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1.
Clin Exp Rheumatol ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31969217

RESUMO

OBJECTIVES: The aim of the study is to evaluate the compliance rate to secondary prophylaxis and the presence of rheumatic heart disease (RHD) in a cohort of Italian patients with acute rheumatic fever (ARF). METHODS: This is a multicentre retrospective study. The patients were divided into two groups by the presence or absence at last follow-up of RHD. Clinical features, ARF recurrences and the rate of compliance to secondary prophylaxis were evaluated. RESULTS: Two-hundred and ninety patients were enrolled (137 females; 153 males). Carditis at onset was present in 244 patients (84.7%). At the end of follow-up, 173 patients manifested RHD. Adherence to secondary prophylaxis was low in 26% of patients. The presence of RHD at follow-up was associated with the presence of carditis and its severity at onset (p=0.001), but it was not related to secondary prophylaxis adherence (p=NS). No association between prophylaxis adherence and ARF recurrence was found (p=NS) nor between ARF recurrence and RHD at the end of follow-up (p=NS). CONCLUSIONS: Poor adherence to secondary prophylaxis does not seem to be associated with increased risk of RHD in developed countries. Further studies are needed to confirm our data in a larger population.

2.
EBioMedicine ; 51: 102567, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31901853

RESUMO

BACKGROUND: Intestinal coeliac auto-antibodies are the marker of coeliac disease (CD). Since the determination of these antibodies is still not widely available, we used immunoassays to identify the most suitable technology for revealing intestinal auto-antibodies in the wide clinical spectrum of CD. METHODS: Intestinal auto-antibodies have been prospectively investigated in CD suspected children using two immunoassays: intestinal-deposits of IgA anti-tissue transglutaminase antibodies (anti-tTG) and biopsy-culture IgA anti-endomysium (AEA). Intestinal IgM antibodies have been determined in IgA-deficient subjects. FINDINGS: Two-hundred and twenty-one suspected CD patients were enrolled. Intestinal antibodies were tested positive for both assays in classical CD patients (n = 178) with villous atrophy and positive serum-CD antibodies, potential CD patients (n = 16) with normal intestinal mucosa and positive serum-CD antibodies, and pre-potential CD patients (n = 14) with normal intestinal mucosa and negative serum-CD antibodies. In 13/221 with normal intestinal mucosa, negative CD-serum antibodies and negative intestinal antibodies CD has been excluded. All classical, 14/16 potential and 11/14 pre-potential CD patients on gluten-free diet (GFD) improved their symptoms. In 9/11 pre-potential patients intestinal antibodies disappeared on GFD. Both assays were negative in 69/71 control subjects. The two assays showed high diagnostic sensitivity (100%) and specificity (99%). INTERPRETATION: Intestinal CD-antibodies make prompt diagnosis in the wide clinical spectrum of CD reducing the delay in diagnosis and treatment, especially in pre-potential CD patients. The easy handling biopsy culture assay is an effective diagnostic tool which should be carried out by any gastroenterology unit to recognize all CD clinical manifestations. FUNDING: Interreg Central-Europe, IRCCS "Burlo Garofolo".

3.
Eur J Med Genet ; 63(1): 103614, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30654153

RESUMO

In everyday practice, a pediatric endocrinologist will face a variety of different endocrine issues (such as short or tall stature, dysthyroidism, abnormal pubertal timing or impaired glucose metabolism), which relevantly contribute to the global care of a number of syndromic conditions. On the other hand, the presence of endocrine features may assist in the diagnostic process, leading to final diagnosis of a syndromic disorder. The intention of this review is to provide a referenced overview of different genetic syndromes characterized by endocrine features, and to present a possible classification, based on whether the endocrinopathy or the syndrome is typically recognized first. Thus, the first part of the manuscript deals with the most common syndromes associated with endocrine dysfunctions, while the second part describes the conditions by which a syndrome is most frequently diagnosed after an endocrine finding. The aim is to provide a practical overview of the assessment of syndromic patients, so that they can be recognized and managed in an integrated, multidisciplinary fashion.

