Superficial and deep white matter diffusion abnormalities in focal epilepsies.

OBJECTIVE: This study was undertaken to evaluate superficial-white matter (WM) and deep-WM magnetic resonance imaging diffusion tensor imaging (DTI) metrics and identify distinctive patterns of microstructural abnormalities in focal epilepsies of diverse etiology, localization, and response to antiseizure medication (ASM). METHODS: We examined DTI data for 113 healthy controls and 113 patients with focal epilepsies: 51 patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) refractory to ASM, 27 with pharmacoresponsive TLE-HS, 15 with temporal lobe focal cortical dysplasia (FCD), and 20 with frontal lobe FCD. To assess WM microstructure, we used a multicontrast multiatlas parcellation of DTI. We evaluated fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), and assessed within-group differences ipsilateral and contralateral to the epileptogenic lesion, as well as between-group differences, in regions of interest (ROIs). RESULTS: The TLE-HS groups presented more widespread superficial- and deep-WM diffusion abnormalities than both FCD groups. Concerning superficial WM, TLE-HS groups showed multilobar ipsilateral and contralateral abnormalities, with less extensive distribution in pharmacoresponsive patients. Both the refractory TLE-HS and pharmacoresponsive TLE-HS groups also presented pronounced changes in ipsilateral frontotemporal ROIs (decreased FA and increased MD, RD, and AD). Conversely, FCD patients showed diffusion changes almost exclusively adjacent to epileptogenic areas. SIGNIFICANCE: Our findings add further evidence of widespread abnormalities in WM diffusion metrics in patients with TLE-HS compared to other focal epilepsies. Notably, superficial-WM microstructural damage in patients with FCD is more restricted around the epileptogenic lesion, whereas TLE-HS groups showed diffuse WM damage with ipsilateral frontotemporal predominance. These findings suggest the potential of superficial-WM analysis for better understanding the biological mechanisms of focal epilepsies, and identifying dysfunctional networks and their relationship with the clinical-pathological phenotype. In addition, lobar superficial-WM abnormalities may aid in the diagnosis of subtle FCDs.

Brazilian guidelines on the frequency of ophthalmic assessment and recommended examinations in healthy children younger than 5 years / Diretrizes brasileiras sobre avaliação oftalmológica de crianças saudáveis menores de 5 anos: exames recomendados e frequência

ABSTRACT Purpose: To provide guidance on the frequency and components of eye examinations for healthy children aged 0 to 5 years. Methods: These guidelines were developed based on the medical literature and clinical experience of an expert committee. PubMed/Medline searches were performed, with selected publications not restricted to systematic reviews, randomized controlled trials, or observational studies. The Grading of Recommendations Assessment, Development, and Evaluation profile was applied when suitable, and for issues without scientific evidence, recommendations were based on expert consensus. Recommendations by the American Academy of Pediatrics, American Association of Pediatric Ophthalmology and Strabismus, American Academy of Ophthalmology, Royal College of Ophthalmologists, and Canadian Ophthalmological Society were also reviewed. The final guideline document was approved by the Brazilian Pediatric Ophthalmology Society and by the Brazilian Pediatric Society. Results: Newborns must undergo the red reflex test and inspection of the eyes and adnexa by a pediatrician within 72 hours of life. The red reflex test should be repeated by the pediatrician during childcare consultations at least three times per year during the first 3 years of life. If feasible, a comprehensive ophthalmologic examination may be performed between 6 and 12 months of age. Until 36 months of age, the pediatrician should assess the infant's visual development milestones, age-appropriate assessment of visual function, ocular fixation, and eye alignment. At least one comprehensive ophthalmologic examination should be performed at 3 to 5 years of age. The examination should minimally include inspection of the eyes and adnexa, age-appropriate visual function assessment, evaluations of ocular motility and alignment (cover tests), cycloplegic refraction, and dilated fundus. Conclusions: Guidelines concerning the frequency of ophthalmic assessment are important tools for directing physicians regarding best practices that avoid treatable vision problems that affect children's development, school, and social performance and cause unnecessary permanent vision loss.

