Immunophenotype Anomalies Predict the Development of Autoimmune Cytopenia in 22q11.2 Deletion Syndrome.

BACKGROUND: Patients with 22q11.2 deletion syndrome (22q11.2DS) may develop severe thrombocytopenic purpura and hemolytic anemia. There are no reliable predictors for the development of hematologic autoimmunity (HA) in these patients. OBJECTIVE: To describe the peculiar B and T subpopulation defects in patients with 22q11DS who have developed HA and test if these defects precede the development of HA. METHODS: We performed a case-control multicenter study. Patients with HA were compared with a control population of 22q11.2DS without HA (non-HA). A complete immunological evaluation was performed at diagnosis and at the last follow-up including extensive T and B phenotypes. RESULTS: Immunophenotype at the last follow-up was available in 23 HA and 45 non-HA patients. HA patients had significantly decreased percentage of naïve CD4+ cells (26.8% vs 43.2%, P = .003) and recent thymic emigrants (48.6% vs 80.5%, P = .046); decreased class-switched B cells (2.0% vs 5.9%, P = .04) and increased naive B cells (83.5% vs 71.4%, P = .02); increased CD16+/56+ both in absolute number (312 vs 199, P = .009) and percentage (20.0% vs 13.0%, P = .03). Immunophenotype was performed in 36 patients (11 HA and 25 non-HA) at diagnosis. Odds ratio (OR) of immune cytopenia were estimated for both CD4 naïve ≤30% (OR 14.0, P = .002) and switched memory B cells ≤2% (OR 44.0, P = .01). The estimated survival curves reached statistical significance, respectively, P = .0001 and P = .002. CONCLUSIONS: Among patients with 22q11.2DS, those with HA have characteristic lymphocyte anomalies that appear considerably before HA onset. Systematic immunophenotyping of patients with 22q11.2DS at diagnosis is advisable for early identification of patients at risk for this severe complication.

Epidemiologic Impact of the New Guidelines for the Diagnosis of Acute Rheumatic Fever.

OBJECTIVES: To estimate the incidence of acute rheumatic fever (ARF) in a metropolitan area of Northern Italy and study how the introduction of the 2015 revised Jones criteria affects the epidemiology in a region with moderate to high incidence of ARF. STUDY DESIGN: The incidence of ARF in children 5-14 years old living in the Province of Turin was estimated using low-risk criteria in a 10-year period (group A patients). The proportion of patients fulfilling only high-risk (HR) criteria (group B patients) was also calculated both prospectively (from July 2015 through December 2016) and retrospectively (from January 2007 through June 2015). RESULTS: One hundred thirty-five group A patients were identified for an annual incidence of 3.2-9.6 out of 100 000 children. The use of HR criteria identified an additional 28 patients (group B), resulting in a 20.7% increase in the incidence of ARF. Age, sex annual incidence, and seasonal distribution pattern were comparable between group A and group B patients. CONCLUSIONS: HR criteria should be used for the diagnosis ARF in our region. The application of these criteria led to a 20% increase in patients with the diagnosis of ARF. The characteristics of patients fulfilling only HR criteria are similar to the remaining patients, suggesting that these criteria are sensitive and specific.

High-normal estimated glomerular filtration rate and hyperuricemia positively correlate with metabolic impairment in pediatric obese patients.

BACKGROUND: Childhood obesity represents a major health concern worldwide due to its well established detrimental effect on cardiovascular and its potential negative effect on kidney functions. However, biomarkers that can help diagnose early stages of kidney damage in obese children represent an unmet clinical need. OBJECTIVES: In this study, we asked whether the prevalence of microalbuminuria, estimated glomerular filtration rate (eGFR) or hyperuricemia recorded in a wide cohort of obese children and adolescents would positively correlate with cardiometabolic dysfunction in these subjects. METHODS: We carried out a cross-sectional study on 360 obese children and adolescents between the ages of 3-18 years, enrolled in a tertiary care center. Clinical and biochemical evaluations including oral glucose tolerance tests (OGTTs) were performed on all patients. Microalbuminuria was defined as urinary albumin-to-creatinine ratio (u-ACR) of 30-300 mg/g. All data are expressed as mean ± standard deviation (SD), absolute values or percentages. Sex age-specific and eGFR SDs were used for statistical analyses. Serum uric acid ≥ 5.5 mg/dL was considered abnormal. RESULTS: The prevalence of microalbuminuria was 6.4%. Except for a lower insulinogenic-index, no correlations between microalbuminuria and cardiometabolic risk factors were detected. eGFR was < -1 SD and > 1 SD in 1.4% and 60.8% of subjects, respectively. Subjects with an eGFR > 1 SD had higher systolic blood pressure, liver enzymes, insulin resistance, glucose and insulin during OGTT, lower insulin sensitivity and a more prevalent microalbuminuria. Hyperuricemia (27.5%) increased the odds of hypertension, HDL ≤ 10th percentile and glucose ≥ 155.0 mg/dL after 60 minutes of OGTT. CONCLUSIONS: A worse cardiometabolic profile was observed in subjects with an eGFR > 1 SD compared to other subgroups. Therefore, pediatric obese patients with eGFR > 1 SD or hyperuricemia should be closely monitored for microalbuminuria and post-challenge glucose and insulin secretion, all potential indicators of renal dysfunction in these young patients.

The Association of Bifidobacterium breve BR03 and B632 is Effective to Prevent Colics in Bottle-fed Infants: A Pilot, Controlled, Randomized, and Double-Blind Study.

