Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 14 de 14
Filtrar
1.
Expert Rev Clin Immunol ; 20(2): 211-223, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37870118

RESUMO

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus with increasing prevalence worldwide. It is a multifactorial disease caused by a combination of immunologic, genetic, and environmental factors. The clinical presentation of EoE varies largely, especially between different age groups. While diagnostic criteria and therapeutic goals are similar in children and adults, there are differences in treatment, with a more cautious approach in children to avoid growth disturbances. In addition, close monitoring and follow-up are essential in children to ensure uninterrupted growth. AREAS COVERED: A search in PubMed/MEDLINE, EMBASE, and SCOPUS databases was conducted to identify relevant studies published between January 2010 and January 2023 to give an overview of the state-of-the-art of EoE epidemiology, diagnosis, and treatment while focusing on similarities and differences between the adult and the pediatric population. EXPERT OPINION: The current state of research indicates that while significant progress has been made in understanding and treating EoE, further research and advances are needed to optimize diagnostic strategies, tailored treatment approaches, monitoring, and follow-up, and improve long-term outcomes for patients. With further innovation, the management of EoE can become more precise and tailored, leading to better patient outcomes and improved quality of life.


Assuntos
Esofagite Eosinofílica , Adulto , Humanos , Criança , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/epidemiologia , Esofagite Eosinofílica/terapia , Qualidade de Vida
3.
Pharmacogenomics J ; 23(5): 112-118, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37016150

RESUMO

Anti-tumor necrosis factor alpha (anti-TNFα) inhibitors are used extensively for the management of moderate to severe inflammatory bowel disease (IBD) in both adult and pediatric patients. Unfortunately, not all patients show an optimal response to induction therapy, while others lose their response over time for reasons yet poorly understood. We report on a pharmacokinetic/pharmacogenetic approach to monitor the therapy with anti-TNFα in a real-world cohort of seventy-nine pediatric patients affected by IBD that was analyzed retrospectively. We evaluated plasma concentrations of infliximab, adalimumab, and related anti-drug antibodies (ADAs), and single nucleotide polymorphisms (SNPs) in genes involved in immune processes and inflammation on the anti-TNFα response. We found a significant association between the SNP in TNFα promoter (-308G>A) and clinical remission without steroids in patients on infliximab therapy. Additionally, a potential connection between HLA-DQA1*05 genetic variant carriers and a higher risk of anti-TNFα immunogenicity emerged.


Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Adulto , Humanos , Criança , Fator de Necrose Tumoral alfa/genética , Infliximab/uso terapêutico , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/genética , Farmacogenética , Adalimumab/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética
4.
Int J Mol Sci ; 22(21)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34768815

RESUMO

Celiac disease (CeD) is triggered by gluten and results in inflammation and villous atrophy of the small intestine. We aimed to explore the role of miRNA-mediated deregulation of the transcriptome in CeD. Duodenal biopsies of CeD patients (n = 33) and control subjects (n = 10) were available for miRNA-sequencing, with RNA-sequencing also available for controls (n = 5) and CeD (n = 6). Differential expression analysis was performed to select CeD-associated miRNAs and genes. MiRNA‒target transcript pairs selected from public databases that also displayed a strong negative expression correlation in the current dataset (R < -0.7) were used to construct a CeD miRNA‒target transcript interaction network. The network includes 2030 miRNA‒target transcript interactions, including 423 experimentally validated pairs. Pathway analysis found that interactions are involved in immune-related pathways (e.g., interferon signaling) and metabolic pathways (e.g., lipid metabolism). The network includes 13 genes previously prioritized to be causally deregulated by CeD-associated genomic variants, including STAT1. CeD-associated miRNAs might play a role in promoting inflammation and decreasing lipid metabolism in the small intestine, thereby contributing unbalanced cell turnover in the intestinal crypt. Some CeD-associated miRNAs deregulate genes that are also affected by genomic CeD-risk variants, adding an additional layer of complexity to the deregulated transcriptome in CeD.


