG was higher in children carrying the A803 allele (P = .02 and P = .03). Moreover, this allele was associated with both oDI and IGI reduction (P = .01). No differences among the NAT2 A803G genotypes for the other parameters were shown. Children homozygous for the A allele presented an odds ratio (OR), to show IGT of 4.9 (P = .01). Children both homozygous and heterozygous for the A allele had higher risk to show elevated-1HPG (OR of 2.7, P = .005; and OR = 2.3, P = .005) compared with patients homozygous for the NAT2 803G allele. CONCLUSIONS NAT2 A803 allele seems to play a role in worsening the destiny of obese children carrying it, predisposing them to elevated-1HPG and IGT and then to a possible future type 2 diabetes mellitus throughout an impairment of pancreatic β-cellular insulin secretion as suggested by oDI and IGI reduction.

Allergic rhinitis is characterized by local inflammation. Nasal lavage may be a useful treatment, however, there are few studies on this topic. This study aims to evaluate the effects of Ischia thermal water nasal irrigation on allergic rhinitis symptoms and airway inflammation during the period of natural exposure to Parietaria pollen in children with allergic rhinitis and intermittent asthma. Forty allergic children were randomly divided into two groups: the first group (Group 1) practiced crenotherapy with thermal water aerosol for 15 days per month, for three consecutive months, the control group (Group 2) was treated with 0.9% NaCl (isotonic) solution. In addition, all children were treated with cetirizine (0.5 gtt./kg/day once daily). Nasal symptom assessment, including Total Symptom Score (TSS), spirometry, and exhaled nitric oxide (FeNO) were considered before the treatment (T0), at the end of the treatment (T1) and again 2 weeks after the end of the treatment (T2). The study was registered in the Clinical Trials.gov (NCT01326247). Thermal water significantly reduced both TSS and FeNO levels and there was a significant relationship between reduction of nasal symptoms and FeNO values at the end of treatment with thermal water. In conclusion, this study shows that nasal crenotherapy with the hyper-mineral chloride-sodium water of Ischia was effective in children with seasonal allergic rhinitis based on the sensitivity to Parietaria. These results demonstrate that this natural treatment may be effective in a common and debilitating disease such as the allergic rhinitis.

Contains fulltext : 80562.pdf (Publisher’s version ) (Open Access) CONTEXT: Obesity and iron deficiency are two of the most common nutritional disorders worldwide. Several studies found higher rates of iron deficiency in obese than in normal-weight children. Hepcidin represents the main inhibitor of intestinal iron absorption, and its expression is increased in adipose tissue of obese patients. Leptin is able, in vitro, to raise hepcidin expression. OBJECTIVES: Aims of this work were 1) to assess the association between poor iron status and obesity, 2) to investigate whether iron homeostasis of obese children may be modulated by serum hepcidin variations, and 3) to assess the potential correlation between leptin and serum hepcidin variations. METHODS: Iron status and absorption as well as hepcidin, leptin, and IL-6 levels were studied in 60 obese children and in 50 controls. RESULTS: Obese children showed lower iron and transferrin saturation (both P < 0.05) and higher hepcidin levels (P = 0.004) compared with controls. A direct correlation between hepcidin and obesity degree (P = 0.0015), and inverse correlations between hepcidin and iron (P = 0.04), hepcidin and transferrin saturation (P = 0.005), and hepcidin and iron absorption (P = 0.003) were observed. A correlation between leptin and hepcidin (P = 0.006) has been found. The correlation remained significant when adjusted for body mass index, sex, pubertal stage, and IL-6 values. CONCLUSIONS: We propose that in obese patients, increased hepcidin production, at least partly leptin mediated, represents the missing link between obesity and disrupted iron metabolism.

