Fitness Levels and Gender Are Related With the Response of Plasma Adipokines and Inflammatory Cytokines in Prepubertal Children.

Background and Aim: Changes in adipokines have been related with the development of metabolic syndrome, frequently associated with obesity, and other risk factors. Fitness seems to promote a healthy cardiovascular status and could be a protector factor, just from childhood. Therefore, the present study aimed to evaluate the relationship between fitness levels with plasma adipokines and inflammatory biomarkers in prepubertal children. Methods: One hundred and thirty-seven healthy normal-weight prepubertal children were recruited from local schools and divided after performing the fitness tests, into two groups according to fitness level-low cardiovascular fitness group (LF) and equal or higher cardiovascular fitness group (HF). Anthropometric variables, blood pressure (BP) and plasma insulin, and leptin, resistin, adiponectin, tumor necrosis factor-alpha, hepatic growth factor, interleukin (IL)-8, monocyte chemoattractant protein-1, nerve growth factor (NGF), and plasminogen activator inhibitor-1 (PAI-1) were measured fasting in both groups to be compared. Univariate analysis of variance, comparative analysis, binary logistic regression, stepwise linear regression, and principal component analysis were conducted to evaluate the association between fitness, BMI, gender, and the biochemical parameters. Results: Girls and boys with HF presented lower waist circumference Z-score, BMI Z-score, systolic BP (only boys) as well as lower levels of leptin and NGF compared with their respective LF group. Regarding the association between variables, fitness showed an inverse relationship with BMI Z-score, leptin, PAI-1, HOMA-IR, resistin, IL-8, and NGF. Conclusion: An adequate level of fitness seems to protect against risk factors related to low-grade inflammation and altered adipokines that are related to the onset of obesity just from the prepubertal stage.

Docosahexaenoic and Eicosapentaenoic Intervention Modifies Plasma and Erythrocyte Omega-3 Fatty Acid Profiles But Not the Clinical Course of Children With Autism Spectrum Disorder: A Randomized Control Trial.

Background: The pathogenesis of autism spectrum disorder (ASD) is under investigation and one of the main alterations relates to the metabolic and inflammatory system dysfunctions. Indeed, based on a possible deficit of omega-3 fatty acids (FAs) of patients with ASD and looking for an anti-inflammatory effect, dietary supplements with omega-3 fatty acids have been proposed. We aimed to evaluate differences in plasma and erythrocyte FA profiles and plasma cytokines in patients with infantile ASD after supplementation with docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids or placebo and both compared at baseline with a reference healthy group. Methods: A double-blind, randomized placebo-controlled intervention with DHA/EPA for 6 months was carried out in 54 children between 2 and 6 years diagnosed with ASD. They were selected and randomly assigned into two groups: 19 children received 800 mg/day of DHA and 25 mg/day of EPA, or placebo. In addition, another reference group of 59 healthy children of the same age was included. Plasma lipids and cytokines, and FA profiles in plasma and erythrocytes were measured at baseline and after 6 months of treatment in ASD children, and at baseline in the reference group. Results: There were no differences in demographic, anthropometric characteristics, and omega-3 intake between the healthy reference group and the ASD children at baseline. Children with ASD showed the higher plasma percentages of palmitic acid and total saturated FA and lower total omega-6 polyunsaturated FA (PUFA) compared with healthy children. An increased level of DHA and reduced EPA level in erythrocytes were detected in the ASD group vs. the reference group. After 6 months of treatment, the ASD group that received DHA enriched product significantly increased the plasma and erythrocyte percentages of DHA, but no differences were observed in the clinical test scores and other parameters as plasma cytokines between the two groups of ASD related to the intervention. Conclusion: Spanish children with ASD exhibit an appropriate omega-3 FA status in plasma and erythrocytes. Neither a clinical improvement of ASD children nor a better anti-inflammatory or fatty acid state has been found after an intervention with DHA/EPA for 6 months. So, the prescription of n-3 LC-PUFA and other dietary supplements in ASD should be only indicated after a confirmed alteration of FA metabolism or omega-3 LC-PUFA deficiency evaluated by specific erythrocyte FA. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03620097].

The Metabolic Impact of Two Different Parenteral Nutrition Lipid Emulsions in Children after Hematopoietic Stem Cell Transplantation: A Lipidomics Investigation.