RESUMO Objetivo: Fornecer orientações sobre a frequência e os componentes dos exames oftalmológicos para crianças saudáveis de 0 a 5 anos. Métodos: Essas diretrizes foram desenvolvidas com base em revisão bibliográfica e experiência clínica de um comitê de especialistas. Foram realizadas buscas PubMed/Medline; documentos selecionados não se restringiram a revisões sistemáticas, ensaios clínicos randomizados e estudos observacionais. Quando adequado, o perfil GRADE foi aplicado para graduá-los e o consenso de especialistas foi usado nos tópicos sem evidência científica. Também foram revisadas as recomendações pela Academia Americana de Pediatria, Associação Americana de Oftalmologia Pediátrica e Estrabismo, Academia Americana de Oftalmologia, Royal College of Ophthalmologist e Sociedade Canadense de Oftalmologia. O documento final foi aprovado pela Sociedade Brasileira de Oftalmologia Pediátrica e Sociedade Brasileira de Pediatria. Resultados: Os recém-nascidos devem ser submetidos ao teste do reflexo vermelho e inspeção dos olhos e anexos pelo pediatra dentro de 72 horas de vida ou antes da alta da maternidade. O teste do reflexo vermelho deve ser repetido pelo pediatra durante as consultas de puericultura pelo menos três vezes ao ano durante os primeiros 3 anos de vida. Se factível, um exame oftalmológico completo pode ser feito entre 6 a 12 meses de vida. Até os 36 meses de idade, os marcos visuais, função visual apropriada para a idade, fixação e alinhamento ocular também devem ser avaliados pelo pediatra ou médico da família. Pelo menos um exame oftalmológico completo deve ser realizados entre 3 e 5 anos de idade. O exame deve conter pelo menos inspeção dos olhos e anexos, avaliação da função visual apropriada para a idade, avaliação da motilidade e alinhamento ocular (testes de cobertura), refração sob cicloplegia e avaliação do fundo de olho dilatado. Conclusões: As diretrizes sobre a frequência da avaliação oftalmológica são ferramentas importantes para orientar os médicos sobre a melhor prática a fim de evitar problemas visuais tratáveis na infância, que poderiam comprometer seu desenvolvimento social, escolar e global, além de causar perda permanente da visão.

Guia Prático de Atualização no tratamento da exacerbação de asma na criança e no adolescente ­ Posicionamento conjunto da Associação Brasileira de Alergia e Imunologia e Sociedade Brasileira de Pediatria / Practical Update Guide on the treatment of asthma exacerbation in children and adolescents ­ Joint position of the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics

Exacerbação aguda de asma é uma condição frequente na criança e no adolescente e uma das causas mais comuns de procura aos pronto atendimentos e de internações. Pode ocorrer em pacientes que ainda não foram diagnosticados como asmáticos, e mesmo naqueles cujo controle da doença não se encontre adequado. Reconhecer a exacerbação e iniciar seu tratamento desde o domicílio até o adequado manejo inicial em ambiente hospitalar é fundamental para evitar sua evolução para complicações que coloquem o paciente em risco de vida. O tratamento compreende o reconhecimento e tratamento da hipoxemia, da obstrução e do processo inflamatório, além de fornecer orientações na alta hospitalar e encaminhamentos para continuidade do tratamento.

Acute exacerbation of asthma is a frequent condition in children and adolescents and one of the most common causes of seeking emergency care and hospitalization. It can occur in patients who have not yet been diagnosed with asthma, and even in those whose disease control is not adequate. Recognizing the exacerbation and starting its treatment from home until proper initial management in a hospital environment is essential to avoid its evolution to complications that put the patient at risk of life. Treatment comprises the recognition and treatment of hypoxemia, obstruction, and the inflammatory process, in addition to providing guidance at hospital discharge and referrals for continued treatment.

Brazilian guidelines on the frequency of ophthalmic assessment and recommended examinations in healthy children younger than 5 years.

PURPOSE: To provide guidance on the frequency and components of eye examinations for healthy children aged 0 to 5 years. METHODS: These guidelines were developed based on the medical literature and clinical experience of an expert committee. PubMed/Medline searches were performed, with selected publications not restricted to systematic reviews, randomized controlled trials, or observational studies. The Grading of Recommendations Assessment, Development, and Evaluation profile was applied when suitable, and for issues without scientific evidence, recommendations were based on expert consensus. Recommendations by the American Academy of Pediatrics, American Association of Pediatric Ophthalmology and Strabismus, American Academy of Ophthalmology, Royal College of Ophthalmologists, and Canadian Ophthalmological Society were also reviewed. The final guideline document was approved by the Brazilian Pediatric Ophthalmology Society and by the Brazilian Pediatric Society. RESULTS: Newborns must undergo the red reflex test and inspection of the eyes and adnexa by a pediatrician within 72 hours of life. The red reflex test should be repeated by the pediatrician during childcare consultations at least three times per year during the first 3 years of life. If feasible, a comprehensive ophthalmologic examination may be performed between 6 and 12 months of age. Until 36 months of age, the pediatrician should assess the infant's visual development milestones, age-appropriate assessment of visual function, ocular fixation, and eye alignment. At least one comprehensive ophthalmologic examination should be performed at 3 to 5 years of age. The examination should minimally include inspection of the eyes and adnexa, age-appropriate visual function assessment, evaluations of ocular motility and alignment (cover tests), cycloplegic refraction, and dilated fundus. CONCLUSIONS: Guidelines concerning the frequency of ophthalmic assessment are important tools for directing physicians regarding best practices that avoid treatable vision problems that affect children's development, school, and social performance and cause unnecessary permanent vision loss.

Inflammatory and neurotrophic factor plasma levels are related to epilepsy independently of etiology.

