Nuestros investigadores

Jaime Gállego Pérez de Larraya

Publicaciones científicas más recientes (desde 2010)

Autores: Moreno, David; Yuste, JR; Martín, Paloma Leticia; et al.
Revista: JOURNAL OF NEUROVIROLOGY
ISSN 1355-0284  Vol. 24  Nº 4  2018  págs. 523 - 525
The human T-lymphotropic virus type 1 (HTLV-1) is a RNA retrovirus that infects a minimum of 5-10 million people worldwide. Transmission by cell-containing blood products and solid organ transplantation has been reported. Clinical disease occurs in about 5-10% of infected individuals and consists mainly in adult T cell leukemia and HTLV-1-associated myelopathy (HAM). We present a 54-year-old woman who underwent kidney transplant from cadaveric donor in March 2015. Donor also underwent cornea extraction for another recipient (corneal transplant protocol includes HTLV-1/2 serology). Twenty-four hours after completion of kidney transplant donor, HTLV-1 serology was revealed positive. Following experts' recommendations, once donor seropositivity was demonstrated, antiviral prophylaxis including zidovudine and raltegravir was initially given to our patient, in spite of which the patient developed HAM. Once the diagnosis of HAM was established, antiretroviral therapy was restarted, and intravenous pulses of methylprednisolone were periodically administered with transient initial improvement. Later on, the patient experienced neurological deterioration becoming wheelchair dependent. Since the occurrence of this case, HTLV-1 screening has become mandatory for solid organ transplantation in the Spanish province of Navarra, and the same should happen worldwide.
Autores: Cayuela, N.; Simo, M. ; Majos, C.; et al.
Revista: EUROPEAN JOURNAL OF NEUROLOGY
ISSN 1351-5101  Vol. 25  Nº 2  2018  págs. 387 - 394
Background and purposeThe main aim of this study was to identify which patients with glioblastoma multiforme (GBM) have a higher risk of presenting seizures during follow-up. MethodsPatients with newly diagnosed GBM were reviewed (n = 306) and classified as patients with (Group 1) and without (Group 2) seizures at onset. Group 2 was split into patients with seizures during follow-up (Group 2A) and patients who never had seizures (Group 2B). The anatomical location of GBM was identified and compared by voxel-based lesion symptom mapping (discovery set). Seizure-susceptible brain regions obtained were assessed visually and automatically in external GBM validation series (n = 85). ResultsIn patients with GBM who had no seizures at onset, an increased risk of presenting seizures during follow-up was identified in the superior frontal and inferior occipital lobe, as well as in inferoposterior regions of the temporal lobe. Conversely, those patients with GBM located in medial and inferoanterior temporal areas had a significantly lower risk of suffering from seizures during follow-up. Additionally, the seizure-susceptible brain region maps obtained classified patients in the validation set with high positive and negative predictive values. ConclusionsTumor location is a useful marker to identify patients with GBM who are at risk of suffering from seizures during follow-up. These results may help to support the use of antiepileptic prophylaxis in a selected GBM population and to improve stratification in antiepileptic clinical trials.
Autores: Aldave, G.; Rubio, A; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 20  Nº 7  2018  págs. 930 - 941
Background: Glioblastoma, the most aggressive primary brain tumor, is genetically heterogeneous. Alternative splicing (AS) plays a key role in numerous pathologies, including cancer. The objectives of our study were to determine whether aberrant AS could play a role in the malignant phenotype of glioma and to understand the mechanism underlying its aberrant regulation. Methods: We obtained surgical samples from patients with glioblastoma who underwent 5-aminolevulinic fluorescence-guided surgery. Biopsies were taken from the tumor center as well as from adjacent normal-appearing tissue. We used a global splicing array to identify candidate genes aberrantly spliced in these glioblastoma samples. Mechanistic and functional studies were performed to elucidate the role of our top candidate splice variant, BAF45d, in glioblastoma. Results: BAF45d is part of the switch/sucrose nonfermentable complex and plays a key role in the development of the CNS. The BAF45d/6A isoform is present in 85% of over 200 glioma samples that have been analyzed and contributes to the malignant glioma phenotype through the maintenance of an undifferentiated cellular state. We demonstrate that BAF45d splicing is mediated by polypyrimidine tract-binding protein 1 (PTBP1) and that BAF45d regulates PTBP1, uncovering a reciprocal interplay between RNA splicing regulation and transcription. Conclusions: Our data indicate that AS is a mechanism that contributes to the malignant phenotype of glioblastoma. Understanding the consequences of this biological process will uncover new therapeutic targets for this devastating disease.