Hematopoietic stem cell transplantation (HSCT) involves the infusion of either bone marrow or blood cells preceded by toxic chemotherapy. However, there is little knowledge about the clinical benefits of parenteral nutrition (PN) in patients receiving high-dose chemotherapy during HSCT. We investigated the lipidomic profile of plasma and the targeted fatty acid profiles of plasma and erythrocytes in children after HSCT using PN with either a fish oil-based lipid emulsion or a classic soybean oil emulsion. An untargeted liquid chromatography high-resolution mass spectrometry platform connected with a novel in silico annotation algorithm was utilized to determine the most relevant chemical subclasses affected. In addition, we explored the interrelation between the lipidomics profile in plasma, the targeted fatty acid profile in plasma and erythrocytes, several biomarkers of inflammation, and antioxidant defense using an innovative data integration analysis based on Latent Components. We observed that the fish oil-based lipid emulsion had an impact in several lipid subclasses, mainly glycerophosphocholines (PC), glycerophosphoserines (PS), glycerophosphoethanolamines (PE), oxidized PE (O-PE), 1-alkyl,2-acyl PS, lysophosphatidylethanolamines (LPE), oxidized PS (O-PS) and dicarboxylic acids. In contrast, the classic soybean oil emulsion did not. Several connections across the different blocks of data were found and aid in interpreting the impact of the lipid emulsions on metabolic health.

Genetic landscape of Segawa disease in Spain. Long-term treatment outcomes.

INTRODUCTION: In 2009, we described a possible founder effect of autosomal dominant Segawa disease in Córdoba (Spain) due to mutation c.265C>T (p. Q89*) in the GCH1 gene. We present a retrospective multicentre study aimed at improving our knowledge of Segawa disease in Spain and providing a detailed phenotypic-genotypic description of patients. METHODS: Clinical-genetic information were obtained from standardized questionnaires that were completed by the neurologists attending children and/or adults from 16 Spanish hospitals. RESULTS: Eighty subjects belonging to 24 pedigrees had heterozygous mutations in GCH1. Seven genetic variants have been described only in our cohort of patients, 5 of which are novel mutations. Five families not previously described with p. Q89* were detected in Andalusia due to a possible founder effect. The median latency to diagnosis was 5 years (IQR 0-16). The most frequent signs and/or symptoms were lower limb dystonia (38/56, 67.8%, p = 0.008) and diurnal fluctuations (38/56, 67.8%, p = 0.008). Diurnal fluctuations were not present in the phenotypes other than dystonia. Fifty-three of 56 symptomatic patients were treated with a levodopa/decarboxylase inhibitor for (mean ± SD) 12.4 ± 8.12 years, with 81% at doses lower than 350 mg/day (≤5 mg/kg/d in children). Eleven of 53 (20%) patients had nonresponsive symptoms that affected daily life activities. Dyskinesias (4 subjects) were the most prominent adverse effects. CONCLUSION: This study identifies 5 novel mutations and supports the hypothesis of a founder effect of p. Q89* in Andalusia. New insights are provided for the phenotypes and long-term treatment responses, which may improve early recognition and therapeutic management.

Dietary Patterns, Eating Behavior, and Nutrient Intakes of Spanish Preschool Children with Autism Spectrum Disorders.

Eating behavior problems are characteristic of children with autism spectrum disorders (ASD) with a highly restricted range of food choices, which may pose an associated risk of nutritional problems. Hence, detailed knowledge of the dietary patterns (DPs) and nutrient intakes of ASD patients is necessary to carry out intervention strategies if required. The present study aimed to determine the DPs and macro-and micronutrient intakes in a sample of Spanish preschool children with ASD compared to typically developing control children. Fifty-four children with ASD (two to six years of age) diagnosed with ASD according to the Diagnostic Manual-5 criteria), and a control group of 57 typically developing children of similar ages were recruited. A validated food frequency questionnaire was used, and the intake of energy and nutrients was estimated through three non-consecutive 24-h dietary registrations. DPs were assessed using principal component analysis and hierarchical clustering analysis. Children with ASD exhibited a DP characterized by high energy and fat intakes and a low intake of vegetables and fruits. Likewise, meat intake of any type, both lean and fatty, was associated with higher consumption of fish and dietary fat. Furthermore, the increased consumption of dairy products was associated with increased consumption of cereals and pasta. In addition, they had frequent consumption of manufactured products with poor nutritional quality, e.g., beverages, sweets, snacks and bakery products. The percentages of children with ASD complying with the adequacy of nutrient intakes were higher for energy, saturated fat, calcium, and vitamin C, and lower for iron, iodine, and vitamins of group B when compared with control children. In conclusion, this study emphasizes the need to assess the DPs and nutrient intakes of children with ASD to correct their alterations and discard some potential nutritional diseases.

