Effect of chronic exposure to fine particulate matter on cardiac tissue of NZBWF1 mice.

Epidemiological and toxicological studies have shown that inhalation of particulate matter (PM) is associated with development of cardiovascular diseases. Long-term exposure to PM may increase the risk of cardiovascular events and reduce life expectancy. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, autoimmune in nature, that is characterized by the production of autoantibodies that affects several organs, including the heart. Air pollution - which can be caused by several different factors - may be one of the most important points both at the onset and the natural history of SLE. Therefore this study aims to investigate whether exposure to air pollution promotes increased inflammation and cardiac remodelling in animals predisposed to SLE. Female NZBWF1 mice were exposed to an environmental particle concentrator. Aspects related to cardiac remodelling, inflammation and apoptosis were analysed in the myocardium. Body weight gain, cardiac trophism by heart/body weight ratio, relative area of cardiomyocytes and the fibrotic area of cardiac tissue were evaluated during the exposure period. Animals exposed to PM2.5 showed increased area of cardiomyocytes, and area of fibrosis; in addition, we observed an increase in IL-1 and C3 in the cardiac tissue, demonstrating increased inflammation. We suggest that air pollution is capable of promoting cardiac remodelling and increased inflammation in animals predisposed to SLE.

Teaching medical students to choose wisely through simulation.

The Choosing Wisely (CW) campaign aims to encourage dialog among physicians and patients about the costs and benefits of medical care. The purpose of the present study was to describe the implementation of the CW campaign among medical students in the pediatrics clerkship using different teaching strategies and to evaluate the students' perception and performance. A prospective, interventionist, open study with a control group was conducted. All sixth-year undergraduate medical students that were on their pediatric clerkship at the Emergency Department during the study period were invited to participate. The study consisted of two strategies: a remote video class about the CW initiative and in situ simulation training. By the end of the rotation, all participants were evaluated through an Objective Structured Clinical Examination (OSCE). A total of 50 students were included, of which 24 watched only the online video (control group) and 26 were exposed to both the online video and the simulation scenarios (intervention group). Students in the intervention group had a significantly higher total score in the OSCE compared to students in the control group (median 90 vs 90; range 78-100 vs 50-100; p: 0.047). Median scores of behavioral items of the OSCE grouped together were significantly higher in the intervention group compared to the control group (median 60 vs 50; range 40-60 vs 20-60; p: 0.002).Conclusion: Simulation training about principles of the CW campaign had a greater impact on behavioral aspects of undergraduate students. This learning strategy was well accepted by participants. What is Known: • The Choosing Wisely (CW) campaign aims to encourage dialog among physicians and patients about the costs and benefits of medical care. • Teaching high-value and cost-conscious care to medical students is highly desired.. What is New: • Simulation training about principles of the CW campaign had a greater impact on behavioral aspects of undergraduate students.

Air pollution influence on serum inflammatory interleukins: A prospective study in childhood-onset systemic lupus erythematous patients.

OBJECTIVE: To assess the effect of individual exposure, in real-time, to traffic-related pollutants on serum interleukin levels of childhood-onset lupus erythematous systemic (c-SLE) patients. METHODS: A longitudinal and observational design was conducted in 12 repeated measures of serum samples and clinical evaluations (totaling 108 measurements) of c-SLE patients over 30 consecutive months. Real-time, individual exposure to fine particles (PM2.5) and nitrogen dioxide (NO2) was measured with portable monitors. Generalized estimating equation was used to evaluate the association between exposure to PM2.5 and NO2 and the following serum cytokine levels on the 7 days preceding clinical assessment and serum collection: MCP1, IL-6, IL-8, IL-10, IL-17, IFN-alpha, and TNF-alpha. Disease activity and other risk factors were also controlled. RESULTS: An interquartile range (IQR) increase in PM2.5 daily concentration was significantly associated with increased levels of TNF-alpha on the third, fourth, and seventh day after exposure; IL-10 on the third and fourth day after exposure; IL-17 on the third and seventh day after exposure; and INF-alpha on the third day after exposure (p < 0.05). An IQR increase in 7-day moving average of PM2.5 was associated with a 6.2 pg/mL (95% CI: 0.5; 11.8; p = 0.04) increase in serum IFN-alpha level. An unexpected significant association was observed between an IQR increase in NO27-day cumulative concentration and a decrease of 1.6 pg/mL (95% CI: -2.6; -0.7; p < 0.001) in serum IL-17. CONCLUSION: Real-time exposure to PM2.5 prospectively associated with increased serum TNF-alpha, INF-alpha, IL-10, and IL-17 levels in c-SLE patients.

Chronic exposure to PM2.5 aggravates SLE manifestations in lupus-prone mice.