Autores: Arbizu, Javier Ignacio, (Autor de correspondencia); Giuliani, A.; Gállego, Jaime; et al.
Revista: THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN 1824-4785  Vol. 61  Nº 4  2017  págs. 386 - 404
PET using F-18-2-fluoro-2-deoxy-D-glucose (FDG-PET) has been gradually introduced in the diagnostic clinical criteria of the most prevalent neurodegenerative diseases. Moreover, an increasing amount of literature has shown that the information provided by FDG-PET enhances the sensitivity of standard imaging biomarkers in less frequent disorders in which an early differential diagnosis can be of paramount relevance for patient management and outcome. Therefore emerging uses of FDG-PET may be important in prion diseases, autoimmune encephalitis (AE) and amyotrophic lateral sclerosis. Interestingly, FDG-PET findings can also be observed in the early phases of these conditions, even in the presence of normal magnetic resonance imaging scans. Thalamic hypometabolism is a common finding in sporadic Creutzfeldt-Jacob disease and fatal familiar insomnia patients, with further cortical synaptic dysfunction in the former. Limbic and extra-limbic metabolic abnormalities (more often hypermetabolism) can be observed in AE, although specific patterns may be seen within different syndromes associated with antibodies that target neuronal surface or synaptic antigens. FDG-PET shows its usefulness by discriminating patients with amyotrophic lateral sclerosis associated to upper motor neuron onset that evolve to frontotemporal dementia. Besides visual and voxel based image analysis, multivariate analysis as interregional correlation analysis and independent/principal component analysis have been successfully implemented to PET images increasing the accuracy of the discrimination of neurodegenerative diseases. The clinical presentation and current diagnostic criteria of these neurologic disorders as well as the emerging usefulness of FDG-PET in the diagnostic workup are presented and discussed in this review.
Autores: Inoges S; Tejada, Sonia; López, A; et al.
Revista: JOURNAL OF TRANSLATIONAL MEDICINE
ISSN 1479-5876  Vol. 15  Nº 1  2017  págs. 104-116
Our results suggest that the addition of tumor lysate-pulsed autologous DCs vaccination to tumor resection and combined radio-chemotherapy is feasible and safe. A multicenter randomized clinical trial is warranted to evaluate the potential survival benefit of this therapeutic approach. Trial registration This phase-II trial was registered as EudraCT: 2009-009879-35 and ClinicalTrials.gov Identifier: NCT01006044 retrospectively registered.
Autores: Arbizu, Javier Ignacio; Giuliani, Maximiliano Andrés; Gállego, Jaime; et al.
