Pediatric patients with COVID-19 admitted to intensive care units in Brazil: a prospective multicenter study / Pacientes pediátricos com COVID-19 admitidos em Unidades de Terapia Intensiva no Brasil: um estudo prospectivo multicêntrico

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.

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.

Diversity and genetic stability in banana genotypes in a breeding program using inter simple sequence repeats (ISSR) markers.

Banana (Musa spp) is a fruit species frequently cultivated and consumed worldwide. Molecular markers are important for estimating genetic diversity in germplasm and between genotypes in breeding programs. The objective of this study was to analyze the genetic diversity of 21 banana genotypes (FHIA 23, PA42-44, Maçã, Pacovan Ken, Bucaneiro, YB42-47, Grand Naine, Tropical, FHIA 18, PA94-01, YB42-17, Enxerto, Japira, Pacovã, Prata-Anã, Maravilha, PV79-34, Caipira, Princesa, Garantida, and Thap Maeo), by using inter-simple sequence repeat (ISSR) markers. Material was generated from the banana breeding program of Embrapa Cassava & Fruits and evaluated at Embrapa Coastal Tablelands. The 12 primers used in this study generated 97.5% polymorphism. Four clusters were identified among the different genotypes studied, and the sum of the first two principal components was 48.91%. From the Unweighted Pair Group Method using Arithmetic averages (UPGMA) dendrogram, it was possible to identify two main clusters and subclusters. Two genotypes (Garantida and Thap Maeo) remained isolated from the others, both in the UPGMA clustering and in the principal cordinate analysis (PCoA). Using ISSR markers, we could analyze the genetic diversity of the studied material and state that these markers were efficient at detecting sufficient polymorphism to estimate the genetic variability in banana genotypes.

Lethality by pneumonia and factors associated to death / Letalidade por pneumonia e fatores associados ao óbito

OBJECTIVE: To describe the case-fatality rate (CFR) and risk factors of death in children with community-acquired acute pneumonia (CAP) in a pediatric university hospital. METHOD: A longitudinal study was developed with prospective data collected from 1996 to 2011. Patients aged 1 month to 12 years were included in the study. Those who left the hospital against medical orders and those transferred to ICU or other units were excluded. Demographic andclinical-etiological characteristics and the initial treatment were studied. Variables associated to death were determined by bivariate and multivariate analysis using logistic regression. RESULTS: A total of 871 patients were selected, of whom 11 were excluded; thus 860 children were included in the study. There were 26 deaths, with a CFR of 3%; in 58.7% of these, penicillin G was the initial treatment. Pneumococcus was the most common pathogen (50.4%). From 1996 to 2000, there were 24 deaths (93%), with a CFR of 5.8% (24/413). From 2001 to 2011, the age group of hospitalized patients was older (p = 0.03), and the number of deaths (p = 0.02) and the percentage of disease severity were lower (p = 0.06). Only disease severity remained associated to death in the multivariate analysis (OR = 3.2; 95%CI: 1.2-8.9; p = 0.02). CONCLUSION: When the 1996-2000 and 2001-2011 periods were compared, a significant reduction in CFR was observed in the latter, as well as a change in the clinical profile of the pediatric in patients at the institute. These findings may be related to the improvement in the socio-economical status of the population. Penicillin use did not influence CFR. .

