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BACKGROUND AND AIM: Recent researches have shown an altered gut microbiota in celiac disease (CD) patients compared with healthy controls (HCs). This study aims to evaluate the composition of the microbiota of CD children at onset and the relationship between bacterial abundances and symptoms. METHODS: Celiac disease patients were consecutively enrolled at a pediatric unit referring for suspected CD. HCs were also included in the study. Stool and duodenal samples were collected and evaluated by a high taxonomic fingerprint microbiota array. RESULTS: Thirty-seven subjects enrolled: 21 CD patients and 16 HCs. Fourteen subjects were male (38%). The mean age was 75 months (standard deviation 31.5) for CD patients and 71 months (standard deviation 34.9) for HCs. Duodenal microbiota of CD patients showed a dominance of Enterobacteriaceae and subdominance of Bacteroidetes/Streptococcus. Stool microbiota showed a lower abundance of Bacteroides-Prevotella (P = 0.013), Akkermansia (P = 0.002), and Staphylococcaceae (P = 0.001) in CD patients compared with HC. At symptoms level, an increased mean relative abundance of Bacillaceae and Enterobaeriaceae in patients with abdominal pain (P = 0.007 and P = 0.010) was found. CD patients with diarrhea had reduced mean relative abundance of Clostridium cluster XIVa (P = 0.044) and Akkermansia (P = 0.033) and an increase in Bacillaceae (P = 0.048) and Fusobacterium (P = 0.048). CONCLUSIONS: Gut microbiota of CD children at disease onset is different from that of HC. Pro-inflammatory microbiota imbalances were associated with CD symptoms. Further studies are needed to assess whether dysbiosis is associated with CD early onset and symptoms.
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Enfermedad Celíaca/epidemiología , Enfermedad Celíaca/microbiología , Microbioma Gastrointestinal , Edad de Inicio , Akkermansia , Bacillaceae , Bacteroidetes , Niño , Duodeno/microbiología , Disbiosis , Enterobacteriaceae , Heces/microbiología , Femenino , Fusobacterium , Humanos , Masculino , Proyectos Piloto , StreptococcusRESUMEN
Phthalates, as other endocrine disrupting chemicals (EDCs), may alter the homeostasis and the action of hormones and signaling molecules, causing adverse health outcomes. This is true especially for infants, who are both more exposed and sensitive to their effects. Phthalates are particularly harmful when the exposure occurs during certain critical temporal windows of the development, such as the prenatal and the early postnatal phases. Phthalates may also interfere with the neuroendocrine systems (e.g., thyroid hormone signaling or metabolism), causing disruption of neuronal differentiation and maturation, increasing the risk of behavioral and cognitive disorders (ADHD and autistic behaviors, reduced mental, psychomotor, and IQ development, and emotional problems). Despite more studies being needed to better understand the role of these substances, plenty of evidence suggests the impact of phthalates on the neuroendocrine system development and function. This review aims to update the knowledge on the neuroendocrine consequences of neonatal and perinatal exposure to phthalates.
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Disruptores Endocrinos/toxicidad , Contaminantes Ambientales/toxicidad , Trastornos del Neurodesarrollo/fisiopatología , Sistemas Neurosecretores/efectos de los fármacos , Ácidos Ftálicos/toxicidad , Exposición a Riesgos Ambientales , Femenino , Humanos , Trastornos del Neurodesarrollo/inducido químicamente , Sistemas Neurosecretores/patología , EmbarazoRESUMEN
BACKGROUND: Peroxisome biogenesis disorders (PBDs) are a group of metabolic diseases caused by dysfunction of peroxisomes. Different forms of PBDs are described; the most severe one is the Zellweger syndrome (ZS). We report on an unusual presentation of Zellweger syndrome manifesting in a newborn with severe and fulminant sepsis, causing death during the neonatal period. CASE PRESENTATION: A term male Caucasian neonate presented at birth with hypotonia and poor feeding associated with dysmorphic craniofacial features and skeletal abnormalities. Blood tests showed progressive leukopenia; ultrasounds revealed cerebral and renal abnormalities. He died on the fourth day of life because of an irreversible Gram-negative sepsis. Post-mortem tests on blood and urine samples showed biochemical alterations suggestive of ZS confirmed by genetic test. CONCLUSIONS: ZS is an early and severe forms of PBDs. Peroxisomes are known to be involved in lipid metabolism, but recent studies suggest their fundamental role in modulating immune response and inflammation. In case of clinical suspicion of ZS it is important to focus the attention on the prevention and management of infections that can rapidly progress to death.