BACKGROUND: Air pollution causes negative impacts on health. Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical manifestations and multifactorial etiology. Recent studies suggest that air pollution can trigger SLE and induce disease activity. However, this association has not been deeply investigated. Thus, the aim of this study was to evaluate whether exposure to fine particulate matter (PM2.5) exacerbates SLE manifestations, focusing on renal complications, in a lupus-prone animal model. Female NZBWF1 mice were exposed daily to 600 µg/m3 of inhaled concentrated ambient particles (CAP) or filtered air (FA). Survival rate, body weight, weight of organs (kidney, spleen, thymus, liver and heart), blood cell count, proteinuria, kidney stereology, renal histopathology, gene expression and oxidative stress were analyzed. RESULTS: Female NZBW mice exposed to CAP showed decreased survival, increased circulating neutrophils, early onset of proteinuria and increased kidney weight with renal cortex enlargement when compared to NZBW mice exposed to FA. CONCLUSIONS: This work shows that air pollution aggravates some SLE manifestations in lupus-prone mice. These results reinforce the need of reducing air pollutant levels in order to promote a better quality of life for individuals diagnosed with SLE.

Influence of air pollution on renal activity in patients with childhood-onset systemic lupus erythematosus.

BACKGROUND: Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune and multifactorial disease that can affect the renal system. Exposure to air pollution can trigger systemic inflammation in cSLE patients and increase risk of disease activity. We evaluated effects of individual real-time exposure to air pollutants on renal activity in cSLE patients using the Systemic Lupus Erythematosus Disease Activity Index 2000. METHODS: Longitudinal panel study of 108 repetitive measures from 9 pediatric lupus patients. Over three consecutive weeks, daily individual levels of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were measured, as well as weekly clinical evaluation and laboratory tests. This was repeated every 10 weeks over a 1-year period. Specific generalized estimating equation models were used to evaluate the impact of these pollutants on risk of nephritis and anti-dsDNA > 20 UI/mL and on 24-h urine protein and serum complement (C3) levels. RESULTS: An interquartile range (IQR) increase of 18.12 µg/m3 in PM2.5 daily concentration was associated with increased risk of nephritis and positive results for anti-dsDNA. Moreover, increase in 24-h urine protein and decrease in C3 serum levels also associated with exposure to pollutants. An IQR increase in PM2.57-day moving average was associated with increased risks of leukocyturia (3.4; 95% CI 2.6:4.3), positive anti-dsDNA (3.1; 95% CI 2.1:4.0), and 36.3-mg increase (95% IC 20.2:52.3) in 24-h urine protein. An IQR increase (63.1 µg/m3) in 7-day cumulative NO2 levels was associated with decreased serum C3 levels. CONCLUSIONS: This prospective study suggests exposure to air pollution can trigger renal activity in cSLE patients.

Higher burnout scores in paediatric residents are associated with increased brain activity during attentional functional magnetic resonance imaging task.

AIM: Burnout syndrome is common in healthcare workers. We evaluated its prevalence in paediatric residents and investigated its influence on cerebral function correlations, using functional magnetic resonance imaging (MRI), when they carried out an attentional paradigm. METHODS: This cross-sectional descriptive study involved 28 residents from the Department of Paediatrics at the University of São Paulo. The functional MRI was carried out while the residents completed the Stroop colour word task paradigm to investigate their attentional task performance. The Maslach Burnout Inventory (MBI) was applied, and stress was assessed using the Lipp Inventory of Stress Symptoms for Adults and by a visual analogue mood scale. RESULTS: The MBI subscales of depersonalisation and emotional exhaustion indicated that 53.1% of the residents had moderate or high burnout syndrome. The whole-brain multivariate analysis showed positive correlations between the blood oxygenation level dependent effect and the MBI depersonalisation and emotional exhaustion indices in the dorsolateral prefrontal cortex, which controls for anxiety. CONCLUSION: Increased brain activation during an attention task, measured using functional MRI, was associated with higher burnout scores in paediatric residents. This study provides a biological basis for the implementation of measures to reduce burnout syndrome at the start of residency training programmes.

Elevated C-reactive protein and spontaneous bacterial peritonitis in children with chronic liver disease and ascites.

OBJECTIVES: The aims of this study were to compare laboratory indices of spontaneous bacterial peritonitis (SBP) and noninfected ascites in children with chronic liver disease and to determine the infectious agents involved in SBP. METHODS: The medical records of 90 children with chronic liver disease and ascites studied between January 2005 and August 2011 were reviewed for laboratory data of diagnostic significance in SBP. Standard laboratory tests included blood cell count, coagulation indices, liver and renal function tests, C-reactive protein (CRP), serum sodium concentration, serum albumin, and serum cultures. Ascitic fluid obtained from 152 paracentesis procedures was assayed for cytology, Gram stains, neutrophil counts, and bacteriological cultures. RESULTS: The SBP group manifested significantly lower albumin levels and elevated CRP levels, prothrombin times, international normalized ratios, and leukocyte number (P<0.05 in each case). CRP was shown to be an independent variable in the prediction of SBP. Values of serum creatinine, sodium concentration, urea, total bilirubin and differential leukocyte shift were comparable in SBP and noninfected ascites. Streptococcus pneumoniae was the most prevalent infectious agent in the ascitic fluid (44%). CONCLUSIONS: CRP may be useful in early detection and monitoring of SBP in children with liver disease.