OBJECTIVE: Inflammation plays an essential role in epilepsy. Studies indicate that cytokines and neurotrophic factors can act in neuroexcitability and epileptogenesis. We aimed to investigate the association between plasma inflammatory and neurotrophic markers, seizure frequency, and chronic epilepsy subtypes. METHODS: We studied 446 patients with epilepsy and 166 healthy controls. We classified patients according to etiology and seizure frequency. We measured plasma levels of interleukin-1 (IL-1), IL-2, IL-4, IL-6, IL-10, IL-17, interferon-γ (IFNγ), tumor necrosis factor α (TNFα), soluble TNF receptor 1 (sTNFr1), sTNFr2, brain-derived neurotrophic factor (BDNF), neurotrophic factor 3 (NT3), NT4/5, ciliary neurotrophic factor (CNTF), nerve growth factor (NGF), and glial cell line-derived neurotrophic factor (GDNF) by enzyme-linked immunosorbent assay or cytometric bead array. RESULTS: The plasma levels of BDNF, NT3, NGF, and sTNFr2 were higher, whereas IL-2, IL-4, IL-6, IL-10, IL-17, IFNγ, TNFα, CNTF, and sTNFr1 were lower in patients than controls. IL1, GDNF, and NT4/5 were similar between groups. These markers did not correlate with age, sex, and epilepsy duration. The molecule sTNFr2 was the best marker to discriminate patients from controls (area under the curve = .857), also differing between patients with frequent and infrequent seizures. SIGNIFICANCE: This large cohort confirmed that patients with epilepsy have abnormal levels of plasma inflammatory and neurotrophic markers independent of the underlying etiology. Plasma level of sTNFr2 was related to seizure frequency and discriminated people with or without epilepsy with good accuracy, making it a potential biomarker for epilepsy and seizure burden.

Transsylvian amygdalohippocampectomy for mesial temporal lobe epilepsy: Comparison of three different approaches.

OBJECTIVE: This study's objective was to compare the transinsular (TI-AH), transuncus (TU-AH), and temporopolar (TP-AH) amygdalohippocampectomy approaches regarding seizure control, temporal stem (TS) damage, and neurocognitive decline. METHODS: We included 114 consecutive patients with unilateral hippocampal sclerosis (HS) who underwent TI-AH, TU-AH, or TP-AH between 2002 and 2017. We evaluated seizure control using Engel classification. We used diffusion tensor imaging and postoperative Humphrey perimetry to assess the damage of the TS. We also performed pre- and postoperative memory performance and intelligence quotient (IQ). RESULTS: There were no significant differences in the proportion of patients free of disabling seizures (Engel IA+IB) among the three surgical approaches in the survival analysis. However, more patients were free of disabling seizures (Engel IA+IB) at 2 years of postsurgical follow-up with TP-AH (69.5%) and TI-AH (76.7%) as compared to the TU-AH (43.5%) approach (p = .03). The number of fibers of the inferior fronto-occipital fasciculus postoperatively was reduced in the TI-AH group compared with the TU-AH and TP-AH groups (p = .001). The rate of visual field defects was significantly higher with TI-AH (14/19, 74%) in comparison to the TU-AH (5/15, 33%) and TP-AH (13/40, 32.5%) approaches (p = .008). Finally, there was a significant postoperative decline in verbal memory in left-sided surgeries (p = .019) and delayed recall for both sides (p < .001) regardless of the surgical approach. However, TP-AH was the only group that showed a significant improvement in visual memory (p < .001) and IQ (p < .001) for both right- and left-sided surgeries. SIGNIFICANCE: The TP-AH group had better short-term seizure control than TU-AH, a lower rate of visual field defects than TI-AH, and improved visual memory and IQ compared to the other groups. Our findings suggest that TP-AH is a better surgical approach for temporal lobe epilepsy with HS than TI-AH and TU-AH.

Sarcopenia in children and adolescents with chronic liver disease / Sarcopenia em crianças e adolescentes com doença hepática crônica

Abstract Objective: To investigate the occurrence of sarcopenia in children and adolescents with chronic liver disease. Methods: A series of cases, with patients aged 6-19 years of both genders, who were treated in Liver Outpatient Clinics. Weight, height, muscle strength (assessed by manual grip strength), and muscle mass (estimated through dual-energy X-ray absorptiometry) were measured. Sarcopenia was diagnosed based on the simultaneous presence of muscle mass and muscle strength déficits, defined as the values below the mean for muscle mass and strength of the studied population, according to gender. A descriptive analysis (mean and standard deviation) was performed, and the difference of means was calculated by Student's t-test. Results: A total of 85 patients were studied, mostly females (64.7%), with a mean age of 11.7 (SD = 3.4) years. Sarcopenia was identified in 40% of the patients. Muscle strength déficit was found in 54.1% of the subjects, and 50.6% showed muscle mass déficit. The mean muscle mass for males was higher than that for females (6.07; SD = 1.22 kg/m2 vs. 5.42; SD = 1.10 kg/m2; p = 0.016). However, there was no significant difference in sex-related muscle strength (male = 0.85; SD = 0.52 kgf/kgm2 and female = 0.68; SD = 0.30 kgf/kgm2; p = 0.113). Conclusion: The research findings identified that sarcopenia is a condition found in pediatric patients treated at a public referral institution for chronic liver disease.

