Failure to thrive: the importance of measuring the electrolytes.

Diabetes insipidus (DI) is characterized by hypoosmotic polyuria related to deficiency of arginine-vasopressin (AVP) secretion (centraldiabetesinsipidus, CDI) or renalinsensitivity to AVP (nephrogenicdiabetesinsipidus, NDI). We report a case of a child with congenital NDI.

Congenital renal anomalies imaging: a valuable tool for pediatricians.

The purpose of this article is to review the main congenital anomalies of kidneys and urinary tract that can be diagnosed prenatally and postnatally by imaging technique. The incidence of congenital anomalies of the kidney and urinary tract during the past decade has been estimated to be 0.4 to 4.0 cases per 1000 births. Congenital kidney disease can evolve in chronic disease in childhood and in adulthood. A diagnostic imaging of the various congenital renal and urological conditions allows pediatricians to make a correct diagnosis and treatment. Because of the concerns about long-term effects of ionizing radiation, the most commonly and first used imaging modality for evaluation of the urinary system is ultrasound.

Monosymptomatic enuresis: the therapeutic weapons.

Nocturnal enuresis (NE) was defined by the World Health Organization (ICD-10) and the American Psychiatric Association (DSM-5) as bed-wetting in children aged >5 years. In cases of mental retardation, the developmental age may be equivalent to 5 years. In this review, we focus on the current knowledge about the etiology of enuresis and the most recent therapeutical options. Both non-pharmacological and pharmacological therapies are included, although the relative effectiveness of each remains uncertain. To date, motivational, alarm and drug therapies are the mainstay of treatment. Alarm therapy remains the first-line treatment modality for NE, while desmopressin is the most commonly used medical treatment.

Cardiac dysfunction in children with essential obesity: preliminary data.

Obesity in children has been recognized as a major underlying factor of the pathogenesis of several diseases and a reduced life expectancy. This study aims to verify if clinical parameters, such as waist circumference and/or body mass index and biohumoral and inflammatory parameters can help predict cardiac structural and functional alterations, through an echocardiogram test in obese children and adolescents. Children were prospectively enrolled at the AUOC outpatients' department of Emergency Paediatrics, University Hospital, Messina, from June to December 2017. Clinical, metabolic parameters and an inflammation marker (HMGB1) were evaluated and a transthoracic echocardiogram was carried out. Twenty-two obese subjects were prospectively enrolled.HMGB1 values were 12.6 ± 2ng/ml, significantly higher compared to a previously studied healthy control group. A significant positive correlation was found both between total cholesterol levels and HMGB1 values (r=0.846, p=0.000) and between LDL cholesterol and HMBG1 values (r=0.663, p=0.001). No correlation was found between clinical, biohumoral and echocardiograph parameters. In obese children cardiac parameters obtained from echocardiogram tests may be in the normal range. However, other parameters may be altered in the early phase, showing that infantile obesity can compromise myocardial functions, even in the absence of comorbidities. Furthermore, the evaluation of concentrations of HMBG1 could explain how an initial inflammation can trigger the condition of meta-inflammation.

Local therapy with ozone in the management of the exit site in a patient undergoing peritoneal dialysis.

The natural history of children with end stage renal disease is dialysis until a transplant can be done. There are two types of dialysis: hemodialysis and peritoneal dialysis (1). Peritoneal dialysis is preferred in young children because getting the vascular access for hemodialysis is challenging (2). Catheters should be surgically placed in a paramedian or lateral abdominal region with an extremity located in Douglas' pouch.

Different concentration of human cord blood HMGB1 according to delivery and labour: A pilot study.

OBJECTIVE: Oxidative stress is involved in several maternal conditions characterized both by an increase in free radicals synthesis and a parallel decrease in the antioxidant activity. Parturition induces considerable oxidative stress and many inflammatory mediators, among which HMGB1, are involved from the beginning of pregnancy to the birth of the infant. We evaluated serum cord blood HMGB1 levels in a population of neonates to investigate correlation with mode of delivery, as well as the influence of labour. SETTING AND PATIENTS: The study subjects were 325 neonates delivered at University Hospital "G. Martino" of Messina over an 18-month period. Following cord separation, venous blood sampling was performed on umbelical cords. RESULTS: In the cord venous blood, we found HMGB1 values significantly more elevated in spontaneous vaginal group when compared to elective or emergency caesarean section group. Regarding labour, umbilical cord venous blood HMGB1 levels were significantly higher in the spontaneous and induced labour group, compared to non-labouring women. CONCLUSION: These results could highlight a possible role of HMGB1 during birth time related to mode of delivery and labour.

