Carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-haematopoietic stem cell transplant: a retrospective cohort study.

BACKGROUND: Risk factors for carbapenem resistance in Enterobacterales bloodstream infections among children with cancer or post-HSCT have not been thoroughly explored. METHODS: All children with cancer or post-HSCT who developed Enterobacterales bloodstream infections in two cancer referral centres in major Colombian cities between 2012 and 2021 were retrospectively examined. When the infection episode occurred, carbapenem resistance mechanisms were evaluated according to the available methods. Data were divided in a training set (80%) and a test set (20%). Three internally validated carbapenem-resistant Enterobacterales (CRE) prediction models were created: a multivariate logistic regression model, and two data mining techniques. Model performances were evaluated by calculating the average of the AUC, sensitivity, specificity and predictive values. RESULTS: A total of 285 Enterobacterales bloodstream infection episodes (229 carbapenem susceptible and 56 carbapenem resistant) occurred [median (IQR) age, 9 (3.5-14) years; 57% male]. The risk of CRE was 2.1 times higher when the infection was caused by Klebsiella spp. and 5.8 times higher when a carbapenem had been used for ≥3 days in the previous month. A model including these two predictive variables had a discriminatory performance of 77% in predicting carbapenem resistance. The model had a specificity of 97% and a negative predictive value of 81%, with low sensitivity and positive predictive value. CONCLUSIONS: Even in settings with high CRE prevalence, these two variables can help early identification of patients in whom CRE-active agents are unnecessary and highlight the importance of strengthening antibiotic stewardship strategies directed at preventing carbapenem overuse.

Pulmonary nodule in pediatrics: Beyond the infection. / Nódulo pulmonar en pediatría: Más allá de la infección.

INTRODUCTION: The study of a pulmonary nodule in pediatrics is a diagnostic challenge where multiple pathologies must be taken into account, especially infections. In developing countries, where tuberculosis infec tion is endemic, it is one of the most likely diagnoses; however, the diagnostic possibility of malig nancy should never be overlooked. OBJECTIVE: To describe a case report of a patient with a pulmonary nodule, that after ruling out the most frequent causes, a primary malignant tumor was diagnosed. CLINICAL CASE: 17-year-old female patient with a one-month history of cough, dyspnea, and hemop tysis, without other symptoms. Since she did not respond to conventional antibiotic management, a chest CT scan with contrast was performed which showed a pulmonary nodule with irregular con tours, and with the bronchoalveolar lavage pulmonary infections were ruled out (pulmonary tuber culosis, fungal infection, and others bacteria). Biopsy of the lesion was performed to complete the study which histopathology was compatible with a mucoepidermoid carcinoma (MEC). The patient underwent right low lobectomy and lymph node resection with good clinical response during three years of follow-up. CONCLUSION: Pulmonary nodule in pediatrics is a finding usually associated with infection, nevertheless, neoplastic conditions have to be considered, not only metastasis but also pri mary pulmonary malignant lesions due to prognosis implications.

Results of the implementation of the PETHEMA LPA 99 protocol for treating children with acute promyelocytic leukemia in Bogotá, Colombia / Resultados de la implementación del protocolo PETHEMA LPA 99 en el tratamiento de niños con leucemia promielocítica aguda en Bogotá, Colombia

