Neurotoxidad inducida por ifosfamida / Ifosfamide-induced neurotoxicity

Introducción: La ifosfamida es un agente alquilante utilizado para el tratamiento de enfermedades oncohematológicas. Entre sus eventos adversos agudos se encuentra la neurotoxicidad. Esta puede presentarse desde el inicio de la infusión hasta tres días después. El tratamiento consiste en suspender la administración y asegurar una adecuada hidratación. Objetivo: Describir eventos neurológicos asociados al uso de ifosfamida en pacientes pediátricos con enfermedades oncohematológicas. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo y transversal. Los datos se obtuvieron de historias clínicas de pacientes internados en el Hospital Garrahan que infundieron ifosfamida y desarrollaron síntomas neurológicos. Se analizaron edad, diagnóstico de base, dosis de ifosfamida, síntomas neurológicos y su relación con la infusión, tratamiento instaurado, exámenes complementarios y posibles factores de riesgo asociados. Resultados: Se registraron un total de catorce eventos neurológicos en doce pacientes, sin diferencia de sexo, con una mediana de edad de 9,5 años. La enfermedad de base más prevalente fue osteosarcoma. Las convulsiones fueron el síntoma más frecuente (50%), seguido de somnolencia y paresias. La combinación de ifosfamida y etopósido con/sin carboplatino se asoció en un 36% cada uno. El 64% desarrolló neurotoxicidad dentro de las primeras cuatro horas. Ningún paciente presentó alteraciones en los exámenes complementarios. Todos presentaron recuperación ad integrum. Conclusión: Este estudio brinda información acerca del tiempo de aparición de esta complicación, lo cual facilitará su detección precoz y tratamiento oportuno (AU)

Introduction: Ifosfamide is an alkylating agent used for the treatment of cancer. Among its acute adverse events is neurotoxicity. This can occur from the beginning of the infusion up to three days afterwards. Treatment consists of discontinuing administration and ensuring adequate hydration. Objective: To describe neurological events associated with the use of ifosfamide in children with cancer. Materials and methods: Observational, descriptive, retrospective, and cross-sectional study. Data were obtained from clinical records of patients admitted to the Garrahan Hospital who received ifosfamide infusion and developed neurological symptoms. Age, baseline diagnosis, ifosfamide dose, neurological symptoms and their relationship with the infusion, treatment, complementary tests, and possible associated risk factors were analyzed. Results: A total of fourteen neurological events were recorded in twelve patients, without difference in sex and with a median age of 9.5 years. The most prevalent underlying disease was osteosarcoma. Seizures were the most frequent symptom (50%), followed by drowsiness and paresis. The combination of ifosfamide and etoposide with/without carboplatin was associated in 36% each. Sixty-four percent developed neurotoxicity within the first four hours. None of the patients presented with abnormalities in the complementary examinations. All recovered ad integrum. Conclusion: This study provides information about the time of onset of this complication, which will facilitate its early detection and timely treatment (AU)

Experiencia en shock séptico en emergencias. Factores asociados a falta de respuesta a fluídos / Experience in septic shock in Emergencies. Factors associated with lack of response to fluid resuscitation

Introducción: La sepsis es una de las principales causas de muerte infantil a nivel mundial. Las guías de tratamiento utilizadas en nuestro servicio se basan en parámetros clínicos para un soporte hemodinámico temprano con énfasis en el uso de fluidos e inotrópicos guiados por metas clínicas. Objetivos: Describir las características epidemiológicas y clínicas en una cohorte de niños con diagnóstico de shock séptico (SS) en el área de emergencias, controlando tasa de respuesta a fluidos, mortalidad y su relación con las características de los pacientes. Materiales y métodos: Estudio observacional de cohorte prospectivo entre Julio del 2009 y Julio del 2010. Se incluyeron 83 pacientes entre 0 a 18 años que cumplieron con los criterios diagnósticos de SS. La respuesta a volumen se definió como: respondedores (RE) a los pacientes que solo requirieron expansión con volumen y no respondedores (nRE) a aquellos que requirieron inotrópicos luego de llegar a 60 ml/kg o aparición de signos de sobrecarga cardíaca. Resultados: 64% fueron varones con mediana de edad de 5,8 años (RIC 2-12). 71% presentaban alguna enfermedad crónica preexistente, siendo 40% pacientes oncológicos. El 25 % requirió asistencia respiratoria mecánica y 65% inotrópicos. La mediana de estadía hospitalaria fue 10 días (RIC 7-16 días). Un 35% fue RE. Solo la hipotensión al ingreso resultó ser factor de riesgo para nRE (p0,035), pero en el modelo multivariado no resultó estadísticamente significativo. El 8% de los pacientes fallecieron. Conclusiones: En nuestra población, los pacientes con enfermedades oncológicas representan un número importante de los casos de SS y posiblemente tengan una mayor mortalidad. La tasa de respuesta a volumen ocurrió en 35% de los casos. La hipotensión inicial constituye un probable factor de riesgo para nRE (AU)

