Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.

BACKGROUND: Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. METHODS: We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. RESULTS: We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. CONCLUSIONS: Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.

Aportaciones morfológicas al origen de la cefalea postpuncióndural / No disponible

La hipotensión de líquido cefalorraquídeo y la tracción de estructuras encefálicas sensibles al dolor ha sido una de las hipótesis más reiterada para justificar la cefalea pospunción dural. En este trabajo se recogen resultados obtenidos de diferentes estudios realizados por nuestro grupo, que se completan con nuevas aportaciones. Se estudió con técnicas con microscopia óptica y electrónica la morfología de los componentes del saco dural espinal humano, las lesiones que se producían con agujas de punción lumbar de diferente diámetro y diseño de punta, y tras la disección de un encéfalo, se señalan detalles del trayecto aparente de los pares craneales que pueden ser traccionados cuando un paciente con hipotensión de líquido cefalorraquídeo está en posición erecta. Los resultados aportan detalles morfológicos que contribuyen al conocimiento de la fisiopatología de la cefalea pospunción dural (AU)

Hypotension caused by cerebrospinal fluid leakage and traction over certain brain structures has been blamed as the main reason for post-dural puncture headache (PDPH) In this paper we review different papers published by our group in which we show old and new data. We light and electron optic microscopy to study the morphology of the human dural sac plus the damage caused by different types of needles with different diameters. We dissected different brain specimens to show the path of the cranial nerves focusing on those that can be affected by traction during orthostatic position. These results show several morphology details that can contribute to the physiopathology of post-dural puncture headache (AU)

[Hypertrophic cranial and spinal pachymeningitis. A description of four new cases and a review of the literature]. / Paquimeningitis hipertrofica craneal y espinal. Descripcion de cuatro casos nuevos y revision de la bibliografia.

INTRODUCTION: Hypertrophic pachymeningitis is an infrequent disease that is characterised by inflammatory hypertrophy of the dura mater. There are cranial, spinal and craniospinal forms of the disease. They may be due to underlying infectious, autoimmune or neoplastic processes, although most of the cases reported in recent years have no base pathology and are known as idiopathic hypertrophic pachymeningitis. The ideal treatment is unknown, but most cases usually respond well to therapy with corticoids. CASE REPORTS: We report two cases of cranial forms, one idiopathic with typical clinical features consisting in cranial polyneuropathy and good response to corticoids, and another case secondary to rheumatoid arthritis that began with epileptic seizures. Both had a parenchymatous oedema. The two forms of spinal pachymeningitis presented as progressive paraparesis that evolved well after surgical removal of the lesion. CONCLUSIONS: On observing pachymeningitis in neuroimaging tests it becomes necessary to conduct a comprehensive aetiological study in search of infectious, autoimmune and neoplastic diseases. In the cranial forms there may be parenchymatous oedema, which would explain the epileptic seizures and the cognitive deterioration of our patients. Response to corticoids is spectacular, although it is often necessary to continue to administer them for prolonged periods of time.

Paquimeningitis hipertrófica craneal y espinal. Descripción de cuatro casos nuevos y revisión de la bibliografía / Hypertrophic cranial and spinal pachymeningitis. A description of four new cases and a review of the literature

Introducción. La paquimeningitis hipertrófica es una enfermedad infrecuente caracterizada por la hipertrofia de carácter inflamatorio de la duramadre. Existen formas craneales, espinales y craneoespinales. Pueden deberse a procesos infecciosos, autoinmunes o neoplásicos subyacentes, aunque la mayoría de los descritos en los últimos años no presenta patología de base, es la paquimeningitis hipertrófica idiopática. Se desconoce el tratamiento idóneo, pero la mayoría de los pacientes suele responder a la terapia corticoidea. Casos clínicos. Presentamos dos formas craneales, una idiopática con clínica típica de multineuropatía craneal y respuesta buena a los corticoides y otro caso secundario a artritis reumatoide que comenzó con crisis epilépticas. Ambos tenían un edema parenquimatoso. Las dos formas de paquimeningitis espinal se presentaron como una paraparesia progresiva con buena evolución tras extirpación quirúrgica de la lesión. Conclusiones. La observación de una paquimeningitis en las pruebas de neuroimagen obliga a un amplio estudio etiológico en busca de enfermedades infecciosas, autoinmunes y neoplásicas. En las formas craneales pueden existir edema parenquimatoso, lo que explicaría las crisis epilépticas y el deterioro cognitivo de nuestros pacientes. La respuesta a los corticoides es espectacular, aunque muchas veces se requiere su mantenimiento de forma continua

Introduction. Hypertrophic pachymeningitis is an infrequent disease that is characterised by inflammatory hypertrophy of the dura mater. There are cranial, spinal and craniospinal forms of the disease. They may be due to underlying infectious, autoimmune or neoplastic processes, although most of the cases reported in recent years have no base pathology and are known as idiopathic hypertrophic pachymeningitis. The ideal treatment is unknown, but most cases usually respond well to therapy with corticoids. Case reports. We report two cases of cranial forms, one idiopathic with typical clinical features consisting in cranial polyneuropathy and good response to corticoids, and another case secondary to rheumatoid arthritis that began with epileptic seizures. Both had a parenchymatous oedema. The two forms of spinal pachymeningitis presented as progressive paraparesis that evolved well after surgical removal of the lesion. Conclusions. On observing pachymeningitis in neuroimaging tests it becomes necessary to conduct a comprehensive aetiological study in search of infectious, autoimmune and neoplastic diseases. In the cranial forms there may be parenchymatous oedema, which would explain the epileptic seizures and the cognitive deterioration of our patients. Response to corticoids is spectacular, although it is often necessary to continue to administer them for prolonged periods of time