Abstract Introduction: In the United States, between 4 and 8% of children with acute myeloid leukemia have acute promyelocytic leukemia (APL), but a higher incidence of this malignancy has been reported in Latin America (20%-28%). The implementation of the PETHEMA LPA 99 protocol, designed for the treatment of APL in adults, has shown an overall survival (OS) >80%. Objective: To describe the results obtained after the implementation of the PETHEMA LPA 99 protocol to treat children with APL at the Fundación Hospital Pediátrico La Misericordia in Bogotá, D.C., Colombia. Materials and methods: Descriptive and retrospective cohort study. The medical records of 30 pediatric patients (<18 years) with APL, who were treated using the PETHEMA LPA 99 protocol between January 2005 and December 2012, were reviewed. Data on the following variables were obtained: early death, death during induction therapy, OS, event-free survival (EFS), and relapse. Results: The male sex was predominant (60%) among the 30 patients included in the study. Regarding risk classification, 13 (43%) were classified as high-risk patients, 12 (40%) as medium-risk, and 5 (17%) as low-risk. Seven individuals died: 2 before receiving cancer treatment, 2 during induction therapy, and 3 after relapse. Relapse was reported in 5 patients. There were no deaths during the consolidation or maintenance phases. OS was 75.4% (95%CI: 55.1-87.5) and EFS was 64.3% (95%CI: 40-80.5). Moreover, OS at 11 years was 80%, 91.7%, and 59.2% for low-risk, intermediate-risk, and high-risk patients, respectively. The median follow-up time was 6.35 years (0-11.43 years). Conclusions: In general, the implementation of the PETHEMA LPA 99 protocol to treat APL in the study population showed very satisfactory results. Therefore, its use in pediatric population is recommended, taking into account the adjustments described in the protocol regarding the characteristics of this age group.

Resumen Introducción. En Estados Unidos de América, entre 4 y 8% de niños con leucemias mieloides agudas tienen leucemia promielocítica aguda (LPA), mientras que en Latinoamérica se ha descrito una mayor incidencia de esta neoplasia (20-28%). La implementación del protocolo PETHEMA LPA 99, diseñado para el tratamiento de LPA en adultos, ha mostrado una supervivencia global (SG) >80%. Objetivo. Describir los resultados de la aplicación del protocolo PETHEMA LPA 99 en el tratamiento de niños con LPA en la Fundación Hospital Pediátrico la Misericordia, en Bogotá D.C., Colombia. Materiales y métodos. Estudio de cohorte descriptivo y retrospectivo. Se revisaron las historias clínicas de 30 pacientes pediátricos (<18 años) con LPA que recibieron tratamiento mediante el protocolo PETHEMA LPA 99 entre enero de 2005 y diciembre de 2012. Se obtuvieron datos sobre las siguientes variables: muerte temprana, muerte en terapia de inducción, SG, supervivencia libre de evento (SLE) y recaída. Resultados. De los 30 pacientes, la mayoría eran de sexo masculino (60%). Respecto a la clasificación de riesgo, 13 (43%) fueron clasificados como pacientes de riesgo alto; 12 (40%), de riesgo intermedio, y 5 (17%), de riesgo bajo. 7 individuos murieron: 2 antes del tratamiento oncológico, 2 durante la terapia de inducción y 3 luego de presentar recaída. Se reportó recaída en 5 pacientes. No hubo muertes durante las fases de consolidación o de mantenimiento. La SG fue de 75.4% (IC95%: 55.1-87.5) y la SLE fue de 64.3% (IC95%: 40-80.5). La SG a 11 años fue de 80%, 91.7% y 59.2% para los pacientes de riesgo bajo, riesgo intermedio y riesgo alto, respectivamente. La mediana de seguimiento fue 6.35 años (0-11.43 años). Conclusiones. En general, la implementación del protocolo PETHEMA LPA 99 en el tratamiento de la LPA en la población de estudio mostró resultados muy satisfactorios, por lo que se recomienda su uso en población pediátrica, teniendo en cuenta los ajustes recomendados por el protocolo en relación con las características de este grupo etario.

Early-onset Cardiotoxicity assessment related to anthracycline in children with leukemia. A Prospective Study.