Revista: THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN 1824-4785  Vol. 61  Nº 4  2017  págs. 386-404
PET using 18F-2-fluoro-2-deoxy-D-glucose (FDG-PET) has been gradually introduced in the diagnostic clinical criteria of the most prevalent neurodegenerative diseases. Moreover, an increasing amount of literature has shown that the information provided by FDG-PET enhances the sensitivity of standard imaging biomarkers in less frequent disorders in which an early differential diagnosis can be of paramount relevance for patient management and outcome. Therefore emerging uses of FDG-PET may be important in prion diseases, autoimmune encephalitis (AE) and amyotrophic lateral sclerosis. Interestingly, FDG-PET findings can also be observed in the early phases of these conditions, even in the presence of normal magnetic resonance imaging scans. Thalamic hypometabolism is a common finding in sporadic Creutzfeldt-Jacob disease and fatal familiar insomnia patients, with further cortical synaptic dysfunction in the former. Limbic and extra-limbic metabolic abnormalities (more often hypermetabolism) can be observed in AE, although specific patterns may be seen within different syndromes associated with antibodies that target neuronal surface or synaptic antigens. FDG-PET shows its usefulness by discriminating patients with amyotrophic lateral sclerosis associated to upper motor neuron onset that evolve to frontotemporal dementia. Besides visual and voxel based image analysis, multivariate analysis as interregional correlation analysis and independent/principal component analysis have been
Autores: García, Marc; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 19  Nº Supl 6  2017  págs. 34
Autores: Tejada, Sonia; Diez Valle, Ricardo; Gállego, Jaime; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 18  Nº Supl.6  2016  págs. 4
Autores: Simonelli, M.; Sepulveda, J.; Brandes, A.; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 18  Nº Supl. 6  2016  págs. 24
BACKGROUND: CC-122 is a novel cereblon binding agent with multiple biological activities including potent immunomodulatory and anti-angiogenic effects. METHODS: Following establishment of oral CC-122 3mg daily (QD) as the maximum tolerated dose (Blood 122:2905 2013), patients with CNS tumors were enrolled in an expansion cohort. RESULTS: As of Jan. 13, 2016, 47 patients with relapsed/refractory GBM and other brain tumors were enrolled: GBM (n=39), grade IV oligodendroglioma (n=1), grade III anaplastic oligoastrocytoma (1) grade II-III astrocytomas (n=4) and PCNSL (n=2). CC-122 was well tolerated at 3¿mg QD (n=28), therefore, further dose escalation was explored in additional patients (n=19) at 4mg, 5mg or 6mg given either QD or on a 5/7days schedule. There were no DLTs, however, dose reduction (n=1) and interruptions (n=8) due to AEs were observed. The most common (¿ 5%) grade 3/4 AEs were neutropenia (10.6%), asthenia (6.4%) and general deterioration (6.4%). Drug-related serious AEs included febrile neutropenia, tumor hemorrhage, increase intracranial pressure, pulmonary embolism, interstitial lung disease, and acute respiratory distress syndrome (ARDS). AEs led to discontinuation in 10.6% of patients. 32 patients were evaluable for efficacy as of the cutoff date. The median PFS for patients was 58 days (Min-Max: 17-295, 95% CI: 50-111), while 21% of patients were progression-free at 6 months. CC-122 treatment resulted in a median increase from baseline of 86%, 133% and 165% in activated and memory cytotoxic T cells and activated helper T cells (all P<0.05), respectively, at Cycle 1 Day 15 in peripheral blood. CC-122 also activated T cells ex vivo as measured by increased levels of IFNg (131%) and IL-2 (685%) compared to baseline (both P<0.05). Preliminary CC-122 PK data suggest dose proportional increase in exposure in GBM patients. CONCLUSION: CC-122 is well tolerated. PK/PD analyses with correlation to clinical response are ongoing.
Autores: Marcos-Jubilar, María; Figueroa, Rocío; et al.
Revista: HAEMATOLOGICA
ISSN 0390-6078  Vol. 101  Nº Supl.4  2016  págs. 231 - 231
Autores: Tejada, Sonia; et al.
Revista: JOURNAL OF NEURO-ONCOLOGY
ISSN 0167-594X  Vol. 116  Nº 1  2014  págs. 169-175
Our purpose was to analyze the pattern of failure in glioblastoma (GBM) patients at first recurrence after radiotherapy and temozolomide and its relationship with different factors. From 77 consecutive GBM patients treated at our institution with fluorescence guided surgery and standard radiochemotherapy, 58 first recurrences were identified and included in a retrospective review. Clinical data including age, Karnofsky performance score, preoperative tumor volume and location, extend of resection, MGMT promoter methylation status, time to progression (PFS), overall survival (OS) and adjuvant therapies were reviewed for every patient. Recurrent tumor location respect the original lesion was the end point of the study. The recurrence pattern was local only in 65.5% of patients and non-local in 34.5%. The univariate and multivariate analysis showed that greater preoperative tumor volume in T1 gadolinium enhanced sequences, was the only variable with statistical signification (p < 0.001) for increased rate of non-local recurrences, although patients with MGMT methylation and complete resection of enhancing tumor presented non-local recurrences more frequently. PFS was longer in patients with non-local recurrences (13.8 vs. 6.4 months; p = 0.019, log-rank). However, OS was not significantly different in both groups (24.0 non-local vs. 19.3 local; p = 0.9). Rate of non-local recurrences in our series of patients treated with fluorescence guided surgery and standard radiochemotherap
Autores: Luquin, María Rosario Isabel; et al.