Resumo Objetivo: Investigar a ocorrência de sarcopenia em crianças e adolescentes com hepatopatias crônicas. Métodos: Série de casos, constituído por pacientes entre 6 e 19 anos, de ambos os sexos, acompanhados em ambulatórios de especialidade em hepatopatias. Foram feitas medidas de peso, altura, força muscular (avaliada pela força de preensão manual) e a massa muscular estimada a partir da absorciometria por dupla emissão de raios X. O diagnóstico de sarcopenia baseou-se na presença simultânea de déficit de massa muscular e de força muscular. Adotaram-se como déficit os valores abaixo da média para massa e força muscular da população estudada, segundo sexo. Realizou-se análise descritiva (média e desvio-padrão), bem como a diferença de médias com o teste do t de Student. Resultados: Foram estudados 85 pacientes, a maioria do sexo feminino (64,7%), com média de 11,7 (DP = 3,4) anos. A sarcopenia foi identificada em 40% dos pacientes, 54,1% apresentaram déficit de força muscular e 50,6% déficit de massa muscular. A média da massa muscular para o sexo masculino foi maior do que no feminino (6,07; DP = 1,22 kg/m2 vs 5,42; DP = 1,10 kg/m2; p = 0,016). No entanto, não houve diferença significante para força muscular com relação aos sexos (masculino = 0,85; DP = 0,52 kgf/kgm2 e feminino = 0,68; DP = 0,30 kgf/kgm2; p = 0,113). Conclusão: Os achados da pesquisa identificaram que a sarcopenia é uma condição presente em pacientes pediátricos atendidos em uma instituição pública de referência para doença hepática crônica.

Interactions between in vivo neuronal-glial markers, side of hippocampal sclerosis, and pharmacoresponse in temporal lobe epilepsy.

OBJECTIVE: To evaluate the interactions of metabolic neuronal-glial changes with the presence and hemispheric-side of hippocampal sclerosis (HS) and its potential role in predicting pharmacoresistance in temporal lobe epilepsy (TLE). METHODS: We included structural magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1 H-MRS) metabolic data for 91 patients with unilateral TLE and 50 healthy controls. We measured the values of total N-acetyl aspartate/total creatine (tNAA/tCr), glutamate/tCr (Glu/tCr), and myo-inositol/tCr (mIns/tCr). To assess the influence of the pharmacoresponse and hemispheric-side of HS on metabolic data, the relationship between clinical and MRI data, and the predictive value of NAA/Cr, we used analysis of variance/covariance and built a logistic regression model. We used bootstrap simulations to evaluate reproducibility. RESULTS: Bilateral tNAA/tCr reduction was associated with pharmacoresistance and with left HS, a decrease of Glu/tCr ipsilateral to the seizure focus was associated with pharmacoresistance, and ipsilateral mIns/tCr increase was related to pharmacoresistance and the presence of left HS. The logistic regression model containing clinical and 1 H-MRS data discriminated pharmacoresistance (area under the curve [AUC] = 0.78). However, the reduction of tNAA/tCr was the main predictor, with the odds 2.48 greater for pharmacoresistance. SIGNIFICANCE: Our study revealed a spectrum of neuronal-glial changes in TLE, which was associated with pharmacoresistance, being more severe in left-sided HS and less severe in MRI-negative TLE. These noninvasive, in vivo biomarkers provide valuable additional information about the interhemispheric differences in metabolic dysfunction, seizure burden, and HS, and may help to predict pharmacoresistance.

Guia prático de abordagem da criança e do adolescente com asma grave: Documento conjunto da Associação Brasileira de Alergia e Imunologia e Sociedade Brasileira de Pediatria / Practical guide to approaching children and adolescents with severe asthma: a joint document of the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics

Asma grave é a asma que requer tratamento com altas doses de corticosteroide inalado associado a um segundo medicamento de controle (e/ou corticosteroide sistêmico) para impedir que se torne "descontrolada" ou permaneça "descontrolada" apesar do tratamento. Asma grave é considerada um subtipo de asma de difícil tratamento. A prevalência em crianças evidenciada pelo International Study of Asthma and Allergies in Childhood variou entre 3,8% e 6,9%. Existem diversos instrumentos para avaliação subjetiva, como diários de sintomas e questionários, bem como para avaliação objetiva com função pulmonar e avaliação da inflamação por escarro induzido, ou óxido nítrico exalado. A abordagem terapêutica varia desde doses altas de corticosteroide inalado e/ou oral, broncodilatadores de longa duração, antaganonistas de receptores muscarínicos, até os mais recentes imunobiológicos que bloqueiam a IgE ou IL-5.

Severe asthma is asthma that requires treatment with high doses of inhaled corticosteroids in combination with a second control drug (and/or a systemic corticosteroid) to prevent it from becoming "uncontrolled" or remaining "uncontrolled" despite treatment. Severe asthma is considered a difficult-to-treat asthma subtype. The prevalence in children found by the International Study of Asthma and Allergies in Childhood ranged from 3.8% to 6.9%. There are several instruments for subjective assessment, such as symptom diaries and questionnaires, as well as for objective assessment, including pulmonary function testing and evaluation of inflammation by induced sputum or exhaled nitric oxide. The therapeutic approach includes high doses of inhaled and/or oral corticosteroids, long-acting bronchodilators, muscarinic receptor antagonists, and the latest biologics that block IgE or IL-5.