Analysis of Global and Local DNA Methylation Patterns in Blood Samples of Patients With Autism Spectrum Disorder.

The goal of this investigation was to determine whether there are alterations in DNA methylation patterns in children with autism spectrum disorder (ASD). Material and Methods: Controlled prospective observational case-control study. Within the ASD group, children were sub-classified based on the presence (AMR subgroup) or absence (ANMR subgroup) of neurodevelopmental regression during the first 2 years of life. We analyzed the global levels of DNA methylation, reflected in LINE-1, and the local DNA methylation pattern in two candidate genes, Neural Cell Adhesion Molecule (NCAM1) and Nerve Growth Factor (NGF) that, according to our previous studies, might be associated to an increased risk for ASD. For this purpose, we utilized blood samples from pediatric patients with ASD (n = 53) and their corresponding controls (n = 45). Results: We observed a slight decrease in methylation levels of LINE-1 in the ASD group, compared to the control group. One of the CpG in LINE-1 (GenBank accession no.X58075, nucleotide position 329) was the main responsible for such reduction, highly significant in the ASD subgroup of children with AMR (p < 0.05). Furthermore, we detected higher NCAM1 methylation levels in ASD children, compared to healthy children (p < 0.001). The data, moreover, showed higher NGF methylation levels in the AMR subgroup, compared to the control group and the ANMR subgroup. These results are consistent with our prior study, in which lower plasma levels of NCAM1 and higher levels of NGF were found in the ANMR subgroup, compared to the subgroup that comprised neurotypically developing children. Conclusions: We have provided new clues about the epigenetic changes that occur in ASD, and suggest two potential epigenetic biomarkers that would facilitate the diagnosis of the disorder. We similarly present with evidence of a clear differentiation in DNA methylation between the ASD subgroups, with or without mental regression.

Children With Autism Spectrum Disorder and Neurodevelopmental Regression Present a Severe Pattern After a Follow-Up at 24 Months.

This study examined the presence of neurodevelopmental regression and its effects on the clinical manifestations and the severity of autism spectrum disorder (ASD) in a group of children with autism compared with those without neurodevelopmental regression at the time of initial classification and subsequently. Methods and Subjects: ASD patients were classified into two subgroups, neurodevelopmental regressive (AMR) and non-regressive (ANMR), using a questionnaire based on the Autism Diagnostic Interview-Revised test. The severity of ASD and neurodevelopment were assessed with the Childhood Autism Rating Scale Test-2, Strengths and Difficulties Questionnaire, and Pervasive Developmental Disorders Behavior Inventory Parent Ratings (PDDBI) and with the Battelle Developmental Inventory tests at the beginning of the study and after 24 months of follow-up. Fifty-two patients aged 2-6 years with ASD were included. Nineteen were classified with AMR, and 33 were classified with ANMR. Results: The AMR subgroup presented greater severity of autistic symptoms and higher autism scores. Additionally, they showed lower overall neurodevelopment. The AMR subgroup at 24 months had poorer scores on the Battelle Developmental Inventory test in the following areas: Total personal/social (p < 0.03), Total Motor (p < 0.04), Expressive (p < 0.01), and Battelle Total (p < 0.04). On the PDDBI test, the AMR subgroup had scores indicating significantly more severe ASD symptoms in the variables: ritual score (p < 0.038), social approach behaviors (p < 0.048), expressive language (p < 0.002), and autism score (p < 0.003). Conclusions: ASD patients exhibited a set of different neurological phenotypes. The AMR and ANMR subgroups presented different clinical manifestations and prognoses in terms of the severity of autistic symptoms and neurodevelopment.

Impaired Antioxidant Defence Status Is Associated With Metabolic-Inflammatory Risk Factors in Preterm Children With Extrauterine Growth Restriction: The BIORICA Cohort Study.