BACKGROUND: Acute leukemias are the most frequent malignancies in children. Advances in treatment have improved the overall survival to 80%. Almost 10% of children with cancer develop clinical cardiac toxicity. Total anthracycline cumulative dose is a risk factor for early-onset cardiotoxicity. OBJECTIVE: To describe the incidence of early-onset cardiotoxicity in children with acute leukemia treated with chemotherapy. METHODS: A prospective descriptive study of patients >1 y and <18 years diagnosed with acute leukemia. Assessed with electrocardiograma, echocardiography, and blood biomarkers at diagnosis and during the follow-up. RESULTS: 94 patients with acute lymphoblastic leukemia and 18 with acute myeloid leukemia were included. 20 patients (17.9%) developed early-onset cardiotoxicity. Statistically significant data was seen after anthracycline dose >150 mg/m2, between the first echocardiographic evaluation and posterior analyses in the left ventricular fraction ejection with Teicholz p 0.05, Simpson p 0.018 and GLS p 0.004. In this study, there was no relation between blood biomarkers and cardiotoxicity. CONCLUSIONS: Cancer therapeutic-related cardiac dysfunction is related to anthracycline cumulative dose. In this study, echocardiographic follow-up was useful to predict risk factors for early cardiac dysfunction.

Early-onset Cardiotoxicity assessment related to anthracycline in children with leukemia. A Prospective Study / Evaluación de la cardiotoxicidad temprana asociada al tratamiento con antraciclinas en niños con Leucemia. Estudio prospectivo

Abstract Background: Acute leukemias are the most frequent malignancies in children. Advances in treatment have improved the overall survival to 80%. Almost 10% of children with cancer develop clinical cardiac toxicity. Total anthracycline cumulative dose is a risk factor for early-onset cardiotoxicity. Objective: To describe the incidence of early-onset cardiotoxicity in children with acute leukemia treated with chemotherapy. Methods: A prospective descriptive study of patients >1 y and <18 years diagnosed with acute leukemia. Assessed with electrocardiograma, echocardiography, and blood biomarkers at diagnosis and during the follow-up. Results: 94 patients with acute lymphoblastic leukemia and 18 with acute myeloid leukemia were included. 20 patients (17.9%) developed early-onset cardiotoxicity. Statistically significant data was seen after anthracycline dose >150 mg/m2, between the first echocardiographic evaluation and posterior analyses in the left ventricular fraction ejection with Teicholz p 0.05, Simpson p 0.018 and GLS p 0.004. In this study, there was no relation between blood biomarkers and cardiotoxicity. Conclusions: Cancer therapeutic-related cardiac dysfunction is related to anthracycline cumulative dose. In this study, echocardiographic follow-up was useful to predict risk factors for early cardiac dysfunction.

Resumen Antecedentes: Las leucemias son la principal causa de cáncer infantil. Los avances en el tratamiento han llevado a los pacientes a una supervivencia global hasta del 80%. Cerca del 10% de los niños con cáncer tienen toxicidad cardiovascular sintomática, la dosis acumulada de antraciclinas es un factor de riesgo para afección cardíaca. Objetivo: Describir la frecuencia de afectación cardíaca temprana en niños con leucemias agudas que recibieron tratamiento antineoplásico. Métodos: Estudio prospectivo observacional, de pacientes <18 años con diagnóstico confirmado de leucemia aguda. Fueron evaluados con electrocardiograma, ecocardiograma bidimensional y biomarcadores séricos en diferentes momentos durante el tratamiento. Resultados: Se evaluaron 94 pacientes con leucemia linfoide aguda y 18 con leucemia mieloide aguda. 20 pacientes (17.9%) tuvieron disfunción cardiaca de inicio temprano. Se observaron diferencias estadísticamente significativas, después de recibir 150 mg/m2 de antraciclinas, entre la evaluación del ecocardiograma basal y evaluaciones posteriores de la fracción de eyección ventricular izquierda por Teicholz p 0.05, fracción de eyección ventricular izquierda por Simpson p 0.018 y la deformación longitudinal global p 0.004. No se encontraron alteraciones en los niveles séricos de las troponinas y péptido natriurético cerebral. Conclusiones: La disfunción cardíaca relacionada con quimioterapia estuvo directamente relacionada con las dosis acumuladas de antraciclinas. En este estudio el uso del ecocardiograma como método de seguimiento permitió identificar factores predictores de riesgo para disfunción cardiaca temprana.