Introduction: Sepsis is one of the main causes of childhood death worldwide. Treatment guidelines used at our department are based on clinical parameters for early hemodynamic support with emphasis on fluid resuscitation and inotropics use guided by clinical goals. Objectives: To describe the epidemiologic and clinical features of a cohort of children with septic shock (SS) seen at the emergency department evaluating response rate to fluid resuscitation and mortality related to patient characteristics. Materials and methods: A prospective, observational cohort study was conducted between July 2009 and July 2010. Overall, 83 patients between 0 and 18 years of age that met the diagnostic criteria of SS were included. Response to fluid resuscitation was defined as: responders (RE), those patients that only required volume expansion, and non-responders (nRE), those that required inotropes after having reached 60 ml/kg or appearance of signs of fluid overload. Results: 64% were boys; median age was 5.8 years (IQR 2-12); 71% had some type of preexisting chronic disease, consisting of cancer in 40%. Overall, 25% required mechanical ventilation and 65% inotropes. Median length of hospital stay was 10 days (IQR 7-16 days). 35% of the patients were RE. Only hypotension on admission was found to be a risk factor for nRE (p 0.035); however, in a multivariate model, this finding did not show to be statistically significant. Eight percent of the patients died. Conclusions: In our cohort, patients with cancer accounted for a large number of those who developed SS; in these patients mortality may be increased. Response rate to fluid resuscitation was 35%. Initial hypotension may be a risk factor for nRE.

Evolución y progresos en el tratamiento de la leucemia finfoblastica aguda / Progress in the treatment of acute lymphoblastic leukemia

Muchos avances se han logrado en los últimos 30 años en el tratamiento de la leucemia linfoblástica aguda (LLA) pediática, a nivel mundial y tamibén en nuestro Hospital. Después de su apertura en agosto de 1987 hasta noviembre de 2002 fueron ingresados 989 pacientes con diagnóstico de LLA de los cuales 896 fueron evaluables. Los mismos fueron tratados con 3 protocolos sucesivos: 92 (7 LLa 87), 374 (1 LLA 90) y 430 (1 LLA 96). Las tasas de remisión completa (RC) fueron de 95,6 en el primer protocolo, 94,4 en el segundo y 96,9 en el tercero y un 2,1, 2,9 y 1,8 de los pacientes fallecieron durante la inducción en los respectivos estudios. El principal evento observado fue la recaída de la enfermedad y fallecieron en RC 6 de los pacientes del 7 LLA 87, 4,8 del 1 LLA 90 y 4,3 del 1 LLA 96. La pSLE (EE) fue de 61 (5), 63 (5) y 72 (6), respectivamente, siendo esta diferencia estadísticamente significativa (p=0,0237). El Hospital ha incorporado los métodos diagnósticos necesarios para una mejor estratificicón de los pacientes, y fueron mejoradas las medidas de soporte ofrecidas a los pacientes. Como consecuencia de los logros mencionados se observó una disminución en las tasas de muerte durante la inducción y en RC, con un aumento gradual y significativo de la pSLE. Estos resultados muestran una mejora a lo largo del tiempo y nuestros esfuerzos deben orientarse a una aún mejor optimización de las herramientas diagnósticas, terpéuticas y de soporte para lograr alcanzar los estándares internacionales pra esta población de pacientes.

Morbi mortalidad por infecciones en pacientes con leucemia linfoblástica aguda: recaida en inducción / Infection associated morbidity and mortality in children with relapsed acute limphoblastic leukemia during induction therapy

Los pacientes con Leucemia Linfoblástica Aguda (LLA) recaída reciben quimioterapia (QMT) intensa que produce neutropenia severa y prolongada que condiciona mayor frecuencia de infecciones. Con el fin de evaluar las características clínicas de las infecciones en estos pacientes con neutrepenia y fiebre (NF) luego de la QMT de inducción se realizó un análisis retrospectivo de estos episodios de NF. La QMT de inducción incluyó 10 días de prednisona 100 mg/m2 VO y altas dosis de QMT de 6 días de duración. Recibieron esta QMT 98 pacientes en el período comprendido entre septiembre de 1994 y Diciembre de 2002. De los 96 pacientes evaluables el 73 eran varones y la edad media fue de 110.5 meses. E 28 eran mayores de 12 años. El 64 tenían catéter implantable. el 77 eran eutróficos y el 21 obesos. Presentaron NF 86 pacientes (90). El 29 tuvo sepsis. Todos los episodios de NF cumplieron criterios de alto riesgo. La media de días de internación fue 19.5. El 19 de los niños requirió en Unidad de Cuidados Intensivos (UCI). Recibieron asistencia respiratoria mecánica (ARM) el 16 de los niños. El 52 de los niños tuvo bacteriemia, donde prevalecieron los cocos Gram positivos (29) seguido de bacilos Gram negativos (22). Ochenta y cinco por ciento de los episodios presentaron foco clínico de infección y prevalecieron el foco pulmonar (33.3) y la mucositis oral (32.3). Fallecieron 9 pacientes (9.4). Todas las muertes fueron debidas a sepsis no controlada. La edad mayor a 12 años fue la única variable estadísticamente significtiva relacionada con la mortalidad (OR 6.3, IC 951.4-27.3; p<0.01). La presencia de foco perianal, enteral y el infiltrado pulmonar se asociaron con la presencia de sepsis. Los pacientes con NF luego de la inducción de LLA recaída tienen alta tasa de mortalidad relacionada con la infección, perticularmente la sepsis. En este grupo de pacientes es necesario extremar los cuidados posteriores a la QMT.

Semicontinuous GC analysis and receptor modelling for source apportionment of ozone precursor hydrocarbons in Bresso, Milan, 2003.

The European Ozone Directive 2002/3/EC specifies the analysis of 30 individual C2-C9 hydrocarbons in urban air with the attribution of emission sources to pollution concentrations as a major objective. In the present study, we investigate an approach for source apportionment of these ozone precursor hydrocarbons in urban air based on reliable semi continuous volatile organic compound (VOC) analysis in the field and in vehicle emission laboratory combined with multivariate receptor modeling. The GC system relies on an hourly analytical cycle based on a trap sample enrichment phase followed by a dual column gas chromatographic flame ionisation detector (FID) analysis and has successfully been tested during an air monitoring campaign at an urban site (Milan, Italy, September 2003) and in the vehicle laboratory performing exhaust emission measurements while running driving cycles on a chassis dynamometer (mopeds, gasoline and diesel cars). The receptor modeling relies on two complementary principles. The chemical mass balance (CMB) modeling apportions well characterized source profiles for the 30 individual C2-C9 hydrocarbons in the Ozone Directive to the concentrations in ambient air and produces source contribution estimates (SCE) as output. The positive matrix factorization (PMF) analyses variability in the ambient air concentration data and searches for latent variables consisting of co-varying hydrocarbons and produces profiles as output, which in this study could be attributed to known emission sources. Both CMB and PMF rely on an estimated uncertainty for each input data. A new approach is presented, by which the uncertainty is allowed to float as function of the photochemical reactivity of the atmosphere and the stability of each individual compound.

Tratamiento ambulatorio secuencial parenteral oral en niños con neutropenia y fiebre de causa hemato oncológíca y bajo riesgo de mortalidad / Secuencial parenteral oral ambulatory treatment of children with cancer and low risk of mortality fever and neutropenia

Con el objetivo de evaluar la eficacia del tratamiento ambulatorio parenteral oral de niños con neutropenia y fiebre (NF) de causa hemato oncológica y bajo riesgo (BR) de mortalidad se reaizó un estudio prospectivo entre los meses de marzo de 2000 y octubre de 2002. Fueron incluídos todos los niños con un recuento de neutrófilos menor a 500/mmm3 y fiebre mayor a 38ºC y bajo riesgo de mortalidad (ej. expectativa de neutropenia menor a 7 días, buen estado general, ausencia de signos de co morbilidad asociados, sin celulitis del catéter, perianal de cara, sin mucositis severa, gingivitis necrotizante o enteritis y sin bacteriemia. Todos los niños recibieron ceftriaxona y ami kacina. A las 24 horas continuaron el tratamiento con ciprofloxacina o continuaron con ceftriaxona únicamente hasta permanecer 24 horas sin fiebre. Todo el tratamiento se realizó en forma ambulatoria. Durante el período de estudio fueron evaluados 715 episodios de NF en 485 pacientes, de los cuales 199 episodios en 123 pacientes fueron incluidos en el estudio. La mediana edad de los niños fue de 70 meses. El 58% de los niños tuvieron leucemias. El 111% recibieron factores estimulantes de colonias y 53% tenía catéter implantable. El 44% de los episodios se presentó con un recuento menor a 100 neutrófilos/mm3. La media de duración de la neutropenia fue de 4 más menos 2.3 días y de la fiebre 1 más menos 1.9 días. El 30% tuvo un foco clínico de infección, siendo la infección respiratoria alta el foco más frecuente. el 17% de los niños requirió algún cambio al tratamiento empírico. Se registraron 11 fallos (5%) terapéuticos. Todos los niños con fallos fueron hospitalizados, ninguno requirió internación en UCI y ninguno falleció. La mediana de tratamiento parenteral fue de 3 días y de tratamiento oral de 5 días. El tratamiento ambulatorio secuencial parenteral realizado en forma ambulatoria con ceftriaxona y amikacina seguido de ciprofloxacina o ceftraxina es seguro.

Oral ciprofloxacin in the management of children with cancer with lower risk febrile neutropenia.

BACKGROUND: Recent reports and a previous randomized trial conducted at the authors' institution suggested that a lower risk subset of children with febrile neutropenia under chemotherapy might benefit of an oral antibiotic outpatient approach. METHODS: The objective of this study was to test the efficacy of oral ciprofloxacin in the treatment of lower risk febrile neutropenia (LRFN) in children treated for malignant diseases. From November 1998 to December 1999, 93 episodes of LRFN in 87 children (median age, 5.5 years; range, 0.9-15.8 years) were included in a prospective randomized controlled single institution trial. Inclusion criteria included fever (> 38 degrees C), severe neutropenia (absolute neutrophil count, < 500/mm(3)), and lower risk features (e.g., absence of severe comorbidity factors, good clinical condition, negative blood cultures, control of local infection, prediction of a period of neutropenia less than 10 days after admission, and compliant parents). After 24 hours of a single intravenous ceftriaxone (100 mg/kg) plus amikacin (15 mg/kg) and completed risk assessment workup, patients were discharged and randomly allocated to two groups. Group A (48 episodes) received ciprofloxacin 20 mg/kg/day orally (p.o.) every 12 hours for 6 days. Group B (45 episodes) received intravenous ceftriaxone plus amikacin for 2 days more followed by cefixime (8 mg/kg/day p.o.) every 24 hours for 4 additional days. Failure was defined as the need of a second hospitalization during the same episode. RESULTS: Most of the patients (59% in Group A and 52% in Group B) were treated for malignant solid tumors. Fifteen (31%) children in Group A and 15 (33%) in Group B presented with fever of unknown origin (P value was not significant). No significant differences were found in sites of initial infection between both groups. Overall results in this study were excellent. Only one patient with respiratory failure was detected in Group B, who did well with secondary treatment. CONCLUSIONS: In febrile neutropenic children after anticancer therapy and lower risk features, oral ciprofloxacin for 6 days after 24 hours of intravenous ceftraxione plus amikacin appears to be as efficacious as intravenous ceftriaxone plus amikacin for 2 days more followed by cefixime for 4 additional days. These results contribute to strengthen the concept of LRFN.

[Criteria of low risk of mortality in children with neutropenia and fever during cancer chemotherapy]. / Criterios de bajo riesgo de mortalidad en niños con neutropenia y fiebre durante la quimioterapia por cáncer.

To validate the use of a lower-risk mortality profile in pediatric febrile neutropenia during anticancer therapy and to evaluate the efficacy of a sequential parenteral-oral antibiotic treatment for these children, a prospective study was conducted between May 1997 and December 1999. During this period 247 episodes in 215 patients were included in the present study. Children with neutropenia (ANC < 500/mm3) and fever (> 38 degrees C) due to anticancer therapy were eligible for the study if they presented the following lower-risk conditions: absence of severe co-morbidity factors, good clinical condition, no risk clinical foci, no bacteremia, and responsible parents. They were initially treated with inpatient parenteral short course of ceftriaxone and amikacin followed by ambulatory oral cefixime or ciprofloxacin to complete 7 days. Mean age was 64 (range: 8-200) months. The most common underlying malignant disease was acute lymphoblastic leukemia in 48% (118) of cases and 57% (141) of patients had an indwelling central venous catheter. Clinical evidence of infection was found in 47% (122) of children and the most common site was the upper respiratory tract (81%). Mean period of fever was 1.1 days (r: 1-8) and the duration of neutropenia was 3.9 days (r: 1-9). Sixty-one% (150) of children was discharged with neutropenia. Mean time of hospitalization was 1.5 days. Four clinical failures were detected (1.6%). They all were satisfactorily treated with a secondary treatment and none underwent any major complications or died. The lower-risk profile used was safe and the sequential antibiotic therapy was adequate to manage febrile neutropenia in this subset of children.

