Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 65
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Crohns Colitis ; 14(1): 71-78, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31162532

RESUMO

INTRODUCTION: The ability to predict risk for poor outcomes in Crohn's disease [CD] would enable early treatment intensification. We aimed to identify children with CD with complications at baseline and throughout the study period who are at risk for surgery 2 years from diagnosis. METHODS: Newly diagnosed children with CD were enrolled into a prospective, multicentre inception cohort. Disease characteristics and serological markers were obtained at baseline and week 12 thereafter. Outcome data including disease activity, therapies, complications and need for surgery were collected until the end of 104 weeks. A chi-square automatic interaction detection [CHAID] algorithm was used to develop a prediction model for early surgery. RESULTS: Of 285 children enrolled, 31 [10.9%] required surgery within 2 years. Multivariate analysis identified stricturing disease at baseline (odds ratio [OR] 5.26, 95% confidence interval [CI] 2.02-13.67 [p = 0.001]), and Paediatric Crohn's Disease Activity Index [PCDAI] >10 at week 12 (OR 1.06, 95% CI 1.02-1.10 [p = 0.005]) as key predictors for early surgery. CHAID demonstrated that absence of strictures at diagnosis [7.6%], corticosteroid-free remission at week 12 [4.1%] and early immunomodulator therapy [0.8%] were associated with the lowest risk of surgery, while stricturing disease at diagnosis [27.1%, p < 0.001] or elevated PCDAI at week 12 [16.7%, p = 0.014] had an increased risk of surgery at follow-up. Anti-OmpC status further stratified high-risk patients. DISCUSSION: A risk algorithm using clinical and serological variables at diagnosis and week 12 can categorize patients into high- and low-risk groups from diagnosis.

2.
Expert Rev Gastroenterol Hepatol ; 13(10): 957-961, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31490707

RESUMO

Introduction: Tumor necrosis factor-α (TNF-α)-blocking agents are drugs approved for the treatment of inflammatory bowel diseases (IBDs). Infliximab and adalimumab are approved for the treatment of IBD in the pediatric setting with the improvement of therapeutic management. Biological agents, also in the pediatric population, can be administered either alone or in combination with immunomodulators. Their use has raised safety concerns regarding the risk of infections and malignancies.Areas covered: A broad review of the safety concerns for the use of anti-TNF-α drugs in children with IBD was performed, and information regarding the risk of infections and malignancies were updated, also in comparison with the safety of traditional drugs such as steroids and/or immunosuppressants.Expert commentary: Anti-TNF-α drugs have shown favorable safety profiles, and adalimumab treatment is associated with lower immunogenicity compared with infliximab. Heightened awareness and vigilant surveillance leading to prompt diagnosis and treatment are important for optimal management.

3.
United European Gastroenterol J ; 7(6): 759-766, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31316780

RESUMO

Background: Very few data regarding the use of infliximab in children with very early-onset inflammatory bowel disease (VEO-IBD) have been reported. Objective: We aimed to assess the efficacy and the safety of infliximab in children with VEO-IBD compared with older children. Methods: Children treated with infliximab were identified within the Italian IBD registry. The primary outcome was the rate of clinical remission at weeks 14 and 54. Secondary outcomes included the proportion of partial clinical response, treatment duration, and incidence of adverse events. Results: Forty-two children with VEO-IBD were compared with 130 children with IBD. Despite significantly higher infliximab withdrawals in VEO-IBD patients during induction (42.9% vs 7.7% p < 0.01), remission rates at week 14 were similar (28.6% vs 43.8%, p = 0.10). At week 54 fewer VEO-IBD children were in remission (15.8% vs 54.3%, p < 0.01). The treatment duration was shorter in VEO-IBD (median 12.0 vs 18.4 months, p < 0.01). During the induction phase, adverse events were more common in the VEO-IBD group (p < 0.01). Conclusion: Compared with older children, VEO-IBD patients have higher rates of infliximab failures, lower remission rates at one year, and more often experience adverse events during induction.