Sarcopenia in children and adolescents with chronic liver disease.

OBJECTIVE: To investigate the occurrence of sarcopenia in children and adolescents with chronic liver disease. METHODS: A series of cases, with patients aged 6-19 years of both genders, who were treated in Liver Outpatient Clinics. Weight, height, muscle strength (assessed by manual grip strength), and muscle mass (estimated through dual-energy X-ray absorptiometry) were measured. Sarcopenia was diagnosed based on the simultaneous presence of muscle mass and muscle strength déficits, defined as the values below the mean for muscle mass and strength of the studied population, according to gender. A descriptive analysis (mean and standard deviation) was performed, and the difference of means was calculated by Student's t-test. RESULTS: A total of 85 patients were studied, mostly females (64.7%), with a mean age of 11.7 (SD=3.4) years. Sarcopenia was identified in 40% of the patients. Muscle strength déficit was found in 54.1% of the subjects, and 50.6% showed muscle mass déficit. The mean muscle mass for males was higher than that for females (6.07; SD=1.22kg/m2vs. 5.42; SD=1.10kg/m2; p=0.016). However, there was no significant difference in sex-related muscle strength (male=0.85; SD=0.52kgf/kgm2 and female=0.68; SD=0.30kgf/kgm2; p=0.113). CONCLUSION: The research findings identified that sarcopenia is a condition found in pediatric patients treated at a public referral institution for chronic liver disease.

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes / Hepatite autoimune em 828 crianças e adolescentes brasileiros: achados clínicos e laboratoriais, perfil histológico, tratamentos e resultados

Abstract Objective: This large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis. Methods: The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments. Results: Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%). Conclusions: In this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.

Resumo Objetivo: Este estudo com acompanhamento de longo prazo visou a avaliar o quadro clínico, os achados laboratoriais, o perfil histológico, os tratamentos e os resultados de crianças e adolescentes com hepatite autoimune. Métodos: Foram analisados os prontuários médicos de 828 crianças e adolescentes com HAI. Foi usado um questionário para coletar os dados anônimos sobre o quadro clínico, os achados bioquímicos e histológicos e os tratamentos. Resultados: De todos os pacientes, 89,6% tinham hepatite autoimune-1 e 10,4% hepatite autoimune-2. O sexo feminino foi predominante nos dois grupos. A idade média no início dos sintomas foi 111,5 (6; 210) e 53,5 (8; 165) meses nos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente. Foi observado início clínico agudo em 56,1% e 58,8% e sintomas insidiosos em 43,9% e 41,2% dos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente. A probabilidade de insuficiência hepática foi 1,6 vezes maior para hepatite autoimune-2; 3,6% e 10,6% dos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente, apresentaram insuficiência hepática fulminante; o risco foi 3,1 vezes maior para hepatite autoimune-2. Os níveis de gamaglobulina e imunoglobulina G foram significativamente maiores nos pacientes com hepatite autoimune-1, ao passo que os níveis de imunoglobulina A e C3 foram menores em pacientes com hepatite autoimune-2; 22,4% dos pacientes apresentaram cirrose e a remissão bioquímica foi atingida em 76,2%. A taxa de sobrevida atuarial foi de 93,0%. Um total de 4,6% pacientes foram submetidos a transplante de fígado e 6,9% morreram (hepatite autoimune-1: 7,5%; hepatite autoimune-2: 2,4%). Conclusões: Nesta grande série clínica de crianças e adolescentes brasileiros, a hepatite autoimune-1 foi mais frequente e os pacientes com hepatite autoimune-2 mostraram maiores taxas de remissão da doença com respostas mais rápidas aos tratamentos. Os pacientes com hepatite autoimune-1 apresentaram maior risco de óbito.

Cost-effectiveness analysis of the treatment of mild and moderate Alzheimer's disease in Brazil

Objective: To perform a cost-effectiveness analysis of donepezil and rivastigmine therapy for mild and moderate Alzheimer's disease (AD) from the perspective of the Brazilian Unified Health System. Method: A hypothetical cohort of 1,000 individuals of both sexes, aged >65 years, and diagnosed with AD was simulated using a Markov model. The time horizon was 10 years, with 1-year cycles. A deterministic and probabilistic sensitivity analysis was performed. Results: For mild AD, the study showed an increase in quality-adjusted life years (QALYs) of 0.61 QALY/21,907.38 Brazilian reais (BRL) for patients treated with donepezil and 0.58 QALY/BRL 24,683.33 for patients treated with rivastigmine. In the moderate AD group, QALY increases of 0.05/BRL 27,414.96 were observed for patients treated with donepezil and 0.06/BRL 34,222.96 for patients treated with rivastigmine. Conclusions: The findings of this study contradict the standard of care for mild and moderate AD in Brazil, which is based on rivastigmine. A pharmacological treatment option based on current Brazilian clinical practice guidelines for AD suggests that rivastigmine is less cost-effective (0.39 QALY/BRL 32,685.77) than donepezil. Probabilistic analysis indicates that donepezil is the most cost-effective treatment for mild and moderate AD.