4.
Pharmacogenomics J ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31792371

RESUMO

The aim of the study was to validate the impact of the single-nucleotide polymorphism rs2413739 (T > C) in the PACSIN2 gene on thiopurines pharmacological parameters and clinical response in an Italian cohort of pediatric patients with acute lymphoblastic leukemia (ALL) and inflammatory bowel disease (IBD). In ALL, PACSIN2 rs2413739 T allele was associated with a significant reduction of TPMT activity in erythrocytes (p = 0.0094, linear mixed-effect model, multivariate analysis considering TPMT genotype) and increased severe gastrointestinal toxicity during consolidation therapy (p = 0.049). A similar trend was present also for severe hematological toxicity during maintenance. In IBD, no significant effect of rs2413739 could be found on TPMT activity, however azathioprine effectiveness was reduced in patients carrying the T allele (linear mixed effect, p = 0.0058). In PBMC from healthy donors, a positive correlation between PACSIN2 and TPMT protein concentration could be detected (linear mixed effect, p = 0.045). These results support the role of PACSIN2 polymorphism on TPMT activity and mercaptopurine adverse effects in patients with ALL. Further evidence on PBMC and pediatric patients with IBD supports an association between PACSIN2 variants, TPMT activity, and thiopurines effects, even if more studies are needed since some of these effects may be tissue specific.

5.
Eur J Pediatr ; 178(8): 1297-1300, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31254072

RESUMO

We report a case series of seven children admitted to a tertiary level pediatric ward for long-lasting physical symptoms with a previous diagnosis of chronic Lyme disease. In these children, medical history and clinical features were strongly suggestive of a psychopathological disorder, mainly a somatic symptom disorder. What is Known: • There is an increasing number of diagnoses of chronic Lyme disease both in North America and in Europe. Adults receive this diagnosis to explain chronic physical complaints often with negative history and serology. What is New: • Somatic symptom disorder should be suspected in children and adolescents with non-specific symptoms diagnosed with chronic Lyme disease.


Assuntos
Erros de Diagnóstico , Síndrome Pós-Lyme/diagnóstico , Transtornos Psicofisiológicos/diagnóstico , Transtornos Somatoformes/diagnóstico , Adolescente , Criança , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Síndrome Pós-Lyme/psicologia , Transtornos Psicofisiológicos/psicologia , Estudos Retrospectivos , Transtornos Somatoformes/psicologia
6.
J Pediatr Gastroenterol Nutr ; 69(4): 474-479, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31149938

RESUMO

OBJECTIVES: Therapeutic drug monitoring is becoming increasingly important in clinical decision-making in children with inflammatory bowel disease (IBD). However, enzyme-linked immunosorbent assay (ELISA) assays do not allow results to be provided in real-time. We sought to compare 2 point-of-care (POC) devices for quantification of serum infliximab concentration with 2 validated ELISA assays in children with IBD. METHODS: We studied 32 serum samples from 19 children with IBD treated with infliximab. Serum samples were collected immediately before drug infusion (trough level). Infliximab was measured using 2 POC infliximab assays, Quantum Blue (POC IFX/QB) and Rida Quick (POC IFX/RQ), and 2 ELISA assays: Lisa-Tracker (used as primary reference), and Promonitor (used as second control). Intraclass correlation coefficient (ICC) was assessed for quantitative comparison. Qualitative analysis was also performed to evaluate whether POC assays would correctly classify infliximab serum according to a target window (between 3 and 7 µg/mL). RESULTS: ICC was 0.82 and 0.87 for POC IFX/QB and POC IFX/RQ with the primary reference ELISA assay, respectively; ICC between the 2 ELISA assays was 0.87. Classification of results according to therapeutic intervals showed good agreement between pairs of assays, with kappa of 0.67 and 0.80 for POC IFX/QB and POC IFX/RQ, respectively, with reference ELISA, and 0.81 between the 2 ELISAs. Accuracy of POC assays was better for drug levels <3 µg/mL. CONCLUSIONS: POC infliximab assays showed good agreement with traditional ELISA assays. POC devices may represent a viable option for real-time therapeutic drug monitoring in children treated with infliximab.