4.
Clin Immunol ; 207: 10-17, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31279857

RESUMO

Autoimmune enteropathy (AIE) is a rare condition that may affect pediatric and adult patients, frequently associated with primary immunodeficiencies. We performed a retrospective study on clinical and histological findings from 40 AIE patients. Histological presentation showed a prevalent celiac disease pattern (50%), followed by the mixed pattern (35%), independently of age, chronic active duodenitis (10%), and GVHD-like pattern (5%). Patients with primary immunodeficiencies (24/40) presented mainly with the celiac disease pattern (72.2% versus 22.2%; p < .0001), while patients without primary immunodeficiencies presented with a mixed histological pattern (61.1% versus 13.6%; p < .0001). Our study shows that the prevalent histological presentation is the celiac disease-like pattern, independently of age, and, for the first time, that the histological presentation of AIE differs significantly between patients with and without primary immunodeficiencies. These findings may be helpful for more precise and timely diagnosis and management of this rare disorder.

6.
J Crohns Colitis ; 13(12): 1518-1526, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31120524

RESUMO

BACKGROUND AND AIM: Acute severe colitis [ASC] is associated with significant morbidity in paediatric patients with ulcerative colitis [UC]. Most outcome studies in ASC since tumour necrosis factor alpha [TNFα] antagonists became available have focused on the first year after admission. The aim of this study was to characterise the longer-term outcomes of paediatric patients admitted with ASC. METHODS: This retrospective study was conducted in 25 centres across Europe and North America. Data on patients with UC aged <18 years, admitted with ASC (defined as paediatric ulcerative colitis activity index [PUCAI] score ≥65) between 2009 and 2011, were collected at discharge and 1, 3 and 5 years after admission. The primary outcome was colectomy-free rates at each time point. RESULTS: Of the 141 patients admitted with ASC, 137 [97.1%] were treated with intravenous corticosteroids. Thirty-one [22.6%] patients were escalated to second-line therapy, mainly to infliximab. Sixteen patients [11.3%] underwent colectomy before discharge. Long-term follow-up showed colectomy-free rates were 71.3%, 66.4% and 63.6% at 1, 3 and 5 years after initial ASC admission, respectively, and were similar across different age groups. Sub-analysis of colectomy rates in patients with new-onset disease [42.5% of the cohort] yielded similar results. In a multivariate analysis, use of oral steroids in the 3 months before admission, erythrocyte sedimentation rate >70 mm/h, and albumin <2.5 g/dL, were significantly associated with 5-year colectomy risk. CONCLUSIONS: High colectomy rates were demonstrated in paediatric UC patients admitted with ASC. Additional studies are required to determine whether intensification of anti-TNFα treatment, close therapeutic drug monitoring, and use of new drugs alter this outcome.

7.
Biologics ; 13: 13-21, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30655661

RESUMO

Background: Adalimumab (Ada) treatment is an available option for pediatric Crohn's disease (CD) and the published experience as rescue therapy is limited. Objectives: We investigated Ada efficacy in a retrospective, pediatric CD cohort who had failed previous infliximab treatment, with a minimum follow-up of 6 months. Methods: In this multicenter study, data on demographics, clinical activity, growth, laboratory values (CRP) and adverse events were collected from CD patients during follow-up. Clinical remission (CR) and response were defined with Pediatric CD Activity Index (PCDAI) score ≤10 and a decrease in PCDAI score of ≥12.5 from baseline, respectively. Results: A total of 44 patients were consecutively recruited (mean age 14.8 years): 34 of 44 (77%) had active disease (mean PCDAI score 24.5) at the time of Ada administration, with a mean disease duration of 3.4 (range 0.3-11.2) years. At 6, 12, and 18 months, out of the total of the enrolled population, CR rates were 55%, 78%, and 52%, respectively, with a significant decrease in PCDAI scores (P<0.01) and mean CRP values (mean CRP 5.7 and 2.4 mL/dL, respectively; P<0.01) at the end of follow-up. Steroid-free remission rates, considered as the total number of patients in CR who were not using steroids at the end of this study, were 93%, 95%, and 96% in 44 patients at 6, 12, and 18 months, respectively. No significant differences in growth parameters were detected. In univariate analysis of variables related to Ada efficacy, we found that only a disease duration >2 years was negatively correlated with final PCDAI score (P<0.01). Two serious adverse events were recorded: 1 meningitis and 1 medulloblastoma. Conclusion: Our data confirm Ada efficacy in pediatric patients as second-line biological therapy after infliximab failure. Longer-term prospective data are warranted to define general effectiveness and safety in pediatric CD patients.

