Gut Immunobiosis and Biomodulators.

The human gastrointestinal (GI) tract hosts complex and dynamic populations of microorganisms (gut microbiota) in advantageous symbiosis with the host organism through sophisticated molecular cross-talk. The balance and diversification within microbial communities (eubiosis) are crucial for the immune and metabolic homeostasis of the host, as well as for inhibiting pathogen penetration. In contrast, compositional dysregulation of the microbiota (dysbiosis) is blamed for the determinism of numerous diseases. Although further advances in the so-called 'omics' disciplines are needed, dietary manipulation of the gut microbial ecosystem through biomodulators (prebiotics, probiotics, symbionts, and postbiotics) represents an intriguing target to stabilize and/or restore eubiosis. Recently, new approaches have been developed for the production of infant formulas supplemented with prebiotics (human milk oligosaccharides [HMOs], galacto-oligosaccharides [GOS], fructo-oligosaccharides [FOS]), probiotics, and postbiotics to obtain formulas that are nutritionally and biologically equivalent to human milk (closer to the reference).

Do Vegetarian Diets Provide Adequate Nutrient Intake during Complementary Feeding? A Systematic Review.

During the complementary feeding period, any nutritional deficiencies may negatively impact infant growth and neurodevelopment. A healthy diet containing all essential nutrients is strongly recommended by the WHO during infancy. Because vegetarian diets are becoming increasingly popular in many industrialized countries, some parents ask the pediatrician for a vegetarian diet, partially or entirely free of animal-source foods, for their children from an early age. This systematic review aims to evaluate the evidence on how vegetarian complementary feeding impacts infant growth, neurodevelopment, risk of wasted and/or stunted growth, overweight and obesity. The SR was registered with PROSPERO 2021 (CRD 42021273592). A comprehensive search strategy was adopted to search and find all relevant studies. For ethical reasons, there are no interventional studies assessing the impact of non-supplemented vegetarian/vegan diets on the physical and neurocognitive development of children, but there are numerous studies that have analyzed the effects of dietary deficiencies on individual nutrients. Based on current evidence, vegetarian and vegan diets during the complementary feeding period have not been shown to be safe, and the current best evidence suggests that the risk of critical micronutrient deficiencies or insufficiencies and growth retardation is high: they may result in significantly different outcomes in neuropsychological development and growth when compared with a healthy omnivorous diet such as the Mediterranean Diet. There are also no data documenting the protective effect of vegetarian or vegan diets against communicable diseases in children aged 6 months to 2-3 years.

Complementary Feeding Caregivers' Practices and Growth, Risk of Overweight/Obesity, and Other Non-Communicable Diseases: A Systematic Review and Meta-Analysis.

Several institutions propose responsive feeding (RF) as the caregivers' relational standard when nurturing a child, from breast/formula feeding onwards. Previous systematic reviews (SRs) on caregivers' feeding practices (CFPs) have included studies on populations from countries with different cultures, rates of malnutrition, and incomes, whereas this SR compares different CFPs only in healthy children (4-24 months) from industrialized countries. Clinical questions were about the influence of different CFPs on several important outcomes, namely growth, overweight/obesity, risk of choking, dental caries, type 2 diabetes (DM2), and hypertension. The literature review does not support any Baby Led Weaning's or Baby-Led Introduction to SolidS' (BLISS) positive influence on children's weight-length gain, nor their preventive effect on future overweight/obesity. RF-CFPs can result in adequate weight gain and a lower incidence of overweight/obesity during the first two years of life, whereas restrictive styles and coercive styles, two kinds of non-RF in CF, can have a negative effect, favoring excess weight and lower weight, respectively. Choking risk: failure to supervise a child's meals by an adult represents the most important risk factor; no cause-effect relation between BLW/BLISS/RF/NRCF and choking could be found. Risks of DM2, hypertension, and caries: different CFPs cannot be considered as a risky or preventive factor for developing these conditions later in life.

Timing of Complementary Feeding, Growth, and Risk of Non-Communicable Diseases: Systematic Review and Meta-Analysis.