Genotype-phenotype correlation in FMF patients: A "non classic" recessive autosomal or "atypical" dominant autosomal inheritance?

BACKGROUND: Uncertainty remains on the pathogenetic mechanisms, model of inheritance as well as genotype-phenotype correlation of FMF disease. OBJECTIVE: To investigate the impact of genetic factors on the FMF phenotype and the disease inheritance model. METHODS: A total of 107 FMF patients were enrolled. Patients were diagnosed clinically. All patients underwent genetic analysis of the FMF locus on 16p13.3. RESULTS: 9 distinct mutations were detected. Specifically, the 85.98% of patients showed a heterozygous genotype. The most common genotypes were p.Met680Ile/wt and p.Met694Val/wt. The most frequent clinical findings were fever, abdominal pain, joint pain, thoracic pain, and erysipelas-like erythema. Analysis of clinical data did not detect any significant difference in clinical phenotype among heterozygous, homozygous as well as compound homozygous subjects, further supporting the evidence that, contrary to the recessive autosomal inheritance, heterozygous patients fulfilled the criteria of clinical FMF. Moreover, subjects with p.Met694Val/wt and p.Met680Ile/wt genotype reported the most severe clinical phenotype. p.Ala744Ser/wt, p.Glu148Gln/Met680Ile, p.Met680Ile/Met680Ile, p.Met680Ile/Met694Val, p.Pro369Ser/wt, p.Met694Ile/wt, p.Glu148Gln/Glu148Gln, p.Lys695Arg/wt resulted in 100% pathogenicity. CONCLUSIONS: The existence of a "non classic" autosomal recessive inheritance as well as of an "atypical" dominant autosomal inheritance with incomplete penetrance and variable expressivity cannot be excluded in FMF.

Serum IL-10, IL-17 and IL-23 levels as "bioumoral bridges" between dyslipidemia and atopy.

BACKGROUND: Although several studies suggest a possible link between dyslipidemia and atopy, literature findings are still unclear. OBJECTIVE: The aim of the study was to investigate the relationship between dyslipidemia and atopy in a pediatric population affected by dyslipidemia or dyslipidemia/atopic predisposition. MATERIALS AND METHODS: Children with dyslipidemia, dyslipidemia and atopy as well as healthy children were recruited. Serum total IgE, IL-10, IL-17, and IL-23 levels as well as fasting lipid values (total cholesterol, LDL, HDL and triglycerides) were performed on all enrolled children. RESULTS: The present study evaluated 23 patients affected by dyslipidemia, 26 patients affected by atopy and dyslipidemia and, 22healthy children. Serum total IgE levels significantly related also with serum cholesterol levels: positively with total cholesterol (p<0.05), LDL (p<0.05), and tryglicerides (p<0.001), but negatively with HDL (p<0.05). Serum levels of IL-10 were lower in children with atopy and dyslipidemia than patients with dyslipidemia (p<0.001). Serum IL-10 levels significantly related also with serum cholesterol levels: negatively with total cholesterol (p<0.001), LDL (p<0.05), and triglycerides (p<0.05), but positively with HDL (p<0.05). Serum IL-17 and IL-23 levels showed the same trend. They were significantly higher in children with atopy and dyslipidemia than patients with dyslipidemia (p<0.001). In particular, serum IL-17 and IL-23 values positively correlated with serum total IgE levels (p<0.05); serum total cholesterol levels (p<0.001); serum LDL levels (p<0.001); serum triglycerides levels (p<0.05). Although not statistically significant, an inverse correlation has been noted between serum IL-17, IL-23 and HDL levels. CONCLUSIONS: These findings support the notion that dyslipidemia and atopic predisposition share the same immune pathways as well as they offer new insights in the complex crosstalk between hyperlipidemia and atopy.

Lateralized exanthem mimicking figurate inflammatory dermatosis of infancy after methimazole therapy.

We reported a case of an 11-year-old girl admitted to our hospital for goiter, tachycardia, sweating, and visible and palpable thyroid. Thyroid function tests revealed a low thyrotropin level (<0.004 mIU/L) and elevated free thyroxine level (3.4 ng/ dL) diagnosed with Graves' disease and treated with methimazole. This anti-thyroid drug is recommended as first-line treatment in children with Graves' disease because it produces minor adverse effects with respect to propylthiouracil. She developed a lateralized exanthem mimicking figurate inflammatory dermatosis of infancy after methimazole therapy. The symptoms resolved after discontinuation of methimazole and treatment with an antihistamine and a corticosteroid. Furthermore, the treatment was changed to propylthiouracil without any adverse effects. According to current literature this is the first case of cutaneous figurate erythema related to methimazole, different from other well-known reactions such as skin eruption or urticaria.