8.
J Pediatr Gastroenterol Nutr ; 68(3): 353-359, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30358740

RESUMO

OBJECTIVE: The aim of the study was to establish an apparent diffusion coefficient (ADC) cut-off value to classify active and non-active lesions in inflammatory bowel disease. METHODS: We reviewed 167 paediatric magnetic resonance enterographies executed for suspected inflammatory bowel disease by using a 1.5- and 3-T scanner. We assessed the presence and activity of the disease by using morphologic and functional parameters such as the ADC. Each patient could have more than 1 examinations. Quantitative assessment of disease activity in the ADC map was measured placing 3 regions of interest in the areas of highest inflammation and the mean value was calculated, patients without sign of inflammation were assessed at 2 standardised site. Ileocolonoscopy, esophagogastroduodenoscopy, surgery, and video-capsule endoscopy were used as standards of reference. RESULTS: We enrolled 34 patients and 35 examinations: radiological findings of disease were identified in 29 examinations and 44 lesions were detected. Six patients had negative results and ADC assessment was taken at the terminal ileum and cecum. A total of 56 bowel segments were included in the study. Image analysis revealed 39 active lesions (69.6%) and their ADC values were lower compared to the ones of non-active segments. For each scanner a cut-off value was found (sensitivity: 0.91, specificity: 0.89 for 1.5 T and 0.81 for 3 T). Inter-rater agreement on disease activity between ADC values and magnetic resonance enterography results and between ADC values and the standard of reference were very good. CONCLUSIONS: ADC can provide a scanner-based quantitative measurement of disease activity.

9.
Environ Microbiol ; 21(1): 50-71, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30246283

RESUMO

The quest to discover the variety of ecological niches inhabited by Saccharomyces cerevisiae has led to research in areas as diverse as wineries, oak trees and insect guts. The discovery of fungal communities in the human gastrointestinal tract suggested the host's gut as a potential reservoir for yeast adaptation. Here, we report the existence of yeast populations associated with the human gut (HG) that differ from those isolated from other human body sites. Phylogenetic analysis on 12 microsatellite loci and 1715 combined CDSs from whole-genome sequencing revealed three subclusters of HG strains with further evidence of clonal colonization within the host's gut. The presence of such subclusters was supported by other genomic features, such as copy number variation, absence/introgressions of CDSs and relative polymorphism frequency. Functional analysis of CDSs specific of the different subclusters suggested possible alterations in cell wall composition and sporulation features. The phenotypic analysis combined with immunological profiling of these strains further showed that sporulation was related with strain-specific genomic characteristics in the immune recognition pattern. We conclude that both genetic and environmental factors involved in cell wall remodelling and sporulation are the main drivers of adaptation in S. cerevisiae populations in the human gut.

10.
J Pediatr Gastroenterol Nutr ; 68(1): 144-153, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30169454

RESUMO

Biologic therapies have changed the outcome of both adult and pediatric patients with Inflammatory Bowel Disease (IBD). In September 2013, the first biosimilar of infliximab was introduced into the pharmaceutical market. In 2015, a first position paper on the use of biosimilars in pediatric IBD was published by the ESPGHAN IBD Porto group. Since then, more data have accumulated for both adults and children demonstrating biosimilars are an effective and safe alternative to the originator. In this updated position statement, we summarize current evidence and provide joint consensus statements regarding the recommended practice of biosimilar use in children with IBD.