No consensus currently exists on the appropriate age for the introduction of complementary feeding (CF). In this paper, a systematic review is conducted that investigates the effects of starting CF in breastfed and formula-fed infants at 4, 4-6, or 6 months of age (i) on growth at 12 months of age, (ii) on the development of overweight/obesity at 3-6 years of age, (iii) on iron status, and (iv) on the risk of developing (later in life) type 2 diabetes mellitus (DM2) and hypertension. An extensive literature search identified seven studies that evaluated the effects of the introduction of CF at the ages in question. No statistically significant differences related to the age at which CF is started were observed in breastfed or formula-fed infants in terms of the following: iron status, weight, length, and body mass index Z-scores (zBMI) at 12 months, and development of overweight/obesity at 3 years. No studies were found specifically focused on the age range for CF introduction and risk of DM2 and hypertension. Introducing CF before 6 months in healthy term-born infants living in developed countries is essentially useless, as human milk (HM) and formulas are nutritionally adequate up to 6 months of age.

Recommendations on Complementary Feeding as a Tool for Prevention of Non-Communicable Diseases (NCDs)-Paper Co-Drafted by the SIPPS, FIMP, SIDOHaD, and SINUPE Joint Working Group.

Adequate and balanced nutrition is essential to promote optimal child growth and a long and healthy life. After breastfeeding, the second step is the introduction of complementary feeding (CF), a process that typically covers the period from 6 to 24 months of age. This process is, however, still highly controversial, as it is heavily influenced by socio-cultural choices, as well as by the availability of specific local foods, by family traditions, and pediatrician beliefs. The Società Italiana di Pediatria Preventiva e Sociale (SIPPS) together with the Federazione Italiana Medici Pediatri (FIMP), the Società Italiana per lo Sviluppo e le Origine della Salute e delle Malattie (SIDOHaD), and the Società Italiana di Nutrizione Pediatrica (SINUPE) have developed evidence-based recommendations for CF, given the importance of nutrition in the first 1000 days of life in influencing even long-term health outcomes. This paper includes 38 recommendations, all of them strictly evidence-based and overall addressed to developed countries. The recommendations in question cover several topics such as the appropriate age for the introduction of CF, the most appropriate quantitative and qualitative modalities to be chosen, and the relationship between CF and the development of Non-Communicable Diseases (NCDs) later in life.

Complementary Feeding and Iron Status: "The Unbearable Lightness of Being" Infants.

The complementary feeding (CF) period that takes place between 6 and 24 months of age is of key importance for nutritional and developmental reasons during the transition from exclusively feeding on milk to family meals. In 2021, a multidisciplinary panel of experts from four Italian scientific pediatric societies elaborated a consensus document on CF, focusing in particular on healthy term infants. The aim was to provide healthcare providers with useful guidelines for clinical practice. Complementary feeding is also the time window when iron deficiency (ID) and iron deficiency anemia (IDA) are most prevalent. Thus, it is appropriate to address the problem of iron deficiency through nutritional interventions. Adequate iron intake during the first two years is critical since rapid growth in that period increases iron requirements per kilogram more than at any other developmental stage. Complementary foods should be introduced at around six months of age, taking into account infant iron status.

Prevention of recurrent respiratory infections : Inter-society Consensus.

Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs.Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs.

Anti-Inflammatory and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body.

Hosting millions of microorganisms, the digestive tract is the primary and most important part of bacterial colonization. On one side, in cases of opportunistic invasion, the abundant bacterial population inside intestinal tissues may face potential health problems such as inflammation and infections. Therefore, the immune system has evolved to sustain the host-microbiota symbiotic relationship. On the other hand, to maintain host immune homeostasis, the intestinal microflora often exerts an immunoregulatory function that cannot be ignored. A field of great interest is the association of either microbiota or probiotics with the immune system concerning clinical uses. This microbial community regulates some of the host's metabolic and physiological functions and drives early-life immune system maturation, contributing to their homeostasis throughout life. Changes in gut microbiota can occur through modification in function, composition (dysbiosis), or microbiota-host interplays. Studies on animals and humans show that probiotics can have a pivotal effect on the modulation of immune and inflammatory mechanisms; however, the precise mechanisms have not yet been well defined. Diet, age, BMI (body mass index), medications, and stress may confound the benefits of probiotic intake. In addition to host gut functions (permeability and physiology), all these agents have profound implications for the gut microbiome composition. The use of probiotics could improve the gut microbial population, increase mucus-secretion, and prevent the destruction of tight junction proteins by decreasing the number of lipopolysaccharides (LPSs). When LPS binds endothelial cells to toll-like receptors (TLR 2, 4), dendritic cells and macrophage cells are activated, and inflammatory markers are increased. Furthermore, a decrease in gut dysbiosis and intestinal leakage after probiotic therapy may minimize the development of inflammatory biomarkers and blunt unnecessary activation of the immune system. In turn, probiotics improve the differentiation of T-cells against Th2 and development of Th2 cytokines such as IL-4 and IL-10. The present narrative review explores the interactions between gut microflora/probiotics and the immune system starting from the general perspective of a biological plausibility to get to the in vitro and in vivo demonstrations of a probiotic-based approach up to the possible uses for novel therapeutic strategies.

Machine learning models predicting multidrug resistant urinary tract infections using "DsaaS".

BACKGROUND: The scope of this work is to build a Machine Learning model able to predict patients risk to contract a multidrug resistant urinary tract infection (MDR UTI) after hospitalization. To achieve this goal, we used different popular Machine Learning tools. Moreover, we integrated an easy-to-use cloud platform, called DSaaS (Data Science as a Service), well suited for hospital structures, where healthcare operators might not have specific competences in using programming languages but still, they do need to analyze data as a continuous process. Moreover, DSaaS allows the validation of data analysis models based on supervised Machine Learning regression and classification algorithms. RESULTS: We used DSaaS on a real antibiotic stewardship dataset to make predictions about antibiotic resistance in the Clinical Pathology Operative Unit of the Principe di Piemonte Hospital in Senigallia, Marche, Italy. Data related to a total of 1486 hospitalized patients with nosocomial urinary tract infection (UTI). Sex, age, age class, ward and time period, were used to predict the onset of a MDR UTI. Machine Learning methods such as Catboost, Support Vector Machine and Neural Networks were utilized to build predictive models. Among the performance evaluators, already implemented in DSaaS, we used accuracy (ACC), area under receiver operating characteristic curve (AUC-ROC), area under Precision-Recall curve (AUC-PRC), F1 score, sensitivity (SEN), specificity and Matthews correlation coefficient (MCC). Catboost exhibited the best predictive results (MCC 0.909; SEN 0.904; F1 score 0.809; AUC-PRC 0.853, AUC-ROC 0.739; ACC 0.717) with the highest value in every metric. CONCLUSIONS: the predictive model built with DSaaS may serve as a useful support tool for physicians treating hospitalized patients with a high risk to acquire MDR UTIs. We obtained these results using only five easy and fast predictors accessible for each patient hospitalization. In future, DSaaS will be enriched with more features like unsupervised Machine Learning techniques, streaming data analysis, distributed calculation and big data storage and management to allow researchers to perform a complete data analysis pipeline. The DSaaS prototype is available as a demo at the following address: https://dsaas-demo.shinyapps.io/Server/.

May Failure to Thrive in Infants Be a Clinical Marker for the Early Diagnosis of Cow's Milk Allergy?

Objectives-Failure to thrive (FTT) in infants is characterized by growth failure. Although, cow's milk allergy (CMA) may have an impact on growth and leads to FTT, data are still limited. We focused on FTT as a possible clinical marker for an early diagnosis of CMA. The aim of the present study was to evaluate the implications of cow's milk hypersensitivity in infants with FTT and the growth catch-up after a cow's milk-free diet (CMFD). Methods-A cross-sectional study of all consecutive infants evaluated at the Pediatric Nutrition and Allergy Unit of the University Hospital of Bari (Italy) from January 2016 to April 2018 with a medical-driven diagnosis of FTT. Eligible infants were investigated for possible IgE mediated or non-IgE mediated CMA. Results-43 infants were included, mean age 5.7 months. 33/43 (77%) FTT presented a CMA related disease: 3/43 (7%) were diagnosed as presenting an IgE mediated CMA, 30 (93%) had a non IgE-mediated CMA, confirmed by the elimination diet for diagnostic purposes, that led to a significant improvement of symptoms and recrudescence after milk reintroduction. A total of 29 out of 30 patients (one patient was lost at follow-up) moved up to their original growth percentile after dietary changes. Growth z-scores were computed based on WHO anthropometric data. In 10 out of 43 patients (23%) were diagnosed with gastro-esophageal reflux disease (GERD). Conclusions-when evaluating an infant with FTT, physicians should include in their evaluation an extensive search for IgE mediated and non IgE mediated CMA. When in vivo and in vitro analysis are not conclusive, a 4- to 8-weeks trial of CMFD and a consecutive re-introduction of milk proteins may be helpful in less common diagnoses.

Skin tests are important in children with ß-lactam hypersensitivity, but may be reduced in number.

BACKGROUND: There is no perfect agreement on how to perform an allergy workup in suspected beta-lactam (BL)-allergic children, since skin test (ST)-induced pain is often a limitation. The aim of the study was to assess the possibility of reducing the number of ST in children when performing a complete allergy workup for BL hypersensitivity reactions. METHODS: A retrospective analysis of all patients referring to the Allergy Unit of the University Hospital of Montpellier (France) with positive responses in immediateand non-immediate-reading ST to a BL over a 16-year period was performed, to determine the positive predictive value (PPV) of ST. All pediatric patients with a suspected BL hypersensitivity were skin-tested with the suspected drug only, during the following 54 months. RESULTS: A total of 319 patients reporting 328 BL reactions were included in the retrospective study. The PPV of ST for the reported drug was of 99.4%. Based on the results, the number of patients to include in the prospective study was estimated to be 101. In the prospective study, 229 children were included. We diagnosed a BL hypersensitivity in 12 children (5.2%): Diagnosis was reached in 6 (50.0%) through ST (delayed reading for all) and in 6 through drug provocation test (DPT). CONCLUSION: ST with BL should therefore be performed as a screening test, before DPT, and testing only the suspected drug may be sufficient when dealing with children.

Cow's Milk Consumption and Health: A Health Professional's Guide.

The most recent scientific evidence supports the consumption of cow's milk and dairy products as part of a balanced diet. However, these days, the public and practicing physicans are exposed to a stream of inconsistent (and often misleading) information regarding the relationship between cow's milk intake and health in the lay press and in the media. The purpose of this article, in this context, is to facilitate doctor-patient communication on this topic, providing physicians with a series of structured answers to frequently asked patient questions. The answers range from milk and milk-derived products' nutritional function across the life span, to their relationship with diseases such as osteoporosis and cancer, to lactose intolerance and milk allergy, and have been prepared by a panel of experts from the Italian medical and nutritional scientific community. When consumed according to appropriate national guidelines, milk and its derivatives contribute essential micro- and macronutrients to the diet, especially in infancy and childhood where bone mass growth is in a critical phase. Furthermore, preliminary evidence suggests potentially protective effects of milk against overweight, obesity, diabetes, and cardiovascular disease, while no clear data suggest a significant association between milk intake and cancer. Overall, current scientific literature suggests that an appropriate consumption of milk and its derivatives, according to available nutritional guidelines, may be beneficial across all age groups, with the exception of specific medical conditions such as lactose intolerance or milk protein allergy. Key teaching points: Milk and its derivatives contribute essential micro and macronutrients to the diet, when consumed according to appropriate national guidelines, especially in infancy and childhood where bone mass growth is in a critical phase. Preliminary evidence suggests potentially protective effects of milk against overweight, obesity, diabetes and cardiovascular disease No clear data are available about the association between milk intake and cancer. Current scientific literature suggests that an appropriate consumption of milk and its derivatives may be beneficial at all ages, with the exception of specific medical conditions such as lactose intolerance or milk protein allergy.

Probiotics in Celiac Disease.

Recently, the interest in the human microbiome and its interplay with the host has exploded and provided new insights on its role in conferring host protection and regulating host physiology, including the correct development of immunity. However, in the presence of microbial imbalance and particular genetic settings, the microbiome may contribute to the dysfunction of host metabolism and physiology, leading to pathogenesis and/or the progression of several diseases. Celiac disease (CD) is a chronic autoimmune enteropathy triggered by dietary gluten exposure in genetically predisposed individuals. Despite ascertaining that gluten is the trigger in CD, evidence has indicated that intestinal microbiota is somehow involved in the pathogenesis, progression, and clinical presentation of CD. Indeed, several studies have reported imbalances in the intestinal microbiota of patients with CD that are mainly characterized by an increased abundance of Bacteroides spp. and a decrease in Bifidobacterium spp. The evidence that some of these microbial imbalances still persist in spite of a strict gluten-free diet and that celiac patients suffering from persistent gastrointestinal symptoms have a desert gut microbiota composition further support its close link with CD. All of this evidence gives rise to the hypothesis that probiotics might play a role in this condition. In this review, we describe the recent scientific evidences linking the gut microbiota in CD, starting from the possible role of microbes in CD pathogenesis, the attempt to define a microbial signature of disease, the effect of a gluten-free diet and host genetic assets regarding microbial composition to end in the exploration of the proof of concept of probiotic use in animal models to the most recent clinical application of selected probiotic strains.

Palm oil and human health. Meeting report of NFI: Nutrition Foundation of Italy symposium.

The use of palm oil by the food industry is increasingly criticized, especially in Italy, for its purported negative effects on human health and environment. This paper summarizes the conclusions of a Symposium on this topic, gathered by the Nutrition Foundation of Italy, among experts representing a number of Italian Medical and Nutritional Scientific Societies. Toxicological and environmental issues were not considered. Participants agreed that: no evidence does exist on the specific health effects of palm oil consumption as compared to other saturated fatty acids-rich fats; the stereospecific distribution of saturated fatty acids in the triacylglycerol molecule of palm oil limits their absorption rate and metabolic effects; in agreement with International guidelines, saturated fatty acids intake should be kept <10% of total energy, within a balanced diet; within these limits, no effect of palm oil consumption on human health (and specifically on CVD or cancer risk) can be foreseen.

Ability of Lactobacillus kefiri LKF01 (DSM32079) to colonize the intestinal environment and modify the gut microbiota composition of healthy individuals.

BACKGROUND: Probiotics have been observed to positively influence the host's health, but to date few data about the ability of probiotics to modify the gut microbiota composition exist. AIMS: To evaluate the ability of Lactobacillus kefiri LKF01 DSM32079 (LKEF) to colonize the intestinal environment of healthy subjects and modify the gut microbiota composition. METHODS: Twenty Italian healthy volunteers were randomized in pre-prandial and post-prandial groups. Changes in the gut microbiota composition were detected by using a Next Generation Sequencing technology (Ion Torrent Personal Genome Machine). RESULTS: L. kefiri was recovered in the feces of all volunteers after one month of probiotic administration, while it was detected only in three subjects belonging to the pre-prandial group and in two subjects belonging to the post-prandial group one month after the end of probiotic consumption. After one month of probiotic oral intake we observed a reduction of Bilophila, Butyricicomonas, Flavonifractor, Oscillibacter and Prevotella. Interestingly, after the end of probiotic administration Bacteroides, Barnesiella, Butyricicomonas, Clostridium, Haemophilus, Oscillibacter, Salmonella, Streptococcus, Subdoligranolum, and Veillonella were significantly reduced if compared to baseline samples. CONCLUSION: L. kefiri LKF01 showed a strong ability to modulate the gut microbiota composition, leading to a significant reduction of several bacterial genera directly involved in the onset of pro-inflammatory response and gastrointestinal diseases.

Non-alcoholic fatty liver disease is associated with early left ventricular dysfunction in childhood acute lymphoblastic leukaemia survivors.

BACKGROUND: Childhood acute lymphoblastic leukaemia (ALL) survivors have an increased risk of metabolic and cardiovascular disease. We aimed to assess the presence of non-alcoholic fatty liver disease (NAFLD) in childhood ALL and if it is associated with early cardiovascular dysfunction. METHODS: In total, 53 childhood ALL survivors and 34 controls underwent auxological evaluation, biochemical assay, liver, heart and vascular ultrasound study. RESULTS: NAFLD was more frequent in ALL patients than in controls (39.6% vs 11.7%, P < 0.01). Patients with NAFLD were more obese and insulin resistant than patients without NAFLD. Flow-mediated dilatation and interventricular septum were lower in the ALL group than those in the control group (P < 0.001 for both). The patients with NAFLD showed lower left ventricular ejection fraction than those without NAFLD (P = 0.011). In ALL survivors, BMI-SDS and subcutaneous fat were the strongest predictors of NAFLD, whereas preperitoneal adipose tissue and C-reactive protein were the strongest predictors of left ventricular ejection fraction. CONCLUSIONS: Childhood ALL survivors had higher prevalence of NAFLD than healthy controls, which is associated with early left ventricular impairment. In the case of fatty liver, a comprehensive heart evaluation is mandatory. We strongly recommend to prevent visceral adiposity in ALL survivors, to search for metabolic syndrome or its components and to reinforce the need of intervention on diet and lifestyle during the follow-up of these patients.

Serum salicylic acid and fruit and vegetable consumption in obese and normal-weight children: a pilot-study.

Salicylic acid (SA), a phenolic compound produced by plants, may play a beneficial role on health. This pilot study evaluated whether there might be an association between serum SA and fruit and vegetable (FV) consumption in obese and normal-weight children. Thirty-four obese children (17 boys and 17 girls) and 34 normal-weight children were recruited. Dietary intake was evaluated by the 7-day dietary record. Serum SA was measured using gas chromatography-mass spectrometry method. FV intake in obese and normal-weight children was not different between groups (175.00 (97.66) g versus 192.29 (90.54) g, p = .455). Obese children had lower serum SA than normal-weight children [mean difference, -0.025; 95% CI (-0.044; -0.006) µmol/L]. Serum SA was not associated with daily intake of FV in obese (p = .111) and normal-weight (p = .092) children. Further studies are needed to evaluate the role of FV on serum SA, taking into account also the quantity and the type.

Prevention of food and airway allergy: consensus of the Italian Society of Preventive and Social Paediatrics, the Italian Society of Paediatric Allergy and Immunology, and Italian Society of Pediatrics.

BACKGROUND: Allergic sensitization in children and allergic diseases arising therefrom are increasing for decades. Several interventions, functional foods, pro- and prebiotics, vitamins are proposed for the prevention of allergies and they can't be uncritically adopted. OBJECTIVE: This Consensus document was developed by the Italian Society of Preventive and Social Paediatrics and the Italian Society of Paediatric Allergy and Immunology. The aim is to provide updated recommendations regarding allergy prevention in children. METHODS: The document has been issued by a multidisciplinary expert panel and it is intended to be mainly directed to primary care paediatricians. It includes 19 questions which have been preliminarily considered relevant by the panel. Relatively to each question, a literature search has been performed, according to the Italian National Guideline Program. Methodology, and a brief summary of the available literature data, has been provided. Many topics have been analyzed including the role of mother's diet restriction, use of breast/formula/hydrolyzed milk; timing of introduction of complementary foods, role (if any) of probiotics, prebiotics, vitamins, exposure to dust mites, animals and to tobacco smoke. RESULTS: Some preventive interventions have a strong level of recommendation. (e.g., the dehumidifier to reduce exposure to mite allergens). With regard to other types of intervention, such as the use of partially and extensively hydrolyzed formulas, the document underlines the lack of evidence of effectiveness. No preventive effect of dietary supplementation with polyunsaturated fatty acids, vitamins or minerals has been demonstrated. There is no preventive effect of probiotics on asthma, rhinitis and allergic diseases. It has demonstrated a modest effect, but steady, in the prevention of atopic dermatitis. CONCLUSIONS: The recommendations of the Consensus are based on a careful analysis of the evidence available. The lack of evidence of efficacy does not necessarily imply that some interventions may not be effective, but currently they can't be recommended.

Pharmacological interventions on early functional gastrointestinal disorders.

BACKGROUND: Functional gastrointestinal disorders (FGIDs) are chronic or recurrent gastrointestinal symptoms without structural or biochemical abnormalities. FGIDs are multifactorial conditions with different pathophysiologic mechanisms including altered motility, visceral hyperalgesia, brain-gut disturbance, genetic, environmental and psychological factors. Although in most cases gastrointestinal symptoms are transient and with spontaneous resolution in infancy multiple dietary changes and pharmacological therapy are often started despite a lack of evidence-based data. Our aim was to update and critically review the current literature to assess the effects and the clinical appropriateness of drug treatment in early (occurring in infants and toddlers) FGIDs. METHODS: We systematically searched the Medline and GIMBE (Italian Group on Medicine Based on Evidence) databases, according to the methodology of the Critically Appraised Topics (CATs). We included reviews, clinical studies, and evidence-based guidelines reporting on pharmacological treatments. Systematic reviews and randomized controlled trials (RCTs) concerning pharmacologic therapies in children with early FGIDs were included, and data were extracted on participants, interventions, and outcomes. RESULTS: We found no evidence-based guidelines or systematic reviews about the utility of pharmacological therapy in functional regurgitation, infant colic and functional diarrhea. In case of regurgitation associated with marked distress, some evidences support a short trial with alginate when other non pharmacological approach failed (stepped-care approach). In constipated infants younger than 6 months of age Lactulose is recommended, whilst in older ages Polyethylene glycol (PEG) represents the first-line therapy both for fecal disimpaction and maintenance therapy of constipation. Conversely, no evidence supports the use of laxatives for dyschezia. Furthermore, we found no RCTs regarding the pharmacological treatment of cyclic vomiting syndrome, but retrospective studies showed a high percentage of clinical response using cyproheptadine, propanolol and pizotifen. CONCLUSION: There is some evidence that a pharmacological intervention is necessary for rectal disimpaction in childhood constipation and that PEG is the first line therapy. In contrast, for the other early FGIDs there is a lack of well-designed high-quality RCTs and no evidence on the use of pharmacological therapy was found.

Change in Metabolic Profile after 1-Year Nutritional-Behavioral Intervention in Obese Children.

Research findings are inconsistent about improvement of specific cardio-metabolic variables after lifestyle intervention in obese children. The aim of this trial was to evaluate the effect of a 1-year intervention, based on normocaloric diet and physical activity, on body mass index (BMI), blood lipid profile, glucose metabolism and metabolic syndrome. Eighty-five obese children aged ≥6 years were analyzed. The BMI z-score was calculated. Fasting blood samples were analyzed for lipids, insulin and glucose. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated and insulin resistance was defined as HOMA-IR >3.16. HOMA-ß%, quantitative insulin sensitivity check index and triglyceride glucose index were calculated. The metabolic syndrome was defined in accordance with the International Diabetes Federation criteria. At the end of intervention children showed a reduction (mean (95% CI)) in BMI z-score (-0.58 (-0.66; -0.50)), triglycerides (-0.35 (-0.45; -0.25) mmol/L) and triglyceride glucose index (-0.29 (-0.37; -0.21)), and an increase in HDL cholesterol (0.06 (0.01; 0.11) mmol/L). Prevalence of insulin resistance declined from 51.8% to 36.5% and prevalence of metabolic syndrome from 17.1% to 4.9%. Nutritional-behavioral interventions can improve the blood lipid profile and insulin sensitivity in obese children, and possibly provide benefits in terms of metabolic syndrome.