ABSTRACT Purpose: To describe the epidemiological and clinical profile of hospitalized patients with retinoblastoma in Brazil. Methods: Using data from the Hospital Cancer Registry of the Instituto Nacional de Câncer, patients with the morphological codes of retinoblastoma who were diagnosed between 2000 to 2018, aged 0–19 years, and followed up in registered hospitals (analytical cases) were selected. The relative and absolute frequencies of demographic, clinical, diagnostic, therapeutic, and outcome variables were described. Hospital performance indicators were calculated and compared between hospitals qualified and not qualified to treat pediatric oncology cases and between hospitals with different case volumes (<20, 20-75, >75 cases). Results: Of the 2,269 identified analytical cases from 86 institutions, 48% were from the Southeast, 54% were male, and 66% were aged <4 years. The proportion of missing data (NA) was too high for several variables. Approximately 84% of the patients were from the public health system, 40% had a positive family history, and 88% had unilateral involvement. The first treatment included surgery in 58.3% of the patients (NA=2), Approximately 36.6% of these patients achieved complete remission, 10.8% achieved partial remission, and 12.7% died (NA=59%). Hospital performance indicators were within the target in >90% of the patients. The median time between the first appointment and diagnosis (6 days, interquartile range [IQR] 1–14) was significantly lower and the median time to death was longer (343 days, IQR, 212-539) in high-volume hospitals (>75 cases) than in medium- and low-volume hospitals. Conclusions: Despite the high proportion of missing data, we found that the delay in diagnosis is due to prehospital factors. Additionally, there is a need for educational programs for healthcare professionals and families that emphasize early identification and referral to specialized centers. Future studies should focus on the impact of Hospital Cancer Registry data completeness on outcomes, causes of delay in diagnosis, regional inequalities, and barriers to accessing specialized services. Purpose Brazil Methods Câncer 200 2018 019 0 19 0–1 years selected demographic diagnostic therapeutic described <20, 20 (<20 2075, 2075 75, 75 20-75 >7 cases. . Results 2269 2 269 2,26 8 institutions 48 Southeast 54 male 66 4 < NA (NA 84 system 40 history 88 involvement 583 58 3 58.3 NA=2, NA2 NA=2 , (NA=2) 366 36 6 36.6 remission 108 10 10.8 127 12 7 12.7 NA=59%. NA59 NA=59% 59 (NA=59%) 90 >90 ( days IQR [IQR 1–14 114 1 14 343 (34 212539 212 539 212-539 highvolume volume (>7 medium lowvolume low Conclusions factors Additionally centers outcomes inequalities services 201 01 0– <20 (<2 207 20-7 > 226 26 2,2 5 58. NA= (NA=2 36. 10. 12. NA5 NA=59 (NA=59% 9 >9 1–1 11 34 (3 21253 21 53 212-53 (> <2 (< 20- 22 2, (NA= NA=5 (NA=59 1– 2125 212-5 (NA=5 212-

Abstract Objective: To evaluate the effect of high-fidelity simulation of pediatric emergencies compared to case-based discussion on the development of self-confidence, theoretical knowledge, clinical reasoning, communication, attitude, and leadership in undergraduate medical students. Methods: 33 medical students were allocated to two teaching methods: high-fidelity simulation (HFS, n = 18) or case-based discussion (CBD, n = 15). Self-confidence and knowledge tests were applied before and after the interventions and the effect of HFS on both outcomes was estimated with mixed-effect models. An Objective Structured Clinical Examination activity was conducted after the interventions, while two independent raters used specific simulation checklists to assess clinical reasoning, communication, attitude, and leadership. The effect of HFS on these outcomes was estimated with linear and logistic regressions. The effect size was estimated with the Hedge’sg. Results: Both groups had an increase in self-confidence (HFS 59.1 × 93.6, p < 0.001; CDB 50.5 × 88.2, p < 0.001) and knowledge scores over time (HFS 45.1 × 63.2, p = 0.001; CDB 43.5 × 56.7, p-value < 0.01), but no difference was observed between groups (group*time effect in the mixed effect models adjusted for the student ranking) for both tests (p = 0.6565 and p = 0.3331, respectively). The simulation checklist scores of the HFS group were higher than those of the CBD group, with large effect sizes in all domains (Hedges g 1.15 to 2.20). Conclusion: HFS performed better than CBD in developing clinical reasoning, communication, attitude, and leadership in undergraduate medical students in pediatric emergency care, but no significant difference was observed in self-confidence and theoretical knowledge. highfidelity high fidelity casebased case based selfconfidence, selfconfidence self confidence, confidence reasoning communication attitude Methods 3 methods HFS, 18 CBD, (CBD 15. 15 . 15) Selfconfidence Self mixedeffect regressions Hedgesg. Hedgesg Hedge sg. sg Hedge’sg Results 591 59 1 59. 936 93 6 93.6 0.001 0001 0 001 505 50 5 50. 882 88 2 88.2 451 45 45. 632 63 63.2 435 43 43. 567 56 7 56.7 pvalue value 0.01, 0.01 , 01 0.01) group*time grouptime ranking 06565 6565 0.656 03331 3331 0.3331 respectively. respectively respectively) Hedges 115 1.1 2.20. 220 2.20 20 2.20) Conclusion care 9 93. 0.00 000 00 8 88. 4 63. 56. 0.0 0656 656 0.65 0333 333 0.333 11 1. 22 2.2 0. 065 65 0.6 033 0.33 2. 06 03 0.3

Abstract Objective: To evaluate exclusive breastfeeding at discharge and hospital length-of-stay in pre-term infants undergoing or not the Kangaroo-Mother Care Method (KMC). Methods: A retrospective cohort study was conducted including preterm infants < 1800 g admitted to the neonatal unit of a KMC reference center. The infants were grouped into the KMC group and the non-KMC group. Multiple logistic and Poisson regressions were performed to evaluate the association between the KMC and two outcomes, exclusive breastfeeding at discharge, and hospital length-of-stay, adjusted for potential confounders. Results: 115 mother-infant dyads were included, 78 in the KMC group and 37 in the non-KMC group. In the bivariate analysis, the KMC group had a lower prevalence of maternal adverse conditions (6% vs. 32%, p < 0.001), a higher number of prenatal visits (median 6 vs. 3.5, p < 0.001), higher gestational ages (median 32 vs. 31 weeks, p < 0.05), higher birth weights (median 1530 vs. 1365 g, p < 0.01), a lower prevalence of necrotizing enterocolitis (3.8% vs. 16.2%, p < 0.05), parenteral nutrition (50% vs. 73%, p < 0.05), and deep vascular access (49.7% vs. 78.4%, p < 0.01), a higher prevalence of exclusive breastfeeding (65% vs. 8%, p < 0.001) and a shorter length of hospital stay (median 28 vs. 42 days, p < 0.001). In the multiple regression analysis, the KMC group was 23 times more likely to be exclusively breastfed at discharge (OR = 23.1; 95% CI = 4,85–109,93) and had a 19% reduction in the hospital length-of-stay (IDR = 0.81; 95% CI = 0.76–0.86) compared to the non-KMC group. Conclusions: The KMC is associated with better short-term neonatal outcomes and should be encouraged in all Brazilian maternity hospitals. Objective lengthofstay pre term KangarooMother Kangaroo Mother KMC. . (KMC) Methods 180 center nonKMC non lengthofstay, stay, confounders Results 11 motherinfant mother infant included 7 3 analysis 6% (6 vs 32% 0.001, 0001 0.001 , 0 001 median 35 5 3.5 weeks 0.05, 005 0.05 05 0.05) 153 136 0.01, 0.01 01 0.01) 3.8% 38 8 (3.8 162 16 2 16.2% 50% 50 (50 73 73% 49.7% 497 49 (49.7 784 4 78.4% 65% 65 (65 8% days 0.001. OR 23.1 231 1 95 4,85–109,93 48510993 85 109 93 19 IDR 0.81 081 81 0.76–0.86 076086 76 86 Conclusions shortterm short hospitals (KMC 18 ( 000 0.00 00 3. 0.0 15 13 3.8 (3. 16.2 (5 49.7 (49. 78.4 23. 9 4,85–109,9 4851099 10 0.8 08 0.76–0.8 07608 0. (3 16. 49. (49 78. 4,85–109, 485109 0.76–0. 0760 (4 4,85–109 48510 0.76–0 076 4,85–10 4851 0.76– 07 4,85–1 485 0.76 4,85– 48 0.7 4,85 4,8 4,

Resumo Introdução: O uso de simulação realística em emergências pediátricas é particularmente valioso, pois permite o treinamento de habilidades técnicas, atitudinais e cognitivas, ajudando a garantir a segurança do paciente. Objetivo: Este estudo tem como objetivo descrever a percepção do aluno sobre o uso da Simulação Realista de Alta Fidelidade nos módulos de emergência pediátrica durante o internato de medicina. Métodos: Estudo observacional, descritivo, com abordagem quantitativa e qualitativa. Um questionário semiestruturado foi aplicado aos estudantes do sexto ano de medicina ao final dos módulos de internato pediátrico, com oito semanas de duração, de agosto a dezembro de 2020. Todos participaram de dois tipos de atividades sobre 14 temas: simulação de alta fidelidade (SRAF) e discussão estruturada de casos clínicos (DCC). Resultados: Dos 33 participantes, 29 responderam ao questionário. A média de idade foi de 24 ± 1,8 anos, sendo 58,6% do sexo feminino. Todos concordaram que a experiência com SRAF contribuiu para um desempenho mais seguro em emergências pediátricas, considerado ótimo por 76% e bom para os demais. A maioria achava que a associação de SRAF e DCC era o método ideal (96%). A análise de conteúdo das respostas sobre a SRAF destacou unidades temáticas em cinco categorias: aprendizagem significativa, contribuição para a formação profissional, habilidades, atitude/comportamento e qualidade da atividade. Conclusões: A reação dos estudantes ao uso da SRAF em emergências pediátricas foi muito positiva, e sua associação com a DCC foi considerada o método de ensino ideal. Conhecer as reações dos alunos ajuda os professores a planejarem suas atividades para melhorar o método de ensino-aprendizagem. Introdução valioso técnicas cognitivas paciente Objetivo Métodos observacional descritivo qualitativa pediátrico duração 2020 1 temas (SRAF DCC. . (DCC) Resultados 3 participantes 2 18 8 1, anos 586 58 6 58,6 feminino 76 demais 96%. 96 96% (96%) categorias significativa profissional atitudecomportamento atitude comportamento atividade Conclusões positiva ensinoaprendizagem. ensinoaprendizagem aprendizagem. ensino-aprendizagem 202 (DCC 5 58, 7 9 (96% 20 (96 (9 (