11.
Inflamm Bowel Dis ; 25(3): 568-579, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30137352

RESUMO

BACKGROUND: We report a prospective, nationwide cohort evaluating the safety and effectiveness of CT-P13. METHODS: A structured database was used to record serious adverse events (SAEs), clinical remission/response, inflammatory biomarkers (CRP and calprotectin), and endoscopic findings. RESULTS: Eight hundred ten patients with inflammatory bowel disease (IBD) (452 Crohn's disease [CD]) were enrolled. Four hundred fifty-nine patients were naïve to anti-TNFα (group A), 196 had a previous exposure (group B), and the remaining 155 were switched to CT-P13 (group C). All patients were included in the safety evaluation with a mean follow-up of 345 ± 215 days and a total number of 6501 infusions. One hundred fifty-four SAEs were reported (19%), leading to cessation of the biosimilar in 103 subjects (12.7%). Infusion reactions were 71, leading to cessation of the biosimilar in 53 subjects (6.5%), being significantly more frequent in patients pre-exposed to anti-TNFα (P = 0.017). The efficacy of therapy was calculated in 754 IBD patients, with a mean follow-up of 329 ± 202 days. Forty-eight patients had a primary failure (6.4%), and 188 (25.6%) lost response during follow-up. Six hundred twenty-eight (364 CD) and 360 IBD patients (222 CD) completed the follow-up at 6 and 12 months, respectively. At 12 months, patients without loss of response were 71%, 64%. and 82% in groups A, B, and C, respectively (log rank P = 0.01). Clinical/endoscopic scores and inflammatory biomarkers dropped significantly in CD and UC patients (P = 0.01 and P < 0.0001) compared with baseline. CONCLUSIONS: In this large prospective cohort, no further signals of difference in safety and effectiveness of CT-P13 in IBD has been observed.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Itália , Masculino , Prognóstico , Estudos Prospectivos , Adulto Jovem
12.
Front Pediatr ; 6: 355, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30525016

RESUMO

Henoch-Schönlein purpura is a systemic vasculitis, commonly affecting children. Gastrointestinal manifestations are observed in 50-75% of patients; it is well known they may occur before skin lesions in about 20% of cases during the first vasculitic episode. Relapses occur in about one third of patients, typically within 4 months from the initial presentation and with milder symptoms. We report the case of a 17-year old girl with an atypical relapse of Henoch-Schönlein purpura, presenting with acute abdominal symptoms 5 years after the first episode. Esophagogastroduodenoscopy showed duodenal multiple hyperemic and hemorrhagic lesions. To our knowledge this is the first case of hemorrhagic-erosive duodenitis representing a relapse of Henoch-Schönlein purpura occurring several years after the initial episode. Duodenojejunal inflammation should be considered as primary manifestation of Henoch-Schönlein purpura, not only during the first episode, but also in relapses. Endoscopy can be helpful for differential diagnosis, especially in patients with atypical manifestations. Further studies are needed to evaluate risk factors for Henoch-Schönlein purpura recurrence and the possible role of fecal calprotectin as an early marker for gastrointestinal involvement.

13.
Aliment Pharmacol Ther ; 48(11-12): 1242-1250, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30450578

RESUMO

BACKGROUND: Paediatric Crohn's disease is characteried by frequently relapsing disease which may lead to hospitalisations and complications. AIM: To develop predictive models for early relapse following first remission. METHODS: The GROWTH CD prospective inception cohort was designed to predict risk for early disease relapse and poor outcomes. Newly diagnosed children underwent endoscopies and imaging. They were phenotyped and followed at scheduled visits through 78 weeks for relapses. Twenty-eight dichotomous and continuous variables were assessed at baseline and week 12, including phenotype, inflammatory markers, disease activity (PCDAI) and other markers. Clinical relapses defined as PCDAI >10 after remission were recorded using a relapse form. Logistic regression & risk modelling was performed. RESULTS: We enrolled 282 eligible patients of whom 178 (63.6%) patients achieved steroid free remission by week 12. Disease complications developed in 22/76(29%) of patients with relapse compared to 20/206 (9.7%) without relapse (P = 0.01). Multivariable analysis demonstrated that while variables from age/gender at diagnosis were not predictive, week 12 variables including PCDAI >5 (P = 0.02), CRP >20 mg/L (P = 0.02), and faecal calprotectin >400 µg/g (P = 0.03) as optimal cut-offs were associated with increased risk of relapse. A prediction model for patients in remission including gender, age, week 12 PCDAI, calprotectin and CRP had sensitivity 43%, specificity 92%, PPV 78%, NPV 71% for relapse. CONCLUSIONS: Early relapses were associated with a higher risk for disease complications at followup. Relapse prediction based on week 12 disease activity or inflammation is superior to prediction using data from diagnosis.