Assuntos
Doença Celíaca/metabolismo , Duodeno/metabolismo , Inflamação , Metabolismo dos Lipídeos , MicroRNAs/genética , Transcriptoma , Autoimunidade , Doença Celíaca/genética , Feminino , Humanos , Interferons/metabolismo , Masculino , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Análise de Sequência de RNA , Transdução de Sinais
5.
Sci Rep ; 11(1): 18076, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508152

RESUMO

Improving the quality of life (QoL) is crucial in the management of pediatric inflammatory bowel disease (IBD). We aimed to (1) Validate the IMPACT-III questionnaire in Italian IBD children; (2) explore factors associated to QoL in pediatric IBD. Internal consistency, concurrent validity, discriminant validity and reproducibility of the Italian version of the IMPACT-III questionnaire was measured in IBD children/adolescents in 8 centers. Associations between patient and disease characteristics and the IMPACT-III domains were analyzed through quantile regression analysis. The IMPACT-III questionnaire, collected in 282 children with IBD (median age: 14.8 years; IQR 12.4-16.4) showed a median total score of 76 (IQR 67-83). Female gender, active disease and age were negatively associated with the total IMPACT-III score. Specifically, female gender was negatively associated with the Bowel/Systemic Symptoms, Emotional and Treatment domain scores, while disease activity was significantly associated with Bowel Symptoms and Treatment/Interventions reported QoL. The IMPACT- III showed good internal consistency (Cronbach's alpha coefficient = 0.87, 95% CI 0.85-0.89) and reproducibility (Concordance Correlation Coefficient = 0.66, 95% CI 0.57-0.74). In Italian children with IBD active disease, female gender and adolescence are associated to a worse QoL, indicating the need of more attention in this subgroup of young patients. IMPACT-III questionnaire is a reliable instrument to measure QoL in Italian children.


Assuntos
Doenças Inflamatórias Intestinais/epidemiologia , Qualidade de Vida , Adolescente , Fatores Etários , Criança , Pré-Escolar , Suscetibilidade a Doenças , Análise Fatorial , Feminino , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/etiologia , Itália/epidemiologia , Masculino , Saúde Mental , Vigilância em Saúde Pública , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Inquéritos e Questionários
6.
Front Pediatr ; 9: 607285, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968841

RESUMO

Objectives: In the era of Coronavirus 2019 (COVID-19), concern has been raised for immunosuppressed patients, including children with inflammatory bowel diseases (IBD). We aimed to collect data from IBD tertiary centers of Lombardy during pandemic. Methods: A cross-sectional survey enrolling IBD children has been completed by seven major IBD centers in Lombardy during lockdown. The clinical form included questions on any symptom consistent with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the IBD adherence treatment. Furthermore, we have reviewed all IBD medical records including new IBD diagnoses and flares in known IBD patients after the lockdown. Results: Questionnaires of 290 IBD children were returned during lockdown. Out of them, 24 children (8%) complained of mild symptoms suspicious of SARS-CoV-2 infection without needing hospitalization or changing IBD treatment. During the lockdown, one patient presented with IBD flare and one had infectious colitis, with no new IBD cases. Conversely, after lockdown, 12/290 (4%) children relapsed and 15 children were newly diagnosed with IBD. Last year, in the same timeframe, 20/300 (7%) children presented with IBD flare, while 17 children had IBD onset with no statistical difference. Conclusions: Our data on children with IBD in a high COVID-19 prevalence region are reassuring. Only a minority of IBD children had mild symptoms, and no hospitalization or treatment modification was needed. Standard IBD treatments including biologics were safely continued. New IBD diagnoses and flares in known IBD children occurred after the lockdown phase, although no significant difference was found compared with the previous year.

7.
Dig Liver Dis ; 53(3): 283-288, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33388247

RESUMO

BACKGROUND: IBD management has been significantly affected during the COVID-19 lockdown with potential clinical issues. AIMS: The aim of this study was to analyse the impact of COVID-19 pandemic on the Italian paediatric IBD cohort. METHODS: This was a multicentre, retrospective, cohort investigation including 21 different Italian IBD referral centres. An electronic data collection was performed among the participating centres including: clinical characteristics of IBD patients, number of COVID-19 cases and clinical outcomes, disease management during the lockdown and the previous 9 weeks. RESULTS: 2291 children affected by IBD were enrolled. We experienced a significant reduction of the hospital admissions [604/2291 (26.3%) vs 1281/2291 (55.9%); p < 0.001]. More specifically, we observed a reduction of hospitalizations for new diagnosis (from n = 44 to n = 27) and endoscopic re-evaluations (from n = 46 to n = 8). Hospitalization for relapses and surgical procedures remained substantially unchanged. Biologic infusions did not significantly vary [393/2291 (17.1%) vs 368/2291 (16%); p = 0.3]. Telemedicine services for children with IBD were activated in 52.3% of the centres. In 42/2291(1.8%) children immunosuppressive therapies were adapted due to the concurrent COVID-19 pandemic. CONCLUSION: Due to the several limitations of the lockdown, cares for children with IBD have been kept to minimal standards, giving priorities to the urgencies and to biologics' infusions and implementing telemedicine services.