Background: In infants under 3 years of age acquired primary hypothyroidism caused by autoimmune thyroiditis is very rare. Hypothyroidism can manifest with different signs and symptoms and has a wide range of presentations from subclinical hypothyroidism to overt form. We describe a child with acquired autoimmune thyroiditis during a very early period of life and with a severe hypothyroidism presentation. Case presentation: A 22-month-old white male patient with normal neonatal screening presented with a six-month history of asthenia and cutaneous pallor. At general clinical and biochemical exams he showed weight gain, statural growth deceleration, poor movements, sleepy expression, instability while walking, myxoedema, bradycardia, open anterior fontanelle, changes in the face habitus, macrocytic anaemia, ascites, and high CPK, creatinine and cholesterol levels. Acquired autoimmune thyroiditis was the final diagnosis. The thyroxine replacement therapy normalized all the clinical and biochemical abnormalities but at the age of 30 months his mental age showed a delay of 6 months. Conclusions: Our case could give useful learning points: i) although the screening for congenital hypothyroidism is routinely performed, a severe hypothyroidism (for example due to autoimmune thyroiditis) can anyway occur early in life and the clinicians should consider this possibility; ii) hypothyroidism can have a misleading and multi-face clinical presentation; iii) anemia, rhabdomyolysis and high creatinine levels should always include the hypothyroidism in the differential diagnosis; iv) thyroxine replacement therapy is able to revert all the clinical manifestations related to the hypothyroidism; v) evaluating the patient's previous pictures could play an important role in resolving a diagnostic conundrum.

Aim To verify if subclinical hypothyroidism (SCH) could be associated to atopy in children. Methods Seven hundred and thirty-two Caucasian children from South Italy presenting symptoms of allergic disease were enrolled and submitted to atopy, obesity, chronic low grade inflammation, and SCH work up. Results Four hundred and forty-five out of 705 (63.12%) children affected by allergic disease were diagnosed as atopic and 260 (36.88%) as not atopic. The SCH prevalence was 6.3%. Significant higher prevalence of SCH among atopic children with average (group 2) and high (group 3) low grade chronic inflammation compared to atopic children with mild (group 1) low grade chronic inflammation was present. Moreover, group 1 and group 2 presented an OR to show SCH of 2.57 (95%CI: 1.55-6.26) and 2.96 (95%CI: 1.01-8.65), respectively. Both in atopic and not atopic children we found C3 serum levels significantly higher in group 3 respect to group 2 and group 1. Noteworthy, among atopic patients, also total immunoglobulin E (IgE) serum levels, were significantly higher in group 3 compared to group 2 and group 1 children. In atopic children, C3 and total IgE serum values increased in parallel with the increase of C-reactive protein values, while in not atopic children this phenomenon was not evident. Conclusion The possibility exists that an increasing atopic inflammation contributes to SCH occurrence. So far this is the first report in literature showing an association between SCH and atopy but further studies are needed to confirm our data.

Background: The central melanocortin system is critical for the long-term regulation of energy homeostasis. Melanocortin-3 receptor (MC3R) knock-out mice, despite being hypophagic, have increased fat mass and higher feed efficiency than do their wild-type littermates. Objective: The aim was to evaluate whether, in childhood obesity, MC3Rvariants are associated with changes in fatness reduction as a consequence of a weight-reduction program. Design: Molecular screening of the MC3R coding region in 184 obese children, 77 girls and 107 boys [x (SEM) body mass index (BMI; in kg/m 2 ) z score: 3.3 2.3; age 9.2 2 y], was performed. BMI was evaluated at baseline and after 6 and 12 mo of the weight loss program. Results: No new mutations were found. Two previously described polymorphisms, C17A (Thr6Lys) and G241A (Val81Ile), were observed in 20 patients in almost complete linkage disequilibrium. No significant differences in BMI z scores were observed at baseline of theweight-lossprogrambetweenthegenotypes;however,atfollowup, heterozygotes showed a significantly higher BMI z score (P 0.03). When the patients were divided according to the amount of weight lost, a higher prevalence of heterozygotes was observed among subjects who lowered their BMI z score 1.5 (P 0.03). Conclusion: These results suggest a gene-diet interaction between theMC3RC17A and G241A variants and a weight loss program for the ability to lose weight in childhood obesity. Am J Clin Nutr 2007;85:950–3.

