ABSTRACT Objective: The aim of this review was to summarize the most common extrapulmonary manifestations in pediatric patients with COVID-19, as well as to discuss clinical, epidemiological, and pathophysiological aspects of these clinical presentations in children. Source of data: An extensive search of literature was performed in order to identify pediatric cases with extrapulmonary manifestations between January 1, 2020 and June 21, 2020. Generic keywords, such as “Novel coronavirus” or “Novel coronavirus 2019” or “2019 nCoV” or “COVID-19” or “SARS-CoV-2” were searched on PubMed database, associated either with age filters or generic pediatric terms. Summary of findings: A total of 28 articles, including 199 patients, were considered suitable to review and data extraction. The main findings were summarized in tables. The main non-pulmonary manifestations in pediatric patients, in decreasing order of frequency, were gastrointestinal, renal, cardiovascular, neurological, hematological and lymphatic, cutaneous, hepatic, ocular, olfactory, and gustatory. Multisystem impairment and Kawasaki-like disease were also described. Conclusions: Differences in immune response of children and variations of tissue expression of angiotensin converting enzyme 2, the virus receptor, are likely to influence clinical, epidemiological, and pathophysiological patterns of the disease.

Abstract The world is looking forward to a prompt response by the scientific community in order to overcome the first pandemic of the 21st century. This study aimed to provide an overview of scientific output on COVID-19 during its first year. We assembled information regarding 60,830 articles related to COVID-19 indexed in the WoS database from January 24 to December 13, 2020. Only 4 countries accounted for about 60% of the articles (USA, China, Italy, and England) and 12 countries accounted for about 95% of the world scientific output on COVID-19 (USA, China, Italy, England, India, Canada, Germany, Spain, Australia, Brazil, Iran, and Turkey). 25 research centers around the world contributed with more than 500 papers on COVID-19. Papers were scattered throughout 6,133 journals, with 12 journals with > 250 articles. 20 articles (0.03%) have already received more than the 1,000 citations. The response of the scientific endeavor to this acute global public health emergency has been fast and robust. The overview provided by the analysis of the scientific response to the pandemic may contribute to further studies aiming to evaluate the impact and changes in the scientific endeavor for the next years in light of the forthcoming new world framework.

Resumo Objetivo Há comprovação do importante papel das alterações no sistema imunológico no desencadeamento e manutenção da síndrome nefrótica idiopática (SNI). O objetivo deste estudo foi investigar a expressão das citocinas em populações de linfócitos de pacientes com SNI em comparação a indivíduos saudáveis e de acordo com a proteinúria. Métodos Este estudo transversal incluiu 44 pacientes com SNI e oito crianças saudáveis, pareados por idade e sexo (controles). Os pacientes foram subdivididos de acordo com a proteinúria: proteinúria persistente ou remissão parcial (PP ≥ 300 mg/24 h, n = 17) e proteinúria baixa ou remissão completa (PB < 300 mg/24 h, n = 27). A análise ex vivo de leucócitos no sangue periférico por citometria de fluxo foi feita utilizando marcadores de superfície para linfócitos T, TCD4, TCD8, células natural killer (NK), linfócitos NKT e B. As frequências das citocinas intracelulares foram analisadas nessas células. Resultados A frequência dos linfócitos B, células NK e células NKT foi menor em pacientes com SNI do que nos controles, ao passo que os pacientes com SNI apresentaram maior frequência de células CD4+fator de necrose tumoral (TNF)-α+ do que nos controles. Os linfócitos T citotóxicos que expressam interferon (IFN)-γ foram menores nos pacientes com SNI do que nos controles. Os pacientes com PP mostraram maiores frequências de linfócitos T CD4 que expressam IFN-γ e TNF-α que os controles. Os linfócitos CD8 que expressam TNF-α apresentaram aumento no grupo com PP, em comparação aos com PB e os controles, apesar de as células CD8+IFN-γ+ serem mais baixas nos pacientes com PB e nos controles. Conclusão Com relação ao nível de proteinúria, os pacientes com SNI apresentaram aumento na expressão de TNF-α nos linfócitos CD4 e expressão reduzida de IFN-γ nos linfócitos CD8. A persistência da proteinúria foi associada a maiores níveis de marcadores inflamatórios.

Abstract Objective: There is evidence of an important role of immune system changes in the triggering and maintenance of idiopathic nephrotic syndrome (INS). The aim of this study was to investigate the expression of cytokines in lymphocyte populations of patients with INS in comparison to healthy individuals, according to proteinuria. Methods: This cross-sectional study included 44 patients with INS and eight healthy children, matched for age and sex (controls). Patients were subdivided according to proteinuria: persistent proteinuria or partial remission (PP ≥ 300 mg/24 h, n = 17) and low proteinuria or complete remission (LP < 300 mg/24 h, n = 27). Ex vivo analysis of peripheral blood leukocytes by flow cytometry was performed using surface markers for T-lymphocytes, TCD4, TCD8, natural killer (NK) cells, NKT, and B-lymphocytes. Frequencies of intracellular cytokines were analyzed in these cells. Results: The frequencies of B-lymphocytes, NK cells, and NKT cells were lower in INS than in controls, whereas INS patients had a higher frequency of CD4+tumor necrosis factor (TNF)-α+ cells than controls. Cytotoxic-T-lymphocytes expressing IFN-γ were lower in INS than in controls. Patients with PP showed higher frequencies of CD4-T-lymphocytes expressing IFN-γ and TNF-α than controls. CD8-lymphocytes expressing TNF-α were increased in PP group when compared with LP and controls, while CD8+interferon (IFN)-γ+ cells were lower than in LP and in controls. Conclusion: Regardless the level of proteinuria, INS patients had increased expression of TNF-α in CD4-lymphocytes and reduced expression of IFN-γ in CD8-lymphocytes. Persistence of proteinuria was associated with higher levels of inflammatory markers.

ABSTRACT Objective Several formulas based in different biomarkers may be used to estimate glomerular filtration rate (GRF). However, all of them have some limitations, and it is very important to evaluate their performances in different groups of patients. Therefore, we compared GFR, as estimated by creatinine-based and cystatin C-based equations, according to albuminuria, in type 1 diabetes (T1DM), in an observational case-control study. Subjects and methods T1DM patients were classified according to albuminuria: normoalbuminuric (n = 63), microalbuminuric (n = 30), macroalbuminuric (n = 32). GFR was calculated using creatinine-based and cystatin C-based (aMDRD, CKD-EPIcr, CKD-EPIcys, MacIsaac, Tan and CKD-EPIcrcys) equations. Spearman Correlation was used to evaluate the correlation of GFR estimated by the formulas with albuminuria. ROC curves were constructed to compare AUCs of GFR estimated by equations, in reference to macroalbuminuria. Sensibility, specificity and accuracy were calculated for a cut-off < 60 mL/min/1.73 m2. Results GFR estimated by creatinine-based and cystatin C-based equations significantly differed among normoalbuminuric, microalbuminuric and macroalbuminuric patients. Spearman correlation and AUCs of GFR estimated by creatinine-based and cystatin C-based formulas were very similar to each other, though cystatin C-based equations presented better correlation with albuminuria and higher AUCs than the creatinine-based ones, and the best accuracy to detect macroalbuminuric patients. Conclusion Although GFR estimated by all creatinine-based and cystatin C-based equations permitted the differentiation between T1DM patients, according to albuminuria, cystatin C-based equations presented best accuracy to detect macroalbuminuria in T1DM patients and should be considered in the clinical routine in order to increase the possibility of early diagnostic of chronic renal disease.

Resumo Objetivo: Avaliar a situação nutricional de crianças com colestase persistente e comparar os índices antropométricos entre crianças com e sem cirrose hepática e crianças com e sem icterícia. Métodos: Foram incluídas crianças com colestase persistente, ou seja, aumento da bilirrubina direta ou alterações na enzima canalicular, gamaglutamiltransferase (GGT). As medidas antropométricas foram peso, estatura ou altura, circunferência do braço (CB), espessura da prega cutânea do tríceps (TST), circunferência muscular do braço (CMB) e índice de massa corporal (IMC). Resultados: Foram avaliadas 91 crianças com colestase, com idade média de 12 meses; 33% e 30,8% dos pacientes apresentaram índices P/I e A/I com escore Z abaixo de –2, respectivamente. Com relação ao índice P/A e IMC, somente 12% e 16% dos pacientes, respectivamente, apresentaram escore Z abaixo de –2. Com relação à CB, 43,8% de 89 pacientes avaliados apresentaram alguma depleção. Observando a TST, 64% dos pacientes que apresentaram depleção, 71,1% dos 45 pacientes avaliados apresentaram algum grau de depleção com relação ao índice de CMB. Conclusão: A avaliação do peso em pacientes com doenças hepáticas crônicas poderá superestimar a situação nutricional devido a visceromegalia, edema subclínico ou ascite. Os índices que correlacionam peso e altura, como P/A e IMC, também podem não mostrar depleção devido à doença crônica em que há depleção tanto do peso quanto da altura. A TST, BC e CMB são parâmetros que estimam melhor a situação nutricional e devem fazer parte de gestão de pacientes com doenças hepáticas e colestase.