Abstract Introduction: The use of realistic simulation in pediatric emergencies is particularly valuable, as it allows the training of technical, attitudinal, and cognitive skills, helping to ensure patient safety. Objective: This study aims to describe the student’s perception of using the High-Fidelity Realistic Simulation in the pediatric emergency modules during the internship. Methods: Observational, descriptive study with a quantitative and qualitative approach. A semi-structured questionnaire was applied to sixth-year medical students at the end of the pediatric internship modules, which lasted eight weeks, from August to December 2020. All of them participated in two types of activities on 14 topics: high-fidelity simulation (HFS) and structured discussion of clinical cases (SDCC). Results: Of the 33 participants, 29 answered the questionnaire. The mean age was 24 ± 1.8 years, and 58.6% were female. All agreed that the experience with HFS contributed to safer performance in pediatric emergencies, considered optimal by 76% and good for the remainder. Most thought the association of HFS and SDCC was the ideal method (96%). The content analysis of the responses on HFS highlighted thematic units in five categories: significant learning, contribution to professional training, skills, attitude/behavior, and quality of the activity. Conclusions: Students’ reaction to using HFS in pediatric emergencies was very positive, and its association with SDCC was considered the ideal teaching method. Knowing the students’ reactions helps teachers plan their activities to improve the teaching-learning method. Introduction valuable technical attitudinal skills safety Objective student s HighFidelity High Fidelity Methods Observational approach semistructured semi sixthyear sixth year weeks 2020 1 topics highfidelity high fidelity (HFS SDCC. . (SDCC) Results 3 participants 2 18 8 1. years 586 58 6 58.6 female 76 remainder 96%. 96 96% (96%) categories learning attitudebehavior attitude behavior attitude/behavior activity Conclusions Students positive teachinglearning 202 (SDCC 5 58. 7 9 (96% 20 (96 (9 (

Resumo Introdução: As experiências adversas na infância podem ter impacto em vários aspectos da saúde humana. É importante termos ferramentas que possam identificá-las e quantificá-las. Objetivo: Descrever as etapas iniciais do processo de adaptação transcultural (ATC) do Questionário Internacional de Experiências Adversas na Infância (ACE-IQ) para o português do Brasil. Método: Realizamos a avaliação da equivalência conceitual, semântica e operacional da ATC nas seguintes etapas: preparação (reuniões multidisciplinares); tradução (dois tradutores independentes); reconciliação (grupo multidisciplinar); tradução reversa (tradutor independente); revisão da tradução reversa (grupo multidisciplinar); pré-testes na população-alvo (gestantes de uma maternidade pública no Rio de Janeiro); revisão dos pré-testes (grupo multidisciplinar); prova de leitura; e relatório final (grupo multidisciplinar). Resultados: Os 43 itens do ACE-IQ foram traduzidos e adaptados para português do Brasil. Antes dos pré-testes, cinco itens dos seguintes domínios foram adaptados: etnia e escolaridade (n=2), convivência familiar (n=1) e violência entre os pares (n=2). Seguiram-se três pré-testes consecutivos (10 gestantes cada). Sete itens sofreram adaptações após o primeiro pré-teste: trabalho (n=1), casamento (n=1), relacionamento com pais/responsáveis (n=2) e ambiente familiar (n=3). Após o segundo pré-teste houve somente alteração no formato das opções de resposta. No terceiro pré-teste obteve-se índice de validade de conteúdo entre 0,89 e 1 em todos os itens. Conclusões: A versão brasileira do ACE-IQ mostrou boa equivalência conceitual, semântica e operacional na amostra estudada. Estudos de validade e confiabilidade devem ser conduzidos para confirmar suas propriedades psicométricas. Introdução humana identificálas identificá las quantificálas. quantificálas quantificá las. quantificá-las Objetivo (ATC ACEIQ ACE IQ (ACE-IQ Brasil Método conceitual reuniões multidisciplinares multidisciplinares) dois independentes independentes) grupo multidisciplinar multidisciplinar) tradutor independente independente) prétestes pré testes populaçãoalvo população alvo Janeiro Janeiro) leitura multidisciplinar. . Resultados 4 prétestes, testes, n=2, n2 n n=2 , 2 n=1 n1 (n=1 n=2. Seguiramse Seguiram se 10 (1 cada. cada cada) préteste teste n=1, paisresponsáveis pais responsáveis (n=2 n=3. n3 n=3 3 (n=3) resposta obtevese obteve 089 0 89 0,8 Conclusões estudada psicométricas n= (n= ( (n=3 08 8 0, (n

Abstract Background: Adverse childhood experiences can impact many aspects of human health. It is important to have tools that can identify and quantify them. Objective: To describe initial phases of the cross-cultural adaptation (CCA) of the Adverse Childhood Experiences International Questionnaire (ACE-IQ) to Brazilian Portuguese. Method: We conducted the conceptual, semantic and operational equivalence of the CCA process in nine steps: preparation (multidisciplinary meetings), translation (two independent translators), reconciliation (multidisciplinary group), back-translation (independent translator), back-translation review (multidisciplinary group), pre-tests with the target population (pregnant women from a public maternity hospital in Rio de Janeiro), review of pre-test results (multidisciplinary group), reading proof (multidisciplinary group); final report (multidisciplinary group). Results: The 43-item ACE-IQ has been translated and adapted to Brazilian Portuguese. Before the pre-tests, five items from the following domains were adapted: ethnicity and education (n=2), family life (n=1) and violence between peers (n=2). Three consecutive pre-tests followed (ten pregnant women, each). Seven more items were adapted after the first pre-test: work (n=1), marriage (n=1), relationship with parents/guardians (n=2), family environment (n=3). After the second pre-test, there was only a layout change in the answer options. In the third pre-test, good content validity indexes were obtained in all items (0.89–1.00). Conclusions: The Brazilian version of ACE-IQ showed good conceptual, semantic and operational equivalence in the studied sample. Validity and reliability studies are necessary to confirm its psychometric properties. Background health them Objective crosscultural cross cultural (CCA ACEIQ ACE IQ (ACE-IQ Portuguese Method conceptual steps multidisciplinary meetings, meetings , meetings) two translators, translators translators) group, group group) backtranslation back translator, translator translator) pretests pre tests Janeiro, Janeiro Janeiro) pretest test group. . Results 43item item 43 pretests, tests, n=2, n2 n n=2 2 (n=2) n=1 n1 1 (n=1 n=2. ten each. each each) n=1, parentsguardians parents guardians n=3. n3 n=3 3 (n=3) pretest, test, options 0.89–1.00. 089100 0.89–1.00 0 89 00 (0.89–1.00) Conclusions sample properties 4 n= (n=2 (n= (n=3 08910 0.89–1.0 8 (0.89–1.00 (n 0891 0.89–1. (0.89–1.0 089 0.89–1 (0.89–1. 08 0.89– (0.89–1 0.89 (0.89– 0.8 (0.89 0. (0.8 (0. (0 (

Abstract Objective To describe the association of maternal and neonatal characteristics with the adherence status to the in-hospital stages of the Kangaroo-Mother Care Method - KMC (full, partial, and no-adherence). Methods Retrospective cohort study including infants < 2500 g admitted to a reference maternity hospital for the KMC in Rio de Janeiro from January to December 2018. Maternal and neonatal characteristics were distributed according to the adherence status to the KMC in-hospital stages. In the first stage, KMC is performed in Neonatal Intensive Care Unit and Conventional Neonatal Intermediate Care Unit. The second stage is completed in Kangaroo Neonatal Intermediate Care Unit. Multinomial multiple regression was performed with KMC adherence as a three-category dependent variable and maternal and neonatal characteristics as independent variables. Results Of 166 dyads, 102 (61.5%) participated in two stages. Those who did not participate in any stage (n = 52; 31.3%) had a lower level of education, a higher frequency of adverse conditions, and were more often single mothers; mothers who participated only in the first stage (n = 12; 7,2%) had more premature and sick infants. Conditions associated with adherence to the two stages compared to no adherence were: high school education (OR = 2.34; 95% CI = 1.08-5.07), presence of a partner (OR = 3.82; 95% CI = 1.7-8.61), no adverse conditions (OR = 3.54; 95% CI = 1.59-7.89) and no neonatal resuscitation (OR = 2.73; 95% CI = 1.22-6.1). Conclusions The study identified maternal and neonatal conditions associated with adherence status to the KMC. The results suggest opportunities to improve adherence. inhospital KangarooMother Mother full, full (full partial noadherence. noadherence . no-adherence) 250 2018 threecategory three category variables 16 dyads 10 61.5% 615 61 5 (61.5% n 52 31.3% 313 31 3 12 7,2% 72 7 2 OR 2.34 234 34 95 1.085.07, 108507 1.08 5.07 , 1 08 07 1.08-5.07) 3.82 382 82 1.78.61, 17861 1.7 8.61 8 1.7-8.61) 3.54 354 54 1.597.89 159789 1.59 7.89 59 89 1.59-7.89 2.73 273 73 1.226.1. 12261 1.22 6.1 22 6 1.22-6.1) no-adherence 25 201 61.5 (61.5 31.3 7,2 2.3 23 9 085 1.085.07 10850 108 1.0 507 5.0 0 1.08-5.07 3.8 38 78 1.78.61 1786 17 1. 861 8.6 1.7-8.61 3.5 35 597 1.597.8 15978 159 1.5 789 7.8 1.59-7.8 2.7 27 226 1.226.1 1226 122 1.2 6. 1.22-6.1 20 61. (61. 31. 7, 2. 1.085.0 1085 50 5. 1.08-5.0 3. 1.78.6 178 86 8. 1.7-8.6 1.597. 1597 15 7. 1.59-7. 1.226. 1.22-6. (61 1.085. 1.08-5. 1.78. 1.7-8. 1.597 1.59-7 1.226 1.22-6 (6 1.085 1.08-5 1.78 1.7-8 1.59- 1.22- ( 1.08- 1.7-