Assuntos
Doença de Crohn/diagnóstico , Doença de Crohn/metabolismo , Fatores Imunológicos/uso terapêutico , Índice de Gravidade de Doença , Adolescente , Biomarcadores/química , Biomarcadores/metabolismo , Criança , Pré-Escolar , Doença de Crohn/tratamento farmacológico , Fezes/química , Feminino , Humanos , Complexo Antígeno L1 Leucocitário/metabolismo , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Recidiva , Indução de Remissão/métodos , Resultado do Tratamento
14.
Ital J Pediatr ; 44(1): 138, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30458885

RESUMO

BACKGROUND: Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant disorder caused by defects involving the TRPS1 gene. It exhibits distinctive craniofacial, ectodermal and skeletal abnormalities, such as sparse hair, bulbous nasal tip and short deformed fingers, with extremely variable expressivity. CASE PRESENTATION: We report the case of a 17 months old girl, who presented growth retardation and dysmorphic features. Postnatal growth was always below - 2 Standard Deviation for both weight and length and physical examination revealed relative macrocephaly, sparse hair, bulbous nasal tip, thin upper lip, protruding ears, prominent forehead, small jaw, and short hands and feet. Patient's mother shared the same facial features, and presented sparse hair and small hands. The maternal grandfather and two uncles presented short stature, bulbous nasal tip, thin hair, and premature alopecia. Molecular analysis of TRPS1 gene showed a heterozygous c.2086C > T;(p.Arg696Ter) mutation both in the patient and her mother, confirming the diagnosis of TRPS, type I. CONCLUSIONS: Clinical phenotype of TRPS can be subtle and the syndrome often remains undiagnosed. A comprehensive clinical examination and an exhaustive family history are crucial to reach the correct diagnosis, which is essential to perform adequate follow-up and timely therapeutic procedures.


Assuntos
Dedos/anormalidades , Doenças do Cabelo/diagnóstico , Síndrome de Langer-Giedion/diagnóstico , Nariz/anormalidades , Proteínas de Ligação a DNA/genética , Diagnóstico Precoce , Feminino , Doenças do Cabelo/genética , Heterozigoto , Humanos , Lactente , Síndrome de Langer-Giedion/genética , Mutação , Fatores de Transcrição/genética
16.
J Pediatr Gastroenterol Nutr ; 66(4): 687-708, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29570147

RESUMO

BACKGROUND AND AIMS: A growing body of evidence supports the need for detailed attention to nutrition and diet in children with inflammatory bowel disease (IBD). We aimed to define the steps in instituting dietary or nutritional management in light of the current evidence and to offer a useful and practical guide to physicians and dieticians involved in the care of pediatric IBD patients. METHODS: A group of 20 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to Nutrition Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition Porto, IBD Interest, and Nutrition Committee. A list of 41 predefined questions was addressed by working subgroups based on a systematic review of the literature. RESULTS: A total of 53 formal recommendations and 47 practice points were endorsed with a consensus rate of at least 80% on the following topics: nutritional assessment; macronutrients needs; trace elements, minerals, and vitamins; nutrition as a primary therapy of pediatric IBD; probiotics and prebiotics; specific dietary restrictions; and dietary compounds and the risk of IBD. CONCLUSIONS: This position paper represents a useful guide to help the clinicians in the management of nutrition issues in children with IBD.


Assuntos
Doenças Inflamatórias Intestinais/dietoterapia , Avaliação Nutricional , Necessidades Nutricionais , Criança , Consenso , Europa (Continente) , Humanos , Doenças Inflamatórias Intestinais/complicações , Desnutrição/complicações , Desnutrição/dietoterapia , Estado Nutricional , Sociedades Médicas
17.
Artigo em Inglês | MEDLINE | ID: mdl-29384890

RESUMO

BACKGROUND AND AIMS: A growing body of evidence supports the need for detailed attention to nutrition and diet in children with IBD. We aimed to define the steps in instituting dietary or nutritional management in light of the current evidence and to offer a useful and practical guide to physicians and dieticians involved in the care of paediatric IBD patients. METHODS: A group of 20 experts in paediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to ESPGHAN Porto, IBD Interest and Nutrition Committee. A list of 41 predefined questions was addressed by working subgroups based on a SR of the literature. RESULTS: A total of 53 formal recommendations and 47 practice points were endorsed with a consensus rate of at least 80% on the following topics: nutritional assessment; nutrition as a primary therapy of paediatric IBD; macronutrients needs; trace Elements, minerals and vitamins; probiotics and prebiotics; specific dietary restrictions; dietary compounds and the risk of IBD. CONCLUSIONS: This position paper represents a useful guide to help the clinicians in the management of nutrition issues in children with IBD.