How to incorporate telemedicine in medical residency: A Brazilian experience in pediatric emergency.

INTRODUCTION: The exponential growth of telehealth services during the COVID-19 pandemic led to the implementation of a telemedicine care service in a tertiary university pediatric hospital. It brought the need to develop a training aimed at remote care within the pediatric emergency rotation program. OBJECTIVE: To describe the implementation of a telemedicine training for pediatric residents and present the preliminary results. METHODS: Descriptive prospective study (pre and post), with 40 resident physicians of the first year of pediatrics. Reaction Assessments were applied before and after training, in addition to a resident physician perception questionnaire at the end of the training. RESULTS: There was a significant difference in the resident's perception of experience and safety after initial training. Most rated the proposal as good or excellent, considered teaching telemedicine relevant and that this experience contributed to their learning on the subject. CONCLUSION: This study describes an innovative proposal for training in telemedicine. The preliminary results were encouraging, demonstrating the program's potential in training future pediatricians.

Pediatric emergency triage systems.

OBJECTIVE: The aim of this study was to perform a narrative review of the leading pediatric triage systems in emergency departments (EDs). DATA SOURCE: Articles published between 1999 and 2019 were identified by searching the MEDLINE, EMBASE, and PubMed databases using the keywords "pediatric triage", "pediatric assessment tools", and "emergency department triage" with an emphasis on studies that evaluated the validation and reliability of triage systems. DATA SYNTHESIS: A total of 105 articles on pediatric emergency triage systems in 12 countries were evaluated. Triage systems were divided into two groups: color-stratified triage systems and alert systems. The color-stratified triage systems included in this review were the Canadian Triage and Acuity Scale (CTAS), Manchester Triage System (MTS), Emergency Severity Index (ESI), and Australasian Triage Scale (ATS), and the alert systems included were the Paediatric Observation Priority Score (POPS), Pediatric Early Warning Score (PEWS), and Pediatric Approach Triangle (PAT). Evidence corroborates the validity and reliability of MTS, PaedCTAS, ESI version 4, PEWS, POPS, and PAT in pediatric emergency services. CONCLUSIONS: These are fundamental tools for risk classification of patients seeking treatment in EDs. Not all triage systems have been assessed for validity and reliability; nor are they well suited for all regions of the world. Employing triage systems in Brazil requires cultural adaptation and rigorous training of the local health staff, in addition to validation and reliability studies in our country, since the social and cultural context of this country differs from those where these tools were developed.

Acute upper gastrointestinal bleeding due to portal hypertension in children: What is the best timing of endoscopy?

OBJECTIVE: To compare initial clinical/laboratory parameters and outcomes of mortality/rebleeding of endoscopy performed <12 h(early UGIE) versus endoscopy performed after 12-24h(late UGIE) of ED admission in children with acute upper gastrointestinal bleeding(AUGIB) due to portal hypertension. METHODS: This is a retrospective cohort study. From January 2010 to July 2017, medical records of all children admitted to a tertiary care hospital with AUGIB due to portal hypertension were reviewed until 60 days after ED admission. RESULTS: A total of 98 ED admissions occurred from 73 patients. Rebleeding was identified in 8/98(8%) episodes, and 9 deaths were observed. UGIE was performed in 92(94%) episodes, and 53(58%) of them occurred within 12 h of ED admission. Episodes with early UGIE and late UGIE were similar in terms of history/complaints/laboratory data at admission, chronic liver disease associated, AUGIB duration, and initial management. No statistically significant associations were found between early UGIE and the outcomes of death/rebleeding and prevalence of endoscopic hemostatic treatment (band ligation or sclerotherapy) compared to late UGIE. In the multivariable logistic regression model, the endoscopic hemostatic treatment showed a negative association with early UGIE(OR=0.33;95%CI=0.1-0.9;p = 0.04). CONCLUSIONS: This study suggests that in pediatric patients with AUGIB and portal hypertension, UGIE may be performed after 12-24 h without harm to the patient, facilitating better initial clinical stabilization/treatment and optimization of resources.

Post-varicella arterial ischemic stroke in children and neurocognitive performance: a 4-year follow-up study.