Introduction: An impaired antioxidant status has been described during foetal growth restriction (FGR). Similarly, the antioxidant defence system can be compromised in preterm children with extrauterine growth restriction (EUGR). The aim of this prospective study was to evaluate the antioxidant status in prepubertal children with a history of prematurity without FGR, with and without EUGR, compared to a healthy group. Methods: In total, 211 children were recruited and classified into three groups: 38 with a history of prematurity and EUGR; 50 with a history of prematurity and adequate extrauterine growth (AEUG); and 123 control children born at term. Catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities were assessed in lysed erythrocytes with spectrophotometric methods. Plasma levels of the antioxidants α-tocopherol, retinol and ß-carotene were determined through solvent extraction and ultra-high-pressure liquid chromatography coupled to mass spectrometry. Results: Children with the antecedent of EUGR and prematurity had lower CAT activity than the other two groups and lower GPx activity than the control children. Lower SOD, GPx and GR activities were observed in the AEUG group compared to the controls. However, higher concentrations of α-tocopherol and ß-carotene were found in the EUGR group compared to the other groups; retinol levels were also higher in EUGR than in AEUG children. In EUGR and AEUG children, enzymatic antioxidant activities and plasma antioxidants were associated with metabolic syndrome components and pro-inflammatory biomarkers. Conclusions: This study reveals, for the first time, that the EUGR condition and prematurity appear to be linked to an impairment of the antioxidant defence status, which might condition an increased risk of adverse metabolic outcomes later in life.

Plasma Adipokines Profile in Prepubertal Children with a History of Prematurity or Extrauterine Growth Restriction.

Adipose tissue programming could be developed in very preterm infants with extrauterine growth restriction (EUGR), with an adverse impact on long-term metabolic status, as was studied in intrauterine growth restriction patterns. The aim of this cohort study was to evaluate the difference in levels of plasma adipokines in children with a history of EUGR. A total of 211 school age prepubertal children were examined: 38 with a history of prematurity and EUGR (EUGR), 50 with a history of prematurity with adequate growth (PREM), and 123 healthy children born at term. Anthropometric parameters, blood pressure, metabolic markers and adipokines (adiponectin, resistin, leptin) were measured. Children with a history of EUGR showed lower values of adiponectin (µg/mL) compared with the other two groups: (EUGR: 10.6 vs. PREM: 17.7, p < 0.001; vs. CONTROL: 25.7, p = 0.004) and higher levels of resistin (ng/mL) (EUGR: 19.2 vs. PREM: 16.3, p =0.007; vs. CONTROL: 7.1, p < 0.001. The PREM group showed the highest values of leptin (ng/mL), compared with the others: PREM: 4.9 vs. EUGR: 2.1, p = 0.048; vs. CONTROL: 3.2, p = 0.029). In conclusion, EUGR in premature children could lead to a distinctive adipokines profile, likely associated with an early programming of the adipose tissue, and likely to increase the risk of adverse health outcomes later in life.

Autism Spectrum Disorder (ASD) with and without Mental Regression is Associated with Changes in the Fecal Microbiota.

New microbiome sequencing technologies provide novel information about the potential interactions among intestinal microorganisms and the host in some neuropathologies as autism spectrum disorders (ASD). The microbiota⁻gut⁻brain axis is an emerging aspect in the generation of autistic behaviors; evidence from animal models suggests that intestinal microbial shifts may produce changes fitting the clinical picture of autism. The aim of the present study was to evaluate the fecal metagenomic profiles in children with ASD and compare them with healthy participants. This comparison allows us to ascertain how mental regression (an important variable in ASD) could influence the intestinal microbiota profile. For this reason, a subclassification in children with ASD by mental regression (AMR) and no mental regression (ANMR) phenotype was performed. The present report was a descriptive observational study. Forty-eight children aged 2⁻6 years with ASD were included: 30 with ANMR and 18 with AMR. In addition, a control group of 57 normally developing children was selected and matched to the ASD group by sex and age. Fecal samples were analyzed with a metagenomic approach using a next-generation sequencing platform. Several differences between children with ASD, compared with the healthy group, were detected. Namely, Actinobacteria and Proteobacteria at phylum level, as well as, Actinobacteria, Bacilli, Erysipelotrichi, and Gammaproteobacteria at class level were found at higher proportions in children with ASD. Additionally, Proteobacteria levels showed to be augmented exclusively in AMR children. Preliminary results, using a principal component analysis, showed differential patterns in children with ASD, ANMR and AMR, compared to healthy group, both for intestinal microbiota and food patterns. In this study, we report, higher levels of Actinobacteria, Proteobacteria and Bacilli, aside from Erysipelotrichi, and Gammaproteobacteria in children with ASD compared to healthy group. Furthermore, AMR children exhibited higher levels of Proteobacteria. Further analysis using these preliminary results and mixing metagenomic and other "omic" technologies are needed in larger cohorts of children with ASD to confirm these intestinal microbiota changes.

Necesidades sanitarias y socioeducativas de niños con enfermedades raras de tipo metabólico y sus familias: estudio cualitativo en un hospital de tercer nivel / Health and socio-educational needs of the families and children with rare metabolic diseases: Qualitative study in a tertiary hospital

INTRODUCCIÓN: Las enfermedades raras suponen un reto para la salud pública debido a la escasa información sobre su magnitud. Entre ellas destacan los errores congénitos del metabolismo. El presente estudio pretende valorar la calidad de vida y las posibles necesidades sanitarias, socioeducativas y económicas de los pacientes pediátricos con diagnóstico de ER de tipo metabólico y de sus familiares o cuidadores principales, atendidos habitualmente en un hospital de tercer nivel. MATERIAL Y MÉTODO: Se desarrolló un cuestionario basado en las necesidades y expectativas recogidas fundamentalmente en el Plan Andaluz para las Enfermedades Raras. Se analizaron variables de los órdenes sociosanitario, económico y educativo en 65 pacientes pediátricos con errores congénitos del metabolismo. RESULTADOS: Los encuestados manifestaron escasas posibilidades para afrontar el gasto de la medicación (61%), alimentación especial (86%) y otras prestaciones sanitarias (79%). El 43% consideraron que la calidad de vida familiar se afectó bastante desde la aparición de la enfermedad. En el 61,5% la cuidadora principal fue la madre, frente al 1,5% de casos en los que fue el padre. El cuidador principal redujo su jornada laboral o abandonó su trabajo en el 77% de los casos. CONCLUSIONES: El tratamiento multidisciplinar se ve afectado por la imposibilidad de las familias para hacer frente a su elevado coste, junto a una difícil accesibilidad a dichos recursos. Además, existe gran repercusión en la calidad de vida de los pacientes y sus cuidadores. Por tanto, deberían evaluarse los resultados de los planes gubernamentales de apoyo sanitario y socioeconómico a pacientes con enfermedades raras, y conseguir una respuesta real a sus necesidades

INTRODUCTION: Rare diseases are a challenge for public health due to the lack of information on their magnitude. These include inborn errors of metabolism. The objective of this study was to assess the quality of life and social, health, economic, and educational needs of a group of paediatric patients with inborn errors of metabolism attended to in a hospital. MATERIAL AND METHOD: A questionnaire was developed based on the needs and expectations, based mainly on the Andalusian Plan for Rare Diseases. An analysis was performed on the variables of health, socioeconomic, and educational needs of 65 paediatric patients with inborn errors of metabolism. RESULTS: The respondents showed few possibilities to cope with medication (61%), special diet (86%), and other health benefits (79%). Just under half of them (43%) believed that the quality of family life had been greatly reduced since the onset of the disease. The main caregiver was the mother in 61.5% of cases, compared to 1.5% of cases in which it was the father. The primary caregivers had to reduce their working hours or give up their job in 77% of cases. CONCLUSIONS: The multidisciplinary treatment is affected by the inability of families to cope with a high cost, as well as with difficult access to these resources. In addition, there is great impact on the quality of life of patients, and their caregivers. Therefore, there is a need to evaluate the results of government health and socio-economic support plans for patients with rare diseases, and make a real response to their needs

[Health and socio-educational needs of the families and children with rare metabolic diseases: Qualitative study in a tertiary hospital]. / Necesidades sanitarias y socioeducativas de niños con enfermedades raras de tipo metabólico y sus familias: estudio cualitativo en un hospital de tercer nivel.