ALMOND MILK: A POTENTIAL THERAPEUTIC WEAPON AGAINST COW’S MILK PROTEIN ALLERGY.

Food allergy is defined as an adverse health effect arising from a specific immune response that occurs reproducibly following exposure to a given food. Cow’s milk protein allergy results from an immunological reaction to one or more milk proteins. The principle key in the treatment of cow’s milk protein allergy is the dietary elimination of cow’s milk protein. Although hydrolyzed and elemental formulas are appropriate replacements, other milk products, including almond milk adequately integrated, could be administered. Here, in the light of encouraging results from our study, we focused on the anti-inflammatory and anti-oxidant properties of almond milk and we also believe that almond milk might be considered as a potential alternative in cow’s milk protein allergy treatment.

ATOPIC DERMATITIS: EXPRESSION OF IMMUNOLOGICAL IMBALANCE.

Atopic dermatitis is a chronic relapsing-remitting inflammatory skin condition, characterized by a skin barrier dysfunction resulting in epidermal damage and altered permeability to allergens and microbes. Although pathogenesis of atopic dermatitis is complex and still not fully understood, it has been hypothesized that genetic predisposition, environmental factors, and skin barrier dysfunction are involved. Innate and adaptive immune system has also a pivotal role in the development, maintenance and flare-up of atopic dermatitis. The immune-pathogenesis of atopic dermatitis is determined by the impairment of different T helper cells, of their cytokine secretion profiles as well as of their specific receptor. In this review, we focus on the current knowledge of the etiopathogenetic pathways of atopic dermatitis in relationship to the critical role of the innate and adaptive immune system, providing a unifying view.

EXHALED BREATH TEMPERATURE IN ASTHMATIC CHILDREN.

Asthma is characterized by chronic inflammation of airways. Currently, no traditional method allows an easy daily evaluation of the degree of airway inflammation. Measuring inflammatory biomarkers in the breath is a very attractive approach to monitor asthma inflammation. In recent years, the measurement of exhaled breath temperature (EBT) has been proposed as a method capable of detecting the inflammatory status of the airways. The objective of this study is to strengthen the role of EBT in the diagnosis and monitoring of asthma. The study sample was represented by a group of 40 patients, of both sexes, aged 6-15 years. The elective criteria for submitting patients to EBT determination were abstaining from drugs in the preceding 24 h, fasting for at least 2 h, physical resting for at least 30 minutes, a body temperature between 35-37°C. The temperature in the room of the surveys ranged from 18 to 25°C. The EBT values of asthmatic patients were higher [(median (IQR): 29.77°C (30.67°C to 29.38°C) range 28.46°C min-max 34.78°C] than those of non-asthmatic ones (median (IQR): 28.22°C (29.09°C-27.7°C), range 27.09°C min-max 30.07°C] and this difference was highly significant (p less than 0.001). Furthermore, no significant difference was found between the EBT values of the following groups of patients: those exposed and not exposed to passive smoking, those receiving and not receiving leukotriene drugs, those receiving and not receiving specific immunotherapy, monoallergic patients and poliallergic ones, those sensitized and not sensitized to house dust, perennial allergic patients and seasonal allergic ones. In addition, the evaluation of the correlation of EBT values with body temperature (r=0.119, p=0.464) and ambient temperature (r=-304, p = 0.057) did not show any significant correlation. Finally, no statistically significant correlation was demonstrated between EBT values and FEV1 (r=-0055, p=0.81, Fig. 4). In conclusion, the data of the present study further support the hypothesis that EBT can be considered a good method for monitoring asthma.

HIGH-MOBILITY GROUP BOX 1 IN ALLERGIC AND NON ALLERGIC UPPER AIRWAY INFLAMMATION.

High mobility group box 1, an evolutionary ancient protein conserved in the eukaryotic kingdom, exerts intra- and extra- cellular functions, orchestrating a homeostatic defensive response in challenged tissues. Its action associated with various inflammatory cells is essential for the occurrence, progression, and persistence of asthma, rhinitis, and nasal polyposis. The recent discovery of High mobility group box 1, as a critical mediator of inflammation, stimulated an increasing interest in the field of inflammation research, suggesting new therapies for atopic and non-atopic inflammatory processes.