Abstract Objective: To evaluate the nutritional status of children with persistent cholestasis and to compare the anthropometric indices between children with and without liver cirrhosis and children with and without jaundice. Methods: Children with persistent cholestasis, i.e. increased direct bilirrubin or changes in the canalicular enzyme gamma-glutamyl transferase (GGT), were included. The anthropometric measures were weight (W), height or length (H), arm circumference (AC), triceps skinfold thickness (TST), arm muscle circumference (AMC), and body mass index (BMI). Results: Ninety-one children with cholestasis, with current median age of 12 months, were evaluated. W/age (A) and H/A indices below −2 Z-scores were observed in 33% and 30.8% of patients, respectively. Concerning the W/H index and BMI, only 12% and 16% of patients, respectively, were below −2 Z-scores. Regarding AC, 43.8% of 89 evaluated patients had some depletion. Observing the TST, 64% of patients had depletion, and 71.1% of the 45 evaluated patients had some degree of depletion regarding the ACM index. Conclusion: Evaluation using weight in patients with chronic liver diseases may overestimate the nutritional status due to visceromegaly, subclinical edema, or ascites. Indices that correlate weight and height, such as W/H and BMI, may also not show depletion because of the chronic condition in which there are depletion of both weight and height. TST, AC, and ACM are parameters that better estimate nutritional status and should be part of the management of patients with liver diseases and cholestasis.

Resumo Objetivo: A infecção do trato urinário (ITU) é a infecção bacteriana mais comum na infância. A ITU pode ser o evento sentinela para alteração renal subjacente. Ainda há muitas controvérsias com relação ao tratamento adequado da ITU. Neste artigo de revisão, discutimos as últimas recomendações para diagnóstico, tratamento, profilaxia e imagiologia da ITU na infância, com base em comprovação e, na sua ausência, no consenso de especialistas. Fonte de dados: Os dados foram coletados após uma revisão da literatura e pesquisa no Pubmed, Embase, Scopus e Scielo. Resumo dos dados: No primeiro ano de vida, as ITUs são mais comuns em meninos (3,7%) do que em meninas (2%). Os sinais e sintomas da ITU são muito inespecíficos, principalmente em neonatos e durante a infância. A febre é o único sintoma em muitos casos. Conclusões: O histórico clínico e exame físico podem sugerir ITU, porém a confirmação deve ser feita por urocultura. Antes da administração de qualquer agente antimicrobiano, deve ser feita coleta de urina. Durante a infância, a coleta de urina adequada é essencial para evitar resultados falso-positivos. O diagnóstico e o início do tratamento imediatos são importantes na prevenção de cicatriz renal de longo prazo. Neonatos febris com ITUs devem ser submetidos a ultrassonografia renal e da bexiga, Agentes antibacterianos intravenosos são recomendados para neonatos e neonatos jovens. Recomendamos também a exclusão de uropatias obstrutivas o mais rapidamente possível e posterior refluxo vesico-ureteral, caso indicado. A profilaxia deve ser considerada em casos de elevada susceptibilidade a ITU e risco elevado de danos renais.

Abstract Objective: Urinary tract infection (UTI) is the most common bacterial infection in childhood. UTI may be the sentinel event for underlying renal abnormality. There are still many controversies regarding proper management of UTI. In this review article, the authors discuss recent recommendations for the diagnosis, treatment, prophylaxis, and imaging of UTI in childhood based on evidence, and when this is lacking, based on expert consensus. Sources: Data were obtained after a review of the literature and a search of Pubmed, Embase, Scopus, and Scielo. Summary of the findings: In the first year of life, UTIs are more common in boys (3.7%) than in girls (2%). Signs and symptoms of UTI are very nonspecific, especially in neonates and during childhood; in many cases, fever is the only symptom. Conclusions: Clinical history and physical examination may suggest UTI, but confirmation should be made by urine culture, which must be performed before any antimicrobial agent is given. During childhood, the proper collection of urine is essential to avoid false-positive results. Prompt diagnosis and initiation of treatment is important to prevent long-term renal scarring. Febrile infants with UTIs should undergo renal and bladder ultrasonography. Intravenous antibacterial agents are recommended for neonates and young infants. The authors also advise exclusion of obstructive uropathies as soon as possible and later vesicoureteral reflux, if indicated. Prophylaxis should be considered for cases of high susceptibility to UTI and high risk of renal damage.