Background Central precocious puberty (CPP) is often familial but its genetic cause is largely unknown. Very recently, the makorin RING finger protein 3 (MKRN3) gene, located on chromosome 15 in the Prader-Willi syndrome (PWS)-associated region (15q11-q13), has been found mutated in 5 families with familial precocious puberty. The MKRN3 is a maternal imprinted gene and the phenotype is expressed only when the MKRN3 mutations are localized on the allele inherited from the father. The function of this gene is not completely known and the phenotype caused by its defect is not yet fully elucidated. We report a new MKRN3 mutation (Pro160Cysfs*14) causing familial CPP. Case presentation The index case is a 7 years old girl showing Tanner stage 3 and pubic hair stage 1. Her bone age evaluated by TW2 method was 10.3 years. Her hormonal data confirmed the diagnosis of central precocious puberty. Familial medical history revealed precocious puberty in a cousin on paternal side. Paternal grandmother had menarche at the age of 9 years and 6 months and premature menopause when she was 36 years old. Genetic analysis revealed a new mutation (c477_485del; Pro160Cysfs*14) in the maternally imprinted MKRN3. Puberty onset was at 5 years in the other affected female family member. Precocious puberty was well controlled by pharmacological therapy. Conclusion We expand the number of the MKRN3 mutations associated with CPP and highlight the importance of an accurate family medical history to disclose the peculiar pattern of inheritance of this gene.

Objective: The insulin variable number of tandem repeats (VNTR) polymorphism located in the insulin gene promoter (INS VNTR) has been associated with insulin levels in obese children. Hyperinsulinemia is a pivotal factor in the development of metabolic syndrome, an emerging complication in childhood obesity. With the present study, we aimed to test the associations between INS VNTR and the metabolic syndrome in juvenile-onset obesity. Subjects and Methods: We screened for the INS VNTR in 320 obese children (152 girls; mean age, 11.2 ± 2.3 yr; mean z-score body mass index, 3.6 ± 1.1). All of them underwent a standard oral glucose tolerance test; baseline measurements included blood pressure and plasma lipid and fasting insulin levels. By using the data derived from the oral glucose tolerance test, the whole-body insulin sensitivity and the insulinogenic index were calculated. Results: The prevalence of metabolic syndrome reached 39%. No differences in INS VNTR genotype distribution were observed between obese subjects and 200 lean, age- and sex-matched children (P = 0.7). Among obese subjects, the prevalence of the metabolic syndrome was significantly higher in subjects with the I/I genotype (P = 0.006); the risk for developing the metabolic syndrome was significantly higher in subjects carrying the I/I genotype (odds ratio, 2.5; 95% confidence interval, 1.5–3.9). Obese subjects homozygous for the class I allele showed higher insulin levels and insulinogenic index but lower whole-body insulin sensitivity. Conclusions: We conclude that the I variant of the insulin promoter, when expressed in homozygotes, can predispose obese children to develop the metabolic syndrome.

Summary: Gyrate atrophy of the choroid and retina is an autosomal recessive chorioretinal dystrophy which leads to a slowly progressive loss of vision. The primary defect is due to a deficiency of the enzyme ornithine δ-aminotransferase, which is responsible for markedly elevated levels of ornithine in plasma and other body fluids. Although several therapeutic regimens have been proposed, the reduction in ornithine accumulation obtained by reducing the intake of its precursor arginine (semisynthetic low-arginine diet) is the one most practised. In this clinical and molecular study we report a patient with hyperornithinaemia and gyrate atrophy of the choroid and retina who had been diagnosed when she was 3 years 9 months old. She also presented mild mental retardation, delayed language development and speech defects. The patient has recently been found to be homozygous for the new Gly91Arg amino acid substitution of the enzyme ornithine δ-aminotransferase. This mutation lies in a region of the mature protein that is considered crucial for the mitochondrial targeting activity. In this patient, a 28-year treatment with a completely natural low-protein diet (0.8 g/kg per day of natural protein) has been able to significantly reduce ornithine plasma levels, and to greatly delay the natural progression of the chorioretinal changes. This study suggests that, in the long-term treatment of gyrate atrophy, the efficacy in slowing the progression of chorioretinal changes and the palatability of a completely natural low-protein diet make this treatment a potentially viable alternative in patients refusing the semisynthetic diet.

