Piperacillin/tazobactam plus amikacin vs. piperacilin/tazobactam: treatment for children with febrile neutropenia / Piperacilina/tazobactam más amikacina vs. piperacilina/tazobactam: tratamiento en niños con neutropenia febril

Background: Pediatric patients with febrile neutropenia usually receive a combination of broad spectrum antimicrobials. Treatment without aminoglycoside seems to have advantages. Objective: To compare the efficacy of piperacillin/tazobactam plus amikacin versus piperacillin/tazobactam. Methods: Randomized, open label, controlled clinical trial. Sample size for an efficacy of 55%, and delta of 25%; 80 episodes were required for each group. Selection criteria were patients with febrile neutropenia, candidates to receive parenteral antimicrobial treatment; they were randomized to one of two groups, piperacillin/tazobactam plus amikacin (Group A), or piperacillin/tazobactam (Group B). The outcomes were failure, adverse events and death. Mantel-Haenszel chi squaretest and exact Fisher test were used. Reduction of relative and absolute risk (RRR and ARR), 95% confidence intervals (CI 95%) and number needed to treat (NNT) were calculated. Results: 88 Episodes were analyzed in group A and 76 in group B. There was no statistical difference in general characteristics of patients or type of infections. There was not significant statistical difference in: failure 31.8% group A, 30.2% group B (RR 1.05, CI 95% 0.66-1.66, p = 0.86), or adverse events (one in each group). The RRR was 1.5%, and ARR 2%, with a NNT of 67. Conclusion: Piperacillin/tazobactam without amikacin was as effective as combination therapy in pediatric patients with febrile neutropenia.

Introducción: los pacientes pediátricos con neutropenia febril habitualmente reciben una combinación de antimicrobianos de amplio espectro. La terapia sin aminoglucósido parece tener ventajas. Objetivo: comparar la eficacia de piperacilina/tazobactam más amikacina frente a la de piperacilina/tazobactam. Métodos: ensayo clínico controlado aleatorizado. Tamaño de muestra para una eficacia de 55%, y delta de 25%; se calcularon 80 episodios por grupo. Fueron seleccionados pacientes con neutropenia febril, candidatos a recibir antimicrobiano parenteral; se aleatorizaron a recibir piperacilina/tazobactam más amikacina (grupo A) o piperacilina/tazobactam (grupo B). Los desenlaces fueron falla, eventos adversos y muerte. Se emplearon las pruebas Chi cuadrada de Mantel-Haenszel y exacta de Fisher. Se calculó la reducción de riesgo relativo y absoluto (RRR y RRA), intervalos de confianza 95% (IC 95%) y número necesario a tratar (NNT). Resultados: se analizaron 88 episodios en el grupo A y 76 en el grupo B. No hubo diferencias estadísticas en características generales ni en el tipo de infecciones. No se encontró diferencia significativa en: falla 31.8% grupo A, 30.2% grupo B (RR 1.05, IC 95% 0.66-1.66, p = 0.86), ni en los eventos adversos (uno en cada grupo). La RRR fue de 1.5%, RRA de 2%, con un NNT de 67. Conclusión: la terapia con piperacilina/tazobactam sin amikacina fue tan efectiva como la terapia combinada para pacientes pediátricos con neutropenia febril.

Circulating microRNAs as Biomarkers for Pediatric Astrocytomas.

BACKGROUND AND AIMS: Since MicroRNAs (miRNAs) are potent regulators of gene expression, their expression and function alterations are associated with different types of cancer, including pediatric astrocytoma. Since the secretion of miRNAs by tumors into corporal fluids has made it possible to identify biomarkers in cancer, their deter mination in pediatric astrocytoma is vital. In order to gain insight into the mechanisms controlled by miRNAs in these neoplasms, we tested the expression of miRNAs 130a, 145, 335, 1303, and let-7g-3p by qPCR in tumors and blood serum from pediatric patients with astrocytoma. The data was analyzed with the DIANA-miRPath v3.0 platform. RESULTS: The data represented expression changes of all mirRNAs tested in both tumors and blood serum, which strongly suggest their use as circulating biomarkers for astrocytic tumors. The bioinformatic analysis -with DIANA-miRPath v3.0- showed the involvement of these miRNAs in extracellular matrix (ECM)-receptor interaction and proteoglycans in cancer, which control many hallmarks of cancer. In fact, the expression of the proteoglycan syndecan 4 (SDC4) and that of its biosynthetic enzymes, Exostosin Glycosyltransferase 1 (EXT1) and Xylosyltransferase 1 (XYLT1), were altered in pediatric astrocytoma. CONCLUSIONS: Our results highlight the role of microRNAs in the biology of pediatric astrocytoma and demonstrated for the first time the potential use of some circulating microRNAs as non-invasive biomarkers for this type of tumors, particularly miRs 130a, 145, and 335.