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes.

OBJECTIVE: This large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis. METHODS: The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments. RESULTS: Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%). CONCLUSIONS: In this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.

Cost-effectiveness analysis of the treatment of mild and moderate Alzheimer's disease in Brazil.

OBJECTIVE: To perform a cost-effectiveness analysis of donepezil and rivastigmine therapy for mild and moderate Alzheimer's disease (AD) from the perspective of the Brazilian Unified Health System. METHOD: A hypothetical cohort of 1,000 individuals of both sexes, aged >65 years, and diagnosed with AD was simulated using a Markov model. The time horizon was 10 years, with 1-year cycles. A deterministic and probabilistic sensitivity analysis was performed. RESULTS: For mild AD, the study showed an increase in quality-adjusted life years (QALYs) of 0.61 QALY/21,907.38 Brazilian reais (BRL) for patients treated with donepezil and 0.58 QALY/BRL 24,683.33 for patients treated with rivastigmine. In the moderate AD group, QALY increases of 0.05/BRL 27,414.96 were observed for patients treated with donepezil and 0.06/BRL 34,222.96 for patients treated with rivastigmine. CONCLUSIONS: The findings of this study contradict the standard of care for mild and moderate AD in Brazil, which is based on rivastigmine. A pharmacological treatment option based on current Brazilian clinical practice guidelines for AD suggests that rivastigmine is less cost-effective (0.39 QALY/BRL 32,685.77) than donepezil. Probabilistic analysis indicates that donepezil is the most cost-effective treatment for mild and moderate AD.

Hepatobiliary disease in children and adolescents with cystic fibrosis / Doença hepatobiliar em crianças e adolescentes com fibrose cística

Abstract Objectives: The aims of the study were to determine the frequency of hepatobiliary disease in patients with cystic fibrosis and to describe the sociodemographic, clinical, and laboratory profile of these patients. Methods: This was a retrospective, descriptive, and analytical study of 55 patients diagnosed with cystic fibrosis, aged between 3 months and 21 years, followed-up from January 2008 to June 2016 in a referral center. Medical records were consulted and sociodemographic, clinical and laboratory data, including hepatobiliary alterations, imaging studies, genetic studies, liver biopsies, and upper digestive endoscopies were registered. Results: Hepatobiliary disease was diagnosed in 16.4% of the patients and occurred as an initial manifestation of cystic fibrosis in 55.6% of these cases. The diagnosis of hepatopathy occurred before or concomitantly with the diagnosis of cystic fibrosis in 88.9% of the children. All patients with hepatobiliary disease were considered non-white, with a predominance of females (77.8%) and median (IQR) of 54 (27-91) months. Compared with the group without hepatobiliary disease, children with liver disease had a higher frequency of severe mutations identified in the CFTR gene (77.8% vs. 39.6%, p = 0.033) and severe pancreatic insufficiency (88.9% vs. 31.6%, p = 0.007). Conclusion: The frequency of hepatobiliary disease was high, with a very early diagnosis of the disease and its complications in the studied series. A statistical association was observed between the occurrence of hepatobiliary disease and the presence of pancreatic insufficiency and severe mutations in the CFTR gene. It is emphasized that cystic fibrosis is an important differential diagnosis of liver diseases in childhood.

Resumo Objetivos: Os objetivos do estudo foram determinar a frequência da doença hepatobiliar em pacientes com fibrose cística e descrever o perfil sociodemográfico, clínico e laboratorial destes. Métodos: Estudo retrospectivo, descritivo e analítico de 55 pacientes com diagnóstico de fibrose cística, entre três meses e 21 anos, acompanhados de janeiro de 2008 a junho de 2016 em um centro de referência. Foi realizada consulta aos prontuários médicos, registrando-se os dados sociodemográficos, clínicos e laboratoriais, incluindo-se alterações hepatobiliares, exames de imagem, estudos genéticos, biópsias hepáticas e endoscopias digestivas altas. Resultados: A doença hepatobiliar foi diagnosticada em 16,4% dos pacientes e ocorreu como manifestação inicial da fibrose cística em 55,6% destes casos. O diagnóstico da hepatopatia ocorreu antes ou concomitante ao diagnóstico da fibrose cística em 88,9% das crianças. Todos os pacientes com doença hepatobiliar foram considerados não brancos, havendo predominância do sexo feminino (77,8%) e mediana (I.I.Q) de idade de 54 (27-91) meses. Em comparação com o grupo sem doença hepatobiliar, as crianças com hepatopatia tiveram maior frequência de mutações graves no gene CFTR identificadas (77,8% vs 39,6%; p = 0,033) e de insuficiência pancreática grave (88,9% vs 31,6%; p = 0,007). Conclusão: A frequência de doença hepatobiliar foi elevada, observando-se um diagnóstico muito precoce da mesma e de suas complicações na casuística estudada. Houve associação estatística entre a ocorrência de doença hepatobiliar e a presença de insuficiência pancreática e de mutações graves do gene CFTR. Enfatiza-se que a fibrose cística represente um importante diagnóstico diferencial de hepatopatias na infância.

