Tolerance to a new free amino acid-based formula in children with IgE or non-IgE-mediated cow's milk allergy: a randomized controlled clinical trial.

BACKGROUND: Amino acid-based formulas (Aaf) are increasingly used in children with cow's milk allergy (CMA). To be labeled hypoallergenic these formulas must demonstrate in clinical studies that they don't provoke reactions in 90% of subjects with confirmed CMA with 95% confidence when given in prospective randomized, double-blind, placebo-controlled challenge (DBPCFC) trials. The majority of available safety data on Aaf derived from patients with IgE-mediated CMA. Considering substantial differences in the immunologic mechanism and clinical presentation of non-IgE-mediated CMA it's important to investigate the hypoallergenicity of these formulas also in these patients. We prospectively assessed the tolerance to a new commercially available Aaf in children affected by IgE- or non-IgE-mediated CMA. METHODS:Consecutive patients affected by IgE- or non-IgE-mediated CMA, aged ≤ 4 years, were enrolled. DBPCFC was carried out with increasing doses of the new Aaf (Sineall, Humana, Milan, Italy), using validated Aaf as placebo. Faecal concentrations of calprotectin (FC) and eosinophilic cationic protein (ECP) were monitored. RESULTS:Sixty patients (44 male, 73.3%, median age 37, 95%CI 34.5-39.6 months, IgE-mediated CMA 29, 48.3%) were enrolled. At the diagnosis clinical symptoms were gastrointestinal (46.6%), cutaneous (36.6%), respiratory (23.3%), and systemic (10.0%). After DBPCFC with the new Aaf, no patient presented early or delayed clinical reactions. Faecal concentration of calprotectin and of ECP remained stable after the exposure to the new Aaf. CONCLUSIONS:The new Aaf is well tolerated in children with IgE- or non-IgE-mediated CMA, and it could be used as a safe dietotherapy regimen for children with this condition. TRIAL REGISTRATION:The trial was registered in the ClinicalTrials.gov Protocol Registration System (ID number: NCT01622426)

Tolerance to a new free amino acid-based formula in children with IgE or non-IgE-mediated cow's milk allergy: a randomized controlled clinical trial.

BACKGROUND: Amino acid-based formulas (Aaf) are increasingly used in children with cow's milk allergy (CMA). To be labeled hypoallergenic these formulas must demonstrate in clinical studies that they don't provoke reactions in 90% of subjects with confirmed CMA with 95% confidence when given in prospective randomized, double-blind, placebo-controlled challenge (DBPCFC) trials. The majority of available safety data on Aaf derived from patients with IgE-mediated CMA. Considering substantial differences in the immunologic mechanism and clinical presentation of non-IgE-mediated CMA it's important to investigate the hypoallergenicity of these formulas also in these patients. We prospectively assessed the tolerance to a new commercially available Aaf in children affected by IgE- or non-IgE-mediated CMA. METHODS:Consecutive patients affected by IgE- or non-IgE-mediated CMA, aged ≤ 4 years, were enrolled. DBPCFC was carried out with increasing doses of the new Aaf (Sineall, Humana, Milan, Italy), using validated Aaf as placebo. Faecal concentrations of calprotectin (FC) and eosinophilic cationic protein (ECP) were monitored. RESULTS:Sixty patients (44 male, 73.3%, median age 37, 95%CI 34.5-39.6 months, IgE-mediated CMA 29, 48.3%) were enrolled. At the diagnosis clinical symptoms were gastrointestinal (46.6%), cutaneous (36.6%), respiratory (23.3%), and systemic (10.0%). After DBPCFC with the new Aaf, no patient presented early or delayed clinical reactions. Faecal concentration of calprotectin and of ECP remained stable after the exposure to the new Aaf. CONCLUSIONS:The new Aaf is well tolerated in children with IgE- or non-IgE-mediated CMA, and it could be used as a safe dietotherapy regimen for children with this condition. TRIAL REGISTRATION:The trial was registered in the ClinicalTrials.gov Protocol Registration System (ID number: NCT01622426)

Randomised clinical trial: efficacy of a new synbiotic formulation containing Lactobacillus paracasei B21060 plus arabinogalactan and xilooligosaccharides in children with acute diarrhoea.

