Colloids for the Initial Management of Severe Sepsis and Septic Shock in Pediatric Patients: A Systematic Review.

AIM: The goal of this study was to perform a systematic review of the literature assessing the use of colloids for the initial treatment of severe sepsis and septic shock in pediatric patients. DESIGN: The PICO [Patient, Intervention, Comparison, Outcome] method was used for the selection of studies, and the Cochrane Bias Tool was used to analyze the quality of the selected studies. DATA SEARCH: Relevant studies were sought using the following databases: EMBASE (1980 to March 2014), PubMed (1970 to March 2014), Cochrane (1980 to March 2014), Web of Science, and Scopus. Searches used the following key words: isotonic solution, crystalloid, saline solution, colloid, resuscitation, fluid therapy, sepsis and septic shock, starch, and gelatin. The filters children and clinical trial were used when possible. REVIEW METHOD: Study selection was performed by 1 examiner. The selected articles were analyzed by 2 examiners who validated the articles according to the Cochrane Bias Tool. Discrepancies were resolved by consensus or by a third examiner. RESULT: A total of 110 articles were selected based on the key words. Of these, 99 were excluded because they assessed postoperative follow-up, burn cases, cardiac surgery, or nutritional therapy or were review articles, guidelines, or editorials. One study was included after an analysis of previous reviews. A total of 12 articles were selected for analysis because they were reports of clinical trials conducted with prospective cohorts and they analyzed the use of crystalloids and colloids or colloids only in the initial treatment of severe sepsis or septic shock in children and adolescents. The total number of patients was 4375, and they ranged in age from 2 months to 15 years, with most patients between 5 and 15 years. Five studies assessed patients diagnosed with malaria, 5 assessed patients with dengue shock syndrome, 1 studied febrile diseases, and 1 examined the progression of patients with septic shock caused by various causes. CONCLUSIONS: The studies analyzed did not find evidence to suggest that the use of colloids is superior to crystalloids. In some studies, the fluid volume needed to achieve initial stabilization was smaller in the group given colloids. Crystalloids are the preferred therapeutic option because of their effectiveness, low cost, and wide availability. Colloids may be the first choice in cases of malaria when the central nervous system is affected.

A multiplex nested PCR for the detection and identification of Candida species in blood samples of critically ill paediatric patients.

BACKGROUND: Nosocomial candidaemia is associated with high mortality rates in critically ill paediatric patients; thus, the early detection and identification of the infectious agent is crucial for successful medical intervention. The PCR-based techniques have significantly increased the detection of Candida species in bloodstream infections. In this study, a multiplex nested PCR approach was developed for candidaemia detection in neonatal and paediatric intensive care patients. METHODS: DNA samples from the blood of 54 neonates and children hospitalised in intensive care units with suspected candidaemia were evaluated by multiplex nested PCR with specific primers designed to identify seven Candida species, and the results were compared with those obtained from blood cultures. RESULTS: The multiplex nested PCR had a detection limit of four Candida genomes/mL of blood for all Candida species. Blood cultures were positive in 14.8% of patients, whereas the multiplex nested PCR was positive in 24.0% of patients, including all culture-positive patients. The results obtained with the molecular technique were available within 24 hours, and the assay was able to identify Candida species with 100% of concordance with blood cultures. Additionally, the multiplex nested PCR detected dual candidaemia in three patients. CONCLUSIONS: Our proposed PCR method may represent an effective tool for the detection and identification of Candida species in the context of candidaemia diagnosis in children, showing highly sensitive detection and the ability to identify the major species involved in this infection.

Body Composition and Phase Angle: How to Improve Nutritional Evaluation in Juvenile Dermatomyositis Patients.

(1) Background: This study aimed to assess body composition (BC) using bioelectrical impedance and food intake in juvenile dermatomyositis (JDM) patients. Associations between BC and physical activity, disease activity/cumulative damage and health-related quality of life parameters were also evaluated; (2) Methods: This was a cross-sectional study with 30 consecutive JDM patients (18 female and 12 male) and 24 healthy volunteers (14 female and 10 male) of both sexes followed at our pediatric rheumatology unit. The gathering of anthropometric and dietary data, and the performance of physical activity and bioelectrical impedance were undertaken in face-to-face meetings and through questionnaires. Clinical and therapeutic data were collected from medical records according to information from routine medical appointments; (3) Results: The frequency of high/very high body fat was significantly higher in controls compared with JDM patients (66.7% vs. 91.7%; p = 0.046). The median phase angle was significantly lower in patients compared with controls (5.2 ± 1.3 vs. 6.1 ± 1.0; p = 0.016). Body fat and lean mass were positively correlated with disease duration (rs = +0.629, p < 0.001 and rs = +0.716, p < 0.001, respectively) and phase angle (PhA) (rs = +0.400, p = 0.029 and rs = +0.619, p < 0.001, respectively). JDM patients with PhA ≥ 5.5 presented higher lean mass when compared with patients with PhA < 5.5 (p = 0.001); (4) Conclusions: Bioelectrical impedance can be a useful auxiliary exam in the medical and nutritional follow-up of JDM patients, because it seems to impact functional ability. These findings may assist professionals when advising JDM patients about the importance of physical activity and healthy eating in the preservation of lean mass.

Clinical Aspects and Etiologic Investigation of Pediatric Patients With Acute Liver Failure.