Assuntos
Produtos Biológicos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Endoscopia Gastrointestinal/tendências , Fármacos Gastrointestinais/uso terapêutico , Hospitalização/tendências , Telemedicina/tendências , Adolescente , COVID-19/epidemiologia , Criança , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/epidemiologia , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Gerenciamento Clínico , Feminino , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Itália/epidemiologia , Masculino , Recidiva , SARS-CoV-2
8.
Dig Liver Dis ; 53(2): 183-189, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33132063

RESUMO

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2, spreading in Italy during the first months of 2020, abruptly changed the way of practicing medicine in this country. As a consequence of the lockdown, the diagnostic and therapeutic management of paediatric chronic conditions, such as inflammatory bowel disease (IBD) has been affected. During the peak of COVID-19 pandemic, elective visits, endoscopies and infusions have been postponed, with potential clinical and psychological impact on disease course and a high likelihood of increasing waiting lists. While slowly moving back towards normality, clinicians need to recognize the best ways to care for patients with IBD, carefully avoiding risk factors for new potential epidemic outbreaks. In this uncertain scenario until the development and spread of COVID-19 vaccine, it is necessary to continue to operate with caution. Hereby we provide useful indications for a safer and gradual restarting of routine clinical activities after COVID-19 peak in Italy.


Assuntos
COVID-19 , Controle de Doenças Transmissíveis/métodos , Gastroenterologia , Doenças Inflamatórias Intestinais , Pediatria , COVID-19/epidemiologia , COVID-19/prevenção & controle , Criança , Gastroenterologia/métodos , Gastroenterologia/organização & administração , Gastroenterologia/tendências , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Itália , Inovação Organizacional , Pediatria/métodos , Pediatria/organização & administração , Pediatria/tendências , Risco Ajustado , SARS-CoV-2
9.
Eur J Med Genet ; 63(9): 103999, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32622956

RESUMO

Celiac disease (CD) screening in patients with Williams-Beuren Syndrome (WBS) is suggested, although data described in literature are discordant regarding CD prevalence in WBS. We retrospectively collected data from 101 WBS Italian patients [mean age: 13.5 years], to clarify the CD prevalence in a large cohort. All patients underwent a CD biochemical screening: IgA and anti-transglutaminase reflex antibodies (tTGA). CD-specific HLA typing was available for 42 patients. Small intestinal biopsy was performed in patients according to ESPGHAN guidelines. In 7 WBS patients an overt celiac disease was diagnosed. In 3 patients CD was confirmed by symptoms, HLA-DQ heterodimers and CD specific antibodies title, whereas in 4 patients, it was confirmed by a small intestinal biopsy. CD prevalence in our cohort is 6.9% (7/101). In 42/101 patients the CD-specific HLA typing was available, detecting 29/42 (69%) patients genetically predisposed to CD. The CD prevalence and CD-specific HLA prevalence are both higher than in the general population (p < 0.001; p < 0.001). Our cohort is the most numerous described confirming that the CD risk in WBS patients is significantly greater than in general population. Moreover, our HLA typing results, as well as scientific literature, suggest that the higher CD prevalence in WBS patients might not be intrinsically related to the genetic disease itself but with the higher HLA prevalence. However, HLA typing should be performed in bigger WBS cohorts to confirm this hypothesis. Our data confirms that HLA typing is mandatory in WBS patients and that CD screening should be performed only if genetically predisposed.


Assuntos
Doença Celíaca/genética , Testes Genéticos/normas , Síndrome de Williams/genética , Adolescente , Anticorpos/imunologia , Doença Celíaca/diagnóstico , Doença Celíaca/epidemiologia , Criança , Pré-Escolar , Feminino , Antígenos HLA-DQ/genética , Humanos , Testes Imunológicos/normas , Lactente , Intestino Delgado/imunologia , Intestino Delgado/patologia , Masculino , Transglutaminases/imunologia , Síndrome de Williams/complicações , Síndrome de Williams/diagnóstico
10.
Am J Med Genet A ; 182(9): 2094-2101, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32648352

RESUMO

Cornelia de Lange syndrome Spectrum (CdLSp) is characterized by intellectual disability, facial dysmorphisms, and growth impairment. Although eating difficulties are a well-known feature of the disease, there is no data regarding the nutritional deficiencies of these patients. The food intake was tracked using a dietary transcription provided by the family/caregivers, biochemical nutritional parameters were measured with laboratory tests and through an accurate clinical evaluation of the incidence of qualitative and quantitative imbalances in a cohort of 73 patients with CdLSp ware determined. Of these 73, 62 (85%) subjects provided a complete and detailed dietary transcription. In the studied population, a quantitative caloric imbalance in 47/62 (76%) subjects was observed. The caloric intake was low in 27/62 (43%) subjects whereas excessive in 20/62 (33%). Only 15/62 (24%) had an optimum caloric intake. Regarding micronutrients, a calcium intake deficiency in 32% of the patients (20/62) was observed. Blood tests revealed a low iron level in 22/73 (30%) of the patients and 25(OH)D deficiency in 49/73 (67%). Serum hypocalcemia was not evidenced. Qualitative and quantitative imbalances resulted in more frequent than expected in CdLSp patients. A qualitative imbalance was more prevalent in younger patients while in older patients prevailed mainly a quantitative disproportion. We found no statistically meaningful correlation between dietary imbalances, genetic, or clinical parameters. Our findings highlight the need for further studies to evaluate the basal metabolic rate of CdLSp patients and find a correlation with their growth impairment.


Assuntos
Síndrome de Cornélia de Lange/genética , Ingestão de Alimentos/genética , Deficiência Intelectual/genética , Desnutrição/genética , Adolescente , Proteínas de Ciclo Celular/sangue , Criança , Pré-Escolar , Proteínas Cromossômicas não Histona/sangue , Estudos de Coortes , Síndrome de Cornélia de Lange/sangue , Síndrome de Cornélia de Lange/metabolismo , Síndrome de Cornélia de Lange/patologia , Feminino , Humanos , Deficiência Intelectual/sangue , Deficiência Intelectual/metabolismo , Deficiência Intelectual/patologia , Ferro/sangue , Itália , Masculino , Desnutrição/sangue , Desnutrição/metabolismo , Desnutrição/patologia , Fenótipo
11.
Am J Med Genet A ; 182(7): 1697-1703, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32436647

RESUMO

Cornelia de Lange spectrum (CdLSp) is a rare genetic condition characterized by intellectual disability, facial dysmorphisms, major malformations, growth impairment, and development delay. Approximately 80% of CdLSp patients have gastroesophageal reflux disease (GERD) with a varied clinical presentation. The aim of this study is to define potential clinical/genetic risk factors based on the clinical phenotype description of CdLSp patients with severe GERD who underwent surgical treatment. We retrospectively collected data from 23 CdLSp patients, 13 females and 10 males. Mean age of the patients undergoing surgical treatment was of 4 years. 21/23 (91%) had a molecular characterization, of which 21/21 (100%) had a NIPBL gene mutation, while 2/23 (9%) did not have a genetical characterization, only a clinical diagnosis. Most of our patients presented a moderate-severe severity score (21/23, 91%) with limb malformations evidenced in 10/23 (44%) of our patients and a moderate-severe intellectual disability in 20/23 (87%). Therefore, CdLSp patients harboring NIPBL variants, upper limb malformations and severe psychomotor delay are more likely to suffer from severe GERD, not responsive to proton pump inhibitors treatment. These features should be considered as clinical markers for potentially severe GERD that might require surgical treatment.


Assuntos
Síndrome de Cornélia de Lange/genética , Síndrome de Cornélia de Lange/cirurgia , Refluxo Gastroesofágico/cirurgia , Adolescente , Adulto , Proteínas de Ciclo Celular/genética , Criança , Pré-Escolar , Síndrome de Cornélia de Lange/complicações , Feminino , Fundoplicatura , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/etiologia , Humanos , Lactente , Deficiência Intelectual/etiologia , Masculino , Mutação , Estudos Retrospectivos , Adulto Jovem
12.
Am J Med Genet A ; 176(9): 1865-1871, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30240081