18.
J Crohns Colitis ; 12(3): 306-312, 2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29165666

RESUMO

Background: Exclusive enteral nutrition [EEN] and corticosteroids [CS] induce similar rates of remission in mild to moderate paediatric Crohn's disease [CD], but differ with regard to mucosal healing. Our goal was to evaluate if EEN at diagnosis was superior to CS for improving long-term outcomes. Methods: We prospectively followed newly diagnosed children aged < 17 years, with mild to moderate CD at baseline, for 2 years in the GROWTH CD study. Patients were evaluated at baseline and at 8, 12, 78, and 104 weeks. Remission, relapses, complications [fibrostenotic disease, penetrating disease, and active perianal disease] and growth were recorded throughout the study. A propensity score analysis was performed. Results: A total of 147 children [mean age 12.9 ± 3.2 years], treated by EEN [n = 60] or CS [n = 87] were included. New complications developed in 13.7% of CS [12/87] versus 11.6% of EEN [7/60], p = 0.29. Remission was achieved in 41/87 [47%] in CS and 38/60 [63%] EEN, p = 0.036. Median time to relapse did not differ [14.4 ± 1 months with CS, 16.05 ± 1.1 EEN, p = 0.28]. Mean height Z scores decreased from Week 0 to Week 78 with CS [-0.34 ± 1.1 to -0.51 ± 1.2, p = 0.01], but not with EEN [-0.32 ± 1.1 to -0.22 ± 0.9, p = 0.56]. In a propensity score analysis, EEN was superior to CS for inducing remission [p = 0.05] and trended to superiority for height Z score [p = 0.055]. Conclusions: Use of EEN was associated with higher remission rates and a trend toward better growth but with similar relapse and complication rates in new-onset mild to moderate paediatric CD.


Assuntos
Corticosteroides/uso terapêutico , Estatura , Doença de Crohn/terapia , Nutrição Enteral , Fístula Retal/etiologia , Indução de Remissão , Abscesso/etiologia , Adolescente , Produtos Biológicos/uso terapêutico , Criança , Constrição Patológica/etiologia , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Masculino , Pontuação de Propensão , Estudos Prospectivos , Recidiva , Índice de Gravidade de Doença , Resultado do Tratamento
19.
J Allergy Clin Immunol ; 141(3): 1036-1049.e5, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29241729

RESUMO

BACKGROUND: Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. OBJECTIVE: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. METHODS: Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. RESULTS: We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. CONCLUSIONS: Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.


Assuntos
Diabetes Mellitus Tipo 1/congênito , Diarreia , Fatores de Transcrição Forkhead , Doenças Genéticas Ligadas ao Cromossomo X , Transplante de Células-Tronco Hematopoéticas , Doenças do Sistema Imunitário/congênito , Imunossupressão , Mutação , Adolescente , Adulto , Aloenxertos , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 1/terapia , Diarreia/genética , Diarreia/imunologia , Diarreia/mortalidade , Diarreia/terapia , Intervalo Livre de Doença , Feminino , Seguimentos , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/mortalidade , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Humanos , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/imunologia , Doenças do Sistema Imunitário/mortalidade , Doenças do Sistema Imunitário/terapia , Lactente , Masculino , Estudos Retrospectivos , Taxa de Sobrevida
20.
Front Microbiol ; 8: 1979, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29081768

RESUMO

Diet is one of the main factors that affects the composition of gut microbiota. When people move from a rural environment to urban areas, and experience improved socio-economic conditions, they are often exposed to a "globalized" Western type diet. Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy). We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11), of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5) and of a group of Italian children (n = 13). We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. Microbiota of rural children retain a geographically unique bacterial reservoir (Prevotella, Treponema, and Succinivibrio), assigned to ferment fiber and polysaccharides from vegetables. Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), a predictive functional profiling of microbial communities using 16S rRNA marker gene. Consequently, we observed a progressive reduction of SCFAs measured by gas chromatography-mass spectrometry, in urban populations, especially in Italian children, respect to rural ones. Our results even if in a limited number of individuals point out that dietary habit modifications in the course of urbanization play a role in shaping gut microbiota, and that ancient microorganisms, such as fiber-degrading bacteria, are at risk of being eliminated by the fast paced globalization of foods and by the advent of westernized lifestyle.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA