RESUMO
Children with Multisystem Inflammatory Syndrome in Children (MIS-C) can present with thrombocytopenia, which is a key feature of hemophagocytic lymphohistiocytosis (HLH). We hypothesized that thrombocytopenic MIS-C patients have more features of HLH. Clinical characteristics and routine laboratory parameters were collected from 228 MIS-C patients, of whom 85 (37%) were thrombocytopenic. Thrombocytopenic patients had increased ferritin levels; reduced leukocyte subsets; and elevated levels of ASAT and ALAT. Soluble IL-2RA was higher in thrombocytopenic children than in non-thrombocytopenic children. T-cell activation, TNF-alpha and IFN-gamma signaling markers were inversely correlated with thrombocyte levels, consistent with a more pronounced cytokine storm syndrome. Thrombocytopenia was not associated with severity of MIS-C and no pathogenic variants were identified in HLH-related genes. This suggests that thrombocytopenia in MIS-C is not a feature of a more severe disease phenotype, but the consequence of a distinct hyperinflammatory immunopathological process in a subset of children.
Assuntos
Linfo-Histiocitose Hemofagocítica , Síndrome de Resposta Inflamatória Sistêmica , Trombocitopenia , Humanos , Linfo-Histiocitose Hemofagocítica/sangue , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/genética , Criança , Masculino , Pré-Escolar , Feminino , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Trombocitopenia/sangue , Trombocitopenia/imunologia , Lactente , Adolescente , Fenótipo , Proteômica , COVID-19/imunologia , COVID-19/sangue , COVID-19/complicaçõesRESUMO
Eosinophilic esophagitis (EoE), when left untreated, may progress from an inflammatory to a fibrostenotic phenotype. Inflammation generally recurs after treatment withdrawal. Thus, long-term treatment has been recommended. Here, we describe a cohort of children with EoE who achieved clinical and histologic remission with elimination diets, and maintained sustained untreated remission (SUR) despite re-introduction of all eliminated food allergens.
Assuntos
Alérgenos/efeitos adversos , Esofagite Eosinofílica/dietoterapia , Hipersensibilidade Alimentar/dietoterapia , Alimentos/efeitos adversos , Suspensão de Tratamento , Criança , Esofagite Eosinofílica/etiologia , Hipersensibilidade Alimentar/complicações , Humanos , Indução de RemissãoRESUMO
OBJECTIVES: The aim of the study was to assess differences in the diagnosis and management of eosinophilic esophagitis (EoE) by European pediatric (PG) and adult gastroenterologists (AG), and their self-reported adherence to guidelines. METHODS: A multiple-choice questionnaire gauged the diagnostic and management strategies of gastroenterologists treating children or adults in 14 European countries and the United Arab Emirates (UAE). RESULTS: Questionnaires were completed by 465 PG and 743 AG. PG were significantly more likely to take biopsies in patients with symptoms of esophageal dysfunction (86.2% PG vs 75.4% AG, Pâ<â0.001) and to perform endoscopic follow-up (86.3% PG vs 80.6% AG, Pâ<â0.001). After failure of proton-pump inhibitors (PPIs), topical steroids were the preferred second-line therapy; however, PG opted more frequently for elimination diets (47.5% PG vs 13.7% AG, Pâ<â0.001). More PG than AG indicated having read recent guidelines (89.4% PG vs 58.2% AG, Pâ<â0.001). Geographic differences in practice were reported, with respondents from the United Kingdom, Portugal, and Spain more often adhering to recommended biopsy protocols. Physicians in the UAE, France, Lithuania, and Poland tended to opt for steroid therapy or elimination diets as first-line therapy, in contrast to most other countries. CONCLUSIONS: Significant differences in general practice between PG and AG were demonstrated with notable divergence from consensus guidelines. International practice variations are also apparent. Among other strategies, educational activities to highlight current recommendations may help harmonize and optimize clinical practice.
Assuntos
Esofagite Eosinofílica , Gastroenterologia , Adulto , Criança , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/epidemiologia , Europa (Continente) , França , Humanos , Polônia , Portugal , Inibidores da Bomba de Prótons/uso terapêutico , Espanha , Reino UnidoRESUMO
OBJECTIVES: Recommendations for diagnosing and treating eosinophilic esophagitis (EoE) are evolving; however, information on real world clinical practice is lacking. To assess the practices of pediatric gastroenterologists diagnosing and treating EoE and to identify the triggering allergens in European children. METHODS: Retrospective anonymized data were collected from 26 European pediatric gastroenterology centers in 13 countries. Inclusion criteria were: Patients diagnosis with EoE, completed investigations prescribed by the treating physician, and were on stable medical or dietary interventions. RESULTS: In total, 410 patients diagnosed between December 1999 and June 2016 were analyzed, 76.3% boys. The time from symptoms to diagnosis was 12â±â33.5 months and age at diagnosis was 8.9â±â4.75 years. The most frequent indications for endoscopy were: dysphagia (38%), gastroesophageal reflux (31.2%), bolus impaction (24.4%), and failure to thrive (10.5%). Approximately 70.3% had failed proton pump inhibitor treatment. The foods found to be causative of EoE by elimination and rechallenge were milk (42%), egg (21.5%), wheat/gluten (10.9%), and peanut (9.9%). Elimination diets were used exclusively in 154 of 410 (37.5%), topical steroids without elimination diets in 52 of 410 (12.6%), both diet and steroids in 183 of 410 (44.6%), systemic steroids in 22 of 410 (5.3%), and esophageal dilation in 7 of 410 (1.7%). Patient refusal, shortage of endoscopy time, and reluctance to perform multiple endoscopies per patient were noted as factors justifying deviation from guidelines. CONCLUSIONS: In this "real world" pediatric European cohort, milk and egg were the most common allergens triggering EoE. Although high-dose proton pump inhibitor trials have increased, attempted PPI treatment is not universal.
Assuntos
Esofagite Eosinofílica/epidemiologia , Sistema de Registros , Adolescente , Criança , Pré-Escolar , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/tratamento farmacológico , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Cohort studies have suggested that early-life antibiotic treatment is associated with increased risk of atopy. We determined whether antibiotic treatment already in the first week of life increases the risk of atopic and non-atopic disorders. METHODS: The INCA study is a prospective observational birth cohort study of 436 term infants, with follow-up of 1 year; 151 neonates received broad-spectrum antibiotics for suspected neonatal infection (AB+), vs a healthy untreated control group (N = 285; AB-). In the first year, parents recorded daily (non-) allergic symptoms. At 1 year, doctors' diagnoses were registered and a blood sample was taken (n = 205). RESULTS: Incidence of wheezing in the first year was higher in AB+ than AB- (41.0% vs 30.5%, P = .026; aOR 1.56 [95%CI 0.99-2.46, P = .06]). Infantile colics were more prevalent in AB+ compared to AB- (21.9% and 14.4% P = .048), and antibiotic treatment was an independent risk factor for infantile colics (aOR 1.66 (95%CI 1.00-2.77) P = .05). Allergic sensitization (Phadiatop >0.70kUA/L) showed a trend toward a higher risk in AB+ (aOR 3.26 (95%CI 0.95-11.13) P = .06). Incidence of eczema, infections, and GP visits in the first year were similar in AB+ and AB-. CONCLUSION: Antibiotic treatment in the first week of life is associated with an increased risk of wheezing and infantile colics. This study may provide a rationale for early cessation of antibiotics in neonates without proven or probable infection.
Assuntos
Antibacterianos/efeitos adversos , Cólica/induzido quimicamente , Hipersensibilidade/etiologia , Sons Respiratórios/etiologia , Estudos de Coortes , Cólica/epidemiologia , Feminino , Humanos , Hipersensibilidade/epidemiologia , Imunização , Imunoglobulina E/sangue , Incidência , Recém-Nascido , Masculino , Estudos Prospectivos , Fatores de RiscoRESUMO
OBJECTIVES: Adalimumab, a humanised anti-tumour necrosis factor antibody, is an effective treatment in adult patients with refractory Crohn disease (CD). The available literature on its efficacy in children remains limited. We aimed to evaluate the real-world efficacy in paediatric patients with CD and compare the efficacy between infliximab (IFX) nonresponders and patients who lost response to IFX. METHODS: All Dutch patients with CD receiving adalimumab before the age of 18 years after previous IFX therapy were identified. We analysed longitudinal disease activity, assessed by the mathematically weighted Pediatric Crohn's Disease Activity Index (wPCDAI) or the physician global assessment (PGA), and adverse events (AEs). RESULTS: Fifty-three patients with CD were included. Twelve patients received monotherapy and the others received combination treatment with thiopurines (nâ=â21), methotrexate (nâ=â11), steroids (nâ=â7), or exclusive enteral nutrition (nâ=â2). Median follow-up was 12 months (interquartile range 5-23). Remission was reached in 34 patients (64%, wPCDAIâ<â12.5 or PGAâ=â0) after a median of 3.3 months, and maintained by 50% for 2 years. Eleven patients (21%) reached response but not remission (decrease in wPCDAIâ≥â17.5 or decrease in PGA). Eighteen patients (34%) failed adalimumab treatment because of nonresponse (nâ=â4), lost response (nâ=â11), or AEs (nâ=â3). More IFX nonresponders failed adalimumab treatment than patients who lost response to IFX (2/3 vs 8/34, hazard ratio 18.8, 95% confidence interval 1.1-303.6). Only 1 patient encountered a serious AE, a severe but nonfatal infection. CONCLUSIONS: In clinical practice, adalimumab induces remission in two-thirds of children with IFX refractory CD.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Doença de Crohn/tratamento farmacológico , Adalimumab , Adolescente , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Criança , Resistência a Medicamentos , Quimioterapia Combinada , Tolerância a Medicamentos , Feminino , Humanos , Infliximab , Masculino , Retratamento , Estudos Retrospectivos , Índice de Gravidade de Doença , Falha de TratamentoRESUMO
Although disease-associated undernutrition is still an important problem in hospitalized children that is often underrecognized, follow-up studies evaluating post-discharge nutritional status of children with undernutrition are lacking. The aim of this multicentre prospective observational cohort study was to assess the rate of acute undernutrition (AU) and/or having a high nutritional risk (HR) in children on admission to seven secondary-care level Dutch hospitals and to evaluate the nutritional course of AU/HR group during admission and post-discharge. STRONGkids was used to indicate HR, and AU was based on anthropometric data (z-score < -2 for weight-for-age (WFA; <1 year) or weight-for-height (WFH; ≥1 year)). In total, 1985 patients were screened for AU/HR over a 12-month period. On admission, AU was present in 9.9% of screened children and 6.2% were classified as HR; 266 (13.4%) children comprised the AU/HR group (median age 2.4 years, median length of stay 3 days). In this group, further nutritional assessment by a dietitian during hospitalization occurred in 44% of children, whereas 38% received nutritional support. At follow-up 4-8 weeks post-discharge, 101 out of orginal 266 children in the AU/HR group (38%) had available paired anthropometric measurements to re-assess nutrition status. Significant improvement of WFA/WFH compared to admission (-2.48 vs. -1.51 SD; p < 0.001) and significant decline in AU rate from admission to outpatient follow-up (69.3% vs. 35.6%; p < 0.001) were shown. In conclusion, post-discharge nutritional status of children with undernutrition and/or high nutritional risk on admission to secondary-care level pediatric wards showed significant improvement, but about one-third remained undernourished. Findings warrant the need for a tailored post-discharge nutritional follow-up.
Assuntos
Avaliação Nutricional , Estado Nutricional , Humanos , Feminino , Estudos Prospectivos , Masculino , Pré-Escolar , Lactente , Criança , Seguimentos , Países Baixos/epidemiologia , Desnutrição/epidemiologia , Desnutrição/diagnóstico , Hospitalização/estatística & dados numéricos , Centros de Cuidados de Saúde Secundários/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Apoio Nutricional , Tempo de Internação/estatística & dados numéricos , Transtornos da Nutrição Infantil/epidemiologia , AdolescenteRESUMO
The neonatal period, during which the initial gut microbiota is acquired, is a critical phase. The healthy development of the infant's microbiome can be interrupted by external perturbations, like antibiotics, which are associated with profound effects on the gut microbiome and various disorders later in life. The aim of this study was to investigate the development of intestinal microbiota and the effect of antibiotic exposure during the first three months of life in term infants. Fecal samples were collected from healthy infants and infants who received antibiotics in the first week of life at one week, one month, and three months after birth. Microbial composition was analyzed using IS-pro and compared between antibiotics-treated and untreated infants. In total, 98 infants, divided into four groups based on feeding type and delivery mode, were analyzed. At one week of age, samples clustered into two distinct groups, which were termed "settler types", based on their Bacteroidetes abundance. Caesarean-born infants belonged to the low-Bacteroidetes settler type, but vaginally-born infants were divided between the two groups. The antibiotics effect was assessed within a subgroup of 45 infants, vaginally-born and exclusively breastfed, to minimize the effect of other confounders. Antibiotics administration resulted in lower Bacteroidetes diversity and/or a delay in Bacteroidetes colonization, which persisted for three months, and in a differential development of the microbiota. Antibiotics resulted in pronounced effects on the Bacteroidetes composition and dynamics. Finally, we hypothesize that stratification of children's cohorts based on settler types may reveal group effects that might otherwise be masked.
Assuntos
Antibacterianos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , DNA Bacteriano/isolamento & purificação , DNA Bacteriano/metabolismo , Fezes/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Análise de Componente Principal , RNA Ribossômico 16S/isolamento & purificação , RNA Ribossômico 16S/metabolismoRESUMO
BACKGROUND: Cystic fibrosis (CF) patients are subjected to increased oxidative stress due to chronic pulmonary inflammation and recurrent infections. Additionally, these patients have diminished skeletal muscle performance and exercise capacity. We hypothesize that a mixture of multiple micronutrients could have beneficial effects on pulmonary function and muscle performance. METHODS: A double-blind, randomized, placebo controlled, cross-over trial with a mixture of multiple micronutrients (ML1) was performed in 22 CF patients (12.9+/-2.5 yrs) with predominantly mild lung disease. Anthropometric measures, pulmonary function, exercise performance by bicycle ergometry, muscular strength and vitamins A and E were determined. RESULTS: Analysis was performed using the paired Student t-test comparing the change in each parameter during ML1 and placebo. Plasma vitamin E and A levels increased during ML1 when compared to placebo. However, no significant difference between the effect of the ML1 or placebo was observed neither for FEV1, FVC, anthropometry, nor for the parameters for muscle performance. CONCLUSIONS: The micronutrient mixture was not superior to placebo with respect to changes in pulmonary function or muscle performance in pediatric CF patients, despite a significant increase in plasma vitamin E concentrations.
Assuntos
Fibrose Cística/dietoterapia , Suplementos Nutricionais , Micronutrientes/uso terapêutico , Minerais/uso terapêutico , Oligoelementos/uso terapêutico , Adolescente , Antioxidantes/uso terapêutico , Criança , Estudos Cross-Over , Método Duplo-Cego , Teste de Esforço/efeitos dos fármacos , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Força Muscular/efeitos dos fármacos , Testes de Função RespiratóriaRESUMO
OBJECTIVES: Coenzyme Q10 (CoQ10) is an effective lipophilic antioxidant and protects against lipid peroxidation by scavenging radicals. Patients with cystic fibrosis generally have fat malabsorption; thus, we hypothesized that overall plasma CoQ10 concentration in pediatric patients with cystic fibrosis might be diminished. Because these patients have increased oxidative stress due to chronic pulmonary inflammation, we also assumed that the oxidized form of CoQ10 might be relatively increased. PATIENTS AND METHODS: The total plasma CoQ10 levels and the oxidized and reduced form were measured by high-performance liquid chromatography in 30 children with cystic fibrosis (mean FEV1 % predicted = 88.5% +/- 18.7%) and 30 age-matched controls. RESULTS: Total plasma CoQ10 levels were significantly lower in the cystic fibrosis group as compared with the control group (0.87 +/- 0.42 micromol/L and 1.35 +/- 0.39 micromol/L, respectively; P < 0.001). When correcting for the lower serum cholesterol level in patients with cystic fibrosis, this difference remained significant: the CoQ10/cholesterol ratio (micromol/mol) was 268.8 +/- 136.7 and 334.0 +/- 102.9 in patients and controls, respectively (P < 0.05). However, the CoQ10 redox status was identical in patients and controls (86.4% +/- 7.1% and 85.4% +/- 7.3%, respectively). CONCLUSIONS: We found that the overall plasma CoQ10 concentration is lower in patients with cystic fibrosis, probably because of fat malabsorption. The CoQ10 redox status was not disturbed, indicating that CoQ10 could still be adequately regenerated in this group of patients with cystic fibrosis with mild-to-moderate pulmonary disease.
Assuntos
Fibrose Cística/sangue , Ubiquinona/análogos & derivados , Adolescente , Criança , Colesterol/sangue , Cromatografia Líquida de Alta Pressão , Coenzimas , Feminino , Humanos , Masculino , Oxirredução , Ubiquinona/sangueRESUMO
BACKGROUND: Stunted children with cystic fibrosis (CF) have less net protein anabolism than do children without CF, and the result is retarded growth in the CF patients. It is not known whether protein intake above that recommended by the Cystic Fibrosis Foundation would further stimulate whole-body protein synthesis. OBJECTIVE: We studied the effects of 3 amounts of protein intake on whole-body protein synthesis and breakdown by using isotopic infusion of [1-(13)C]valine and [(15)N(2)]urea in children with stable CF who required tube feeding. DESIGN: In 8 pediatric CF patients, we administered 3 randomly allocated isocaloric diets with normal (NP), intermediate (IP), and high (HP) amounts of protein (1.5, 3, and 5 g . kg(-1) . d(-1), respectively) by continuous drip feeding during a 4-d period at 6-wk intervals. Each patient acted as his or her own control. On the fourth day of feeding, whole-body protein synthesis and breakdown were measured. RESULTS: Protein synthesis was significantly higher in the HP group (x +/- SEM: 1.78 +/- 0.07 micromol . kg(-1) . min(-1)) than in the IP (1.57 +/- 0.08 micromol . kg(-1) . min(-1); P=0.001) and NP (1.37 +/- 0.07 micromol . kg(-1) . min(-1); P < 0.001) groups. There were no significant differences in protein breakdown. Net retention of nitrogen was significantly higher in the HP group (12.93 +/- 1.42 micromol . kg(-1) . min(-1)) than in the IP (7.61 +/- 1.40 micromol . kg(-1) . min(-1); P=0.01) and HP (2.48 +/- 0.20 micromol . kg(-1) . min(-1); P < 0.001) groups. CONCLUSION: In stunted children with CF requiring tube feeding, the highest stimulation of whole-body protein synthesis was achieved with a short-term dietary protein intake of 5 g . kg(-1) . d(-1).