RESUMO

Cornelia de Lange syndrome (CdLS) is a genetic condition characterized by intellectual disability, peculiar facial dysmorphisms, multiorgan malformations, and growth problems. Majority cases of CdLS are caused by mutations in genes of Cohesin pathway. Although feeding problems are a well-known feature, no specific data have been published about the use of nutritional devices. We analyzed use, type, time of introduction, and duration of nutritional devices in 73 CdLS patients. In total, 29/73 (40%) used a device; nasogastric tube (NGT) in 28/73 (38%) and percutaneous endoscopic gastrostomy (PEG) in 7/73 (10%). NGT was placed during the first days/weeks of life. 19/28 (68%) maintained it for less than 3 months, 7/28 (25%) for a period between 3 and 12 months, while 2/28 (7%) for more than 1 year. PEG was placed within the first year in 4/7 (57%) and removed in two patients after 4 years These data have been matched with a wide number of genetic and clinical variables. Presence of upper limb malformations is positively correlated with the need of a device. From the opposite side, the use of a device positively correlates with a more severe prognosis as regard growth, intellectual development and disease severity. Our data show that nutritional devices are frequently used by CdLS patients, also if the majority of them (93.1%) succeed with time in achieving a normal oral nutrition. Finally, the need, the type of device used and the duration of NGT or/plus PEG can be considered a further sign of worse prognosis of the disease itself.


Assuntos
Síndrome de Cornélia de Lange/dietoterapia , Apoio Nutricional/instrumentação , Apoio Nutricional/métodos , Criança , Pré-Escolar , Estudos de Coortes , Hibridização Genômica Comparativa , Síndrome de Cornélia de Lange/diagnóstico , Síndrome de Cornélia de Lange/genética , Feminino , Estudos de Associação Genética , Marcadores Genéticos , Humanos , Lactente , Itália , Masculino , Fenótipo , Índice de Gravidade de Doença
13.
Am J Med Genet C Semin Med Genet ; 172(2): 206-13, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27164219

RESUMO

Cornelia de Lange syndrome (CdLS) is a rare genetic condition related to mutation of various cohesion complex related genes. Its natural history is quite well characterized as regard pediatric age. Relatively little information is available regarding the evolution of the disease in young-adult age. In medical literature, only one specific study has been published on this topic. We report on our experience on 73 Italian CdLS patients (40 males and 33 females) with and age range from 15 to 49 years. Our results confirm the previous study indicating that gastroesophageal reflux disease (GERD) is the main medical problem of these patients in childhood and young-adult age. Other medical features that should be considered in the medical follow-up are tendency to overweight/frank obesity, constipation, discrepancy of limbs' length, epilepsy, hearing, and visual problems. Behavioral problems are particularly frequent as well. For this reason, every source of hidden pain should be actively searched for in evaluating a patient showing such a disorder. Finally, recommendations for medical follow-up in adult age are discussed. © 2016 Wiley Periodicals, Inc.


Assuntos
Síndrome de Cornélia de Lange/complicações , Síndrome de Cornélia de Lange/patologia , Adolescente , Adulto , Epilepsia , Feminino , Refluxo Gastroesofágico , Transtornos da Audição , Humanos , Itália/epidemiologia , Deformidades Congênitas dos Membros , Masculino , Transtornos Mentais , Pessoa de Meia-Idade , Obesidade , Transtornos da Visão , Adulto Jovem
14.
Genes Nutr ; 10(5): 482, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26233308

RESUMO

Celiac disease is an intestinal disease which shows different symptoms and clinical manifestations among pediatric and adult patients. These variations could be imputable to age-related changes in gut architecture and intestinal immune system, which could be characterized by gene expression differences possibly regulated by miRNAs. We analyzed a panel of miRNAs and their target genes in duodenal biopsies of Marsh 3AB and 3C pediatric celiac patients, compared to controls. Moreover, to assess variation of expression in plasma samples, we evaluated circulating miRNA levels in controls and patients at diagnosis or on gluten-free diet. We detected a decreased miR-192-5p expression in celiac patients, but no variations in NOD2 and CXCL2, targets previously identified in adults. Conversely, we detected a significant increase in mRNA and protein levels of another target, MAD2L1, protein related to cell cycle control. miR-31-5p and miR-338-3p were down-regulated and their respective targets, FOXP3 and RUNX1, involved in Treg function, resulted up-regulated in celiac patients. Finally, we detected, in celiac patients, an increased expression of miR-21-5p, possibly caused by a regulatory loop with its putative target STAT3, which showed an increased activation in Marsh 3C patients. The analysis of plasma revealed a trend similar to that observed in biopsies, but in presence of gluten-free diet we could not detect circulating miRNAs values comparable to controls. miRNAs and their gene targets showed an altered expression in duodenal mucosa and plasma of celiac disease pediatric patients, and these alterations could be different from adult ones.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...