OBJETIVO: Descrever a taxa de letalidade (TL) e os fatores de risco de óbito em crianças com pneumonia grave adquirida na comunidade (CAP) em um hospital universitário pediátrico. MÉTODO: Foi desenvolvido um estudo longitudinal com dados prospectivos coletados de 1996 a2011. Foram incluídos no estudo pacientes com idade entre 1 mês e 12 anos de idade. Foram excluídos aqueles que deixaram o hospital desconsiderando as recomendações médicas e aqueles transferidos para UTI ou outras unidades. Foram estudadas as características demográficas, clínicas e etiológicas e o tratamento inicial. As variáveis associadas a óbito foram determinadas por análise bivariada e multivariada utilizando regressão logística. RESULTADOS: Foi selecionado um total de 871 pacientes, dos quais 11 foram excluídos; assim, foram incluídas no estudo 860 crianças. Houve 26 óbitos, com uma TL de 3%; em 58,7% desses, penicilina G foi o tratamento inicial. Pneumococo foi o patógeno mais comum (50,4%). De 1996 a 2000, houve 24 óbitos (93%), com uma TL de 5,8% (24/413). De 2001 a 2011, a faixa etária de pacientes internados foi mais velha (p = 0,03) e o número de óbitos (p = 0,02) e o percentual de gravidade das doenças foram menores (p = 0,06). Apenas a gravidade das doenças continuou associada a óbito na análise multivariada (RC = 3,2; IC de 95%: 1,2-8,9; p = 0,02). CONCLUSÃO: Quando os períodos de 1996-2000 e 2001-2011 foram comparados, foi observada uma redução significativa na TL no último período, bem como uma alteração no perfil clínico dos pacientes hospitalizados no instituto. Esses achados podem estar relacionados à melhora na situação socioeconômica da população. O uso de penicilina não influenciou a TL. .

Chronic pain in leprosy: new aspects to be considered.

Leprosy is still considered to be endemic in several developing countries, such as India and Brazil. Infection with Mycobacterium leprae leads to chronic granulomatous inflammation in skin and peripheral nerves that can lead to sensory, motor and autonomic impairments. Since the disease causes severe sensory loss, little attention has been given to pain in leprosy. However, chronic pain in leprosy is being increasingly recognized as an important late complication of leprosy. This article discusses the assessment of pain in leprosy and suggests factors that can contribute to the chronicity. We also consider pain as a multiple system output, bringing the possibility of new treatment options for chronic pain in leprosy.

New insights into opioid regulatory pathways: influence of opioids on Wnt1 expression in zebrafish embryos.

Opioids are the most potent analgesics known today, but their prolonged administration produces severe adverse effects such as constipation, bradycardia, besides addiction, a concept not fully understood at present, which represents one of the most important challenges of modern bioscience. Wnts constitute an important family of vertebrate genes that encode secreted signaling proteins implicated in various developmental processes (patterning of the neural tube, neuronal differentiation), and are extensively conserved through evolution. In this study we have focused on Wnt1, an essential signal in axis polarity, as well as in proliferation and the development and differentiation of the CNS, roles shared by opioid receptors. Our previous studies in zebrafish show that morphine, the most potent analgesic known today, increases cell proliferation and induces neuronal protection and dopaminergic differentiation by activating the opioid receptors. The aim of the present study is to determine whether these effects are a consequence of an interaction between Wnt1 and the endogenous opioid system, which may act as a transcription regulator of Wnt1. Hence, we have exposed embryos to morphine, the endogenous delta opioid agonist Met-Enkephalin-Glu-Tyr (MEGY) (it binds with high affinity to both zebrafish delta opioid receptors, ZfDORs), and SNC80, a highly specific delta agonist, which displays low affinity towards the ZfDORs. Although at earlier stages, all opioids reduced the expression level of Wnt1, further on development, mainly during the differentiation of the CNS (24-48 h post fertilization (hpf)), morphine and MEGY increased Wnt1 expression. Our results point to the possibility that opioid signaling controls the transcription of Wnt1 and that through Wnt1, the opioid system regulates cell proliferation and neuronal differentiation. The present work opens a door to the discovery of new mechanisms that regulate opioid activity and its adverse effects, and hence, it might provide a good target to design new drugs that prevent or avoid these effects.

Immunoreactivity of five antigens of Mycobacterium tuberculosis in patients attending a public health care facility in an area with high endemicity for TB.

The objective of this study was to evaluate people attending a primary health clinic in Rio de Janeiro, Brazil for immunoreactivity to five Mycobacterium tuberculosis antigens, as these antigens are markers of immune response and factors associated with active TB. The serum antibody titers of different categories of patients (defined by microbiological and radiological characteristics and by response to therapy on follow-up) to 38 kDa, 16 kDa, MPT64, ESAT-6 and MT10.3 antigens were determined blind with ELISA. Positive tests to each antigen were defined with ROC analysis. OR were calculated for factors associated with humoral response in patients with active TB. A total of 201 patients underwent serological testing. Patients with confirmed active TB responded more frequently to MPT64 (44%), 16 kDa (37.7%) and 38 kDa (36.1%). ESAT-6 and MT10.3 were also able to distinguish people in TB groups from controls. TB infected subjects responded less frequently to ESAT-6 and MT10.3 (3.7% and 11%, respectively). Sensitivity and specificity to all antigens combined were 58.4% and 60.7%, respectively. Reactivity to 38 kDa and to MPT64 was more likely among alcohol users OR 2.61 (95%CI;1.05-6.94) and OR 3.27 (95%CI;1.33-8.15), respectively. 16 kDa antigen elicited a more protective response among smokers, OR 0.29 (95%CI; 0.10-0.83). It was concluded that reactivity to all antigens tested represented markers of active disease. ESAT-6 and MT10.3 could not be identified as markers of TB infection in this community. Sensitivity was higher to all antigens combined, but at a cost of lower specificity. Interestingly, among factors associated with positive immunoreactivity, alcohol use and smoking seem to polarize the humoral response in different directions. This finding deserves further investigation.

Predictive model for the diagnosis of tuberculous pleural effusion.

This study developed a predictive model to identify pleural tuberculosis. A consecutive cases study of patients investigating the cause of pleural effusion, in an area of high prevalence of tuberculosis (Rio de Janeiro, Brazil). Clinical and laboratory variables were compared among patients with tuberculosis (TB) and without tuberculosis (NTB), individually and using logistic regression. The performance was described as diagnostic accuracy, compared to a gold standard in a masked way. We have studied 104 TB patients, 41 with malignant, 29 transudates, 28 parapneumonic, 13 with miscellaneous diseases. After identification of individual discrimination power aided by clinical, radiological and laboratory variables, the following ones were included in a multivariate analysis: ADA, total leukocytes, percentile of lymphocytes, protein, lactate dehydrogenase, duration of disease, age and gender. A logistic regression model to predict pleural tuberculosis including the five first variables showed the best performance. A receiver operating characteristic curve identified the best cutoff at 0.7, resulting in a sensitivity and specificity of more then 95%. The predictive model improved the specificity of ADA alone, keeping its sensitivity. This model seems helpful when a microbiological or histological diagnosis of pleural tuberculosis could not be established. External validation of these results is necessary before recommendation for routine application.

Predictive model for the diagnosis of tuberculous pleural effusion

This study developed a predictive model to identify pleural tuberculosis. A consecutive cases study of patients investigating the cause of pleural effusion, in an area of high prevalence of tuberculosis (Rio de Janeiro, Brazil). Clinical and laboratory variables were compared among patients with tuberculosis (TB) and without tuberculosis (NTB), individually and using logistic regression. The performance was described as diagnostic accuracy, compared to a gold standard in a masked way. We have studied 104 TB patients, 41 with malignant, 29 transudates, 28 parapneumonic, 13 with miscellaneous diseases. After identification of individual discrimination power aided by clinical, radiological and laboratory variables, the following ones were included in a multivariate analysis: ADA, total leukocytes, percentile of lymphocytes, protein, lactate dehydrogenase, duration of disease, age and gender. A logistic regression model to predict pleural tuberculosis including the five first variables showed the best performance. A receiver operating characteristic curve identified the best cutoff at 0.7, resulting in a sensitivity and specificity of more then 95 percent. The predictive model improved the specificity of ADA alone, keeping its sensitivity. This model seems helpful when a microbiological or histological diagnosis of pleural tuberculosis could not be established. External validation of these results is necessary before recommendation for routine application.