Revista: NEUROLOGÍA (BARCELONA. ED. IMPRESA)
ISSN 0213-4853  Vol. 30  Nº 3  2014  págs. 144 - 152
Introducción Las prionopatías representan hasta el 62% de los casos de demencia rápidamente progresiva (DRP) en los que se alcanza un diagnóstico definitivo. La variabilidad de los síntomas y signos iniciales y las diferencias en su evolución dificultan el diagnóstico precoz. Métodos Estudio retrospectivo en el que se incluye a pacientes con prionopatía probable o definitiva, que acudieron a la consulta de Neurología de nuestro centro durante el periodo 1999-2012. Se describen las características clínicas y los resultados de las exploraciones complementarias (proteína 14-3-3, EEG, RM, PET-FDG y análisis genético), con la finalidad de identificar qué marcadores permiten un diagnóstico precoz. Resultados Se describe a 14 pacientes: 6 con enfermedad de Creutzfeldt-Jakob esporádica (ECJe) definitiva, 3 con ECJe probable, 4 con insomnio familiar fatal y uno con la nueva variante de la enfermedad de Creutzfeldt-Jakob. La mediana de edad al diagnóstico fue de 54 años y la mediana de supervivencia de 9,5 meses. El trastorno del ánimo fue el síntoma inicial más frecuente, seguido de inestabilidad de la marcha y deterioro cognitivo. La proteína 14-3-3 fue positiva en el líquido cefalorraquídeo en 7 de 11 pacientes y el EEG mostró signos típicos en 2 de 12 pacientes explorados. El estudio de neuroimagen mostró alteraciones en 13 de los 14 pacientes. Conclusiones Además de la DRP, el trastorno conductual y de la marcha son síntomas iniciales frecuentes en las prionopatías. En nuestra serie, las pruebas complementarias más útiles para apoyar el diagnóstico fueron la RM y la PET-FDG.
Autores: Esteve, Patricia; et al.
Revista: CLINICAL NEUROLOGY AND NEUROSURGERY
ISSN 0303-8467  Vol. 115  Nº 1  2013  págs. 19-25
Introduction: Leptomeningeal carcinomatosis (LC) is a devastating complication occurring in 5% of all patients with cancer. To date there are no well-established prognostic markers in patients with LC, except for the presence of cerebrospinal fluid (CSF) blocks and the Karnofsky performance status scale (KPS). We aimed to identify clinical, neuroradiologic and CSF prognostic factors related to LC survival and to develop an easy-to-use Prognostic Scoring Scale (PSS) to identify patients who are more likely to benefit from receiving treatment. Methods: Single-center retrospective study evaluating patients who had a diagnosis of LC during a 10-year period. Diagnosis was made by malignant cytology or imaging; suspicious cases treated as LC were also included. Results: Fifty patients with LC were analyzed (58% women). Median age was 54.4 years, and KPS was 60%. The most common types of tumor were breast (35%), lung (24%), and hematologic malignancies (16%). Thirty-two percent of patients were diagnosed by imaging, 22% by cytology, and 40% by both. Median overall survival (OS) was 10 weeks (95% confidence interval 5.1-14.9). Median OS for patients who received specific treatment was 21.2 weeks vs. 6.38 weeks for patients receiving supportive care only (p < 0.001). In multivariate analysis, initial KPS, initial CSF protein level (<112 mg/dL) and time from diagnosis of primary tumor to diagnosis of LC (>67 weeks) were significant and independent predictors of increased survival. Conclusions: Prognosis remains poor in LC. The predictive factors for patients with LC here identified could help to improve the selection of patients who are more likely to benefit from receiving treatment. (C) 2012 Elsevier B.V. All rights reserved.