7.
Genes (Basel) ; 10(4)2019 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987408

RESUMO

The contribution of candidate genetic variants involved in azathioprine biotransformation on azathioprine efficacy and pharmacokinetics in 111 young patients with inflammatory bowel disease was evaluated. Azathioprine doses, metabolites thioguanine-nucleotides (TGN) and methylmercaptopurine-nucleotides (MMPN) and clinical effects were assessed after at least 3 months of therapy. Clinical efficacy was defined as disease activity score below 10. Candidate genetic variants (TPMT rs1142345, rs1800460, rs1800462, GSTA1 rs3957357, GSTM1, and GSTT1 deletion) were determined by polymerase chain reaction (PCR) assays and pyrosequencing. Statistical analysis was performed using linear mixed effects models for the association between the candidate variants and the pharmacological variables (azathioprine doses and metabolites). Azathioprine metabolites were measured in 257 samples (median 2 per patient, inter-quartile range IQR 1-3). Clinical efficacy at the first evaluation available resulted better in ulcerative colitis than in Crohn's disease patients (88.0% versus 52.5% responders, p = 0.0003, linear mixed effect model, LME). TGN concentration and the ratio TGN/dose at the first evaluation were significantly higher in responder. TPMT rs1142345 variant (4.8% of patients) was associated with increased TGN (LME p = 0.0042), TGN/dose ratio (LME p < 0.0001), decreased azathioprine dose (LME p = 0.0087), and MMPN (LME p = 0.0011). GSTM1 deletion (58.1% of patients) was associated with a 18.5% decrease in TGN/dose ratio and 30% decrease in clinical efficacy. GSTA1 variant (12.8% of patients) showed a trend (p = 0.049, LME) for an association with decreased clinical efficacy; however, no significant effect on azathioprine pharmacokinetics could be detected. In conclusion, GSTs variants are associated with azathioprine efficacy and pharmacokinetics.


Assuntos
Azatioprina/farmacocinética , Glutationa Transferase/genética , Imunossupressores/farmacocinética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Variantes Farmacogenômicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Azatioprina/administração & dosagem , Biotransformação , Feminino , Deleção de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunossupressores/administração & dosagem , Doenças Inflamatórias Intestinais/genética , Masculino , Metiltransferases/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Resultado do Tratamento , Adulto Jovem
9.
Minerva Pediatr ; 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30916514

RESUMO

BACKGROUND: Long term growth may be compromised in patients with Inflammatory Bowel Disease (IBD). The aims of the study were to evaluate the final height in a cohort of patients with pediatric-onset IBD with respect to genetic target and to determine factors influencing long-term growth. METHODS: This is a monocentric retrospective cohort study. All patients with diagnosed prepubertal onset IBD were enrolled. Patients were classified into two groups on the basis of the achievement of target height at time of the last follow-up. Clinical parameters were also recorded. RESULTS: 82 patients were identified: 42 with Crohn's Disease (CD) and 40 with Ulcerative Colitis (UC). The mean age at diagnosis was 11.0 (SD 4.0) years. Eighty-nine percent of patients achieved final target height. Mean difference between final and target height was -1.2 cm (SD: 5,4). No statistical significance was detected between CD and UC patients final height (p=0.16). Growth failure at the diagnosis and disease severity were the only factors associated with final height achievement failure (p=0.001 and p=0.01 respectively). CONCLUSIONS: Most part of CD and UC patients achieve the target final height. Disease severity and low height at diagnosis seem to be the two best predictive factors for low final height.

10.
J Immunol ; 202(4): 1079-1087, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30635394

RESUMO

An unbalance between Abs that recognize an autoantigen (idiotypes; IDs) and Igs that bind such Abs (anti-IDs) is considered a functional event in autoimmune disorders. We investigated the presence of an ID/anti-ID network in celiac disease (CD), a condition in which antitissue transglutaminase 2 (TG2) Abs are suspected to contribute to CD pathogenesis. To characterize the ID side, we reproduced by in vitro yeast display the intestine-resident Abs from CD and control patients. These TG2-specific IDs were used to identify potential anti-IDs in the serum. We observed elevated titers of anti-IDs in asymptomatic patients with predisposition to CD and demonstrated that anti-ID depletion from the serum restores a detectable humoral response against TG2. Our study provides an alternative approach to quantify CD-related autoantibodies in cases that would be defined "negative serology" with current diagnostic applications. Therefore, we suggest that developments of this technology could be designed for perspective routine tests.


Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Autoanticorpos/imunologia , Doença Celíaca/imunologia , Glutens/genética , Idiotipos de Imunoglobulinas/imunologia , Intestinos/imunologia , Adolescente , Adulto , Autoanticorpos/sangue , Doença Celíaca/genética , Criança , Pré-Escolar , Feminino , Proteínas de Ligação ao GTP/imunologia , Proteínas de Ligação ao GTP/metabolismo , Glutens/imunologia , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Intestinos/patologia , Masculino , Pessoa de Meia-Idade , Transglutaminases/imunologia , Transglutaminases/metabolismo , Adulto Jovem
11.
J Pediatr Gastroenterol Nutr ; 68(4): 547-551, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30499881

RESUMO

OBJECTIVES: Available data indicate that liver involvement is present in a significant proportion of children with celiac disease (CD) at the diagnosis (elevated transaminases 15%-57%, autoimmune liver disease 1%-2%). We sought to evaluate prevalence, clinical course, and risk factors for liver involvement in a large cohort of children with CD. METHODS: Children (age 0-18 years) diagnosed with CD from March 2010 to April 2016 were enrolled. Liver involvement was considered to be present when alanine transaminase (ALT) levels were >40 U/L (hypertransaminasemia [HTS]). Patients with HTS were re-evaluated after at least 12 months of a gluten-free diet. RESULTS: CD was diagnosed in 806 patients during the study period; of these, ALT levels were available for 700 patients (86.9%), and were elevated in 27 (3.9%, HTS group); median ALT and aspartate transaminase levels in the HTS group were 57 U/L (interquartile range 49-80 U/L) and 67 U/L (interquartile range 53-85 U/L), respectively. Younger age, malabsorption symptoms, and low hemoglobin or ferritin were significantly more common in the HTS group at univariate analysis. At multivariate analysis, only age ≤4.27 years correlated with risk of liver involvement (odds ratio 3.73; 95% confidence interval: 1.61-8.66). When retested on a gluten-free diet, all but 3 patients normalized ALT levels; of these, 1 was diagnosed with sclerosing cholangitis. CONCLUSIONS: Liver involvement in celiac children is now less frequent than previously reported, possibly due to changing CD epidemiology. Younger age is the only risk factor. Associated autoimmune liver disease is rare.

12.
Acta Paediatr ; 108(2): 328-332, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29972706

RESUMO

AIM: This retrospective study reviewed the prevalence and long-term prognosis of children aged 0-18 with palpitations who were admitted to the emergency department (ED) of an Italian paediatric hospital. METHODS: We examined all admissions to the ED of the IRCCS Burlo Garofolo between January 2009 and December 2015 by selecting triage diagnoses of palpitations. The hospital discharge cards were reviewed to assess vital parameters, physical examinations, diagnostic tests, cardiology consultations and final diagnoses. RESULTS: Of the 142 803 patients who attended our ED for any reason, 96 (0.07%) complained of palpitations. Despite this low prevalence, it was noteworthy that 13.5% had a real underlying arrhythmic cause and needed medical assistance. Over half (52.1%) were women and the mean age was 12.7 years. At the long-term follow-up, at a mean of 47 ± 23 months, 53.8% of patients with a cardiac arrhythmia had received medical therapy and 46.1% had undergone trans-catheter ablation for supraventricular tachycardia. A heart rate above 146 beats per minute or palpitations for more than an hour was statistically related to a cardiac arrhythmia. CONCLUSION: Palpitations were an infrequent cause of admission to our ED, but 13.5% who displayed them had an underlying cardiac arrhythmia.

13.
J Pediatr Gastroenterol Nutr ; 68(1): 37-44, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30211845

RESUMO

OBJECTIVES: Anti-tumor necrosis factor antibodies have led to a revolution in the treatment of inflammatory bowel diseases (IBD); however, a sizable proportion of patients does not respond to therapy. There is increasing evidence suggesting that treatment failure may be classified as mechanistic (pharmacodynamic), pharmacokinetic, or immune-mediated. Data regarding the contribution of these factors in children with IBD treated with infliximab (IFX) are still incomplete. The aim was to assess the causes of treatment failure in a prospective cohort of pediatric patients treated with IFX. METHODS: This observational study considered 49 pediatric (median age 14.4) IBD patients (34 Crohn disease, 15 ulcerative colitis) treated with IFX. Serum samples were collected at 6, 14, 22 and 54 weeks, before IFX infusions. IFX and anti-infliximab antibodies (AIA) were measured using enzyme linked immunosorbent assays. Disease activity was determined by Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative Colitis Activity Index. RESULTS: Clinical remission, defined as a clinical score <10, was obtained by 76.3% of patients at week 14 and by 73.9% at week 54. Median trough IFX concentration was higher at all time points in patients achieving sustained clinical remission. IFX levels during maintenance correlated also with C-reactive protein, albumin, and fecal calprotectin. After multivariate analysis, IFX concentration at week 14 >3.11 µg/mL emerged as the strongest predictor of sustained clinical remission. AIA concentrations were correlated inversely with IFX concentrations and directly with adverse reactions. CONCLUSIONS: Most cases of therapeutic failure were associated with low serum drug levels. IFX trough levels at the end of induction are associated with sustained long-term response.