Objectives Studies of adults and children with celiac disease have reported an increased risk of overweight during gluten-free diet (GFD). The fat mass and obesity-associated gene (FTO) variant rs9939609 has been associated with increased risk of developing obesity in children and adults. Methods In our study, we analyzed the effect of this variant on weight gain in a cohort of 280 children with celiac disease on GFD. Results We found that after a mean follow-up time of 3.0 years on GFD, FTO polymorphism influenced significantly the mean change in body mass index z score (P = 0.01). Conclusions We conclude that the FTO gene contributes to determine weight changes in children with celiac disease on GFD.

Background The prevalence of obesity is increasing among children/adolescents. Subtle cardiovascular abnormalities, responsible for a higher mortality later in life, have been reported in obese children/adolescents. The aims of the study were to evaluate cardiovascular autonomic regulation, by means of spectrum analysis of R-R interval variability, and myocardial function, by means of standard and tissue Doppler echocardiography, in a group of non-hypertensive asymptomatic obese children and adolescents; furthermore, the influence of insulin resistance was tested. Subjects and Methods R-R interval variability was analyzed during both the 70° head-up tilt and 24-hour electrocardiographic holter monitoring. Spectrum analysis of R-R interval variability provided the indices of sympathetic (low frequency [LFRR]) and vagal (high frequency [HFRR]) modulation of the sinoatrial node. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to classify obese children/adolescents (n=72) as insulin resistant (n=37) and non-insulin resistant (n=35). Results In obese subjects: a) left ventricular mass was significantly (p

Background The ovary is an important site where gene variants modulate pubertal timing. The cannabinoid receptor 2 (CB2) is expressed in the ovary, plays a role in folliculogenesis and ovulation, and can be modulated by estrogens. Obesity is strictly associated with early menarche and is characterized by sex hormone and endocannabinoid derangement. Aim In this study, we investigated the role of the CB2 receptor in determining the age at menarche in obese girls. Methods We studied a cohort of 240 obese girls (age 11.9±3 years; BMI z-score 2.8±0.8). The age at menarche (if it had already occurred) was recorded at the time of the visit or via phonecall. The CNR2 rs35761398 polymorphism, which leads to the CB2 Q63R variant, was detected by the TaqMan assay. Results In total, 105 patients were homozygous for the R63-coding allele (RR), 113 were QR and 22 were QQ. Variance analysis revealed a significantly earlier age of menarche in subjects carrying the Q63 allele, which was also found after adjusting for BMI z-score (11±1.2 vs. 11.6±1.2 years, p = 0.0003). Logistic regression analysis demonstrated that patients homozygous for the Q allele had a 2.2-fold higher risk (odds ratio = 2.2; CI1.1-3.4; p = 0.02) of presenting with an early menarche (age at menarche

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Obesity in children/adolescents has been associated with subtle cardiac abnormalities, including myocardial dysfunction and cardiac autonomic dysregulation at rest, both likely responsible for a higher mortality in adulthood. Food intake induces remarkable adjustments of cardiovascular autonomic activity in healthy subjects.The objective of the study was to evaluate in obese children/adolescents meal-induced cardiac autonomic response and the role played by insulin resistance.Sixty-eight obese and 30 matched normal-weight children/adolescents underwent blood sampling and cardiovascular autonomic analysis while recumbent and 20 minutes after a mixed meal ingestion. Spectrum analysis of the R-R interval and systolic blood pressure (SBP) variability provided the indices of sympathetic [low frequency (LFRR)] and vagal [high frequency (HFRR)] modulation of the sinoatrial node and the low frequency component of SBP. The homeostasis model assessment of insulin resistance served to separate insulin resistant (n = 35) from non insulin resistant (n = 33) obese children/adolescents.At baseline, C-reactive protein, the LFRR to HFRR ratio, SBP, and low frequency oscillatory component of SBP variability in obese children/adolescents were significantly (P.05) greater than in referent subjects, whereas high-density lipoprotein cholesterol and HFRR were lower; meal-induced increase in the LFRR to HFRR ratio was significantly less than in controls and exaggeratedly scanty (or opposite) among insulin resistant subjects. The homeostasis model assessment of insulin resistance index strongly and inversely correlated (r = -0.871; P.001) with meal-induced changes in the LFRR to HFRR ratio among obese subjects.Autonomic modulation of the heart was impaired after eating in obese children/adolescents. This abnormality was exaggerated among insulin resistant subjects and strongly correlated with the degree of insulin resistance.

