Desempenho do PRISM III e do PIM 2 em unidade de terapia intensiva pediátrica oncológica / Performance of PRISM III and PIM 2 scores in a cancer pediatric intensive care unit

RESUMO Objetivo: Avaliar o desempenho do Pediatric Risk of Mortality (PRISM) III e do Pediatric Index of Mortality (PIM) 2 em unidade de terapia intensiva pediátrica. Métodos: Estudo de coorte retrospectivo. Os dados retrospectivos foram coletados dos prontuários de todos os pacientes admitidos na unidade de terapia intensiva pediátrica de um hospital infantil oncológico, entre janeiro de 2017 a junho de 2018. Resultados: A média do PRISM III foi de 15 e do PIM 2 de 24%. Dos 338 pacientes estudados, 62 (18,34%) morreram. A mortalidade estimada pelo PRISM III foi de 79,52 (23,52%) e pelo PIM 2 de 80,19 (23,72%) pacientes, correspondendo a taxa padronizada de mortalidade (intervalo de confiança de 95%) de 0,78 para o PRISM II e 0,77 para o PIM 2. O teste de ajuste de Hosmer-Lemeshow obteve qui-quadrado de 11,56, 8df, com p = 0,975, para PRISM III, e qui-quadrado de 0,48, 8df, p = 0,999, para o PIM 2. Foi obtida área sob a curva Característica de Operação do Receptor de 0,71 para o PRISM III e 0,76 para o PIM 2. Conclusão: Os dois escores superestimaram a mortalidade e demonstraram poder regular de discriminação entre sobreviventes e não sobreviventes. Devem ser desenvolvidos modelos para quantificar a gravidade de pacientes pediátricos com câncer em unidade de terapia intensiva pediátrica e predizer o risco de mortalidade que contemplem suas peculiaridades.

ABSTRACT Objective: To assess the performance of Pediatric Risk of Mortality (PRISM) III and Pediatric Index of Mortality (PIM) 2 scores in the pediatric intensive care unit. Methods: A retrospective cohort study. Data were retrospectively collected from medical records of all patients admitted to the pediatric intensive care unit of a cancer hospital from January 2017 to June 2018. Results: The mean PRISM III score was 15, and PIM 2, 24%. From the 338 studied patients, 62 (18.34%) died. The PRISM III estimated mortality was 79.52 patients (23.52%) and for PIM 2 80.19 patients (23.72%), corresponding to a standardized mortality ratio (95% confidence interval: 0.78 for PRISM II and 0.77 for PIM 2). The Hosmer-Lemeshow chi-square test was 11.56, 8df, 0.975 for PRISM II and 0.48, 8df, p = 0.999 for PIM 2. The area under the Receiver Operating Characteristic curve was 0.71 for PRISM III and 0.76 for PIM 2. Conclusion: Both scores overestimated mortality and have shown a regular ability to discriminate between survivors and non-survivors. Models should be developed to quantify the severity of cancer pediatric patients in Pediatric Intensive Care Units and to predict the mortality risk accounting for their peculiarities.

Comparación de una escala, un indice y un biomarcador como predictores de mortalidad en niños con choque séptico que ingresan a la unidad de terapia intensiva del hospital Dr. José Renán Esquivel. Agosto 2015- marzo 2016 / Comparison of a scale, an index and a biomarker as predictors of mortality in children with septic shock admitted to the intensive care unit of the Dr. José Renán Esquivel hospital. August 2015- March 2016

Resumen El choque séptico es una entidad que en la población pediátrica se ve asociado a altas tasas de morbilidad y mortalidad. En las unidades de terapia intensiva es importante estimar el riesgo de muerte en los pacientes ingresados para así redirigir metas en el manejo de los mismos. Sin embargo, la falta de consistencia y la subjetividad del clínico han sido factores determinantes para el desarrollo de escalas de mortalidad con el fin de lograr mediciones cuantitativas certeras. Existen muchas escalas, índices y biomarcadores desarrollados con el fin de predecir mortalidad. Entre estos se encuentra la escala PIM-2, el índice de choque y el lactato. Objetivo: Comparar la escala PIM-2, el índice de choque y el lactato como marcadores precoces de mortalidad en los niños con choque séptico. Metodología: Se realizó un estudio de cohorte prospectivo, en el cual se incluyeron todos los pacientes con criterios de choque séptico que ingresaron a la Unidad de Terapia intensiva del Hospital del Niño entre agosto del 2015 y marzo del 2016. Se realizaron los cálculos de PIM-2, índice de choque y valor de lactato al ingreso en los pacientes sobrevivientes y fallecidos y se compararon los resultados de estos marcadores como predictores de mortalidad. Resultados: La escala PIM-2 resultó un excelente predictor de mortalidad con un área bajo la curva de 94% comparada con el índice de choque que osciló entre 53% a 61% y el valor de lactato que fue de 77%. Conclusión: El PIM-2, resultó una prueba sencilla, gratuita y fácil de calcular, con una excelente sensibilidad para la predicción de mortalidad en niños críticos con diagnóstico de choque séptico. A pesar de la facilidad de cálculo del índice de choque, este resultó ser un pobre predictor de mortalidad. El lactato es un marcador aceptable para predecir mortalidad, sin embargo, debe correlacionarse con otras escalas ya que puede ser sesgado por otras causas que produzcan su aumento o disminución.

Summary: In the pediatric population, septic shock is an entity associated with high mortality and morbidity rates. In the intensive care unit, it is important to estimate the risk of death of the patients admitted in order to re-direct the goals of treatment. However, the lack of consistency and the subjectivity of the clinician have been determinant factors for the development of mortality scales with the purpose of achieving accurate quantitative measurements. Many scales, indexes and biomarkers exist which have been developed to predict mortality. Among these are the PIM-2 scale, the shock index and serum lactate. Objective: To compare the PIM-2 scale, the shock index and serum lactate as early markers of mortality in children with septic shock. Methods: A prospective cohort study was performed in which all patients with septic shock criteria admitted to the intensive care unit of the Hospital del Niño between August 2015 and March 2016 were included. Calculations of PIM-2, shock index and serum lactate value at admission of the surviving and the deceased patients were performed, and the results of these markers were compared as predictors of mortality. Results: The PIM-2 scale resulted in an excellent mortality predictor with an under the curve area of 94% compared to the shock index which oscillated between 53 and 61%, and the value of lactate which was of 77%. Conclusion: The PIM-2 scale turned out to be a simple, free and easy to calculate test, with an excellent sensibility to predict mortality in critically ill children with septic shock. Despite the ease of use of the shock index, it resulted to be a poor predictor of mortality. However, it should be correlated with other scales since it can be biased by other causes which produce its increase or decrease.

Ectopic over-expression of oncogene Pim-2 induce malignant transformation of LO2 / 中国现代普通外科进展

Objective:To research whether ectopic over-expression of Pim-2 could cause chang-liver cell (LO2) malignant transformation,to explore the relationship between Pim-2 protein and hepatocellular carcinoma.Methods:Three groups of cells were arranged including human chang liver cell line LO2 (group C),LO2 cells transfected with empty-vector (group B) and LO2 cells transfected with Pim-2 gene (group A).Pim-2 expression levels were detected.The morphology,proliferation level,apoptosis rate and migration ability of the cells were detected respectively.The cells were subcutaneously inoculated into athymic mice and the microstructures of the neoplasm were observed by optical and electron microscopy.Results:Compared with group B,Pim-2 expression levels were significantly higher in group A (P＜0.05),and their morphology had obvious malignant changes.They also showed a significantly increased proliferation rate (P＜0.05) and migration capacity (P＜0.05),as well as a significantly decreased apoptosis rate (P＜0.05).Only the athymic mice inoculated with group A could generate neoplasm,and the morphology of the neoplasm coincided with that of the hepatoma.Conclusion:Both the morphological and biological changes of LO2/Pim-2 cells indicate the trend of malignant transformation,which could generate hepatoma in athymic mice.Pim-2 could induce malignant transformation of human liver.

Validación del índice pediátrico de mortalidad 2 (PIM2) en Argentina: un estudio prospectivo, multicéntrico, observacional / Validation of the Pediatric Index of Mortality 2 (PIM2) in Argentina: a prospective, multicenter, observational study