Knowledge about STD/AIDS and sexual behavior among high school students in Rio de Janeiro, Brazil

The incidence of AIDS and other sexually transmitted diseases (STDs) is increasing among adolescents. In order to better understand high-risk sexual behavior among students, a cross-sectional study based on a self-answered anonymous questionnaire was conducted in 10 public and private high schools in Rio de Janeiro, Brazil. Data were obtained on sociodemographics, knowledge of STD/AIDS, and sexual behavior. Among 945 students aged 13-21, 59 percent were sexually initiated, and the median age at first sexual intercourse was 15 years (range: 7-19). Although 94 percent reported being aware of the need for condom use for protection, only 34 percent informed always using condoms during sex. Low family income was associated with unsatisfactory knowledge (OR = 9.40; 95 percent CI = 6.05-14.60) and inconsistent condom use (OR = 11.60; 95 percent CI = 5.54-24.30). However, unsatisfactory knowledge was not associated with inconsistent condom use. School-based educational programs should focus on sexual behavior more than on transmission of knowledge, as well as targeting low-income students

Dosimetric and radiation protection considerations based on some cases of patient skin injuries in interventional cardiology.

Recently, several cases of skin injuries have been detected in patients undergoing cardiac radiofrequency catheter ablation. These procedures were performed on a biplane X-ray system used in a large Spanish hospital for interventional cardiology procedures. Interventional procedures performed and radiation lesions produced on patients are described. The radiation lesions were mainly erythematous lesions and chronic radiodermatitis. Results of the dosimetric evaluations and an analysis of the operational aspects of radiological protection are discussed. Poor image quality could have influenced the length of the procedures. Dose rate at the image intensifier entrance was within usual reported values in literature. However, the focus-to-skin distance for the horizontal X-ray beam was too short, resulting in a high skin dose rate. Additionally, X-ray beams are of fixed orientation, and accumulated skin dose in the patient's right side has been estimated as 11-15 Gy per procedure. In conclusion, practical radiation protection considerations to avoid further incidents of this sort are proposed, concerning the use of X-ray systems specially designed for interventional radiology, the improvement of cardiologists' training in radiation protection and routine patient dose measurements for complex interventional procedures.

Iontophoresis for anesthesia during pulsed dye laser treatment of port-wine stains.

Port-wine stains (PWS) are benign, congenital vascular malformations found in approximately 0.3% of newborns. PWS may be effectively treated with the flashlamp pulsed dye laser (FPDL) at 585 nm. However, laser therapy of vascular lesions often produces pain. We performed a prospective double-blind, placebo-controlled evaluation of the iontophoresis of lidocaine 5% with epinephrine 1:50,000 and mepivacaine 2% with epinephrine 1:50,000. Thirty-six patients with facial PWS were included in the study; 13 of them were treated with lidocaine 5% with epinephrine, another 13 were treated with mepivacaine 2% with epinephrine, and the other 13 were treated with preservative-free 0.9% NaCl. The pain was graded by the patient on a visual analog scale from 0 to 10, comparing the iontophoretically treated area with an adjacent area treated without anesthesia. Pain evaluation by patients demonstrated a significant decrease in the pain of pulsed dye laser impulses using the iontophoresis of lidocaine 5% with epinephrine. No change in the efficacy of pulsed dye laser treatment of PWS or important side effects were observed in our patients. Iontophoresis of lidocaine 5% with epinephrine is a safe and effective method of local anesthesia for pulsed dye laser and it is more effective than the iontophoresis of mepivacaine 2% with epinephrine.

Complications of 585-nm pulsed dye laser therapy.