ALLERGIC RHINITIS AND ADENOID HYPERTROPHY IN CHILDREN: IS ADENOIDECTOMY ALWAYS REALLY USEFUL?

Allergic rhinitis (AR) and adenoid hypertrophy (AH) are common in children and are often associated with each other. Recent studies have shown improvement of respiratory symptoms and reduction in the adenoid volume after anti-allergic medical therapy (intranasal corticosteroids, antihistamines). The aim of our retrospective study is to evaluate the effectiveness of adenoidectomy on respiratory symptoms in pediatric patients with AR. We recruited 404 pediatric patients with AR, and we divided them into 4 groups (1. intermittent-mild rhinitis; 2. intermittent-moderate/severe rhinitis; 3. persistent-mild rhinitis; 4. persistent-moderate/severe rhinitis), using ARIA classification. For each patient we evaluated: age at onset of AR; family history of allergy; the presence of other allergic diseases; serum total IgE values; skin prick test (SPT) results; presence of AH evaluated by rhino-laringeal fibroscopy; adenoidectomy and its efficacy on respiratory symptoms. Our data show an association between AR and AH: 90 of 404 (22%) children with AR had AH of a degree greater than 2nd. A significant percentage (80%) of children suffering from AR did not present satisfactory benefits from adenoidectomy. They reported persistence or recurrence of rhinitic symptoms after surgery or only partial benefits, especially of recurrent respiratory tract infections and nasal obstruction. The local allergic persistent inflammation on nasal mucosa and adenoid tissue is probably the cause of the unsatisfactory results of adenoidectomy, therefore surgery cannot be the first therapeutic step for these children. It is important to extinguish the local inflammation by medical anti-allergic therapy to obtain improvements of nasal symptoms and to prevent adenoid regrowth.

RELATION OF BODY MASS INDEX WITH IgE LEVELS, ALLERGIC SENSITIZATION AND LUNG FUNCTION IN ASTHMATIC CHILDREN: OUR EXPERIENCE AND REVISION OF LITERATURE.

In recent decades, there has been an increase in the prevalence of asthma and obesity in pediatric age. In this regard several studies have provided controversial data to demonstrate the link between Body Mass Index (BMI) and asthma, both in adults and in children. In this prospective study we evaluated the relationship between body mass index value, total IgE immunoglobulin E levels, skin prick test (SPT) sensitization and lung function in children affected by asthma. According to the analysis of data on the comparison of normal-weight patients versus overweight/obese patients, there was no significant difference in the values of FEV1 (86%±12 vs 90%±19), FVC (81%±11 vs 88%±18), skin prick tests (22.72% vs 36.66%) and total IgE values (192.22±368.28 vs 503±914.04). We carried out a sub-analysis to study the difference between three groups of patients: normal weight, overweight and obese. Obese patients showed higher total IgE values than normal-weight patients with a statistically significant difference. Conversely, there was no significant difference between the normal weight group and the obese group in the respiratory function tests and the SPT. Moreover, we found a higher value of total IgE in female overweight/obese compared with normal weight, while there was no significant difference in relation to parameters of lung function and SPT. However, the same analysis in the male sample did not show any statistically significant difference. This study confirms the higher incidence of atopy in obese children, especially in female gender, but not a direct relationship with either allergens sensitization or abnormal lung function.

POTENTIAL USE OF MELATONIN IN PROCEDURAL ANXIETY AND PAIN IN CHILDREN UNDERGOING BLOOD WITHDRAWAL.

The recognition of the value of pain, especially in the pediatric population, has increased over the last decade. It is known that pain-related anxiety can increase perceived pain intensity. There are several different approaches to the treatment of pre-procedural anxiety and procedural pain in children. Melatonin, a neurohormone with the profile of a novel hypnotic-anaesthetic agent, plays an important role in anxiolysis and analgesia. This study investigated the effects of oral melatonin premedication to reduce anxiety and pain in children having blood samples taken. The investigations were carried out on 60 children, aged 1-14 years, divided into 2 equal groups. Using a computer-generated randomization schedule, patients were given either melatonin orally (0.5 mg/kg BW, max 5 mg) or placebo 30 min before blood draw. Pre-procedural anxiety was assessed using the scale from the Children’s Anxiety and Pain Scales, while procedural pain used the Face, Legs, Activity, Cry and Consolability assessment tool for children under the age of 3 years, Faces Pain Scale-Revised for children aged 3-8 years and Numeric Rating Scale for children over the age of 8 years. Oral administration of melatonin before the blood withdrawal procedure significantly reduced both anxiety (p<0.0005) and pain levels than placebo (p<0.0002 for children under 3 years and p<0.0039 for children over 3 years). These data support the use of melatonin for taking blood samples due to its anxiolytic and analgesic properties. Further studies are needed to support the routine use of melatonin to alleviate anxiety and pain in pediatric patients having blood samples taken.

Acute pulmonary exacerbation and lung function decline in patients with cystic fibrosis: high-mobility group box 1 (HMGB1) between inflammation and infection.

Airway inflammation plays a central role in cystic fibrosis (CF) lung disease, and biomarkers of inflammation, such as high-mobility group box 1 (HMGB1) could be used to monitor disease activity. The main aim of this study was to confirm the role of HMGB1 in CF patients, correlating its serum and sputum levels with pulmonary function and inflammation. Serum and sputum HMGB1 were evaluated in a cohort of 31 CF patients and 30 non-smoking healthy subjects (HS group). Acute pulmonary exacerbation events and lung function decline have been also evaluated during a 3-year follow-up period. Serum HMGB1 levels were significantly higher than those measured in HS, such as sputum HMGB1. Kaplan-Meier survival curves revealed that patients with high HMGB1 values experienced a significantly faster evolution to decline of lung function. A multiple Cox regression analysis assessed that an increase of serum HMGB1 was associated with 5% increased risk of pulmonary disease progression, whereas elevated sputum HMGB1 was related to a 10% increased risk of lung function decline. In CF patients, HMGB1 closely reflects the entity of pulmonary impairment and represents a strong and independent risk marker for progression of lung function decline.

Central precocious puberty: from physiopathological mechanisms to treatment.

Puberty is a complex, coordinated biological process with multiple levels of regulations. The timing of puberty varies greatly in children and it is influenced by environmental, endocrine and genetic factors. Precocious puberty (PP) is an important issue, affecting between 1 in 5.000-10.000 children. The physiopathological mechanism is still unknown. From an etiological point of view, PP may be subdivided into gonadotropin-releasing hormone (GnRH) -dependent and independent causes. GnRH-dependent PP, often called central precocious puberty (CPP), is based on hypothalamic-pituitary-gonadal axis activation associated with progressive pubertal development, accelerated growth rate and advancement of skeletal age. Conversely, peripheral precocious puberty (PPP) is related to sex steroid exposure, independently of hypothalamic-–pituitary-–gonadal (HPG) axis activation. Kisspeptins play a central role in the modulation of GnRH secretion with peripheral factors that influence the timing of puberty, such as adipokines and endocrine disrupting chemicals. Moreover, PP could be related to genetic disorders, involving pivotal genes of the HPG axis. The standard test used to verify HPG activity is the gonadotropin response to administered GnRH analogs. We describe the physiopathological mechanisms of PP and its clinical implications, analysing diagnostic flow-chart and new potential biomarkers that could reveal PP. An update of the current literature was also carried out regarding the recent novelty for treatment.

CO(2) pneumoperitoneum induces in vitro hypoxic response culminating in apoptosis of human neuroblastoma cells.

The ablative role of minimally invasive surgery (MIS) in neuroblastoma (NB) is still controversial due to the possible CO2 pneumoperitoneum side-effects on tumor aggressiveness. It is known that CO2 produces hypoxic condition with changes in tumor microenvironment influencing cell functions. Here we investigated whether CO2 exposure affects the transcription factor HIF-1α and the apoptotic signalling pathway in SH-SY5Y NB cells. SH-SY5Y cells were exposed to a pressure of 15 mmHg CO2 (100%) for 4 h (T0) and then moved to normal condition for 24 h (T24). In control and CO2 -exposed cells, we analyzed the mRNA levels and DNA binding activity of HIF-1α. We also evaluated the proliferative activity and cell viability as well as caspase-9/3 cleavage and nuclear fragmentation. A significant increase in HIF- 1α activation was observed in SH-SY5Y cells exposed to CO2 compared to control cells. CO2 treatment also decreased the proliferation rate and the percentage of viable cells. In addition, the expression and cleavage of caspase-9 and -3 were significantly increased in NB cells exposed to CO2. These data correlated with apoptotic feature observed in CO2 -treated NB cells. Our findings show that CO2 -induced hypoxic condition exerts cytotoxic effects on NB cells by eliciting mitochondrial apoptotic pathway and thereby improving the understanding of the possible clinical impact of CO2 pneumoperitoneum on NB behaviour.