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OBJECTIVE: Inflammatory hand arthritis (IHA) results in impaired function. Local gene therapy with ART-I02, a recombinant adeno-associated virus (AAV) serotype 5 vector expressing interferon (IFN)-ß, under the transcriptional control of nuclear factor κ-B responsive promoter, was preclinically shown to have favorable effects. This study aimed to investigate the safety and tolerability of local gene therapy with ART-I02 in patients with IHA. METHODS: In this first-in-human, dose-escalating, cohort study, 12 IHA patients were to receive a single intra-articular (IA) injection of ART-I02 ranging 0.3 × 1012-1.2 × 1013 genome copies in an affected hand joint. Adverse events (AEs), routine safety laboratory and the clinical course of disease were periodically evaluated. Baseline- and follow-up contrast enhanced magnetic resonance images (MRIs), shedding of viral vectors in bodily fluids, and AAV5 and IFN-ß immune responses were evaluated. A data review committee provided safety recommendations. RESULTS: Four patients were enrolled. Long-lasting local AEs were observed in 3 patients upon IA injection of ART-I02. The AEs were moderate in severity and could be treated conservative. Given the duration of the AEs and their possible or probable relation to ART-I02, no additional patients were enrolled. No systemic treatment emergent AEs were observed. The MRIs reflected the AEs by (peri)arthritis. No T-cell response against AAV5 or IFN-ß, nor IFN-ß antibodies could be detected. Neutralizing antibody titers against AAV5 raised post-dose. CONCLUSION: Single IA doses of 0.6 × 1012 or 1.2 × 1012 ART-I02 vector genomes were administered without systemic side effects or serious AEs. However, local tolerability was insufficient for continuation. TRIAL REGISTRATION: NCT02727764.
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Artritis/terapia , Dependovirus , Terapia Genética/métodos , Vectores Genéticos , Articulaciones de la Mano , Interferón beta/administración & dosificación , Anciano , Estudios de Cohortes , Dependovirus/metabolismo , Femenino , Terapia Genética/efectos adversos , Humanos , Interferón beta/biosíntesis , Persona de Mediana EdadRESUMEN
Primary bone tumors of the spine are less common than metastases or multiple myeloma. Based on the patient's age and the radiologic pattern and topography of the tumor, a very approximate differential diagnosis can be established for an osseous vertebral lesion. This article shows the radiologic manifestations of the principal primary bone tumors of the spine from a practical point of view, based on our personal experience and a review of the literature. If bone metastases, multiple myeloma, lymphomas, hemangiomas, and enostoses are excluded, only eight types of tumors account for 80% of all vertebral tumors. These are chordomas, osteoblastomas, chondrosarcomas, giant-cell tumors, osteoid osteomas, Ewing's sarcomas, osteosarcomas, and aneurysmal bone cysts.
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Neoplasias de la Columna Vertebral/diagnóstico por imagen , HumanosRESUMEN
RATIONALE AND OBJECTIVES: Denosumab is a monoclonal antibody used neo-adjuvantly in giant cell tumor of bone (GCTB) to facilitate surgery, or long term for axial tumors where surgery comes with high morbidity. Time intervals for treatment effects to occur are unclear and monitoring tools are limited, complicating optimal drug dose titration. We assessed changes in time intensity curve (TIC) - derived perfusion features on DCE-MRI in GCTB during denosumab treatment and evaluated the duration of treatment effects on tumor perfusion. MATERIALS AND METHODS: Patients with GCTB who underwent dynamic contrast enhanced (DCE) MRI before (t = 0) and after 3 (t = 3), 6 (t = 6) or 12 (t = 12) months of denosumab treatment were retrospectively included in a single center. Regions of interest were placed on tumor compartments with visually most intense enhancement and TICs were created. Time-to-enhancement (TTE), wash-in rate (WIR), maximal relative enhancement (MRE), and area-under-the-curve (AUC) were calculated. Differences in perfusion features were calculated with the Wilcoxon signed-rank test. RESULTS: In all 24 patients decreased perfusion on DCE-MRI after start of denosumab treatment was seen. TTE increased between t = 0 and t = 3 (p < 0.001). WIR, MRE and AUC decreased between t = 0 and t = 3 (p < 0.001, p = 0.01 and p = 0.02, respectively). No significant differences in features were found between t = 3 and t = 6 or t = 6 and t = 12. No significant perfusion differences in primary versus recurrent, or axial versus appendicular tumors, were found. CONCLUSION: MRI perfusion significantly changed in GCTB within 3 months of denosumab treatment compared to baseline. No further significant change occurred between 3 and 6, and 6 and 12 months of treatment. These findings suggest that evaluation of treatment response and subsequent consideration of maintenance with lower doses of denosumab, may already be indicated after 3 months. In cases where long term denosumab is the preferred therapy, monitoring change in tumor characteristics on DCE-MRI may aid optimal drug dose titration, minimizing side effects.
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Denosumab , Tumores de Células Gigantes , Humanos , Denosumab/uso terapéutico , Estudios Retrospectivos , Perfusión , Imagen por Resonancia MagnéticaRESUMEN
Objective: Malignancy in giant cell tumor of bone (mGCTB) is categorized as primary (concomitantly with conventional GCTB) or secondary (after radiotherapy or other treatment). Denosumab therapy has been suggested to play a role in the etiology of secondary mGCTB. In this case series from a tertiary referral sarcoma center, we aimed to find distinctive features for malignant transformation in GCTB on different imaging modalities. Furthermore, we assessed the duration of denosumab treatment and lag time to the development of malignancy. Methods: From a histopathology database search, 6 patients were pathologically confirmed as having initial conventional GCTB and subsequently with secondary mGCTB. Results: At the time of mGCTB diagnosis, 2 cases were treated with denosumab only, 2 with denosumab and surgery, 1 with multiple curettages and radiotherapy, and 1 with surgery only. In the 4 denosumab treated patients, the mean lag time to malignant transformation was 7 months (range 2-11 months). Imaging findings suspicious of malignant transformation related to denosumab therapy are the absence of fibro-osseous matrix formation and absent neocortex formation on CT, and stable or even increased size of the soft tissue component. Conclusion: In 4 patients treated with denosumab, secondary mGCTB occurred within the first year after initiation of treatment. Radiotherapy-associated mGCTB has a longer lag time than denosumab-associated mGCTB. Close clinical and imaging follow-up during the first months of denosumab therapy is key, as mGCTB tends to have rapid aggressive behavior, similar to other high-grade sarcomas. Nonresponders should be (re) evaluated for their primary diagnosis of conventional GCTB.
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The study analyzes the current status of personalized medicine in pediatric oncology in Spain. It gathers national data on the tumor molecular studies and genomic sequencing carried out at diagnosis and at relapse, the centers that perform these studies, the technology used and the interpretation and clinical applicability of the results. Current challenges and future directions to achieve a coordinated national personalized medicine strategy in pediatric oncology are also discussed. Next generation sequencing-based (NGS) gene panels are the technology used in the majority of centers and financial limitations are the main reason for not incorporating these studies into routine care. Nowadays, the application of precision medicine in pediatric oncology is a reality in a great number of Spanish centers. However, its implementation is uneven and lacks standardization of protocols; therefore, national coordination to overcome the inequalities is required. Collaborative work within the Personalized Medicine Group of SEHOP is an adequate framework for encouraging a step forward in the effort to move precision medicine into the national healthcare system.
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Hematología , Neoplasias , Niño , Consenso , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Neoplasias/genética , Neoplasias/patología , Neoplasias/terapia , Medicina de Precisión/métodos , EspañaRESUMEN
BACKGROUND: Clinical heterogeneity reflects the complexity of genetic events associated with neuroblastoma (NB). To identify the status of all described genetic loci with possible prognostic interest, high-throughput approaches have been used, but only with tumour cell content >60%. In some tumours, necrotic, haemorrhagic and/or calcification areas influence the low amount of neuroblasts. We evaluated the effect of tumour cell content in the detection of relevant aberrant genetic markers (AGM) diagnosed by fluorescence in situ hybridisation (FISH) on tissue microarrays (TMA) in NB. METHODS: Two hundred and thirty-three MYCN non-amplified primary NB included in 12 TMAs were analysed. RESULTS: Presence of AGM reduced event-free survival (EFS) (P=0.004) as well as overall survival (OS) (P=0.004) of patients in the whole cohort. There were no differences in prognostic impact of presence of AGM according to tumour cell content. CONCLUSION: We propose the use of FISH to diagnose AGM of all NB samples having the above-mentioned areas to determine patient risk.