We investigated serum leptin levels in 103 mother-newborn-pairs; Cord leptin was significantly higher than mother's leptin (5.7 ± 5.5 vs. 22.1 ± 19.9 ng/ml; p

The ability to assure a correct regulation of energy balance is a major determinant of species survival and brain has been proposed as the central controller of energy intake, expenditure and storage. Rapid advances in understanding the genetic control of appetite and fatness regulation have been recently performed. Several single gene defects in experimental animals with genetic obesity and associated feeding disorders have been shown within the past 4 years providing an important frame-work for understanding molecular basis of obesity in humans. Leptin, a protein secreted by adipocytes, able to play a role in the regulation of body fat, has been intensively investigated both at the biochemical and at the genetical level. Despite these efforts there are few evidences suggesting a major role of this protein in influencing body weight. A number of other proteins and relative genes, potentially involved in the genetic control of energy balance, are currently under investigation.

Serum leptin levels and the relationship between leptin, gender, and anthropometric measurements were assessed in a group of 40 obese and 33 lean Italian children. The coding region of OB gene was screened by polymerase chain reaction (PCR) and single strand conformational polymorphism (SSCP) for mutations in 30 unrelated obese subjects. Mean fasting leptin level was significantly higher in the obese than in the control group (18.2 ±2.1 vs 7.1 ± 1.0 ng/ml; p

OBJECTIVE: Allergic rhinitis (AR) is caused by an IgE-mediated inflammatory reaction consequent to the exposure to causal allergen. Resveratrol is a natural non-flavonoid polyphenol, exerting anti-inflammatory activity; β-glucan is a polysaccharide with immuno-modulatory properties. Thus, this study aimed to investigate whether these combined compounds are able of relieving nasal symptoms in children with AR due to pollen allergy. RESEARCH DESIGN AND METHODS: The present study was conducted as placebo-controlled, double-blinded, and randomized. Globally, 68 children (36 males; mean age 7.9 years) were treated with resveratrol plus β-glucan or placebo (the diluent of active drug) two sprays (100 µL/spray) in each nostril three times/day for 2 months. Nasal symptoms, including itching, sneezing, rhinorrhea, and obstruction, were assessed at baseline and after treatment. Use of rescue medication, such as cetirizine syrup, was also evaluated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02130440. RESULTS: Children treated with active drug achieved a significant reduction in all nasal symptoms: itching (p = 0.0001), sneezing (p = 0.0009), rhinorrhea (p = 0.009), and obstruction (0.002) as well as antihistamine use (p = 0.003). Placebo did not affect nasal complaints and cetirizine use. The intergroup analysis showed that active treatment was significantly superior to placebo about reduction of AR symptoms and rescue medication use. CONCLUSIONS: The present preliminary study firstly showed that intranasal resveratrol plus carboxymethyl-β-glucan is capable of significantly improving nasal symptoms in children with pollen-induced AR.