INTRODUCTION: Rare diseases are a challenge for public health due to the lack of information on their magnitude. These include inborn errors of metabolism. The objective of this study was to assess the quality of life and social, health, economic, and educational needs of a group of paediatric patients with inborn errors of metabolism attended to in a hospital. MATERIAL AND METHOD: A questionnaire was developed based on the needs and expectations, based mainly on the Andalusian Plan for Rare Diseases. An analysis was performed on the variables of health, socioeconomic, and educational needs of 65 paediatric patients with inborn errors of metabolism. RESULTS: The respondents showed few possibilities to cope with medication (61%), special diet (86%), and other health benefits (79%). Just under half of them (43%) believed that the quality of family life had been greatly reduced since the onset of the disease. The main caregiver was the mother in 61.5% of cases, compared to 1.5% of cases in which it was the father. The primary caregivers had to reduce their working hours or give up their job in 77% of cases. CONCLUSIONS: The multidisciplinary treatment is affected by the inability of families to cope with a high cost, as well as with difficult access to these resources. In addition, there is great impact on the quality of life of patients, and their caregivers. Therefore, there is a need to evaluate the results of government health and socio-economic support plans for patients with rare diseases, and make a real response to their needs.

Children With Autism Spectrum Disorder With Regression Exhibit a Different Profile in Plasma Cytokines and Adhesion Molecules Compared to Children Without Such Regression.

Background: In the etiopathogenesis of autism spectrum disorder (ASD), it has been suggested that a proinflammatory condition, as well as an alteration in adhesion molecules in the early stages of neurodevelopment, may play a role in the pathophysiology of the disorder. This study set out to evaluate the plasma levels of certain inflammatory cytokines, adhesion molecules, and growth factors in a sample of pediatric patients with ASD and compare them to the levels in a control group of healthy children. Methods: Fifty-four children (45 males and nine females) aged 2-6, who were diagnosed with ASD, and a control group of 54 typically-developing children of similar ages were selected. The diagnosis of ASD was carried out in accordance with the DSM-5 criteria and the data obtained from a developmental semi-structured clinical interview and the ADOS evaluation test. Additional testing was carried out to identify the children's developmental level and severity of ASD symptomatology. Patients with ASD were further divided into two subgroups based on developmental parameters: ASD children with neurodevelopmental regression (AMR) and ASD children without neurodevelopmental regression (ANMR). Analyses of plasma molecules, such as cathepsin, IL1ß, IL6, IL8, MPO, RANTES, MCP, BDNF, PAI NCAM, sICAM, sVCAM and NGF, were performed. Results: Higher levels of NGF were observed in the ASD group compared with the levels in the control group (p < 0.05). However, in the analysis of the ASD subgroups, lower plasma levels of NCAM and higher levels of NGF were found in the group of ASD children without developmental regression compared to the levels in the group of typically-developing children. Conclusions: These results suggest differences that could be related to different pathophysiological mechanisms in ASD. There is not a specific profile for the expression of relevant plasma cytokines, adhesion molecules or growth factors in children with ASD compared with that in typically-developing children. However, in the ANMR and AMR subgroups, some of the adhesion molecules and neuronal growth factors show differences that may be related to synaptogenesis.

Efficacy of Paracetamol in Closure of Ductus Arteriosus in Infants under 32 Weeks of Gestation.

BACKGROUND: Standard medical treatment for patent ductus arteriosus (PDA) closure has been indomethacin/ibuprofen or surgical ligation. Up to date, new strategies have been reported with paracetamol. The aim of this study was to present our experience with intravenous paracetamol for closing PDA in preterm neonates presenting contraindication to ibuprofen or ibuprofen had failed and no candidates for surgical ligation because of huge instability. MATERIALS AND METHODS: We conducted a retrospective case series study in a neonatal intensive care unit from a tertiary hospital. 9 preterm infants ≤32 weeks of gestational age with hemodynamically significant PDA (hsPDA) were enrolled. They received 15 mg/kg/6h intravenous paracetamol for ductal closure. Demographic data and transaminase levels before and after treatment were collected. RESULTS: 30 preterm babies were diagnosed of hsPDA. 11/30 received ibuprofen with closure in 81.1%. 9 received intravenous paracetamol mainly due to bleeding disorders or thrombocytopenia. Successful closure on paracetamol was achieved in seven of nine babies (77.7%). There was a significant increase in transaminase levels in two patients. They required no treatment for normalization. CONCLUSION: Paracetamol is an effective option in closure PDA. It should be a first-line therapeutic option when there are contraindications for ibuprofen treatment. Transaminases must be checked during treatment.