14.
Expert Rev Gastroenterol Hepatol ; 12(8): 797-810, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29957083

RESUMO

INTRODUCTION: Anti-tumor necrosis factor (TNF) agents have changed the therapeutic approach to inflammatory bowel disease (IBD). However, a considerable proportion of patients either do not primarily respond or lose response to treatment. Despite the long-standing experience in the use of these drugs, still there is the need of identifying the possible predictors of efficacy. Areas covered: We critically review the current knowledge on predictors of response to anti-TNF therapy - both those available in clinical practice and those still under investigation. Multiple factors are involved in treatment success, including disease phenotype and severity, adherence to medications, and pharmacogenomic, pharmacokinetic, and immunologic factors. Literature search was conducted in PubMed using keywords 'inflammatory bowel disease,' 'Crohn's disease,' and 'ulcerative colitis,' matched with 'antitumor necrosis factor,' 'biologic therapy,' 'clinical response,' 'predictors,' and 'efficacy,' Relevant articles were selected for review. Expert commentary: While the role of several factors in clinical practice is clearly established, other investigational markers have been proposed, mostly in small studies, yet for many of them little external validation exists. Therapeutic drug monitoring is emerging as a pivotal strategy to guide decisions in clinical practice. In the near future, novel markers could improve our ability to direct treatment and personalize therapy.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Terapia Biológica , Humanos , Seleção de Pacientes , Prognóstico , Resultado do Tratamento
15.
J Rheumatol ; 45(10): 1418-1421, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29907671

RESUMO

OBJECTIVE: This study aimed to test fecal calprotectin (FC) as a screening tool to identify inflammatory bowel disease (IBD) among patients with juvenile idiopathic arthritis (JIA). METHODS: FC level < 100 g/kg was considered normal. Patients with 2 consecutive FC dosage ≥ 100 g/kg underwent endoscopic evaluation. RESULTS: There were 113 patients with JIA enrolled. FC was raised in 7 patients out of 113. All patients had IBD. In 3/7 patients, high FC levels were the only sign consistent with IBD. CONCLUSION: FC is a useful, economical, and noninvasive diagnostic tool to identify JIA patients with underlying IBD.


Assuntos
Artrite Juvenil/complicações , Fezes/química , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/diagnóstico , Complexo Antígeno L1 Leucocitário/análise , Adolescente , Biomarcadores/análise , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Programas de Rastreamento , Estudos Retrospectivos , Adulto Jovem
16.
Gastrointest Endosc ; 88(3): 521-526, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29807020

RESUMO

BACKGROUND AND AIMS: Anti-tissue transglutaminase antibodies (anti-tTG) have simplified celiac disease (CD) diagnosis. However, in atypical forms of CD, intestinal biopsy sampling is still required. This prospective study investigates whether histologic analysis of the duodenal bulb combined with intestinal IgA anti-tTG deposit immunoassay makes CD diagnosis possible in at-risk children with low concentrations of serum anti-tTG. METHODS: Histologic and intestinal IgA anti-tTG deposit immunoassays were used. RESULTS: Two hundred forty-five symptomatic children positive for serum anti-tTG (>7 U/mL) were enrolled and divided into 3 groups: extensive duodenal atrophy (n = 209), with IgA anti-tTG deposits throughout the duodenum and high serum anti-tTG concentrations (157 ± 178 U/mL); bulb duodenal atrophy (n = 22), with widespread IgA anti-tTG deposits in 9 and in the bulb alone in 13 and low serum anti-tTG concentrations (13.9 ± 8.7 U/mL); and normal duodenum (n = 14), with widespread IgA anti-tTG deposits in 8 and in the bulb alone in 6 and low serum anti-tTG concentrations (10.6 ± 6.2 U/mL). All patients in the first 2 groups were diagnosed with CD and 8 from the third group. All improved after 1 year of gluten-free diet. Bulb duodenal analysis led to a 12% (30/245) increase in CD diagnosis. No CD-related lesions were observed in the 30 control subjects. CONCLUSIONS: In children at risk for CD, bulb duodenum biopsy sampling is essential to identify villous atrophy and detect IgA anti-tTG deposits even in absence of intestinal lesions. These mucosal autoantibodies could well represent a new standard for diagnosing CD.