Highlights • We present an otherwise healthy boy of 12 years old with unilateral breast masses. No abnormalities were found on ultrasonography and on all endocrine parameters. • We present a new “modified” Webster technique. The results confirmed validity of this technique in terms of esthetic and functional results, and patient satisfaction. • The evaluation of unilateral gynecomastia can therefore be complex. • The surgical treatment of unilateral gynecomastia requires an individual approach, based on an appropriate diagnostic algorithm., INTRODUCTION Gynecomastia is the benign proliferation of the glandular tissue in the male breast. This condition is thought to be caused by the imbalance between estrogen action relative to androgen action at the breast tissue level. Bilateral gynecomastia is frequently found in the neonatal period, early in puberty, and with increasing age. Prepubertal unilateral gynecomastia in the absence of endocrine abnormalities is extremely rare, with only a few cases in literature. PRESENTATION OF CASE We present an otherwise healthy boy of 12 years old with unilateral breast masses. No abnormalities were found on ultrasonography and on all endocrine parameters. Treatment consisted in a new “modified” Webster technique. DISCUSSION The results confirmed validity of this technique in terms of esthetic and functional results, and patient satisfaction. Atypical presentations of gynecomastia are often not recognized. The main pathophysiology of gynecomastia is alteration in the balance between the stimulatory effect of estrogen and the inhibitory effects of androgens on the development of the breast. If there is no causal treatment, surgical resection is the therapy of first choice. CONCLUSION The exact mechanism of unilateral gynecomastia formation in our case is unclear. The evaluation of unilateral gynecomastia can therefore be complex. In conclusion, the surgical treatment of unilateral gynecomastia requires an individual approach, based on an appropriate diagnostic algorithm.

Background Rubinstein-Taybi syndrome (RTS) is a rare autosomal dominant disorder (prevalence 1:125,000) characterised by broad thumbs and halluces, facial dysmorphism, psychomotor development delay, skeletal defects, abnormalities in the posterior fossa and short stature. The known genetic causes are point mutations or deletions of the cAMP-response element binding protein-BP (CREBBP) (50-60% of the cases) and of the homologous gene E1A-binding protein (EP300) (5%). Case presentation We describe, for the first time in literature, a RTS Caucasian girl, 14-year-old, with growth hormone (GH) deficiency, pituitary hypoplasia, Arnold Chiari malformation type 1, double syringomyelic cavity and a novel CREBBP mutation (c.3546insCC). Conclusion We hypothesize that CREBBP mutation we have identified in this patient could be responsible also for RTS atypical features as GH deficiency and pituitary hypoplasia.

Background Prepubertal gynecomastia is characterized by the presence of palpable uni- or bilateral breast tissue in boys without other signs of sexual maturation. It may be the endocrine expression of rare syndromes such as PeutzJeghers syndrome (PJS). This study aimed to evaluate the effectiveness of anastrozole and to describe an innovative surgical approach. Methods This report presents twins with PJS, bilateral prepubertal gynecomastia, and testicular multifocal calcifications. Both twins were treated with anastrozole for 2 years. After finishing treatment, both were followed before subcutaneous mastectomy was performed by the ‘‘modified’’ Webster technique. Results Growth velocity decreased and gynecomastia diminished during anastrozole treatment. After discontinuation of therapy due to a sharp reduction in growth velocity, both twins showed regrowth of gynecomastia, with painful and strained breasts. A significant reduction in breast volume with glandular removal was achieved. Conclusions The findings of this study showed a multidisciplinary approach to prepubertal gynecomastia due to the synergy of pediatricians, radiologists, and plastic surgeons. The follow-up evaluation after the anastrozole treatment showed it to be an efficacious medical treatment, as an alternative to orchidectomy, to control the effects of circulating estrogens. Moreover, the results observed in the patients confirmed the validity and feasibility of the ‘‘modified’’ Webster technique in terms of aesthetic and functional results, patient satisfaction, and absence of complications. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Type 1 diabetes mellitus may be associated with many autoimmune diseases with the common autoimmune pathogenesis. We describe the case of a girl suffering from Type 1 diabetes mellitus and autoimmune Hashimoto's thyroiditis since the childhood and, due to the onset of Juvenile Idiopathic Arthritis during adolescence, for three years practiced therapy with an anti-TNF drug, etanercept . Currently her inflammatory markers are normal, arthritis is inactive and diabetes is well controlled. During the treatment with anti-TNF drug we observed a significative reduction of insulin dose, probably due to an increased tissue sensitivity secondary to the suppression of the activity of TNF-alpha. Several clinical trials that have evaluated the effect of immunomodulatory agents in diabetic patients, especially in those with recent onset of disease, were already performed but further studies of longer duration on a larger population are needed to assess the role of biologic drugs and immunotherapy in this group of patients.