Oxidative stress and inflamatory plasma biomarkers in respiratory syncytial virus bronchiolitis.

INTRODUCTION: Oxidative stress (OS) plays a crucial role in the pathogenesis of inflammatory lung diseases. OBJECTIVES: (i) We determined whether acute bronchiolitis (AB) caused by respiratory syncytial virus (RSV) induced OS; (ii) assessed whether OS biomarkers correlated with the severity of RSV-AB; and (iii) studied whether the levels of interleukins are associated with OS biomarkers. METHODS: We performed an observational study by comparing healthy infants (Group 1) with RSV-AB infants, classified as Group 2 (pulse oximetry (SpO2 ) >93%), and Group 3 (SpO2 ≤ 92%), which needed oxygen therapy. Blood samples were collected to determine the levels of lipid peroxidation (LPO) products (LPO), total glutathione (TG), oxidised glutathione (GSSG), reduced glutathione (GSH), glutathione peroxidase (GPx), interleukins (ILs) IL-10, IL-6, IL-8, interferon-gamma (IFNγ), tumour necrosis factor-alpha (TNFα) and macrophage inflammatory proteins (MIP α and MIP ß). RESULTS: Forty-six RSV-AB infants (47% needed oxygen therapy) and 27 healthy infants were included. The GSH/GSSG ratio was lower in RSV-AB infants than in Group 1 (P<0.001). GSSG and GPx were significantly higher in Group 3. GSSG predicted the need for oxygen therapy with an optimal cut-off point of 15 µM/g for haemoglobin. The GSH/GSSG ratio negatively correlated with IL-6 (P: 0.014), IL-8 (P: 0.014) and IL-10 (P: 0.033). Group 3 exhibited a direct correlation between GPx and IL-10 levels (P: 0.024) and between LPO and MIP ß (P: 0.003). CONCLUSIONS: RSV induced OS in AB. An increase in GSSG correlated with the disease severity in the infants. OS may contribute to the pathogenesis of RSV-AB.

Inflammatory Response Using Different Lipid Parenteral Nutrition Formulas in Children After Hematopoietic Stem Cell Transplantation.

Nutritional support is an integral part of the supportive care of hematopoietic stem cell transplantation (HSCT) patients. Omega-3 fatty acids (n-3 FA) emulsions in parenteral nutrition (PN) may modify the inflammatory response. The purpose of this study is to compare plasma cytokine levels in children after HSCT using an n-3 FA-containing lipid emulsion (LE) and a soybean oil-based formulation in PN. A randomized double-blind controlled trial was conducted on 14 children following HSCT. Children were randomized to receive either a fish oil or a soybean oil LE. Blood samples were drawn at baseline, on Day 10 and after completion of PN to analyze plasma interleukin 1 beta (IL-1ß), 2 (IL-2), 6 (IL-6), 8 (IL-8), 10 (IL-10), and tumor necrosis factor alpha (TNF-α). After 10 days of PN, there were no significant changes in interleukins levels when comparing the two groups or time points (baseline vs. Day 10 of PN). In children requiring PN >21 days, IL-10 and TNF-α levels (P ≤ 0.05) were lower in the fish-oil-containing LE group. Fish oil- and soybean oil-supplemented PN administered for at least 10 days does not cause inflammatory changes. Prolonged PN based on fish oil LE may modulate the inflammatory response.

Early Modification in Drainage of Interleukin-1ß and Tumor Necrosis Factor-α Best Predicts Surgical-Site Infection After Cervical Neck Dissection for Oral Cancer.