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ATPasas Asociadas con Actividades Celulares Diversas/genética , Infecciones por Bacterias Gramnegativas/genética , Mutación , Peroxisomas/inmunología , Sepsis/genética , Síndrome de Zellweger/genética , ATPasas Asociadas con Actividades Celulares Diversas/deficiencia , ATPasas Asociadas con Actividades Celulares Diversas/inmunología , Resultado Fatal , Expresión Génica , Infecciones por Bacterias Gramnegativas/inmunología , Infecciones por Bacterias Gramnegativas/microbiología , Infecciones por Bacterias Gramnegativas/patología , Humanos , Inmunidad Innata , Recién Nacido , Masculino , Peroxisomas/microbiología , Peroxisomas/patología , Sepsis/inmunología , Sepsis/microbiología , Sepsis/patología , Síndrome de Zellweger/inmunología , Síndrome de Zellweger/microbiología , Síndrome de Zellweger/patologíaRESUMEN
BACKGROUND: The aim of this study is to investigate free carnitine (C0) and total acylcarnitine levels (AC) in preterm infants with BW < 1800 g and the relationship with neonatal and perinatal factors. METHODS: Ninety-three thousand two hundred and ninety-three newborns were screened between 2011 and 2013. Dried blood samples (DBS) were collected at 48-72 h, 14, and 30 days of age. We studied 92 consecutive preterm (BW < 1800 g) infants with low carnitine levels at 30 days of life (Group 1). As controls, we included the first 92 cases (BW < 1800 g) with normal carnitine levels (Group 2) and another 92 at or near-term newborns with BW > 1800 g (Group 3). RESULTS: Compared to 48-72 h levels, C0 and AC decreased at 14 and 30 days of life in Groups 1 and 2 (p < 0.001). In Group 2, the percentage of children with carnitine-free parenteral nutrition (PN) and BW < 1000 g was lower than in Group 1 (p < 0.001). Only in Group 2 did C0 increase at 30 days (p < 0.001). The multivariate regression analysis confirmed the influence of body weight and type of nutrition on C0 and AC. CONCLUSION: Body weight and type of nutrition influenced the carnitine longitudinal pattern.
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Peso al Nacer , Carnitina/sangre , Recien Nacido Prematuro/sangre , Estudios de Casos y Controles , Pruebas con Sangre Seca , Humanos , Recién Nacido , Estudios LongitudinalesRESUMEN
PURPOSE: To study the current practice for assessing comorbidity in adults with 21-hydroxylase CAH and to assess the prevalence of comorbidity in these adults. METHODS: A structured questionnaire was sent to 46 expert centres managing adults with CAH. Information collected included current therapy and surveillance practice with a particular focus on osteoporosis/osteopaenia, hyperlipidaemia, type 2 diabetes/hyperinsulinaemia, hypertension, CV disease, obesity. RESULTS: Of the 31 (67%) centres from 15 countries that completed the survey, 30 (97%) screened for hypertension by measuring blood pressure, 30 (97%) screened for obesity, 26 (84%) screened for abnormal glucose homoeostasis mainly by using Hb1Ac (73%), 25 (81%) screened for osteoporosis mainly by DXA (92%), 20 (65%) screened for hyperlipidaemia and 6 (19%) screened for additional CV disease. Of the 31 centres, 13 provided further information on the six co-morbidities in 244 patients with a median age of 33 yrs (range 19, 94). Of these, 126 (52%) were females and 174 (71%) received fludrocortisone in addition to glucocorticoids. Of the 244 adults, 73 (30%) were treated for at least one comorbidity and 15 (21%) for more than 2 co-morbidities. Of 73, the patients who were treated for osteoporosis/osteopaenia, hyperlipidaemia, type 2 diabetes/hyperinsulinaemia, hypertension, CV disease, obesity were 43 (59%), 17 (23%), 16 (22%), 10 (14%), 8 (11), 3 (4%) respectively. CONCLUSION: Cardiometabolic and bone morbidities are not uncommon in adults with CAH. There is a need to standardise the screening for these morbidities from early adulthood and to explore optimal therapy through routine collection of standardised data.