Autores: Gállego, Jaime; Irimia, Pablo; Martínez Vila, E.; et al.
Revista: JOURNAL OF CLINICAL ULTRASOUND
ISSN 0091-2751  Vol. 40  Nº 8  2012  págs. 479 - 485
Background. The assessment of carotid intima-media thickness (CIMT) may improve cardiovascular risk prediction. The optimal protocol for CIMT measurement is unclear. CIMT may be measured in the common carotid artery (CCA), carotid bifurcation (CB), and internal carotid artery (ICA), but measurements from CB and ICA are more difficult to obtain. We studied the influence of body mass index (BMI) and atheroma plaques on the capacity to obtain CIMT measurements at different carotid sites. Methods. Using an automatic system, CIMT was measured in 700 subjects aged 4575, in the near and far walls of CCA, CB, and ICA bilaterally. The presence of atheroma plaques, BMI and vascular risk factors were recorded. Results. CIMT measurements in CCA were possible in all except one subject. It was not possible to obtain CIMT measurements at CB or ICA in 24.1% of normal weight and 58.8% of obese subjects. The likelihood of obtaining CIMT measurement at all carotid sites decreased as the BMI increased. Atheroma plaques in a carotid segment did not preclude CIMT measurement at this site. Conclusions. CIMT measurements in distal carotid segments are more challenging in obese subjects. Measuring CIMT at CCA remains feasible in obese subjects and should be the primary endpoint in these subjects. Nevertheless, CB and ICA measurements, when feasible, would improve risk classification.
Autores: Diez Valle, Ricardo; López, A; Inoges S; et al.
Revista: WORLD JOURNAL OF CLINICAL ONCOLOGY
ISSN 2218-4333  Vol. 3  Nº 11  2012  págs. 142-149
Active immunotherapy with tumor lysate-pulsed, autologous dendritic cells is feasible, safe, well tolerated and biologically efficacious. A phase-II study is ongoing to possibly improve further on our very encouraging clinical results.
Autores: Gállego, Jaime; et al.
Revista: JOURNAL OF NEURO-ONCOLOGY
ISSN 0167-594X  Vol. 103  Nº 3  2011  págs. 603 - 609
Central nervous system (CNS) prophylaxis is required during initial treatment of non-Hodgkin lymphoma (NHL) subtypes that carry a high risk of CNS involvement. Intrathecal (IT) liposomal cytarabine, a formulation with prolonged half-life, has been shown to be safe and effective in the treatment of meningeal disease in patients with high-grade lymphoma. We retrospectively reviewed all adult patients with high-grade NHL that received prophylactic therapy with IT liposomal cytarabine and developed neurologic complications in our institution between April 2007 and May 2009. We recorded information on hospital admission, chemotherapy regimens, clinical features, neuroimaging, cerebrospinal fluid, neurophysiology data, and outcome. Neurotoxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Four of fourteen patients (28%) developed moderate or severe neurotoxicity (grades 2 and 3 of the NCI-CTC), manifested as conus medullaris/cauda equine syndrome or pseudotumour cerebri-like syndrome, after a median of 3.5 IT courses of liposomal cytarabine. All patients had received corticosteroids to prevent arachnoiditis. Liposomal cytarabine given via the IT route, even with concomitant corticosteroid administration, can result in significant neurotoxicity in some patients. We discuss the potential pathogenesis of these effects and suggest hypothetical therapeutic measures to prevent these complications. Specialists should be aware of these possible complications when administering prophylactic IT liposomal cytarabine in high-grade NHL patients, and additional prospective studies should be conducted to more clearly delineate the frequency and characteristics of these complications.
Autores: Arbizu, Javier Ignacio; Gállego, Jaime; et al.
Libro:  Medicina Nuclear en la práctica clínica
2012  págs. 355-378
Autores: Irimia, Pablo; Gállego, Jaime; Martínez Vila, E.;
Libro:  Neurosonología. Aplicaciones diagnósticas para la práctica clínica
2011  págs. 93 - 102