OBJECTIVE: To analyze data from children who were previously healthy and presented with post-varicella arterial ischemic stroke upon arrival when admitted to the emergency room, with focus on the clinical/laboratory aspects, and neurocognitive performance after four-year follow-up. METHODS: Seven children presenting with arterial ischemic stroke after varicella were evaluated at pediatric emergency services in the city of São Paulo (SP), Brazil. Ischemic stroke was determined by magnetic resonance imaging/magnetic resonance angiography in a topography compatible with the areas supplied by the middle cerebral or internal carotid arteries. IgG-class antibodies against varicella zoster virus and varicella-zoster virus DNA by polymerase chain reaction in cerebrospinal fluid were tested. Patients with prothrombotic conditions were excluded. The Pediatric Stroke Outcome Measure was applied upon admission and 4-years after the stroke. RESULTS: All patients (age range: 1.3 to 4 years) included presented chickenpox 5.1 (±3.5) months before. All patients had analysis of anti-varicella-zoster-virus-IgG in cerebrospinal fluid, but only three (43%) had a positive result. Of the patients 43% had no vascular lesions identified in magnetic resonance angiography. All patients showed improvement in their sequela scores. After 4 years, five patients displayed good evolution in the Pediatric Stroke Outcome Measure, and only one patient presented with a score of 2 in the sensorimotor and cognition areas. No recurrence of arterial ischemic stroke was observed. CONCLUSION: We reinforced the non-progressive course of post-varicella arterial ischemic stroke after 4-year follow-up. The presence of varicella-zoster-virus-DNA detected by polymerase chain reaction, and/or intrathecal IgG antibody against varicella zoster virus, and angiopathy location in magnetic resonance angiography were not determining for the diagnosis. Invasive tests, with low sensitivity, should be well considered in the diagnosis of post-varicella arterial ischemic stroke.

SARS-CoV-2 and rhinovirus infections: are there differences in clinical presentation, laboratory abnormalities, and outcomes in the pediatric population?

This study aims to assess COVID-19 and other respiratory viruses in pediatric patients. Between April 17 and September 30, 2020, we collected 1,566 respiratory samples from 1,044 symptomatic patients who were younger than 18 years old to assess SARS-CoV-2 infection. Of these, 919 were analyzed for other respiratory pathogens (ORP). Patients with laboratory-confirmed COVID-19 or ORP were included. We evaluated 76 pediatric COVID-19 infections and 157 other respiratory virus infections. Rhinovirus occurred in 132/157 (84%). COVID-19 patients who were significantly older, had more fevers, headaches and pneumonia than those with ORP. The median white blood cell count was lower in patients with SARS-CoV-2 than in those with ORP (6,470 versus 8,170; p=0.02). COVID-19 patients had significantly worse symptoms than those with ORP.

The Heart of Pediatric Patients with COVID-19: New Insights from a Systematic Echocardiographic Study in a Tertiary Hospital in Brazil. / O Coração de Pacientes Pediátricos com COVID-19: Novos Insights a Partir de um Estudo Ecocardiográfico Sistemático em um Hospital Terciário no Brasil.

BACKGROUND: COVID-19 pandemic represents a huge burden to the health system in the world. Although pediatric COVID-19 patients have been relatively spared compared with adults, recent reports showed an increasing number of critically ill patients with multisystemic inflammatory syndrome in children (MIS-c), with marked cardiovascular impairment. Nevertheless, little is known about the relationship between cardiac abnormalities and inflammatory and coagulation biomarkers. OBJECTIVES: to investigate echocardiographic abnormalities in pediatric patients with COVID-19 admitted to tertiary hospital. METHODS: this was a retrospective longitudinal study, based on the review of medical records and echocardiograms of patients (0-19 years) admitted to a tertiary hospital between March 30 and June 30, 2020. For statistical analysis, the significance level was set at 5% (p < 0.05). RESULTS: Forty-eight patients were enrolled, 73% with preexisting diseases, 20 (41.7%) with MIS-c. Median age was 7.5 (0-18.6) years; 27 (56.2%) were male. Median duration of hospitalization was 15.4 (2-92) days and seven (14.6%) patients died. A total of 70 echocardiograms were performed; 66.7% patients were scanned only once and 33.3% multiple times. Twenty-three (48%) patients showed echocardiographic abnormalities: eight (16.6%) left ventricle (LV) systolic dysfunction, six (12.5%) right ventricle (RV) systolic dysfunction and 12 (25%) coronary dilatation (Z-score>+2.5). Echocardiographic abnormalities were significantly associated with MIS-c, admission to the pediatric intensive care unit, multiple organ dysfunction, ventilatory/vasoactive support, and death (p<0.05). Significantly higher d-dimer (ng/mL) levels were detected in patients with LV dysfunction [16733(4157-115668) vs. 2406.5(190-95040)], RV dysfunction [25769(3422-115668) vs. 2803.5(190-95040)] and coronary artery dilation [9652.5(921-115668) vs. 2724(190- 95040)] (p<0.05). CONCLUSION: Echocardiographic abnormalities in COVID-19 pediatric patients were frequent and associated with worse clinical outcomes. Exacerbation of the inflammation and coagulation pathways may play an important role in cardiovascular injury in those patients.