Abstract Objective: To evaluate the validity of the computerized version of the pediatric triage system CLARIPED. Methods: Prospective, observational study in a tertiary emergency department (ED) from Jan-2018 to Jan-2019. A convenience sample of patients aged 0-18 years who had computerized triage and outcome variables registered. Construct validity was assessed through the association between urgency levels and patient outcomes. Sensitivity, specificity, positive and negative predictive values (PPVand NPV), undertriage, and overtriage rates were assessed. Results: 19,122 of 38,321 visits were analyzed. The urgency levels were: RED (emergency) 0.02%, ORANGE (high urgency) 3.21%, YELLOW (urgency) 35.69%, GREEN (low urgency) 58.46%, and BLUE (no urgency) 2.62%. The following outcomes increased according to the increase in the level of urgency: hospital admission (0.4%, 0.6%, 3.1%, 11.9% and 25%), stay in the ED observation room (2.8%, 4.7%, 15.9%, 40.4%, 50%), ≥ 2 diagnostic or therapeutic resources (7.8%, 16.5%, 33.7%, 60.6%, 75%), and ED length of stay in minutes (18, 24, 67,120, 260). The odds of using ≥ 2 resources or being hospitalized were significantly greater in the most urgent patients (Red, Orange, and Yellow) compared to the least urgent (Green and Blue): OR 7.88 (95%CI: 5.35-11.6) and OR 2.85 (95%CI: 2.63-3.09), respectively. The sensitivity to identify urgency was 0.82 (95%CI: 0.77-0.85); specificity, 0.62 (95%CI: 0.61-0.6; NPV, 0.99 (95%CI: 0.99-1.00); overtriage rate, 4.28% and undertriage, 18.41%. Conclusion: The computerized version of CLARIPED is a valid and safe pediatric triage system, with a significant correlation with clinical outcomes, good sensitivity, and low undertriage rate.

Abstract Objectives: To describe the concept of toxic stress, present the basics of epigenetics and discuss their relationship with child development. Data source: Narrative literature review through a search in the SciELO, Lilacs, Medline databases using the terms Adverse Childhood Experience OR Early Life Stress, Epigenomic OR Epigenetic, Child Development OR Infant Development. Data synthesis: Continuing stress response, known as toxic stress, can occur when a child experiences intense, frequent, and/or prolonged adversity–such as physical or emotional abuse, chronic neglect, for example–without adequate adult support. This toxic stress can have harmful effects on learning, behavior, and health throughout life. Epigenetics, an emerging scientific research area, shows how environmental influences affect gene expressions and explains how early experiences can impact throughout life. Conclusions: Toxic stress causes changes in the human body response systems that can be explained in part by epigenetic changes, which can be temporary or long-lasting. Pediatricians must be aware of these mechanisms and their consequences, seeking to prevent them and thus promote the health, well-being, and quality of life of children, contributing to their full development.

Abstract Objectives To study the impact of the implementation of the Pediatric Surviving Sepsis Campaign protocol on early recognition of sepsis, 1 -h treatment bundle and mortality. Methods Retrospective, single-center study, before and after the implementation of the sepsis protocol. Outcomes: sepsis recognition, compliance with the 1 -h bundle (fluid resuscitation, blood culture, antibiotics), time interval to fluid resuscitation and antibiotics administration, and mortality. Patients with febrile neutropenia were excluded. The comparisons between the periods were performed using non-parametric tests and odds ratios or relative risk were calculated. Results We studied 84 patients before and 103 after the protocol implementation. There was an increase in sepsis recognition (OR 21.5 [95% CI: 10.1-45.7]), in the compliance with the 1 -h bundle as a whole (62% x 0%), and with its three components: fluid resuscitation (OR 31.1 [95% CI: 3.9−247.2]), blood culture (OR 15.9 [95% CI: 3.9−65.2]), and antibiotics (OR 35.6 [95% CI: 8.9−143.2]). Significant reduction between sepsis recognition to fluid resuscitation (152min × 12min, p < 0.001) and to antibiotics administration (137min × 30min) also occurred. The risk of death before protocol implementation was four times greater (RR 4.1 [95% CI: 1.2-14.4]), and the absolute death risk reduction was 9%. Conclusion Even if we considered the low precision of some estimates, the lower limits of the Confidence Intervals show that the implementation of the Pediatric Surviving Sepsis Campaign guidelines alongside a qualitive assurance initiative has led to improvements in sepsis recognition, compliance with the 1 -h treatment bundle, reduction in the time interval to fluid resuscitation and antibiotics, and reduction in sepsis mortality.