BACKGROUND: Acute diarrhoea is a frequent problem in children with heavy economic burden for families and society. AIM: To test the efficacy of a new synbiotic formulation containing Lactobacillus paracasei B21060, arabinogalactan and xilooligosaccharides in children with acute diarrhoea. METHODS: Double-blind, randomised, placebo-controlled trial, including children (age 3-36 m) with acute diarrhoea who were allocated to placebo or synbiotic group. Major outcome was resolution rate of diarrhoea at 72 h. Total duration of diarrhoea, daily stool outputs, stool consistency, working days lost by parents, adjunctive medications, and hospitalisation were also assessed. RESULTS: We enrolled 55 children in placebo group and 52 in synbiotic group. The two groups were similar for demographic and clinical characteristics. Resolution rate of diarrhoea at 72 h was significantly higher in synbiotic group (67%) compared to placebo group (40%, P = 0.005). Children in synbiotic group showed a significant reduction in the duration of diarrhoea (90.5 h, 78.1-102.9 vs. 109.8 h, 96.0-123.5, P = 0.040), daily stool outputs (3.3, 2.8-3.8 vs. 2.4, 1.9-2.8, P = 0.005) and stool consistency (1.3, 0.9-1.6 vs. 0.6, 0.4-0.9, P = 0.002) compared to placebo group (data expressed as mean, 95% CI). Rate of parents that missed at least one working day (41.8% vs. 15.4%, P = 0.003), rate of children that needed adjunctive medications (25.5% vs. 5.8%, P = 0.005) or hospitalisation (10.9% vs. 0%, P = 0.014) after the first 72 h of treatment, were reduced in synbiotic group. CONCLUSION: The synbiotic formulation studied is effective in children with acute diarrhoea. Australian New Zealand Clinical Trials Registry (ACTRN12611000641998)

Migraine and cluster headache show impaired neurosteroids patterns

Background: Perturbation of neuronal excitability contributes to migraine. Neurosteroids modulate the activity of γ-aminobutyric acid A and N-methyl-d-aspartate receptors, and might be involved in the pathogenesis of migraine. Here, we measured plasma levels of four neurosteroids, i.e., allopregnanolone, epiallopregnanolone, dehydroepiandrosterone and deydroepiandrosterone sulfate, in patients affected by episodic migraine, chronic migraine, or cluster headache. Methods: Nineteen female patients affected by episodic migraine, 51 female patients affected by chronic migraine, and 18 male patients affected by cluster headache were recruited to the study. Sex- and age-matched healthy control subjects (31 females and 16 males) were also recruited. Patients were clinically characterized by using validated questionnaires. Plasma neurosteroid levels were measured by liquid chromatography-tandem mass spectrometry. Results: We found disease-specific changes in neurosteroid levels in our study groups. For example, allopregnanolone levels were significantly increased in episodic migraine and chronic migraine patients than in control subjects, whereas they were reduced in patients affected by cluster headache. Dehydroepiandrosterone and dehydroepiandrosterone sulfate levels were reduced in patients affected by chronic migraine, but did not change in patients affected by cluster headache. Conclusion: We have shown for the first time that large and disease-specific changes in circulating neurosteroid levels are associated with chronic headache disorders, raising the interesting possibility that fluctuations of neurosteroids at their site of action might shape the natural course of migraine and cluster headache. Whether the observed changes in neurosteroids are genetically determined or rather result from exposure to environmental or intrinsic stressors is unknown. This might also be matter for further investigation because stress is a known triggering factor for headache attacks in both migraineurs and cluster headache patients

Harnessing the power of biologic agents on the oral microbiota: a way to promote oral and systemic health?