Differentially Expressed Long Non-Coding RNAs Were Predicted to Be Involved in the Control of Signaling Pathways in Pediatric Astrocytoma.

Expression changes for long non-coding RNAs (lncRNAs) have been identified in adult glioblastoma multiforme (GBM) and in a mixture of adult and pediatric astrocytoma. Since adult and pediatric astrocytomas are molecularly different, the mixture of both could mask specific features in each. We determined the global expression patterns of lncRNAs and messenger RNA (mRNAs) in pediatric astrocytoma of different histological grades. Transcript expression changes were determined with an HTA 2.0 array. lncRNA interactions with microRNAs and mRNAs were predicted by using an algorithm and the LncTar tool, respectively. Interactomes were constructed with the HIPPIE database and visualized with the Cytoscape platform. The array showed expression changes in 156 and 207 lncRNAs in tumors (versus the control) and in pediatric GBM (versus low-grade astrocytoma), respectively. Predictions identified lncRNAs that have putative microRNA binding sites, which might suggest that they function as sponges in these tumors. Also, lncRNAs were shown to interact with many mRNAs, such as Pleckstrin homology-like domain, family A, member 1 (PHLDA1) and sulfatase 2 (SULF2). For example, qPCR found long intergenic non-coding RNA regulator of reprogramming (linc-RoR) expression levels upregulated in pediatric GBM when they were compared with control tissues or with low-grade tumors. Meanwhile, PHLDA1 and ELAV-like RNA binding protein 1 (ELAV1) showed expression changes in tumors relative to the control. Our data showed many lncRNAs with expression changes in pediatric astrocytoma, which might be involved in the regulation of different signaling pathways.

Biomarcadores moleculares y su asociación con la supervivencia en niños con astrocitomas / Molecular biomarkers and their association with survival in children with astrocytomas

Los tumores del sistema nervioso central (SNC) representan los tumores sólidos más frecuentes en la edad pediátrica, los tumores del tallo suponen un 10% al 25%, y de ellos, los tumores difusos intrínsecos del puente (TDIP) presentan infiltración difusa en su patrón de crecimiento; el 95% de los niños mueren a causa de la enfermedad dentro de los tres primeros años con una mediana de supervivencia de 4 a 15 meses. Existen biomarcadores que se han puesto de manifiesto mediante técnicas de inmunohistoquímica. Objetivo: Determinar la asociación entre los marcadores tumorales Bcl2, CD133, p53 y Ki67 con la histología y la supervivencia de pacientes con tumor difuso intrínseco del puente. Pacientes y métodos: Se realizó un estudio ambilectivo, longitudinal, descriptivo de pacientes diagnosticados con TDIP en un período de 6 años con tipificación de los marcadores CD133, p53, Ki67, Bcl-2 mediante inmunohistoquímica, se analizó la asociación de dichos marcadores con la estirpe histológica y la supervivencia de los pacientes. Resultados: Se incluyeron en total 15 pacientes; por histología 11 (73%) tenían gliomas, y 4 (26.6%) presentaban tumores neuro ectodérmicos primitivos (TNEP). De los gliomas, 8 (72%) eran de bajo grado y 3 (28%) de alto grado, el marcador p53 estuvo sobre expresado en 8 de 14 pacientes (57%), p = 0.3802; Ki67 dio positivo en 7 de 14 pacientes (50%) p = 0.7363; el CD133 no presentó sobre expresión en ninguno de los enfermos, en tanto que Bcl-2 se encontró alterado en 9 de 14 sujetos (64%), p = 0.4858. La mediana de supervivencia en estos pacientes es de 13 meses. Conclusión: El biomarcador que muestra una asociación significativa con la supervivencia es Ki67, lo queda pie a la ideación de medidas terapéuticas de forma individualizada...