Abstract Objective To describe the clinical, laboratory, and radiological characteristics, as well as the outcomes of children with MIS-C. Method Multicenter, prospective cohort study, conducted in 17 pediatric intensive care units in five states in Brazil, from March to July 2020. Patients from 1 month to 19 years who met the MIS-C diagnostic criteria were included consecutively. Results Fifty-six patients were included, with the following conditions: Kawasaki-like disease (n = 26), incomplete Kawasaki disease (n = 16), acute cardiac dysfunction (n = 10), toxic shock syndrome (n = 3), and macrophage activation syndrome (n = 1). Median age was 6.2 years (IQR 2.4−10.3), 70% were boys, 59% were non-whites, 20% had comorbidities, 48% reported a contact with COVID-19 cases, and 55% had a recent SARS-CoV-2 infection confirmed by RT-PCR and/or serology. Gastrointestinal symptoms were present in 71%, shock symptoms in 59%, and severe respiratory symptoms in less than 20%. -Dimer was increased in 80% and cardiac dysfunction markers in more than 75%. Treatment included immunoglobulin (89%); corticosteroids, antibiotics, and enoxaparin in about 50%; and oseltamivir and antifungal therapy in less than 10%. Only 11% needed invasive mechanical ventilation, with a median duration of five days (IQR 5–6.5). The median length of PICU stay was six days (IQR 5–11), and one death occurred (1.8%). Conclusions Most characteristics of the present MIS-C patients were similar to that of other cohorts. The present results may contribute to a broader understanding of SARS-CoV-2 infection in children and its short-term consequences. Long-term multidisciplinary follow-up is needed, since it is not known whether these patients will have chronic cardiac impairment or other sequelae.

RESUMO Objetivo: Apresentar as atuais evidências sobre as características clínicas e laboratoriais da infecção pelo coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2) durante a infância e a adolescência. Fonte de dados: Revisão narrativa realizada nas bases de dados Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Literatura Latino-Americana e do Caribe em Ciências da Saúde na Biblioteca Virtual em Saúde (LILACS/BVS), Scopus, Web of Science, Cochrane Library, portal da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Scientific Electronic Library Online (SciELO), ScienceDirect e Cumulative Index to Nursing and Allied Health Literature (CINAHL), com o uso dos termos SARS-CoV-2, COVID-19 e novo coronavírus e criança, recém-nascido e adolescente. Síntese dos dados: Diferentemente dos adultos, as crianças infectadas pelo SARS-CoV-2 apresentam formas clínicas leves ou assintomáticas na maior parte dos casos. As crianças sintomáticas apresentam predominantemente febre baixa e tosse, com alguns sintomas gastrointestinais associados. Casos graves são a minoria e ocorrem especialmente abaixo de um ano de idade. A detecção de partículas virais em fezes parece ser mais persistente em crianças, podendo servir como ferramenta diagnóstica e de controle do tempo de quarentena. Diferentemente dos adultos, as crianças podem apresentar respostas inflamatórias distintas, como tem ocorrido nos novos casos de síndrome de Kawasaki-like associada à infecção pelo SARS-CoV-2. Conclusões: Crianças, na sua maioria, apresentam quadros assintomáticos ou leves, com predomínio de febre, tosse e sintomas gastrointestinais. Novos relatos de diferentes reações sistêmicas inflamatórias em crianças têm sido notados, com manifestações clínicas distintas daquelas tipicamente observadas em adultos.

ABSTRACT Objective: To present the current evidence on clinical and laboratory characteristics of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during childhood and adolescence. Data source: This is a narrative review conducted in the databases: Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Latin American and Caribbean Health Sciences Literature in the Virtual Health Library (LILACS/VHL), Scopus, Web of Science, Cochrane Library, portal of the Coordination for the Improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES), Scientific Electronic Library Online (SciELO), ScienceDirect, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The terms used were SARS-CoV-2, COVID-19, novel coronavirus, child, newborn, and adolescent. Data synthesis: Unlike adults, most children infected by SARS-CoV-2 have mild or asymptomatic clinical presentations. Symptomatic children mainly have low fever and cough, with some associated gastrointestinal symptoms. Severe cases are rare and occur especially in infants under one year of age. Detection of viral particles in feces seems to be more persistent in children and can be used as a tool for diagnosis and control of the quarantine period. Different from adults, children can present distinct inflammatory responses, as has happened in new cases of Kawasaki-like syndrome associated with SARS-CoV-2 infection. Conclusions: Most children have asymptomatic or mild presentations, with a prevalence of fever, cough, and gastrointestinal symptoms. New cases with different systemic inflammatory reactions in children have been reported, with clinical manifestations distinct from those typically found in adults.