Objetivo O objetivo deste trabalho foi avaliar as propriedades psicométricas da versão em português da Escala de Responsividade Social-2 (ERS-2) para crianças e adolescentes com transtorno do espectro autista (TEA). Métodos A ERS-2 foi respondida pelos pais de 90 pacientes com TEA e 25 controles saudáveis. Análises quanto à validade discriminante, índices de confiabilidade e separação, de adequação e calibração dos itens pelo modelo Rasch foram realizadas. Resultados A ERS-2 demonstrou boa consistência interna (alfa de Cronbach = 0,952), um ponto de corte de 41, sensibilidade de 96,8%, especificidade de 100% e valor preditivo negativo de 99,9% para a identificação de TEA. As subescalas apresentaram, de forma geral, adequação ao modelo. No entanto, alguns itens se apresentaram pouco consistentes do ponto de vista estatístico (correlação item-total negativas e misfitting). O mapa de itens mostrou má cobertura da variável latente, especialmente no espectro mais leve do TEA. Conclusão Os resultados deste estudo mostraram que a versão em português da ERS-2 pode ser utilizada como ferramenta de triagem para o reconhecimento de TEA em crianças e adolescentes brasileiros. A escala pode ter versões futuras aprimoradas com a substituição dos itens com pior desempenho.

Objective The purpose of this research was to assess the psychometric properties of the Portuguese version of the Social Responsiveness Scale-2 (SRS-2) for children and adolescents with autism spectrum disorder (ASD). Methods Parents of 90 patients with ASD and 25 healthy controls responded to the SRS-2. Analyses about the discriminant validity, reliability and separation indexes, fitness and items calibration according to Rasch model were carried on. Results SRS-2 showed good internal consistency (Cronbach's alpha = 0.952), a cutoff score of 41, sensitivity of 96.8%, specificity of 100%, and negative predictive value of 99.9% for the diagnosis of ASD. The subscales generally fitted the model. However, some items presented suboptimal statistics performance (negative item-total correlation and misfitting). The item map showed that the latent variable was not entirely covered by the items, especially on the mildest end of the autistic spectrum. Conclusion The results of this study showed that the Portuguese version of SRS-2 can be used as a screening tool to improve the recognition of ASD in Brazilian children and adolescents. The scale might have improved versions in the future with the substitution of items with worse performance.

Em 23 de maio de 2011, faleceu o Professor José Silvério Santos Diniz, um dos expoentes da Nefrologia Pediátrica brasileira. Este editorial descreve de forma sumária a trajetória desse grande professor, médico e pesquisador de nosso País.

Professor José Silvério Santos Diniz, an exponent of the Brazilian Pediatric Nephrology, died on 23 May, 2011. This editorial is a brief description of the career of this great Brazilian teacher, physician and researcher.

O transplante renal é a melhor modalidade de terapia renal substutiva até o momento. Infelizmente, a sobrevida do enxerto é interrompida pelos episódios de rejeição aguda ou mesmo de fibrose intersticial/atrofia tubular. A dosagem de quimiocinas e citocinas urinárias como ferramenta alternativa para o diagnóstico dessas complicações tem sido relatada nos últimos anos. Estas substâncias estão sabidamente relacionadas com os mecanismos imunoinflamatórios do transplante renal, podendo ser detectadas no tecido renal, no plasma e na urina de pacientes transplantados. Drogas anti-inflamatórias, inibidores do sistema renina angiotensina e alguns antagonistas de receptores de citocinas, ainda utilizados em nível experimental, podem interferir com a expressão desses mediadores do sistema imune e, por conseguinte, alterar a evolução do transplante renal. Neste sentido, pretende-se neste artigo fazer uma revisão dos estudos sobre a mensuração de citocinas/quimiocinas e dos seus receptores na urina, no plasma e no tecido renal de pacientes transplantados, no intuito de avaliar uma possível associação entre os níveis desses mediadores e as complicações do transplante renal e sobrevida do enxerto.

Renal transplantation is currently the best modality of renal substitutive therapy. Unfortunately graft survival is interrupted by episodes of acute rejection or even interstitial fibrosis/tubular atrophy. The measurement of urinary chemokines and cytokines as an alternative tool to diagnose these complications has been reported in past years. Those substances are clearly related to the immunoinflammatory mechanisms of renal transplantation, and can be detected in renal tissue, plasma, and urine samples of transplant recipients. Anti-inflammatory drugs, renin-angiotensin system inhibitors, and some antagonists of cytokines' receptors, although used only experimentally, can interfere with the expression of these immune system mediators and consequently alter renal transplantation outcome. This article reviewed studies on the measurement of cytokines/ chemokines and their receptors in urine, plasma, and renal tissue of transplant recipients, aiming at evaluating a possible association of the levels of those mediators with renal transplantation complications and allograft survival.