GOALS: To assess the effectiveness of Bifidobacterium breve B632 and BR03 association in the reduction of infants crying over time. The second endpoint was to observe the effect of the same strains on daily evacuations and on the number of regurgitations and vomits. BACKGROUND: Infant colics represent a clinical condition in childhood, characterized by an uncontrollable crying that occurs without any apparent organic cause. An altered intestinal microbiota composition in the very first months may induce intestinal colics in infants. Thus far, no treatment is really effective for this problem, but recent literature shows an increasing attention toward probiotics. STUDY: A total of 83 subjects were enrolled, 60 breastfed infants and 23 bottle-fed infants. Sixty of them carried out the study: 29 infants were given probiotics, whereas 31 placebo. During the 90 days of the study, parents were asked to give 5 drops of active product (10 viable cells/strain) or placebo and to daily take note of: minutes of crying, number, color, and consistency of evacuations, and number of regurgitations or vomits. RESULTS: No significant differences were detected in the infants treated with probiotics, compared with placebo group (P=0.75). The analysis of the 3 months of treatment demonstrated that during the third month, the probiotic group cried 12.14 minutes on average and the placebo cried 46.65 minutes. This difference is statistically significant (P=0.016). CONCLUSIONS: The evidence of the usefulness of some probiotic strains in the treatment and prevention of infant colics is growing, and therefore their use in clinical practice is spreading.

Influence of Ultraviolet Radiation on the Association between 25-Hydroxy Vitamin D Levels and Cardiovascular Risk Factors in Obesity.

OBJECTIVE: To establish if the correction with estimates of ultraviolet (UV) exposure influences the association between 25-OH-vitamin D (25OHD) levels and metabolic variables. STUDY DESIGN: A cross-sectional study was performed in 575 obese children and adolescents (>6 years of age) in a tertiary referral center. Cardiovascular risk factors were measured. The estimate of UV exposure was evaluated by 3 methods: (1) season; (2) mean of UV radiation (UVR); and (3) mean of UV index (UVI). UVR and UVI were considered at 1 (UVR 1 month prior to testing [UVR1], UVI 1 month prior to testing [UVI1]) or 3 (UVR 3 months prior to testing [UVR3], UVI 3 months prior to testing [UVI3]) months prior to testing. All analyses were corrected for confounders (sex, age, puberty, body mass index, waist circumference, the inclusion and exclusion of estimates of UV exposure). RESULTS: The 25OHD levels were associated with seasons, UVR1, UVR3, UVI1, and UVI3, and best associations with UVR3 and UVI3. In all models, total cholesterol, low-density lipoprotein cholesterol and triglycerides were negatively associated with 25OHD levels. The strength of the association increased with no correction, correction for seasons, UVR, and UVI. UVR3 and UVI3 performed better than UVR1 and UVI3. CONCLUSIONS: Higher lipid concentrations were associated with low 25OHD levels in obese children and adolescents with the power of the association dependent on the estimates of UVR. As the mean values 3 months prior to testing for both UVR and UVI determined the best associations, the interval of the steady state time of 25OHD levels could be preferentially used in the metabolic studies. Controlling for an estimate of UVR is important to decrease the heterogeneity of studies.

Systematic review of ghrelin response to food intake in pediatric age, from neonates to adolescents.

OBJECTIVE: Food intake and energy balance are regulated during the lifespan with critical changes in each specific period (infancy, adulthood, aging). Some of ghrelin's changes may contribute to the regulation of food intake and weight in children. We aimed to analyze the ghrelin response to feeding in lean or obese subjects from birth to adolescence. METHODS: We searched PubMed, Scopus, Google Scholar, Cochrane, and EMBASE (December 1999 to February 2013) and identified 62 relevant articles, of which 29 were suitable to be included. RESULTS AND CONCLUSIONS: Total ghrelin response to meals is particular, with refractoriness in neonates and lean children and an inhibition that starts from puberty. Total ghrelin levels are decreased after meals, irrespective of pubertal stages in obese children and adolescents. Conversely, total ghrelin is decreased after an oral glucose tolerance test in all ages, with the exception of neonates. Data on unacylated ghrelin response are scant but resemble those of total ghrelin. The acylated ghrelin response to meals or oral glucose tolerance test is discordant, although a precocious inhibition followed by a rise back is present in both lean and obese children. The post-feeding profile in children with Prader-Willi syndrome is also peculiar, with a conserved and deeper inhibition of all ghrelin forms.

Obesity and infection: two sides of one coin.

The prevalence of obesity has exponentially risen worldwide. The etiology of obesity is multifactorial, and genetic inheritance and behavioral/environmental causes are considered the main etiological factors. Moreover, evidence that specific infections might promote the development of obesity has steadily accumulated. Only a few works investigate the impact of obesity on the immune response to infections and the risk of infections in the obese population. The aim of this paper was to review the available data regarding the various aspects of the association between obesity and infections and to highlight the possibility that infectious agents may have an etiological role in obesity, an idea known as "infectobesity". Several microbes have been considered as possible promoter of obesity, but most of the data concern adenovirus-36 that exerts an adipogenic action mainly via a direct effect on adipose tissue leading to weight gain, at least in animal models.Obesity affects the immune response leading to an increased susceptibility to infections. Obese adults and children show an increased incidence of both nosocomial and community-acquired infections. Furthermore, obesity may alter the pharmacokinetics of antimicrobial drugs and impact on vaccine response. However, the various aspects of the association of obesity infections remain poorly studied, and a call to research is necessary to better investigate the problem.In conclusion, obesity impacts millions globally, and greater understanding of its etiology and its effects on immunity, infections, and prevention and management strategies is a key public health concern.