Resumo Objetivo: Descrever as características clínicas de crianças e adolescentes internados em unidade de terapia intensiva com COVID-19 confirmada. Método: Estudo prospectivo, multicêntrico, observacional, em 19 unidades de terapia intensiva pediátrica. Foram incluídos pacientes entre um mês e 19 anos, admitidos consecutivamente (março a maio de 2020). As características demográficas, clínico-epidemiológicas, o tratamento e os resultados foram coletados. Os subgrupos foram comparados de acordo com as comorbidades, idade < 1 ano e necessidade de ventilação mecânica invasiva. Um modelo de regressão logística multivariável foi utilizado para preditores de gravidade. Resultados: Setenta e nove pacientes foram incluídos (10 com síndrome inflamatória multi-ssistêmica). Mediana de idade, quatro anos; 54% eram do sexo masculino (síndrome inflamatória multissistêmica, 80%); 41% tinham comorbidades (síndrome inflamatória multissistêmica, 20%). Febre (76%), tosse (51%) e taquipneia (50%) foram comuns nos dois grupos. Sintomas graves egastrointestinais e marcadores inflamatórios mais elevados foram mais frequentes na presença de síndrome inflamatória multissistêmica. Infiltrados intersticiais pulmonares foram comuns em ambos os grupos, mas o derrame pleural foi mais prevalente no grupo com síndrome inflamatória multissistêmica (43% vs. 14%). A ventilação mecânica invasiva foi utilizada em 18% (mediana 7,5 dias); antibióticos, oseltamivir e corticosteroides foram utilizados em 76%, 43% e 23%, respectivamente, mas não a hidroxicloroquina. A mediana do tempo de permanência na unidade de terapia intensiva pediátrica foi de 5 dias; duas mortes ocorreram (3%) no grupo não- síndrome inflamatória multissistêmica. Os pacientes com comorbidades eram mais velhos, e as comorbidades foram independentemente associadas à necessidade de ventilação mecânica invasiva(OR 5,5; IC95%, 1,43-21,12; P 0,01). Conclusões: Nas unidades de terapia intensiva pediátrica brasileiras, a COVID-19 apresentou baixa mortalidade, a idade inferior a um ano não foi associada a um pior prognóstico, os pacientes com síndrome inflamatória multissistêmica apresentaram sintomas mais graves, biomarcadores inflamatórios mais elevados e uma grande predominância no sexo masculino, mas apenas a presença de comorbidades e doenças crônicas foi um preditor independente de gravidade.

Abstract Objective: To describe the clinical characteristics of children and adolescents admitted to intensive care with confirmed COVID-19. Method: Prospective, multicenter, observational study, in 19 pediatric intensive care units. Patients aged 1 month to 19 years admitted consecutively (March-May 2020) were included. Demographic, clinical-epidemiological features, treatment, and outcomes were collected. Subgroups were compared according to comorbidities, age < 1 year, and need for invasive mechanical ventilation. A multivariable logistic regression model was used for predictors of severity. Results: Seventy-nine patients were included (ten with multisystemic inflammatory syndrome). Median age 4 years; 54% male (multisystemic inflammatory syndrome, 80%); 41% had comorbidities (multisystemic inflammatory syndrome, 20%). Fever (76%), cough (51%), and tachypnea (50%) were common in both groups. Severe symptoms, gastrointestinal symptoms, and higher inflammatory markers were more frequent in multisystemic inflammatory syndrome. Interstitial lung infiltrates were common in both groups, but pleural effusion was more prevalent in the multisystemic inflammatory syndrome group (43% vs. 14%). Invasive mechanical ventilation was used in 18% (median 7.5 days); antibiotics, oseltamivir, and corticosteroids were used in 76%, 43%, and 23%, respectively, but not hydroxychloroquine. The median pediatric intensive care unit length-of-stay was five days; there were two deaths (3%) in the non- multisystemic inflammatory syndrome group. Patients with comorbidities were older and comorbidities were independently associated with the need for invasive mechanical ventilation (OR 5.5; 95% CI, 1.43-21.12; p = 0.01). Conclusions: In Brazilian pediatric intensive care units, COVID-19 had low mortality, age less than 1 year was not associated with a worse prognosis, and patients with multisystemic inflammatory syndrome had more severe symptoms, higher inflammatory biomarkers, and a greater predominance of males, but only comorbidities and chronic diseases were independent predictors of severity.