During the long history of their evolution, higher organisms, including mammals, have learnt to take great advantage from living in close contact with selected populations of microbes.1 By living in close contact, animals and microbes underwent a progressive and mutual co-evolutive process that is believed to be a major driving force in the development of adaptive immunity of vertebrates.2 As a result of this co-evolutive process, humans and other animals are characterized by their own unique microbiomes, each consisting of many hundred species of viruses, bacteria, archaea, fungi, and protozoa, unevenly distributed to colonize the different accessible regions of the body.3 The human microbiome is believed to account for 1-3% of body weight and to comprise more than 100 trillion cells.4 The microbiota is involved in complex host-microbe and microbe-microbe interactions, thus modulating nutrient acquisition, adjusting immune system development and general homeostasis (via epigenetic modifications of host genes5), and playing the role of protective barrier to pathogens.4 When a microbiota undergoes qualitative and quantitative changes with regard to distribution in a site and metabolic activity, this condition is defined dysbiosis and is expected to be associated with local and/ or distant pathologic signs.6 Bacterial products released by a dysbiotic microbiota interact with homeostatic mechanisms of the human host and cooperate to the pathogenesis of major human diseases, including diabetes mellitus, inflammatory bowel syndrome, atherosclerosis, obesity, liver disease, and cancer.4,7 he oral microbiota is the second more abundant and one of the most diverse and unique microbial communities in the human body.8 Although many of the most relevant oral and dental diseases, including caries, periodontal and peri-implant diseases, have been long recognized as of microbial origin, only recently the application of culture independent molecular methods using 16S rRNA gene comparative analyzes enabled us to understand that they are caused by dysbiosis rather than by the action of specific pathogens.9-11 The effects of oral dysbiosis are not limited to oral tissues: periodontal diseases, for example, are among the most common human diseases and their associations with diabetes, cardiovascular disease, metabolic disease and obesity, rheumatoid arthritis, certain cancers, respiratory diseases, and cognitive disorders is now supported by increasing evidence.12 Recent molecular investigations showed that some potentially pathogenic oral bacteria (named pathobionts), as for example Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Fusobacterium nucleatum, colonize in low numbers the oral cavity of healthy individuals, without alerting sentinel systems of mucosal defences.13,14 Conditions able to disrupt the eubiotic equilibrium promote the overgrowth of pathobionts, which suddenly become pathogens (with support from commensal

The effects of dietary counseling on children with food allergy: a prospective, multicenter intervention study.

Although dietary counseling is generally recommended in children with food allergy (FA), its effect on the nutritional status of these patients has not yet been evaluated. Our nonrandomized multicenter prospective intervention study was undertaken to investigate the effects of dietary counseling on children with FA. Anthropometric data, dietary intakes, and laboratory biomarkers of nutritional status were evaluated in children with FA (aged 6 to 36 months) before and after dietary counseling, by multidisciplinary teams composed of pediatricians, dietitians, and nurses. Ninety-one children with FA (49 boys and 42 girls; mean age 18.9 months, 95% CI 16.5 to 21.3) were evaluated; 66 children without FA (41 boys and 25 girls; mean age 20.3 months, 95% CI 17.7 to 22.8) served as controls providing baseline values only. At enrollment, energy and protein intakes were lower in children with FA (91 kcal/kg/day, interquartile range [IQR]=15.1, minimum=55.2, maximum=130.6; and 2.2 g/kg/day, IQR=0.5, minimum=1.5, maximum=2.7, respectively) than in children without FA (96 kcal/kg/day, IQR=6.1, minimum=83.6, maximum=118.0; and 4.6 g/kg/day, IQR=1.2, minimum=2.0, maximum=6.1, respectively; P<0.001). A weight to length ratio <2 standard deviations was more frequent in children with FA than in children without FA (21% vs 3%; P<0.001). At 6 months following dietary counseling, the total energy intake of children with FA was similar to the baseline values of control children. Dietary counseling also resulted in a significant improvement of their anthropometric and laboratory biomarkers of nutritional status. The results of our study support the crucial role of dietary counseling in the clinical management of children with FA

The effects of dietary counseling on children with food allergy: a prospective, multicenter intervention study.