FUNDAMENTO: A pandemia da COVID-19 representa uma enorme carga para o sistema de saúde do mundo. Apesar de pacientes pediátricos terem sido relativamente poupados em comparação a adultos, estudos recentes mostraram um número crescente de pacientes críticos com Síndrome Inflamatória Multisistêmica Pediátrica (SIM-P) com disfunção cardiovascular importante. No entanto, pouco se conhece a respeito da relação entre anormalidades cardíacas e biomarcadores inflamatórios e de coagulação. OBJETIVOS: Investigar anormalidades ecocardiográficas em pacientes pediátricos com COVID-19 admitidos em um hospital terciário. MÉTODOS: Este foi um estudo longitudinal retrospectivo, baseado na revisão de prontuários médicos e ecocardiogramas de pacientes (0-19 anos) admitidos em um hospital terciário entre 30 de março e 30 de junho de 2020. Para a análise estatística, o nível de significância foi estabelecido em 5% (p<0,05). RESULTADOS: Foram incluídos 48 pacientes, 73% com doenças pré-existentes, 20 (41,7%) com SIM-P. A idade mediana foi 7,5 (0-18,6) anos; 27 (56,2%) eram do sexo masculino. A duração mediana de internação foi 15,4 (2-92) dias e sete (14,6%) pacientes morreram. Um total de 70 ecocardiografias foram realizadas, 66,7% submeteram-se ao exame somente uma vez, e 33,3% várias vezes. Vinte e três (48%) pacientes apresentaram anormalidades no ecocardiograma: oito (16.6%) disfunção sistólica do ventrículo esquerdo, seis (12.5%) disfunção sistólica do ventrículo direito, e 12 (25%) dilatação da artéria coronária (Z-score>+2,5). Anormalidades ecocardiográficas foram significativamente associadas com SIM-P, admissão na unidade de terapia intensiva pediátrica, suporte ventilatório/vasoativo, e morte ( p <0,05). Níveis significativamente mais altos de d-dímero (ng/mL) foram detectados em pacientes com disfunção ventricular esquerda [16733(4157-115668) vs. 2406.5(190-95040)], disfunção ventricular direita [25769(3422-115668) vs. 2803.5(190-95040)] e dilatação da artéria coronária [9652.5(921-115668) vs. 2724(190- 95040)] (p<0,05). CONCLUSÃO: Anormalidades ecocardiográficas eram frequentes nos pacientes pediátricos com COVID-19 e associadas com piores desfechos clínicos. Exacerbação das vias de inflamação e coagulação pode exercer um importante papel na lesão cardiovascular nesses pacientes.

Changing the view: Video versus direct laryngoscopy for intubation in the pediatric emergency department.

The aim of this study was to compare the success of first-attempt tracheal intubation in pediatric patients >1-year old performed using video versus direct laryngoscopy and compare the frequency of tracheal intubation-associated events and desaturation among these patients.Prospective observational cohort study conducted in an Academic pediatric tertiary emergency department. We compared 50 children intubated with Mcgrath Mac video laryngoscope (VL group) and an historical series of 141 children intubated with direct laryngoscopy (DL group). All patients were aged 1 to 18 years.The first attempt success rates were 68% (34/50) and 37.6% (53/141) in the VL and DL groups (P < .01), respectively. There was a lower proportion of tracheal intubation-associated events in the VL group (VL, 31.3% [15/50] vs DL, 67.8% [97/141]; P < .01) and no significant differences in desaturation (VL, 35% [14/50] vs DL 51.8% [72/141]; P = .06). The median number of attempts was 1 (range, 1-5) for the VL group and 2 (range, 1-8) for the DL group (P < .01). Multivariate logistic regression showed that video laryngoscope use was associated with higher chances of first-attempt intubation with an odds ratio of 4.5 (95% confidence interval, 1.9-10.4, P < 0.01).Compared with direct laryngoscopy, VL was associated with higher success rates of first-attempt tracheal intubations and lower rates of tracheal intubation-associated events.

Severe clinical spectrum with high mortality in pediatric patients with COVID-19 and multisystem inflammatory syndrome.