Resultados del Protocolo ACHOP 2006 en los niños con leucemia linfoblástica aguda en la Fundación HOMI Hospital de la Misericordia de Bogotá, en el periodo 2007 - 2012 / Results of the 2006 ACHOP protocol on children with acute lymphoblastic leukemia at the HOMI Hospital of Misericordia Foundation in Bogotá in the period 2007 to 2012

RESUMEN Introducción: la leucemia aguda es la neoplasia más común en niños, constituye aproximadamente el 25 % de todos los tumores en la infancia. En Colombia la proporción de curación, alrededor del 50 %, es inferior a lo informado en países desarrollados. Objetivo: el objetivo principal es determinar la supervivencia global y libre de eventos, la proporción de abandono y recaída de los niños con el diagnóstico de leucemia linfoide aguda tratados con el Protocolo ACHOP 2006. Materiales y métodos: estudio descriptivo de tipo cohorte de 183 pacientes menores de 18 años, con el diagnóstico confirmado de leucemia linfoide aguda, que recibieron tratamiento en la Fundación HOMI desde el 2007 hasta el 2012. Los análisis de supervivencia se obtuvieron con curvas de Kaplan-Meier. Resultados: se analizó la supervivencia global a 2, 3 y 5 años con resultados de 89 %, 87,3 % y 74,7 % (IC 95 % 67-80,9), respectivamente. A los 5 años la supervivencia para el grupo de riesgo estándar fue de 78,6 % (IC 95 % 68,3 - 85,1) y para el de riesgo alto 61,9 % (IC 95 % 50,7- 73). La supervivencia libre de evento, al considerar el abandono y traslado a otra institución como evento, fue de 56,3 % (IC 95 % 45,5-65,8) a los 5 años. La mortalidad en inducción fue de 3,8 %, la mortalidad relacionada con el tratamiento fue 3,4 %. Treinta y dos pacientes (17 %) recayeron, el abandono fue de 16,4 % y los traslados de 10,4 %. La principal complicación del tratamiento fueron las infecciones. Conclusiones: la supervivencia global es aceptable para un país de recursos limitados. Los eventos de abandono y traslado son muy altos. Deben aunarse esfuerzos para disminuir estas situaciones que empeoran el pronóstico de la enfermedad.

SUMMARY Introduction: Acute leukemia is the most common neoplasm in children, accounting for approximately 25% of all tumors in childhood. In Colombia the cure proportion, around 50%, are lower than reported in developed countries. Objective: The main objective is to determine the global and event-free survival of children with diagnosis of lymphoblastic leukemia, all treated with the ACHOP Protocol 2006, from 2007 to 2012. The secondary objectives are to describe mortality, abandonment, relapse and major complications related to treatment. Material and methods: A descriptive cohort study of 183 patients under 18 years of age, with a confirmed diagnosis of acute lymphoblastic leukemia, who were treated at the Foundation of the Misericordia (HOMI) from 2007 to 2012, was performed. The survival dates were obtained by analysis with Kaplan-Meier curves. Results: We analyzed overall survival at 2, 3 and 5 years with results of 89%, 87.3% and 74.7 % (95% CI 67 - 80.9) respectively. At 5 years survival for the standard risk group was 78.6 % (95 % CI 68.3-85.1) and 61.9 % (95 % CI 50.7-73) for the high risk group. The event-free survival, considering the abandonment and transfer to another institution as an event, was 56.3 % (95% CI 45.5 - 65.8) at 5 years. Mortality in induction was 3.8 %, mortality related to treatment was 3.4 %, 32 patients (17 %) relapsed, abandonment was 16.4 % and transfers 10.4 %. The main complication of the treatment was infections. Conclusions: Overall survival is acceptable for a country with limited resources, the events of abandonment and transfers are very high. Efforts should be made to reduce these situations that worsen the prognosis of the disease.

Evaluation of the diagnostic performance of platelet-derived indices for the differential diagnosis of thrombocytopenia in pediatrics / Evaluación del rendimiento diagnóstico de los índices plaquetarios en el diagnóstico diferencial de las trombocitopenias en pediatría

Background. Platelet-derived indices have a well-established correlation with the differential diagnosis of thrombocytopenia in adult-based research. These indices include mean platelet volume, platelet distribution width, and platelet-large cell ratio. Objective. To determine the values of platelet-derived indices in a pediatric population with diagnoses of thrombocytopenia and their etiologic correlation. Materials and methods. Analytic observational diagnostic-test study. The population for this analytical study was pediatric patients between 6 months and 18 years of age who had thrombocytopenia (<100x10(9)/L). The study period was 18 months long. Results. Of 54 subjects, 18 (33.3%) were diagnosed with idiopathic thrombocytopenic purpura, and 36 (66.7%) were diagnosed with acute leukemia. Mean age was 7.4 years and 6.8 years for immune thrombocytopenic purpura and acute leukemia, respectively. Mean platelet distribution width values for immune thrombocytopenic purpura and acute leukemia were 15.08 fL and 10.73, respectively. Mean MPV for immune thrombocytopenic purpura and acute leukemia was 11.7 fL and 9.8 fL, respectively. Mean platelet-large cell ratio was 38.26% and 24.97% for idiopathic thrombocytopenic purpura and acute leukemia, respectively. Differences in these three distinct platelet indices between idiopathic thrombocytopenic purpura and acute leukemia were statistically significant (p=0.00). The area under the ROC curve for platelet-derived indices showed that they were adequate for defining the causes of thrombocytopenia. MPV and platelet-large cell ratio had an area under the curve of 0.89 and 0.88, respectively, while platelet size deviation width had an area under the curve of 0.903. Conclusions. Platelet-derived indices could be useful in the initial approach for the differential diagnosis of pediatric patients with thrombocytopenia.

Antecedentes. Los índices plaquetarios tienen buena correlación con la etiología de la trombocitopenia en estudios realizados en adultos. Estos son: volumen plaquetario medio, ancho de distribución plaquetaria y porcentaje de plaquetas grandes. Objetivo. Determinar las características de los índices plaquetarios en población pediátrica con trombocitopenia y su posible correlación etiológica. Materiales y métodos. Estudio de prueba diagnóstica observacional analítico. Realizado con pacientes entre 6 meses y 18 años ingresados en un período de 18 meses con trombocitopenia <100x10(9)/L. Resultados. 54 pacientes: 18 (33,3%) con púrpura trombocitopénica inmune y 36 (66,7%) con leucemia aguda. Edad media para púrpura trombocitopénica inmune 7,4 años y 6,8 para leucemia aguda. Valores de ancho de distribución plaquetaria con media de 15,08 fL en púrpura trombocitopénica inmune y 10,73 para leucemia aguda. Media del volumen plaquetario medio para púrpura trombocitopénica inmune 11,7 fL y de 9,8 fL para leucemia aguda. Porcentaje de plaquetas grandes la media para púrpura trombocitopénica inmune 38,26% y 24,97% para leucemia aguda. Las diferencias de los tres índices para cada una de las enfermedades fueron estadísticamente significativas (p=0,00). Las curvas de Característica Operativa del Receptor de los índices plaquetarios fueron parámetros suficientes para distinguir las causas de trombocitopenia: volumen plaquetario medio y porcentaje de plaquetas grandes con un área bajo la curva de 0,89 y 0,88 y ancho de distribución plaquetaria 0,903. Conclusiones. Los índices plaquetarios fueron útiles para el acercamiento inicial al diagnóstico diferencial de trombocitopenias en niños.