Assuntos
Doença Celíaca/diagnóstico , Duodeno/imunologia , Imuno-Histoquímica/métodos , Adolescente , Autoanticorpos/análise , Autoanticorpos/sangue , Autoanticorpos/imunologia , Doença Celíaca/sangue , Doença Celíaca/imunologia , Criança , Pré-Escolar , Duodeno/química , Feminino , Humanos , Imunoglobulina A/análise , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Lactente , Masculino , Estudos Prospectivos , Transglutaminases/análise , Transglutaminases/antagonistas & inibidores , Transglutaminases/sangue , Transglutaminases/imunologia
17.
Int J Mol Sci ; 19(5)2018 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-29738455

RESUMO

The aim of this research was the identification of novel pharmacogenomic biomarkers for better understanding the complex gene regulation mechanisms underpinning glucocorticoid (GC) action in paediatric inflammatory bowel disease (IBD). This goal was achieved by evaluating high-throughput microRNA (miRNA) profiles during GC treatment, integrated with the assessment of expression changes in GC receptor (GR) heterocomplex genes. Furthermore, we tested the hypothesis that differentially expressed miRNAs could be directly regulated by GCs through investigating the presence of GC responsive elements (GREs) in their gene promoters. Ten IBD paediatric patients responding to GCs were enrolled. Peripheral blood was obtained at diagnosis (T0) and after four weeks of steroid treatment (T4). MicroRNA profiles were analyzed using next generation sequencing, and selected significantly differentially expressed miRNAs were validated by quantitative reverse transcription-polymerase chain reaction. In detail, 18 miRNAs were differentially expressed from T0 to T4, 16 of which were upregulated and 2 of which were downregulated. Out of these, three miRNAs (miR-144, miR-142, and miR-96) could putatively recognize the 3’UTR of the GR gene and three miRNAs (miR-363, miR-96, miR-142) contained GREs sequences, thereby potentially enabling direct regulation by the GR. In conclusion, we identified miRNAs differently expressed during GC treatment and miRNAs which could be directly regulated by GCs in blood cells of young IBD patients. These results could represent a first step towards their translation as pharmacogenomic biomarkers.


Assuntos
Biomarcadores , Glucocorticoides/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , MicroRNAs/genética , Adolescente , Criança , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/administração & dosagem , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Masculino , Receptores de Glucocorticoides/genética , Transcriptoma/efeitos dos fármacos
18.
Ital J Pediatr ; 44(1): 43, 2018 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-29615074

RESUMO

BACKGROUND: The simultaneous occurrence of Klinefelter Syndrome (KS) and Congenital Adrenal Hyperplasia (CAH) is an exceptional event: there are just three case reports (two children and a 51 years old man) describing males affected by both KS and 21OHD (21-hydroxylase deficiency) CAH, the first causing androgen deficiency, the latter leading to androgen excess. CASE REPORT: We report the 4th case of association of KS and CAH in a young man with CAH with good androgen control and with normal secondary sex characteristics, whose Klinefelter syndrome was diagnosed because of reduced testicular volume. He was the first reported case of association of KS and CAH who started androgen replacement therapy in the pubertal age and whose pubertal development was described and followed up step by step. CONCLUSION: In a boy with CAH and small testicular volume, it's important to consider that hypogonadism may be masked by the adrenal androgens excess and a karyotype should be performed once testicular adrenal rests have been ruled out.