BACKGROUND: Port-wine stains (PWS) are a congenital, progressive ectasia of the superficial cutaneous vascular plexus that occur in 0.3%-0.5% of children at birth. They should be considered a disease with physical and psychologic complications. Treatment with the flashlamp pulsed dye laser (FPOL) has proven to be effective. Because treatment results in selective vascular injury, the risk of complications is minimal. The purpose of this study was to determine the cutaneous side-effects and complications and their frequency in patients with PWS treated with the FPDL. Eighty-nine patients who had been treated with the FPDL for PWS were included in this study. METHODS: Patients were treated at 3-month intervals using slightly overlapping pulses with fluences of 6.0-9.0 J/cm2. Treating physicians were responsible for evaluating the patients. All patients were reviewed and side-effects and complications were recorded. RESULTS: Pigmentary changes were the most frequently observed complications. Hyper- and hypopigmentation appeared in 16.8% and 2.4% of patients, respectively. Cutaneous depressions occurred in 2.2% of patients. One patient developed a hypertrophic scar, and another patient presented with transient cutaneous pustulosis. All these changes usually resolved spontaneously and completely in a few months. CONCLUSIONS: Most of the side-effects and complications produced by the FPDL are usually transitory, and it is essentially a very secure technique.

Evaluation of agreement among dermatologists in the assessment of the color of port wine stains and their clearance after treatment with the flashlamp-pumped dye laser.

BACKGROUND: Color classification and its subjective clearance evaluation in response to treatment are essential in the management of patients with port wine stains (PWS). But color perception by physicians is not an objective measurement so that it can change among observers. Agreement among physicians is essential for the reliability of the color classification and the clinical assessment of the response to laser treatment. OBJECTIVE: The purpose of our study was to determine the reliability of the clinical color classification of port wine stains and of their color change or clearance in response to laser treatment. The study was not designed to evaluate the outcome of laser treatment in PWS or the factors that could predict the final response. METHODS: We used the kappa index to evaluate the proportion of agreement in color and clearance perception among dermatologists. Six dermatologists classified the initial color of PWS in 80 patients. Three of them also assessed the amount of clearance achieved after treatment with the flashlamp-pumped dye laser. These three dermatologists were usually dedicated to treat patients with PWS, while the other three were not. RESULTS: The kappa index showed a substantial agreement in both cases. No difference in the initial color perception was observed between the group of dermatologists specialized in PWS and the other three dermatologists. CONCLUSION: These results favor the reliability of the clinical method in the assessment of PWS before and after laser treatment. So, although subjective, color perception by physicians can be used in the study of laser treatment outcome in PWS and its related factors, and the results of different authors can be compared.

Progressive ascending telangiectasia treated with the 585 nm flashlamp-pumped pulsed dye laser.

BACKGROUND AND OBJECTIVE: Progressive ascending telangiectasia (PAT) is a distinct entity with telangiectatic superficial vessels on lower extremities as its main clinical feature. A relationship with occult infections and response to antibiotic and antifungal drugs have been described, although not all cases can be successfully managed with these therapies. Our objective was to treat a woman with PAT that had failed to respond to systemic antibiotic and antifungal drugs. STUDY DESIGN/PATIENTS AND METHODS: A 44-year-old woman with PAT was treated with the flashlamp-pumped pulsed dye laser at 585 nm, with fluences varying from 7 to 7.25 J/cm2. RESULTS: A successful outcome was obtained with this treatment approach, with no relevant adverse effects except for mild pigmentary changes. CONCLUSIONS: Although ectatic vessels on lower extremities are often resistant to dye laser therapy, superficial thin capillaries like those featuring PAT can be eliminated with the pulsed dye laser at 585 nm. Transient pigmentary changes occur on treated areas but they are expected to disappear in 6 to 12 months after treatment. Laser treatment should be considered in PAT despite the extension and location of the lesions.

Cutaneous xanthomatous tumours as an expression of chronic myelomonocytic leukaemia?

Nonspecific cutaneous xanthomas have been reported in a variety of lymphocytic neoplastic processes, but to date only three cases of xanthomatous lesions associated with monocytic leukaemias have been described. We now report a patient with a chronic myelomonocytic leukaemia (CMML) associated with these lesions. The clinical and immunohistochemical features do not correspond to any entity previously described and suggest that xanthomas is are a cutaneous expression of the CMML.