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Hiperplasia Suprarrenal Congénita , Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Hiperinsulinismo , Hipertensión , Osteoporosis , Femenino , Humanos , Adulto Joven , Adulto , Masculino , Hiperplasia Suprarrenal Congénita/complicaciones , Hiperplasia Suprarrenal Congénita/epidemiología , Hiperplasia Suprarrenal Congénita/diagnóstico , Obesidad/epidemiología , Hipertensión/epidemiología , Prevalencia , Osteoporosis/epidemiología , Osteoporosis/etiologíaRESUMEN
Context: There is growing evidence of the role of epigenetic regulation of growth, and miRNAs potentially play a role. Objective: The aim of this study is to identify changes in circulating miRNAs following GH treatment in subjects with isolated idiopathic GH deficiency (IIGHD) after the first 3 months of treatment, and verify whether these early changes can predict growth response. Design and Methods: The expression profiles of 384 miRNAs were analyzed in serum in 10 prepubertal patients with IIGHD (5 M, 5 F) at two time points before starting GH treatment (t-3, t0), and at 3 months on treatment (t+3). MiRNAs with a fold change (FC) >+1.5 or <-1.5 at t+3 were considered as differentially expressed. In silico analysis of target genes and pathways led to a validation step on 8 miRNAs in 25 patients. Clinical and biochemical parameters were collected at baseline, and at 6 and 12 months. Simple linear regression analysis and multiple stepwise linear regression models were used to explain the growth response. Results: Sixteen miRNAs were upregulated and 2 were downregulated at t+3 months. MiR-199a-5p (p = 0.020), miR-335-5p (p = 0.001), and miR-494-3p (p = 0.026) were confirmed to be upregulated at t+3. Changes were independent of GH peak values at testing, and levels stabilized after 12 months. The predicted growth response at 12 months was considerably improved compared with models using the common clinical and biochemical parameters. Conclusions: MiR-199a-5p, miR-335-5p, and miR-494-3p changed after 3 months of GH treatment and likely reflected both the degree of GH deficiency and the sensitivity to treatment. Furthermore, they were of considerable importance to predict growth response.
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MicroARN Circulante , MicroARNs , MicroARN Circulante/genética , Epigénesis Genética , Humanos , MicroARNs/metabolismoRESUMEN
INTRODUCTION: Few data are available regarding the trend of IgA anti-transglutaminase antibodies (TGA-IgA) in children with celiac disease (CD) on a gluten-free diet (GFD). Our aim is to examine the normalization time of CD serology in a large pediatric population, and its predictors. MATERIAL AND METHODS: We retrospectively evaluated the normalization time of TGA-IgA and its predictive factors (age, sex, ethnicity, symptoms, associated diabetes/thyroiditis, Marsh stage, TGA-IgA and endomysial antibody levels at diagnosis, diet adherence), in 1024 children diagnosed from 2000 to 2019 in three pediatric Italian centers, on a GFD. RESULTS: TGA-IgA remission was reached in 67,3%, 80,7%, 89,8% and 94,9% after 12, 18, 24 and 36 months from starting a GFD, respectively (median time = 9 months). TGA-IgA >10´upper limit of normal at diagnosis (HR = 0.56), age 7-12 years old (HR = 0.83), poor compliance to diet (HR = 0.69), female sex (HR = 0.82), non-Caucasian ethnicity (HR = 0.75), and comorbidities (HR = 0.72) were independent factors significantly associated with longer time to normalization. CONCLUSIONS: Our population is the largest in the literature, with the majority of patients normalizing CD serology within 24 months from starting a GFD. We suggest a special attention to patients with comorbidities, language barriers or age 7-12 years for a proper management and follow-up.