Diretrizes da Associação Brasileira de Alergia e Imunologia e Sociedade Brasileira de Pediatria para sibilância e asma no pré-escolar / Guidelines of the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics for wheezing and asthma in preschool children

A asma é uma das doenças crônicas de maior frequência na infância. Parcela significativa de crianças com asma desenvolve sintomas nos primeiros anos de vida, mas nem sempre a sua confirmação diagnóstica é fácil. Outras causas de sibilância que podem gerar confusão diagnóstica, além da complexidade para a obtenção de medidas objetivas, tais como a realização de provas de função pulmonar nessa faixa etária, são justificativas para esse fato. Especialistas na abordagem desses pacientes, da Associação Brasileira de Alergia e Imunologia e da Sociedade Brasileira de Pediatria, após revisão extensa da literatura pertinente elaboraram esse documento, onde são comentados os possíveis agentes etiológicos, prevalência, diagnóstico diferencial, assim como tratamento e prevenção da sibilância e asma em pré-escolares.

Asthma is one of the most frequent chronic diseases in childhood. A significant portion of children with asthma develop symptoms in the first years of life, but diagnostic confirmation is not always easy. The difficulty is justified by other causes of wheezing that can generate diagnostic confusion, and by the complexity involved in obtaining objective measures ­ such as pulmonary function tests ­ in this age group. Specialists with expertise in the approach of these patients, from both the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics, after extensive review of the pertinent literature, developed this document to discuss possible etiological agents, prevalence, differential diagnosis, as well as treatment and prevention of wheezing and asthma in preschool children.

IV Brazilian Consensus on Rhinitis - an update on allergic rhinitis, / IV Consenso Brasileiro sobre Rinite - atualização em rinite alérgica,

Abstract Introduction The guidelines on allergic rhinitis aim to update knowledge about the disease and care for affected patients. The initiative called "Allergic Rhinitis and its Impact on Asthma", initially published in 2001 and updated in 2008 and 2010, has been very successful in disseminating information and evidence, as well as providing a classification of severity and proposing a systemized treatment protocol. In order to include the participation of other medical professionals in the treatment of allergic rhinitis, it is important to develop algorithms that accurately indicate what should and can be done regionally. Objective To update the III Brazilian Consensus on Rhinitis - 2012, with the creation of an algorithm for allergic rhinitis management. Methods We invited 24 experts nominated by the Brazilian Association of Allergy and Immunology, Brazilian Association of Otorhinolaryngology and Head and Neck Surgery and Brazilian Society of Pediatrics to update the 2012 document. Results The update of the last Brazilian Consensus on Rhinitis incorporated and adapted the relevant information published in all "Allergic Rhinitis and its Impact on Asthma" Initiative documents to the Brazilian scenario, bringing new concepts such as local allergic rhinitis, new drugs and treatment evaluation methods. Conclusion A flowchart for allergic rhinitis treatment has been proposed.

Resumo Introdução As diretrizes sobre rinite alergica visam atualizar os conhecimentos sobre a doença e os cuidados para com esses pacientes. A iniciativa designada "Rinite Alergica e seu Impacto na Asma", cujo relatorio inicial foi publicado em 2001 e atualizada em 2008 e 2010, tem sido muito bem sucedida na disseminaçao de informaçoes e evidencias, bem como na formulaçao da classificaçao de gravidade e proposta de sistematizaçao do tratamento. Entretanto, visando a participaçao de outros profissionais medicos no atendimento da rinite alergica, e importante o desenvolvimento de algoritmos que indiquem com precisao o que deve e pode ser feito regionalmente. Objetivo Atualizar o III Consenso Brasileiro sobre Rinites-2012, com elaboraçao de algoritmo para conduta da rinite alergica. Método Foram convidados 24 especialistas indicados pelas Associaçao Brasileira de Alergia e Imunologia, Associaçao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial e Sociedade Brasileira de Pediatria para atualizaçao do documento de 2012. Resultados A atualizaçao do ultimo Consenso Brasileiro sobre Rinites, incorporou e adaptou para a realidade brasileira as informaçoes relevantes publicadas em todos os documentos da Iniciativa "Rinite Alergica e seu Impacto na Asma", trazendo novos conceitos como a rinite alergica local, novos medicamentos e metodos de avaliaçao de tratamento. Conclusão Proposto um fluxograma de tratamento para a rinite alergica.

Hepatobiliary disease in children and adolescents with cystic fibrosis.