Although dietary counseling is generally recommended in children with food allergy (FA), its effect on the nutritional status of these patients has not yet been evaluated. Our nonrandomized multicenter prospective intervention study was undertaken to investigate the effects of dietary counseling on children with FA. Anthropometric data, dietary intakes, and laboratory biomarkers of nutritional status were evaluated in children with FA (aged 6 to 36 months) before and after dietary counseling, by multidisciplinary teams composed of pediatricians, dietitians, and nurses. Ninety-one children with FA (49 boys and 42 girls; mean age 18.9 months, 95% CI 16.5 to 21.3) were evaluated; 66 children without FA (41 boys and 25 girls; mean age 20.3 months, 95% CI 17.7 to 22.8) served as controls providing baseline values only. At enrollment, energy and protein intakes were lower in children with FA (91 kcal/kg/day, interquartile range [IQR]=15.1, minimum=55.2, maximum=130.6; and 2.2 g/kg/day, IQR=0.5, minimum=1.5, maximum=2.7, respectively) than in children without FA (96 kcal/kg/day, IQR=6.1, minimum=83.6, maximum=118.0; and 4.6 g/kg/day, IQR=1.2, minimum=2.0, maximum=6.1, respectively; P<0.001). A weight to length ratio <2 standard deviations was more frequent in children with FA than in children without FA (21% vs 3%; P<0.001). At 6 months following dietary counseling, the total energy intake of children with FA was similar to the baseline values of control children. Dietary counseling also resulted in a significant improvement of their anthropometric and laboratory biomarkers of nutritional status. The results of our study support the crucial role of dietary counseling in the clinical management of children with FA

Anthropometric comparison between young Estonian and Chinese swimmers

Due to the progressive lowering of the age of peak performance among swimmers, it became important to better understand the factors influencing performance in prepuberal boys and girls. Aim of this study is to compare two different racial/ethnic groups of young swimmers, one from Nord-Europe, Estonia (Tartuma Region), and the other from China (Shanghai District) in order to assess existing differences in respect to body dimension, body fat, technical parameters of swimming performance and maximum lactate production. 26 Estonian and 7 Chinese female and 25 Estonian and 10 Chinese male, from two swimming schools, took part in the study. Anthropometric parameters were measured in accord with ISAK guidelines. BMI, Stroke Index, Stroke Length, mean velocity on a 200 m freestyle all out, and blood lactate after three minutes were measured. Significant differences exist in anthropometry between Nord-European and Asian young swimmers. These differences are more pronounced in female, with higher fat tissue in Nordic girls. Leg lengths are different between Chinese and Estonian girls having the Estonian longer legs. Hands lengths are different both in male and in female subjects. Being the Chinese groups of higher level of performance (higher mean velocity in the 200 m freestyle, such differences seems not to be as major determinants of the performance, also if they are often indicated as determinants of buoyancy and stroke efficiency

Cardiovascular events and treatment of children with high risk medulloblastoma

Background: Children with high-risk medulloblastoma are treated with chemotherapeutic protocols which may affect heart function. We aimed to assesscardiovascular events (CVE) in children with medulloblastoma/primitive neuroectodermal tumors (PNET). Methods: We retrospectively collected data from a case series of 22 children with high-risk medulloblastoma/PNET admitted to the Santobono-Pausilipon Hospital, Naples, Italy from 2008 to 2016. All patients received the Milan HART protocol for high-risk brain malignancies as first line treatment (induction phase), followed by a consolidation phase with Thiotepa and hematopoietic stem cells transplantation, except for 1 patient who received the Milan HART as second line therapy. Four patients also received second line treatment, while 4 patients also received maintenance therapy. Patients underwent cardiac examination, including ECG, echocardiography and serum biomarkers, before antineoplastic treatment initiation and then when clinically needed. Six patients developed CVE (CVE group); 16 patients had no CVE (NO-CVE group). Findings: In the CVE group, 3 patients presented acute CVE during chemotherapy (2 patients with left ventricular (LV) dysfunction, 1 patient with arterial hypertension), while 3 patients presented chronic CVE after chemotherapy completion (2 patients with LV dysfunction, 1 patient with ectopic atrial tachycardia). After a 51 months median follow-up, 9 patients died: 4 from the CVE group (in 2 cases heart failure-related deaths) and 5 from the NO-CVE group (progression of disease). Interpretation: A relevant percentage of children treated for medulloblastoma/PNET develops CVE. Heart failure potentially due to chemotherapy may represent a cause of death. Hence, in these patients, strict cardiac surveillance is essential. Funding: No funding was associated with this study