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Autoanticuerpos/sangre , Enfermedad Celíaca/sangre , Dieta Sin Gluten , Inmunoglobulina A/sangre , Transglutaminasas/inmunología , Enfermedad Celíaca/dietoterapia , Niño , Femenino , Humanos , Inmunoglobulina A/inmunología , Masculino , Cooperación del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Hashimoto's thyroiditis (HT) is a common endocrinopathy in children, particularly in females. Clinical overt presentation of hypothyroidism in HT includes mild to very severe forms, characterised by impairment of many body functions and organs, such as heart, brain, muscles, ovaries and liver. CASE: we report the case of a 14-year-old girl, with severe hypothyroidism due to a late diagnosis of HT during the Covid-19 pandemic. Routine biochemical and hormonal exams were carried out at presentation. Moderate pericardial effusion was detected by echocardiography and polycystic ovarian morphology (PCOM) was found on the pelvic ultrasound. Furthermore, high levels of creatine phosphokinase (CPK), Lactic Acid Dehydrogenase (LDH) and hepatic liver enzymes, associated with muscular pseudohypertrophy and bilateral weakness of the lower limbs, were suggestive of a rare presentation of long-standing hypothyroidism defined Kocher-Debre-Semelaigne syndrome (KDSS). Levothyroxine replacement therapy was started immediately, leading to a rapid improvement of symptoms and a progressive normalization of the biochemical parameters. Due to persistent lower limb weakness, further neurological investigations were performed, showing bilateral peripheral polyneuropathy (PNP), ascribable to the longstanding and severe hypothyroidism. A pelvic ultrasound, performed after thyroid hormones had normalised and menses had turned to be regular, showed normal ovarian features supporting the hypothesis of the Van Wyk and Grumbach syndrome in a post-menarcheal girl. CONCLUSIONS: although clinical manifestation of hypothyroidism are usually mild, more severe and rare presentations such as ovarian dysfunction and myopathy are possible, particularly if the diagnosis is delayed and replacement therapy is not promptly administered.
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COVID-19 , Hipotiroidismo Congénito , Adolescente , Niño , Control de Enfermedades Transmisibles , Diagnóstico Tardío , Femenino , Estudios de Seguimiento , Humanos , Pandemias , SARS-CoV-2RESUMEN
A significant increase in precocious puberty, rapidly progressive puberty and precocious menarche has been reported in Italy since the initial lockdown because of the pandemic, and this could represent a new emergency to be addressed during this pandemic. There is a need, therefore, for further understanding and research. Many causes could account for this. Initially, it was thought that the changes in life-style, in screen time, and sleeping habits could be the cause but if considered individually these are insufficient to explain this phenomenon. Likely, changes in central nervous mediators, and an increase in catecholamines could contribute as a trigger, however, these aspects are poorly studied and understood as well as the real perceptions of these children. Finally, staying more indoors has certainly exposed these children to specific contaminants working as endocrine disruptors which could also have had an effect. It would be of utmost importance to compare this phenomenon worldwide with appropriate studies in order to verify what is happening, and gain a new insight into the consequences of the covid-19 pandemic and into precocious puberty and for future prevention.
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BACKGROUND: Non-typhoid Salmonella (NTS) is an important cause of bacterial meningitis in newborn and infants in developing countries, but rarely in industrialized ones. We describe an unusual presentation of bacterial meningitis in an infant, focusing on his diagnostic and therapeutic management. CASE REPORT: An Italian two-month old male presented high fever and diarrhea with blood, associated with irritability. Inflammatory markers were high, cerebrospinal fluid analysis was compatible with bacterial meningitides but microbiological investigations were negative. Salmonella enteritidis was isolated from blood. Cerebral ultrasound and MRI showed periencephalic collection of purulent material. Specific antibiotic therapy with cefotaxime was initiated with improvement of clinical conditions and blood tests. Brain MRI follow up improved progressively. CONCLUSIONS: Most of pediatric patients with NTS infection develop self-limited gastroenteritis, but in 3-8% of the cases complications such as bacteremia and meningitis may occur, especially in weak patients. Cerebral imaging can be useful to identify neurological findings. Although there is no standardized treatment for this condition, specific antibiotic therapy for at least four weeks is recommended. Neuroimaging follow up is required due to high risk of relapse.