OBJECTIVES: The aims of the study were to determine the frequency of hepatobiliary disease in patients with cystic fibrosis and to describe the sociodemographic, clinical, and laboratory profile of these patients. METHODS: This was a retrospective, descriptive, and analytical study of 55 patients diagnosed with cystic fibrosis, aged between 3 months and 21 years, followed-up from January 2008 to June 2016 in a referral center. Medical records were consulted and sociodemographic, clinical and laboratory data, including hepatobiliary alterations, imaging studies, genetic studies, liver biopsies, and upper digestive endoscopies were registered. RESULTS: Hepatobiliary disease was diagnosed in 16.4% of the patients and occurred as an initial manifestation of cystic fibrosis in 55.6% of these cases. The diagnosis of hepatopathy occurred before or concomitantly with the diagnosis of cystic fibrosis in 88.9% of the children. All patients with hepatobiliary disease were considered non-white, with a predominance of females (77.8%) and median (IQR) of 54 (27-91) months. Compared with the group without hepatobiliary disease, children with liver disease had a higher frequency of severe mutations identified in the CFTR gene (77.8% vs. 39.6%, p=0.033) and severe pancreatic insufficiency (88.9% vs. 31.6%, p=0.007). CONCLUSION: The frequency of hepatobiliary disease was high, with a very early diagnosis of the disease and its complications in the studied series. A statistical association was observed between the occurrence of hepatobiliary disease and the presence of pancreatic insufficiency and severe mutations in the CFTR gene. It is emphasized that cystic fibrosis is an important differential diagnosis of liver diseases in childhood.

IV Brazilian Consensus on Rhinitis - an update on allergic rhinitis.

INTRODUCTION: The guidelines on allergic rhinitis aim to update knowledge about the disease and care for affected patients. The initiative called "Allergic Rhinitis and its Impact on Asthma", initially published in 2001 and updated in 2008 and 2010, has been very successful in disseminating information and evidence, as well as providing a classification of severity and proposing a systemized treatment protocol. In order to include the participation of other medical professionals in the treatment of allergic rhinitis, it is important to develop algorithms that accurately indicate what should and can be done regionally. OBJECTIVE: To update the III Brazilian Consensus on Rhinitis - 2012, with the creation of an algorithm for allergic rhinitis management. METHODS: We invited 24 experts nominated by the Brazilian Association of Allergy and Immunology, Brazilian Association of Otorhinolaryngology and Head and Neck Surgery and Brazilian Society of Pediatrics to update the 2012 document. RESULTS: The update of the last Brazilian Consensus on Rhinitis incorporated and adapted the relevant information published in all "Allergic Rhinitis and its Impact on Asthma" Initiative documents to the Brazilian scenario, bringing new concepts such as local allergic rhinitis, new drugs and treatment evaluation methods. CONCLUSION: A flowchart for allergic rhinitis treatment has been proposed.

Guia prático de atualização em dermatite atópica - Parte I: etiopatogenia, clínica e diagnóstico. Posicionamento conjunto da Associação Brasileira de Alergia e Imunologia e da Sociedade Brasileira de Pediatria / Updated practical guide on atopic dermatitis - Part I: etiopathogenesis, clinical features, and diagnosis. Joint position paper of the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics

A dermatite atópica (DA) é uma doença crônica e recidivante que acomete principalmente pacientes da faixa etária pediátrica. A fisiopatologia inclui fatores genéticos, alterações na barreira cutânea e imunológicas. A prevalência da DA no Brasil, entre adolescentes, oscila entre 7,1% e 12,5%, com tendência à estabilização. O diagnóstico é clínico, e exames complementares auxiliam na determinação dos fatores desencadeantes. A identificação dos fatores irritantes e/ou desencadeantes envolvidos permite melhor controle das crises. Entre os fatores desencadeantes destacam-se os agentes infecciosos, alérgenos alimentares e aeroalérgenos. Tomando-se como ponto de partida o "Guia Prático para o Manejo da Dermatite Atópica ­ opinião conjunta de especialistas em alergologia da Associação Brasileira de Alergia e Imunopatologia e da Sociedade Brasileira de Pediatria" publicado em 2006, foi realizada revisão e atualização dos conceitos apresentados por grupo de alergologistas, dermatologistas e pediatras especializados no tratamento de pacientes com DA. O objetivo desta revisão foi elaborar um documento prático e que auxilie na compreensão dos mecanismos envolvidos na DA, assim como dos possíveis fatores de risco associados a sua apresentação, bem como sobre a avaliação subsidiária disponível para a identificação dos fatores associados à DA.

Atopic dermatitis (AD) is a chronic, recurrent skin disease that mainly affects pediatric patients. The pathophysiology of AD includes genetic factors, skin barrier abnormalities, and immunological factors. The prevalence of AD in Brazil, among adolescents, ranges from 7.1% to 12.5%, with a trend towards stabilization. The diagnosis of AD is clinical, and complementary tests can help determine the triggering factors. Identification of the irritating and/or triggering factors involved allows better control of exacerbations. Among the triggering factors, infectious agents, food allergens, and aeroallergens stand out. Taking as a starting point the Practical Guide for the Management of Atopic Dermatitis ­ joint opinion of specialists in allergology of the Brazilian Association of Allergy and Immunopathology and of the Brazilian Society of Pediatrics, published in 2006, the present paper describes the results of the review and update of different concepts related to AD, conducted by a group of allergists, dermatologists, and pediatricians specializing in the treatment of patients with AD. The objective of this review was to design a practical document that can help improve our understanding of the mechanisms involved in AD, possible risk factors associated with its presentation, as well as ancillary tests available to identify factors associated with AD.