OBJECTIVES: To assess the outcomes of pediatric patients with laboratory-confirmed coronavirus disease (COVID-19) with or without multisystem inflammatory syndrome in children (MIS-C). METHODS: This cross-sectional study included 471 samples collected from 371 patients (age<18 years) suspected of having severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The study group comprised 66/371 (18%) laboratory-confirmed pediatric COVID-19 patients: 61 (92.5%) patients tested positive on real-time reverse transcription-polymerase chain reaction tests for SARS-CoV-2, and 5 (7.5%) patients tested positive on serological tests. MIS-C was diagnosed according to the criteria of the Center for Disease Control. RESULTS: MIS-C was diagnosed in 6/66 (9%) patients. The frequencies of diarrhea, vomiting, and/or abdominal pain (67% vs. 22%, p=0.034); pediatric SARS (67% vs. 13%, p=0.008); hypoxemia (83% vs. 23%, p=0.006); and arterial hypotension (50% vs. 3%, p=0.004) were significantly higher in patients with MIS-C than in those without MIS-C. The frequencies of C-reactive protein levels >50 mg/L (83% vs. 25%, p=0.008) and D-dimer levels >1000 ng/mL (100% vs. 40%, p=0.007) and the median D-dimer, troponin T, and ferritin levels (p<0.05) were significantly higher in patients with MIS-C. The frequencies of pediatric intensive care unit admission (100% vs. 60%, p=0.003), mechanical ventilation (83% vs. 7%, p<0.001), vasoactive agent use (83% vs. 3%, p<0.001), shock (83% vs. 5%, p<0.001), cardiac abnormalities (100% vs. 2%, p<0.001), and death (67% vs. 3%, p<0.001) were also significantly higher in patients with MIS-C. Similarly, the frequencies of oxygen therapy (100% vs. 33%, p=0.003), intravenous immunoglobulin therapy (67% vs. 2%, p<0.001), aspirin therapy (50% vs. 0%, p<0.001), and current acute renal replacement therapy (50% vs. 2%, p=0.002) were also significantly higher in patients with MIS-C. Logistic regression analysis showed that the presence of MIS-C was significantly associated with gastrointestinal manifestations [odds ratio (OR)=10.98; 95%CI (95% confidence interval)=1.20-100.86; p=0.034] and hypoxemia [OR=16.85; 95%CI=1.34-211.80; p=0.029]. Further univariate analysis showed a positive association between MIS-C and death [OR=58.00; 95%CI=6.39-526.79; p<0.0001]. CONCLUSIONS: Pediatric patients with laboratory-confirmed COVID-19 with MIS-C had a severe clinical spectrum with a high mortality rate. Our study emphasizes the importance of investigating MIS-C in pediatric patients with COVID-19 presenting with gastrointestinal involvement and hypoxemia.

Safety and immunogenicity of the tetravalent, live-attenuated dengue vaccine Butantan-DV in adults in Brazil: a two-step, double-blind, randomised placebo-controlled phase 2 trial.

BACKGROUND: The Butantan Institute has manufactured a lyophilised tetravalent live-attenuated dengue vaccine Butantan-DV, which is analogous to the US National Institutes of Health (NIH) TV003 admixture. We aimed to assess the safety and immunogenicity of Butantan-DV. METHODS: We did a two-step, double-blind, randomised placebo-controlled phase 2 trial at two clinical sites in São Paulo, Brazil. We recruited healthy volunteers aged 18-59 years; pregnant women, individuals with a history of neurological, heart, lung, liver or kidney disease, diabetes, cancer, or autoimmune diseases, and individuals with HIV or hepatitis C were excluded. Step A was designed as a small bridge-study between Butantan-DV and TV003 in DENV-naive participants. In step A, we planned to randomly assign 50 dengue virus (DENV)-naive individuals to receive two doses of Butantan-DV, TV003, or placebo, given 6 months apart. In step B, we planned to randomly assign 250 participants (DENV-naive and DENV-exposed) to receive one dose of Butantan-DV or placebo. Participants were randomly assigned, by computer-generated block randomisation (block sizes of five); participants in step A were randomly assigned (2:2:1) to receive Butantan-DV, TV003, or placebo and participants in step B were randomly assigned (4:1) to receive Butantan-DV or placebo. Participants and study staff were unaware of treatment allocation. The primary safety outcome was the frequency of solicited and unsolicited local and systemic adverse reactions within 21 days of the first vaccination, analysed by intention to treat. The primary immunogenicity outcome was seroconversion rates of the DENV-1-4 serotypes measured 91 days after the first vaccination, analysed in the per-protocol population, which included all participants in step A, and all participants included in step B who completed all study visits with serology sample collection. This trial is registered with ClinicalTrials.gov, NCT01696422. FINDINGS: Between Nov 5, 2013, and Sept 21, 2015, 300 individuals were enrolled and randomly assigned: 155 (52%) DENV-naive participants and 145 (48%) DENV-exposed participants. Of the 155 DENV-naive participants, 97 (63%) received Butantan-DV, 17 (11%) received TV003, and 41 (27%) received placebo. Of the 145 DENV-exposed participants, 113 (78%) received Butantan-DV, three (2%) received TV003, and 29 (20%) received placebo. Butantan-DV and TV003 were both immunogenic, well-tolerated, and no serious adverse reactions were observed. In step A, rash was the most frequent adverse event (16 [845] of 19 participants in the Butantan-DV group and 13 [76%] of 17 participants in the TV003 group). Viraemia was similar between the Butantan-DV and TV003 groups. Of the 85 DENV-naive participants in the Butantan-DV group who attended all visits for sample collection for seroconversion analysis and thus were included in the per-protocol analysis population, 74 (87%) achieved seroconversion to DENV-1, 78 (92%) to DENV-2, 65 (76%) to DENV-3, and 76 (89%) to DENV-4. Of the 101 DENV-exposed participants in the Butantan-DV group who attended all visits for sample collection for seroconversion analysis, 82 (81%) achieved seroconversion to DENV-1, 79 (78%) to DENV-2, 83 (82%) to DENV-3, and 78 (77%) to DENV-4. INTERPRETATION: Butantan-DV and TV003 were safe and induced robust, balanced neutralising antibody responses against the four DENV serotypes. Efficacy evaluation of the Butantan-DV vaccine is ongoing. FUNDING: Intramural Research Program US NIH National Institute of Allergy and Infectious Diseases, Brazilian National Bank for Economic and Social Development, Fundação de Amparo à Pesquisa do Estado de São Paulo, and Fundação Butantan.