A new outbreak of hepatitis of unknown origin raised awareness in the international community. A few reports have attempted to associate new cases with adenovirus infection and the immunologic effects of previous SARS-CoV-2 infections through a superantigen mechanism. Moreover, according to a case series, viral isolates were identified in 7 of 10 cases of pediatric patients with hepatitis of unknown origin and acute liver failure. Adenovirus was detected by respiratory secretion polymerase chain reaction in 2 patients, with neither presenting with SARS-CoV-2 acute infection. Clinical and laboratory descriptions and cross-referencing epidemiologic and pathophysiological data can help identify possible disease etiologies.

Development of a prognostic model for pediatric acute liver failure in a Brazilian center.

OBJECTIVE: Pediatric acute liver failure (PALF) is a heterogeneous, rare, and severe condition, which outcome is survival due to liver spontaneous recovery or death. The patients who do not recover may be allocated to liver transplantation, which is the standard treatment. This study aimed to build a prognostic model to support the clinical decision to indicate liver transplantation for patients with PALF in a Brazilian center. METHODS: The authors retrospectively analyzed the clinical variables of 120 patients in the liver transplantation program of the 'Children's Institute of the University of São Paulo, Brazil. The authors conducted a univariate analysis of variables associated with survival in PALF. Logistic multivariate analysis was performed to find a prognostic model for the outcome of patients with pediatric acute liver failure. RESULTS: Risk factors were analyzed using univariate analysis. Two prognostic models were built using multiple logistic regression, which resulted in 2 models: model 1(INR/ALT) and model 2 (INR/Total bilirubin). Both models showed a high sensitivity (97.9%/96.9%), good positive predictive value (89.5%/90.4%), and accuracy (88.4%/88.5%), respectively. The receiver operating characteristic was calculated for both models, and the area under the curve was 0.87 for model 1 and 0.88 for model 2. The Hosmer-Lemeshow test showed that model 1 was good. CONCLUSION: The authors built a prognostic model for PALF using INR and ALT that can contribute to the clinical decision to allocate patients to liver transplantation.

Increased nutrition risk at admission is associated with longer hospitalization in children and adolescents with COVID-19.

BACKGROUND: We investigated the association of nutritional risk and inflammatory marker level with length of stay (LOS) in children and adolescents hospitalized for COVID-19 infection in two pediatric teaching hospitals in a developing country. METHODS: This was a cross-sectional analytical retrospective study performed in two pediatric hospitals. We included the data from all children and adolescents who were hospitalized with a SARS-CoV-2 infection between March and December 2020. Demographic, anthropometric, clinical, and laboratory data were extracted from electronic medical records. Nutritional risk was assessed according to the STRONGkids tool within 24 hours of admission and was categorized into two levels: ≥4 (high risk) and <4 (moderate or low risk). Means or medians were compared between nutritional risk groups using the t test and Mann-Whitney U test, respectively. The association of nutritional risk and inflammatory markers with LOS was estimated using the Kaplan-Meier method and log-rank test. Cox proportional-hazard and linear regression models were performed, and adjusted for sex, age, and respiratory symptoms. RESULTS: From a total of 73 patients, 20 (27.4%) had a STRONGkids score ≥4 at admission, which was associated with a longer LOS even after adjusting (ß = 12.30; 1.74-22.9 95% CI; P = 0.023). The same association was observed between LOS and all laboratory markers except for D-dimer. CONCLUSION: Among children and adolescents with COVID-19, a STRONGkids score ≥4 at admission, lower values of albumin, lymphocytes, and hemoglobin, and higher CRP values were associated with longer LOS.

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.

An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C.

BACKGROUND: COVID-19 in children is usually mild or asymptomatic, but severe and fatal paediatric cases have been described. The pathology of COVID-19 in children is not known; the proposed pathogenesis for severe cases includes immune-mediated mechanisms or the direct effect of SARS-CoV-2 on tissues. We describe the autopsy findings in five cases of paediatric COVID-19 and provide mechanistic insight into the mechanisms involved in the pathogenesis of the disease. METHODS: Children and adolescents who died with COVID-19 between March 18 and August 15, 2020 were autopsied with a minimally invasive method. Tissue samples from all vital organs were analysed by histology, electron microscopy (EM), reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). FINDINGS: Five patients were included, one male and four female, aged 7 months to 15 years. Two patients had severe diseases before SARS-CoV-2 infection: adrenal carcinoma and Edwards syndrome. Three patients were previously healthy and had multisystem inflammatory syndrome in children (MIS-C) with distinct clinical presentations: myocarditis, colitis, and acute encephalopathy with status epilepticus. Autopsy findings varied amongst patients and included mild to severe COVID-19 pneumonia, pulmonary microthrombosis, cerebral oedema with reactive gliosis, myocarditis, intestinal inflammation, and haemophagocytosis. SARS-CoV-2 was detected in all patients in lungs, heart and kidneys by at least one method (RT-PCR, IHC or EM), and in endothelial cells from heart and brain in two patients with MIS-C (IHC). In addition, we show for the first time the presence of SARS-CoV-2 in the brain tissue of a child with MIS-C with acute encephalopathy, and in the intestinal tissue of a child with acute colitis. Interpretation: SARS-CoV-2 can infect several cell and tissue types in paediatric patients, and the target organ for the clinical manifestation varies amongst individuals. Two major patterns of severe COVID-19 were observed: a primarily pulmonary disease, with severe acute respiratory disease and diffuse alveolar damage, or a multisystem inflammatory syndrome with the involvement of several organs. The presence of SARS-CoV-2 in several organs, associated with cellular ultrastructural changes, reinforces the hypothesis that a direct effect of SARS-CoV-2 on tissues is involved in the pathogenesis of MIS-C. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Bill and Melinda Gates Foundation.