Abstract Introduction The association between prenatal Zika virus infection and hearing alterations in offspring has been the object of some studies, although few have assessed children without microcephaly. However, a current trend to include prenatal Zika virus exposure in the group of risk indicators for hearing loss is noted. Objective To present a series of 27 children prenatally exposed to the Zika virus submitted to multiple hearing assessments over time. Methods A cohort of children born to symptomatic mothers with laboratorial Zika virus infection confirmation during pregnancy was submitted to an otoacoustic emission test, auditory brainstem response test (automated, neurodiagnostic and frequency-specific), audiometry, and imitanciometry over a period of 36 months since birth. The hearing assessment was performed independently of the presence of microcephaly or other apparent signs of congenital Zika syndrome. Results The hearing tests presented predominantly normal results. Some children had signs of middle ear pathology. The only microcephalic child had normal electrophysiological tests, as well as preserved audiometric thresholds, but presented altered motor responses to sound. Conclusion Prenatal exposure to Zika virus does not always determine hearing impairment. This risk seems to be more associated to the severity of the central nervous system damage. Hearing screening and follow-ups of the affected children are important, as well as further research in this area.

Resumo Introdução: Possíveis associações entre a infecção pelo Zika vírus e perda auditiva foram observadas durante a epidemia nas Américas. Objetivo: Descrever as alterações auditivas, a patogênese e as recomendações de seguimento em indivíduos com infecção por Zika vírus pré-natal ou adquirida. Método: Uma pesquisa bibliográfica foi realizada em março/2018 a abril/2019 nas principais bases de dados disponíveis. A seleção dos artigos, extração de dados e avaliação de qualidade foram realizadas por dois revisores independentes. Estudos com avaliação auditiva de pacientes com infecção por Zika vírus congênita ou adquirida; e/ou hipóteses ou evidências sobre a fisiopatologia do comprometimento auditivo associado ao Zika vírus; e/ou recomendações sobre triagem e seguimento de pacientes com comprometimento auditivo pelo Zika vírus foram incluídos na pesquisa. Resultados: Um total de 27 artigos foram selecionados. Perdas auditivas neurossensorial e transitória foram relatadas em seis adultos com infecção pelo Zika vírus adquirida. Das 962 crianças estudadas, 482 apresentavam microcefalia e 145 tinham confirmação diagnóstica do Zika vírus; 515 das 624 crianças com avaliação auditiva haviam realizado apenas testes de triagem com teste de emissões otoacústicas e/ou teste de potencial evocado auditivo de tronco encefálico automático com estímulo clique. Estudos em crianças expostas no período pré-natal foram muito heterogêneos e grandes variações na frequência de emissões otoacústicas e potencial evocado auditivo de tronco encefálico automático alterados ocorreram ao longo dos estudos; alterações nas emissões otoacústicas variaram de 0% a 75%, enquanto as alterações no potencial evocado auditivo de tronco encefálico automático variaram de 0% a 29,2%. Não foi possível descartar comprometimento neurossensorial, retrococlear ou de origem central. Um estudo com camundongos infectados não encontrou dano microscópico nas células ciliadas da cóclea. Estudos sobre a patogênese das alterações auditivas em humanos estão limitados a hipóteses e recomendações ainda apresentam pontos de controvérsia. Conclusão: Os dados disponíveis ainda são insuficientes para compreender todo o espectro do envolvimento dos órgãos auditivos pelo Zika vírus, a patogênese desse envolvimento ou até mesmo para confirmar a associação causal entre o envolvimento auditivo e a infecção pelo vírus. As recomendações de triagem e seguimento ainda apresentam pontos de controvérsia.

Abstract Introduction: Possible associations between Zika virus infection and hearing loss were observed during the epidemic in the Americas. Objective: To describe the auditory alterations, pathogenesis and recommendations for follow-up in individuals with prenatal or acquired Zika virus infection. Methods: Bibliographic research conducted in March/2018-April/2019 at the main available databases. Article selection, data extraction and quality evaluation were carried out by two independent reviewers. Studies containing auditory evaluation of patients with congenital or acquired Zika virus infection; and/or hypotheses or evidences on the pathophysiology of auditory impairment associated with Zika virus; and/or recommendations on screening and follow-up of patients with auditory impairment by Zika virus were included. Results: A total of 27 articles were selected. Sensorineural and transient hearing loss were reported in six adults with acquired Zika virus infection. Of the 962 studied children, 482 had microcephaly and 145 had diagnostic confirmation of Zika virus; 515 of the 624 children with auditory evaluation performed only screening tests with otoacoustic emissions testing and/or automated click-stimuli auditory brainstem response testing. Studies in prenatally exposed children were very heterogeneous and great variations in the frequency of altered otoacoustic emissions and automated click-stimuli auditory brainstem response occurred across the studies. Altered otoacoustic emissions varied from 0% to 75%, while altered automated click-stimuli auditory brainstem response varied from 0% to 29.2%. Sensorineural, retrocochlear or central origin impairment could not be ruled out. One study with infected mice found no microscopic damage to cochlear hair cells. Studies on the pathogenesis of auditory changes in humans are limited to hypotheses and recommendations still include points of controversy. Conclusion: The available data are still insufficient to understand the full spectrum of the involvement of the auditory organs by Zika virus, the pathogenesis of this involvement or even to confirm the causal association between auditory involvement and virus infection. The screening and follow-up recommendations still present points of controversy.