Pediatric emergency triage systems / Sistemas de triagem em emergência pediátrica

ABSTRACT Objective: The aim of this study was to perform a narrative review of the leading pediatric triage systems in emergency departments (EDs). Data source: Articles published between 1999 and 2019 were identified by searching the MEDLINE, EMBASE, and PubMed databases using the keywords "pediatric triage", "pediatric assessment tools", and "emergency department triage" with an emphasis on studies that evaluated the validation and reliability of triage systems. Data synthesis: A total of 105 articles on pediatric emergency triage systems in 12 countries were evaluated. Triage systems were divided into two groups: color-stratified triage systems and alert systems. The color-stratified triage systems included in this review were the Canadian Triage and Acuity Scale (CTAS), Manchester Triage System (MTS), Emergency Severity Index (ESI), and Australasian Triage Scale (ATS), and the alert systems included were the Paediatric Observation Priority Score (POPS), Pediatric Early Warning Score (PEWS), and Pediatric Approach Triangle (PAT). Evidence corroborates the validity and reliability of MTS, PaedCTAS, ESI version 4, PEWS, POPS, and PAT in pediatric emergency services. Conclusions: These are fundamental tools for risk classification of patients seeking treatment in EDs. Not all triage systems have been assessed for validity and reliability; nor are they well suited for all regions of the world. Employing triage systems in Brazil requires cultural adaptation and rigorous training of the local health staff, in addition to validation and reliability studies in our country, since the social and cultural context of this country differs from those where these tools were developed.

RESUMO Objetivo: Realizar uma revisão narrativa dos principais sistemas de triagem pediátrica nos serviços de emergência. Fontes de dados: Artigos publicados entre 1999 e 2019, obtidos por meio de busca nos bancos de dados Medical Literature Analysis and Retrieval System Online (Medline), Embase e PubMed usando as palavras-chave "pediatric triage", "pediatric assessment tools" e "emergency department triage", com ênfase em estudos que avaliaram a validação e a confiabilidade desses sistemas. Síntese dos dados: Foram avaliados 105 artigos sobre sistemas de triagem na emergência pediátrica de 12 países. Os sistemas de triagem foram divididos em dois grupos: estratificados por cores e de alerta. Os sistemas de triagem com estratificação por cores incluídos nesta revisão foram: Canadian Triage and Acuity Scale (CTAS), Manchester Triage System (MTS), Emergency Severity Index (ESI) e Australian Triage Scale (ATS). Os sistemas de alerta incluídos foram: Paediatric Observation Priority Score (POPS), Pediatric Early Warning Score (PEWS) e Pediatric Approach Triangle (PAT). Há evidências que corroboram a validade e a confiabilidade do MTS, PedCTAS, ESI v.4, PEWS, POPS e PAT em serviços de emergência de pediátricos. Conclusões: Os sistemas de triagem são ferramentas fundamentais para o atendimento de pacientes que procuram serviços de emergência. Nem todos os sistemas de triagem foram avaliados para validação e confiabilidade nem se aplicam a todas as regiões do mundo. Para a aplicação de sistemas de triagem no Brasil, devem ser feitos adaptação cultural e treinamento do estafe de saúde local, bem como estudos de validação e confiabilidade em nosso país, dado o seu contexto social e cultural diferente daquele dos países onde essas ferramentas foram desenvolvidas.

Risk Factors Associated with Juvenile Idiopathic Arthritis: Exposure to Cigarette Smoke and Air Pollution from Pregnancy to Disease Diagnosis.