Over the last decade, there has been a growing interest in the use of probiotics for allergic diseases. In the last years, some studies showed a significant improvement for atopic eczema by the administration of probiotics during pregnancy and postnatally. About food allergy, probiotics administration seems to be effective in the management of food allergy symptoms but has no effect on the prevention of sensitization. In the international literature, there are few studies that evaluated the probiotic effect on allergic rhinitis, and authors reported that probiotics might have a beneficial effect in AR by reducing symptom severity and medication use. Another major potential benefit of probiotics has been suggested in patients with asthma. On this topic, several studies have been carried out using different probiotics and the results have not been univocal. Indeed, probiotics seems to be able to offer protection about common cold and respiratory infections in healthy and hospitalized children.

International asthma guidelines recommend increasing the dose of ICS or adding leukotriene modifiers or the use of long-acting inhaled beta2-agonists (LABAs) in combination with inhaled corticosteroids (ICS) when uncontrolled asthma occurs in adult and children in treatment with low-dose inhaled corticosteroids. However, in children, the effects of this last treatment option are unclear because there are few studies on the efficacy and safety of these drugs in pediatric age. Furthermore, salmeterol is licensed for use in children over 4 years and formoterol in children of more than 6 years. Finally, recent data provides evidence that repeated bronchoconstriction induces epithelial cell stress that may lead to remodeling and these findings may have potential implications for asthma management, particularly for LABAs treatment in the future.

Few data are available on cardiac morphology and function in children with heterozygous familial hypercholesterolemia (FH). Such patients represent a unique clinical model to assess the effect of pure hypercholesterolemia on cardiac morphology and function, excluding the effect of comorbidities. Speckle-tracking echocardiography, a relatively new echocardiographic modality, allows the assessment of myocardial deformation properties. The aim of this study was to define in children with FH the preclinical effects of isolated hypercholesterolemia on the cardiovascular system by examining left ventricular (LV) function using speckle-tracking echocardiography.Ninety children (45 with FH and 45 controls; mean age, 11 ± 3 years) were prospectively studied.Children with FH showed thicker LV walls and significantly higher LV mass indexed for height(2.7) (P = .0008) and for body surface area (P.0001). LV ejection fractions were similar in both groups. Assessment of diastolic function demonstrated longer deceleration times (P.0001), reduced early diastolic mitral annular velocities (P.0001), and higher transmitral early/early diastolic mitral annular velocity ratios (P = .0003) in children with FH. Longitudinal and circumferential myocardial deformation of the left ventricle were significantly reduced (P.0001) whereas radial deformation was increased in children with FH (P = .04) compared with controls.This study demonstrates that hypercholesterolemia is associated with significant LV morphologic and functional alterations during childhood. The findings also suggest that reductions in longitudinal and circumferential deformation are compensated for by increasing radial strain in children with FH with normal LV ejection fractions. This study raises the questions of the clinical importance of these findings and the opportunity for cholesterol-lowering therapy. The potential benefits and risks of such treatment at a young age need to be addressed in larger long-term studies.

Adults with normal glucose tolerance (NGT) but exaggerated plasma glucose excursion at 1 h (1HPG) following the oral glucose tolerance test (OGTT) have significantly higher risk of developing impaired glucose tolerance (IGT) or diabetes. Aim of the study will be to characterize the metabolic phenotype of NGT obese youth according to values of 1HPG. To accomplish this aim, obese patients (N = 1,454; 761 men; 79 IGT; BMI z-score 2.56 ± 0.16 SDS; age 11 ± 0.7 years) from two data sets were analyzed. In all patients, empirical parameters of insulin metabolism were calculated in fasting condition and following an OGTT (1.75 mg of glucose per kilogram/ body weight). Receiver-operating characteristic (ROC) analysis was performed in the first group (training set, N = 920) to establish the cutoff value of 1HPG best identifying IGT. The second set (validation set, N = 534) served to verify the goodness of the model and the identified cutoff values. 1HPG ≥ 132.5 mg/dl identified IGT with 80.8% sensitivity and 74.3% specificity in the training set (AUC 0.855, 95% CI 0.808-0.902, P

Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of disease ranging from simple steatosis to inflammatory steatohepatitis (NASH) with different degrees of fibrosis that can ultimately progress to cirrhosis. Accumulating evidence suggests the involvement of the endocannabinoid-system in liver disease and related complications. In particular, hepatoprotective properties for Cannabinoid Receptor type 2 (CB2) have been shown both through experimental murine models of liver injury and association study between a CB2 functional variant, Q63R, and liver enzymes in Italian obese children with steatosis. Here, in order to clarify the role of CB2 in severity of childhood NAFLD, we have investigated the association of the CB2 Q63R variant, with histological parameters of liver disease severity in 118 Italian children with histologically-proven NAFLD. CB2 Q63R genotype was assigned performing a TaqMan assay and a general linear model analysis was used to evaluate the association between the polymorphism and the histological parameters of liver damage. We have found that whereas CB2 Q63R variant is not associated with steatosis or fibrosis, it is associated with the severity of the inflammation (p = 0.002) and the presence of NASH (p = 0.02). Our findings suggest a critical role for CB2 Q63R variant in modulating hepatic inflammation state in obese children and in the consequent increased predisposition of these patients to liver damage.

Background and aims Pediatric obesity is an important health problem representing a major public health concern worldwide in the last decades. An isolated elevation of Thyroid Stimulating Hormone (TSH) with normal levels of thyroid hormones is frequently found in obese children. It has been named Isolated Hyperthyreotropinemia or Subclinical Hypothyroidism (SCH) and may be considered a consequence of obesity. Evidence exists that SCH is related to impairment of both systolic and diastolic myocardial function in the adult population. The aim of our study is to establish if obesity-related SCH influences myocardial function in children. Methods and results We examined 34 obese children and adolescents with SCH and 60 obese children with normal TSH levels who underwent Doppler echocardiographic to evaluate myocardial function. Global systolic function as assessed by Ejection Fraction (EF) was comparable between groups, however Right Ventricle pressure global systolic function and pressure were significantly reduced in SCH group. Mitral annulus peak systolic (MAPSE) excursion lateral and MAPSE septum resulted significantly reduced in SCH group. Tissue Doppler imaging peak systolic motion (TDI-S) was reduced in SCH group. Diastolic function also showed significant modifications in SCH group. Conclusion These results suggest possible involvement of cardiac function in obese children with SCH resulting in both abnormal diastolic function and reduced longitudinal systolic function. This new insight into cardiovascular consequences of obesity-related SCH in children could influence clinical approach to such patients by pediatric endocrinologists.

Background and aimsA polymorphism in adiponutrin/patatin-like phospholipase-3 gene (PNPLA3), rs738409 C->G, encoding for the I148M variant, is the strongest genetic determinant of liver fat and ALT levels in adulthood and childhood obesity. Aims of this study were i) to analyse in a large group of obese children the role of the interaction of not-genetic factors such as BMI, waist circumference (W/Hr) and insulin resistance (HOMA-IR) in exposing the association between the I148M polymorphism and ALT levels and ii) to stratify the individual risk of these children to have liver injury on the basis of this gene-environment interaction.Methods1048 Italian obese children were investigated. Anthropometric, clinical and metabolic data were collected and the PNPLA3 I148M variant genotyped.ResultsChildren carrying the 148M allele showed higher ALT and AST levels (p = 0.000006 and p = 0.0002, respectively). Relationships between BMI-SDS, HOMA-IR and W/Hr with ALT were analysed in function of the different PNPLA3 genotypes. Children 148M homozygous showed a stronger correlation between ALT and W/Hr than those carrying the other genotypes (p: 0.0045) and, therefore, 148M homozygotes with high extent of abdominal fat (W/Hr above 0.62) had the highest OR (4.9, 95% C. I. 3.2-7.8, p = 0.00001) to develop pathologic ALT.ConclusionsWe have i) showed for the first time that the magnitude of the association of PNPLA3 with liver enzymes is driven by the size of abdominal fat and ii) stratified the individual risk to develop liver damage on the basis of the interaction between the PNPLA3 genotype and abdominal fat.