PURPOSE: Surgical-site infection (SSI) after cervical neck dissection (CND) for head and neck squamous cell carcinoma (HNSCC) increases morbidity and delays adjuvant treatment. This study assessed changes in cytokines levels in postsurgical drainage fluid after CND and examined their predictive value for the early diagnosis of SSI. PATIENTS AND METHODS: An observational prospective pilot study was conducted in 39 consecutively recruited patients with HNSCC undergoing CND who were treated at the authors' service within the past 2 years. Patients met the following inclusion criteria: no previous chemotherapy or radiotherapy, closed-suction drainage, 30-day follow-up, prophylactic treatment with amoxicillin plus clavulanic acid and dexamethasone, no chronic inflammatory disease, and no previous neck surgery. Drainage samples were collected at postoperative days +1 and +3. Sample size was estimated based on SSI incidence after HNSCC surgery (∼15%; α risk, 0.05; ß risk, 0.2; 2-sided test). Interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-α (TNF-α) levels were measured. Patients were followed to detect SSI. Sensitivity, specificity, and prognostic values were calculated for each cytokine at days +1 and +3 to diagnose SSI. RESULTS: SSI was diagnosed in 6 of 39 patients. Bilateral CND, tracheostomy, surgery duration longer than 7 hours, HNSCC stage T3 or T4, and reconstruction with pedicled flaps versus microvascular flaps for advanced-stage tumors were considered risk factors for SSI. All cytokines except IL-10 showed statistical differences between patients with SSI and those without SSI. The best receiver operating characteristic curves yielded cutoff values at day +1 (TNF-α >14.5 pg/mL; sensitivity, 100%; specificity, 87.88%) and day +3 (IL-1ß >115 pg/mL; sensitivity, 83.33%; specificity, 78.79%). Also, IL-2 levels higher than 6.5 pg/mL at day +1 (sensitivity, 83.33%; specificity, 69.7%) and day +3 (sensitivity, 100%; specificity, 69.7%) and IL-6 levels higher than 3,300 pg/mL at day +3 (sensitivity, 100%; specificity, 60.61%) yielded adequate diagnostic profitability. CONCLUSION: The results of this study suggest that the assessment of cytokine levels in drainage fluid soon after CND could provide a novel method for the early detection of SSI.

Low serum 25-hydroxyvitamin D levels and bronchiolitis severity in Spanish infants.

UNLABELLED: This cross-sectional study was performed to examine the prevalence of hypovitaminosis D in infants with acute bronchiolitis compared with control subjects and to evaluate the relationship between serum 25-hydroxyvitamin D (25(OH) D) and the severity of bronchiolitis. Serum 25(OH) D levels were measured by radioimmunoassay in 48 infants with acute bronchiolitis (2.5 ± 2.0 months) and in 30 healthy infants (3.2 ± 2.3 months). 25(OH) D levels (ng/ml) in children with acute bronchiolitis were significantly lower than in the control group (median 29.9 ng/ml (interquartile range (IQR) 21.4-37.5) versus median 38.2 ng/ml ((IQR 26.1-48.1), p = 0.022), mainly in infants with moderate-severe bronchiolitis (median 29.8 ng/ml, IQR 19.2-35.9). The prevalence of hypovitaminosis D was remarkably greater among infants with bronchiolitis than in control subjects (52.1 versus 26.6%). A significant inverse correlation was found between serum 25-hydroxyvitamin D levels and disease severity (rho = -0.457, p < 0.001). CONCLUSION: The prevalence of hypovitaminosis D is high in Spanish infants with bronchiolitis. The severity of acute bronchiolitis increases with a decline in serum 25 (OH) D level.

Prepubertal children with a history of extra-uterine growth restriction exhibit low-grade inflammation.

Intra-uterine growth restriction (IUGR) may induce significant metabolic and inflammatory anomalies, increasing the risk of obesity and CVD later in life. Similarly, alterations in the adipose tissue may lead to metabolic changes in children with a history of extra-uterine growth restriction (EUGR). These mechanisms may induce alterations in immune response during early life. The aim of the present study was to compare pro-inflammatory markers in prepubertal EUGR children with those in a reference population. A total of thirty-eight prepubertal children with a history of EUGR and a reference group including 123 healthy age- and sex-matched children were selected. Perinatal data were examined. In the prepubertal stage, the concentrations of inflammatory biomarkers were measured in both groups. The serum concentrations of C-reactive protein (CRP) and plasma concentrations of hepatocyte growth factor (HGF), IL-6, IL-8, monocyte chemotactic protein type 1 (MCP-1), neural growth factor, TNF-α and plasminogen activator inhibitor type 1 were determined. The plasma concentrations of inflammatory biomarkers CRP, HGF, IL-8, MCP-1 and TNF-α were higher in the EUGR group than in the reference group (P< 0·001). After adjustment for gestational age, birth weight and length, blood pressure values and TNF-α concentrations remained higher in the EUGR group than in the reference group. Therefore, further investigations should be conducted in EUGR children to evaluate the potential negative impact of metabolic, nutritional and pro-inflammatory changes induced by the EUGR condition.