Assuntos
Hiperplasia Suprarrenal Congênita/complicações , Hiperplasia Suprarrenal Congênita/diagnóstico , Androgênios/administração & dosagem , Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/diagnóstico , Testículo/anormalidades , Adolescente , Hiperplasia Suprarrenal Congênita/sangue , Androgênios/sangue , Seguimentos , Terapia de Reposição Hormonal/métodos , Humanos , Síndrome de Klinefelter/sangue , Masculino , Doenças Raras , Medição de Risco
19.
J Crohns Colitis ; 12(7): 870-879, 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29518184

RESUMO

Background and Aims: Ocular extraintestinal manifestations [O-EIMs] are known complications of Crohn's disease [CD], ulcerative colitis [UC], and inflammatory bowel disease unclassified [IBD-U]. However, data on their prevalence in children are scarce and there are no clear recommendations on what follow-up should be offered. We aimed to review available data on O-EIMs in children. Methods: In January 2018, we performed a systematic review of published English literature using PubMed and EMBASE databases and disease-specific queries. Results: Fifteen studies [7467 patients] reported data on O-EIMs prevalence in children. Overall prevalence of O-EIMs was 0.62-1.82%. Uveitis was the most common O-EIM. Meta-analysis showed that children with CD are at increased risk of O-EIMs as compared with children with UC and IBD-U (odds ratio [OR] 2.70, 95% confidence interval [CI] 1.51-4.83). Five studies [357 patients] reported data on ophthalmological screening in asymptomatic children: mild asymptomatic uveitis was identified in a variable proportion of patients [1.06-23.1%], more frequently in male patients with CD and colonic involvement. No evidence of ocular complications from untreated uveitis was detected. A total of 23 case reports [24 patients] were identified. Conclusions: Data on O-EIMs in children are scarce. Prevalence of O-EIMs is lower than in adults but may be underestimated because of the possibility of asymptomatic uveitis; however, the long-term significance of this condition is unknown. Children with CD may be at increased risk of O-EIMs. No recommendations on routine ophthalmological examination can be made, but a low threshold for ophthalmological referral should be maintained. Larger studies in paediatric IBD populations are needed.


Assuntos
Colite Ulcerativa/complicações , Doença de Crohn/complicações , Oftalmopatias/epidemiologia , Adolescente , Catarata/epidemiologia , Catarata/etiologia , Criança , Pré-Escolar , Oftalmopatias/etiologia , Humanos , Prevalência , Uveíte/epidemiologia , Uveíte/etiologia
20.
Ital J Pediatr ; 44(1): 20, 2018 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-29386058

RESUMO

BACKGROUND: Clinical observation is a key component of medical ability, enabling immediate evaluation of the patient's emotional state and contributing to a clinical clue that leads to final decision making. In medical schools, the art of learning to look can be taught using medical humanities and especially visual arts. By presenting a Ramsay sedation score (RSS) integrated with Caravaggio's paintings during a procedural sedation conference for pediatric residents, we want to test the effectiveness of this approach to improve the quality of learning. METHODS: In this preliminary study, we presented videos showing sedated pediatric patients in the setting of a procedural sedation lesson to two randomized groups of residents, one attending a lesson on RSS explained through the masterpieces of Caravaggio, the other without artistic support. A week later we tested their learning with ten multi-choice questions focused on theoretical questions about sedation monitoring and ten more questions focused on recognizing the appropriate RSS viewing the videos. The primary outcome was the comparison of the total number of RSS layers properly recognized in both groups. We also evaluated the appreciation of the residents of the use of works of art integrated with the lesson. RESULTS: Eleven students were randomized to each group. Two residents in the standard lesson did not attend the test. The percentage of correct answers on the theoretical part was similar, 82% in the art group and 89% in the other (p > 0.05). No difference was found in the video recognition part of the RSS recognition test. Residents exposed to paintings shown great appreciation for the integration of the lesson with the Caravaggio's masterpieces. CONCLUSIONS: Adding artwork to a standard medical conference does not improve the performance of student tests, although this approach has been greatly appreciated by residents.


Assuntos
Competência Clínica , Sedação Consciente , Educação de Pós-Graduação em Medicina/métodos , Medicina nas Artes , Pinturas , Sedação Profunda , Feminino , Hospitais Universitários , Humanos , Internato e Residência/métodos , Itália , Masculino , Monitorização Fisiológica , Medição da Dor , Pediatria/educação , Gravação em Vídeo
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