OBJECTIVE: To evaluate exposure to environmental factors inhaled during pregnancy and after birth until juvenile idiopathic arthritis (JIA) diagnosis among residents of a large city. METHODS: This is an exploratory case-control study that consists of 66 patients with JIA and 124 healthy controls matched by age and sex, living in the São Paulo, Brazil, metropolitan area until JIA diagnosis, and whose mothers had resided in this region during pregnancy. A structured and reliable questionnaire (κ index for test-retest was 0.80) assessed demographic data, gestational and perinatal-related factors, and exposure to inhalable environmental elements during pregnancy and after birth (occupational exposure to inhalable particles and/or volatile vapor, exposure to cigarette smoke, and the presence of industrial activities or gas stations near the home, work, daycare, or school). Tropospheric pollutants included particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), and carbon monoxide (CO). RESULTS: During pregnancy, intrauterine cigarette smoke exposure (OR 3.43, 95% CI 1.45-8.12, p = 0.005) and maternal occupational exposure (OR 13.69, 95% CI 4.4-42.3, p < 0.001) were significant independent risk factors for JIA diagnosis. In contrast, maternal employment (OR 0.06, 95% CI 0.02-0.2, p < 0.001) and ideal maternal weight gain (OR 0.36, 95% CI 0.2-0.8, p = 0.017) presented negative associations. Secondhand smoke exposure from birth to JIA diagnosis (OR 3.6, 95% CI 1.8-7.3, p < 0.001) and exposure to O3 during the second year of life (OR 2.76, 95% CI 1.20-6.37, p = 0.017) were independent and significant risk factors for the pathogenesis of JIA. CONCLUSION: In our study, cigarette smoke exposure (intrauterine and after birth), exposure to O3 in the second year of life, and maternal occupational exposure were identified as potential risk factors for JIA, warranting further study.

How to incorporate telemedicine in medical residency: A Brazilian experience in pediatric emergency

ABSTRACT Introduction: The exponential growth of telehealth services during the COVID-19 pandemic led to the implementation of a telemedicine care service in a tertiary university pediatric hospital. It brought the need to develop a training aimed at remote care within the pediatric emergency rotation program. Objective: To describe the implementation of a telemedicine training for pediatric residents and present the preliminary results. Methods: Descriptive prospective study (pre and post), with 40 resident physicians of the first year of pediatrics. Reaction Assessments were applied before and after training, in addition to a resident physician perception questionnaire at the end of the training. Results: There was a significant difference in the resident's perception of experience and safety after initial training. Most rated the proposal as good or excellent, considered teaching telemedicine relevant and that this experience contributed to their learning on the subject. Conclusion: This study describes an innovative proposal for training in telemedicine. The preliminary results were encouraging, demonstrating the program's potential in training future pediatricians.

Influence of air pollution on airway inflammation and disease activity in childhood-systemic lupus erythematosus.

Exposure to fine particles may trigger pulmonary inflammation/systemic inflammation. The objective of this study was to investigate the association between daily individual exposure to air pollutants and airway inflammation and disease activity in childhood-onset systemic lupus erythematosus (cSLE) patients. A longitudinal panel study was carried out in 108 consecutive appointments with cSLE patients without respiratory diseases. Over four consecutive weeks, daily individual measures of nitrogen dioxide (NO2), fine particulate matter (PM2.5), ambient temperature, and humidity were obtained. This cycle was repeated every 2.5 months along 1 year, and cytokines of exhaled breath condensate-EBC [interleukins (IL) 6, 8, 17 and tumoral necrose factor-α (TNF-α)], fractional exhaled NO (FeNO), and disease activity parameters were collected weekly. Specific generalized estimation equation models were used to assess the impact of these pollutants on the risk of Systemic Lupus Erythematous Disease Activity Index 2000 (SLEDAI-2K) ≥ 8, EBC cytokines, and FeNO, considering the fixed effects for repetitive measurements. The models were adjusted for inflammatory indicators, body mass index, infections, medication, and weather variables. An IQR increase in PM2.5 4-day moving average (18.12 µg/m3) was associated with an increase of 0.05 pg/ml (95% CI 0.01; 0.09, p = 0.03) and 0.04 pg/ml (95% CI 0.02; 0.06, p = 0.01) in IL-17 and TNF-α EBC levels, respectively. Additionally, a short-term effect on FeNO was observed: the PM2.5 3-day moving average was associated with a 0.75 ppb increase (95% CI 0.38; 1.29, p = 0.03) in FeNO. Also, an increase of 1.47 (95% CI 1.10; 1.84) in the risk of SLEDAI-2K ≥ 8 was associated with PM2.5 7-day moving average. Exposure to inhalable fine particles increases airway inflammation/pulmonary and then systemic inflammation in cSLE patients.