Criterios de bajo riesgo de mortalidad en niños con neutropenia y fiebre durante la quimioterapia por cáncer. / [Criteria of low risk of mortality in children with neutropenia and fever during cancer chemotherapy]

To validate the use of a lower-risk mortality profile in pediatric febrile neutropenia during anticancer therapy and to evaluate the efficacy of a sequential parenteral-oral antibiotic treatment for these children, a prospective study was conducted between May 1997 and December 1999. During this period 247 episodes in 215 patients were included in the present study. Children with neutropenia (ANC < 500/mm3) and fever (> 38 degrees C) due to anticancer therapy were eligible for the study if they presented the following lower-risk conditions: absence of severe co-morbidity factors, good clinical condition, no risk clinical foci, no bacteremia, and responsible parents. They were initially treated with inpatient parenteral short course of ceftriaxone and amikacin followed by ambulatory oral cefixime or ciprofloxacin to complete 7 days. Mean age was 64 (range: 8-200) months. The most common underlying malignant disease was acute lymphoblastic leukemia in 48

(118) of cases and 57

(141) of patients had an indwelling central venous catheter. Clinical evidence of infection was found in 47

(122) of children and the most common site was the upper respiratory tract (81

). Mean period of fever was 1.1 days (r: 1-8) and the duration of neutropenia was 3.9 days (r: 1-9). Sixty-one

(150) of children was discharged with neutropenia. Mean time of hospitalization was 1.5 days. Four clinical failures were detected (1.6

). They all were satisfactorily treated with a secondary treatment and none underwent any major complications or died. The lower-risk profile used was safe and the sequential antibiotic therapy was adequate to manage febrile neutropenia in this subset of children.

Langerhans cell histiocytosis: retrospective evaluation of 123 patients at a single institution.

The aim of this study was to retrospectively evaluate clinical characteristics at diagnosis and outcome of patients with Langerhans cell histiocytosis (LCH). From October 1987 to March 1996, 133 patients with confirmed LCH were admitted to Hospital JP Garrahan in Buenos Aires (123 evaluable). Median age was 5 years (range 15 days to 18 years). Initial organ involvement included bone 114 patients, ear 34, skin 30, liver 18, lung 14, lymph nodes 14, spleen 12, diabetes insipidus 9, and bone marrow 2. Nineteen patients had organ dysfunction, pulmonary 14, hematological 14, and hepatic 12. Two groups were defined: Group A included patients with single system disease (uni- or multifocal) and group B multisystem (with or without organ dysfunction). In group A (n = 82), 24 patients were treated with chemotherapy (prednisone and vinblastine), 21 with surgery, 15 received radiotherapy, and 22 were only observed. Patients of group B (n = 41) were treated with chemotherapy consisting of prednisone and vinblastine, DALHX 83, or LCH1-based chemotherapy. At a median follow-up of 3 years (range 1 month-8 5/12 years) 93% of patients of group A and 39% of group B survive free of reactivation. In group B, 22% had a reactivation and 39% died of progressive disease. Sequelae were detected in 35 patients (28%), which included diabetes insipidus in 17, hearing loss in 13, bony sequelae in 11, sclerosing cholangitis in 6, and lung fibrosis with bullae in 6. Two patients had a subsequent malignant disease. A total of 17 (14%) patients died and 16 of them belonged to the group B: 13 died of progressive disease, 2 due to sclerosing cholangitis (with sepsis in one case and encephalitis in the other one), 1 with progressive disease and associated myelofibrosis, and 1 patient of group A with active disease and brain stem tumor. Patients who had organ dysfunction had a reactivation free survival of 32%. All these patients survived with sequelae. Logistic regression analysis showed that organ dysfunction and hematological involvement had significant predictive values in relation to death. Patients of group A had an excellent survival rate, whereas in those of group B a high mortality was found, especially in the subgroup of patients with organ dysfunction. Lahey's criteria should be revised. Sequelae were also more common in this group.