Introducción. El índice pediátrico de mortalidad 2 (Pediatric Index of Mortality 2; PIM2, por sus siglas en inglés) es uno de los puntajes más utilizados para la predicción de la mortalidad en pacientes ingresados en las Unidades de Cuidados Intensivos Pediátricos (UCIP) argentinas. El objetivo de este estudio fue validar el puntaje PIM2 en las UCIP integrantes del Programa de Calidad de Atención de la Sociedad Argentina de Terapia Intensiva. Población y métodos. Estudio multicéntrico, prospectivo, observacional, de corte transversal. Se incluyeron todos los pacientes de entre 1 mes y 16 años de edad, ingresados en las UCIP participantes entre el 01-01-2009 y el 31-122009. Se evaluó la discriminación y calibración del puntaje PIM2 en toda la población y en diferentes subgrupos (riesgo de mortalidad, edad, diagnósticos de ingreso). Resultados. Se incluyeron 2832 pacientes. El PIM2 predijo 246 muertes; sin embargo, fallecieron 297 pacientes (p <0,01). La razón de mortalidad estandarizada fue 1,20 (IC 95%: 1,01-1,43). El área bajo la curva ROC fue 0,84 (IC 95%: 0,82-0,86). Se detectaron diferencias estadísticamente significativas entre las muertes observadas y las predichas para toda la población y en los distintos intervalos de riesgo (χ² 71,02; df 8; p <0,001). También se detectaron diferencias estadísticamente significativas entre las muertes observadas y esperadas en los pacientes adolescentes (37/22, p= 0,03) y en aquellos ingresados con patología respiratoria (105/81, p= 0,03). Conclusiones. El puntaje PIM2 permite diferenciar adecuadamente los pacientes que sobreviven de aquellos que fallecen. Sin embargo, subvalora el riesgo de muerte en forma global, especialmente en los pacientes adolescentes y en aquellos ingresados por causa respiratoria. Es fundamental considerar estas diferencias al interpretar los resultados.

Introduction. The Pediatric Index of Mortality 2 (PIM2) is one of the most commonly used scoring systems to predict mortality in patients admitted to pediatric intensive care units (PICU) in Argentina. The objective of this study was to validate the PIM2 score in PICUs participating in the Quality of Care Program promoted by the Argentine Society of Intensive Care.Population and Methods. Multicenter, prospective, observational, cross-sectional study.All patients between 1 month and 16 years old admitted to participating PICUs between January 1st, 2009 and December 31st, 2009 were included. The discrimination and calibration of the PIM2 score were assessed in the entire population and in different subgroups (risk of mortality, age, diagnoses on admission).Results. Two thousand, eight hundred and thirty-two patients were included. PIM2 predicted 246 deaths; however, 297 patients died (p < 0.01). The standardized mortality ratio was 1.20 (95% confidence interval [CI]: 1.01-1.43). The area under the ROC curve was 0.84 (95% CI: 0.82-0.86). Statistically significant differences were detected between the observed and the predicted mortality for the entire population and for the different risk intervals (χ²: 71.02, df: 8, p < 0.001). Statistically significant differences were also found between observed and predicted mortality in adolescent patients (37/22, p = 0.03) and in those hospitalized due to respiratory disease (105/81, p = 0.03).Conclusions. The PIM2 score adequately discriminates survivors from non-survivors. However, it underscores the overall risk of death, especially in adolescent patients and those hospitalized due to respiratory disease. It is critical to take such differences into account when interpreting results.

Ectopic Over-expression of Oncogene Pim-2 Induce Malignant Transformation of Nontumorous Human Liver Cell Line L02

In order to prove that ectopic over-expression of Pim-2 could induce malignant transformation of human liver cell line L02, three groups of cells were set up including human liver cell line L02 (L02), L02 cells transfected with Pim-2 gene (L02/Pim-2) and L02 cells transfected with empty-vector (L02/Vector). Pim-2 expression levels were detected. The morphology, proliferation level, apoptosis rate and migration ability of the cells were detected respectively. Then the cells were subcutaneously inoculated into athymic mice and the microstructures of the neoplasm were observed. Compared with the controls, Pim-2 expression levels were significantly higher in L02/Pim-2 cells (P<0.05), and their morphology had obvious malignant changes. They also showed a significantly increased proliferation rate (P<0.05) and migration capacity (P<0.05), as well as a significantly decreased apoptosis rate (P<0.05). Only the athymic mice inoculated with L02/Pim-2 cells could generate neoplasm, and the morphology of the neoplasm coincided with that of the hepatoma. The results manifest that ectopic Pim-2 gene could be stably expressed in L02/Pim-2 cells. Both the morphological and biological changes of L02/Pim-2 cells demonstrate the trend of malignant transformation. L02/Pim-2 cells could generate hepatoma in athymic mice. In conclusion, Pim-2 could induce malignant transformation of human liver cell line L02.