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Marcadores Genéticos , Neuroblastoma/diagnóstico , Neuroblastoma/genética , Mapeo Cromosómico , Femenino , Amplificación de Genes , Humanos , Hibridación Fluorescente in Situ , Lactante , Masculino , Proteína Proto-Oncogénica N-Myc , Estadificación de Neoplasias , Neuroblastoma/clasificación , Proteínas Nucleares/genética , Proteínas Oncogénicas/genética , Pronóstico , Tasa de Supervivencia , Análisis de Matrices TisularesRESUMEN
BACKGROUND: In neuroblastoma (NB), the presence of segmental chromosome alterations (SCAs) is associated with a higher risk of relapse. METHODS: In order to analyse the role of SCAs in infants with localised unresectable/disseminated NB without MYCN amplification, we have performed an array CGH analysis of tumours from infants enrolled in the prospective European INES trials. RESULTS: Tumour samples from 218 out of 300 enroled patients could be analysed. Segmental chromosome alterations were observed in 11%, 20% and 59% of infants enroled in trials INES99.1 (localised unresectable NB), INES99.2 (stage 4s) and INES99.3 (stage 4) (P<0.0001). Progression-free survival was poorer in patients whose tumours harboured SCA, in the whole population and in trials INES99.1 and INES99.2, in the absence of clinical symptoms (log-rank test, P=0.0001, P=0.04 and P=0.0003, respectively). In multivariate analysis, a SCA genomic profile was the strongest predictor of poorer progression-free survival. CONCLUSION: In infants with stage 4s MYCN-non-amplified NB, a SCA genomic profile identifies patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas in infants with localised unresectable NB, a genomic profile characterised by the absence of SCA identifies patients in whom treatment reduction might be possible. These findings will be implemented in a future international trial.
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Aberraciones Cromosómicas , Neuroblastoma/patología , Proteínas Nucleares/genética , Proteínas Oncogénicas/genética , Humanos , Lactante , Proteína Proto-Oncogénica N-Myc , Neuroblastoma/genética , Pronóstico , Estudios Prospectivos , Recurrencia , Análisis de SupervivenciaRESUMEN
PURPOSE: The COVID-19 pandemic has forced healthcare stakeholders towards challenging decisions. We analyse the impact of the pandemic on the conduct of phase I-II trials for paediatric cancer during the first month of state of alarm in Spain. METHODS: A questionnaire was sent to all five ITCC-accredited Spanish Paediatric Oncology Early Phase Clinical Trial Units, including questions about impact on staff activities, recruitment, patient care, supply of investigational products, and legal aspects. RESULTS: All units suffered personnel shortages and difficulties in enrolling patients, treatment continuity, or performing trial assessments. Monitoring activity was frequently postponed (73%), and 49% of on-going trials interrupted recruitment. Only two patients could be recruited during this period (75% reduction in the expected rate). CONCLUSIONS: The COVID-19 crisis has significantly impacted clinical research practice and access to innovation for children with cancer. Structural and functional changes are under way to better cope with the expected future restrictions.
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COVID-19/epidemiología , Ensayos Clínicos como Asunto , Neoplasias/terapia , COVID-19/prevención & control , Niño , Humanos , Oncología Médica/organización & administración , Oncología Médica/estadística & datos numéricos , Cuerpo Médico de Hospitales/provisión & distribución , Neoplasias/epidemiología , Atención al Paciente , Selección de Paciente , SARS-CoV-2 , España/epidemiología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Neuroblastoma (NB) is a heterogeneous tumor with extremely diverse prognosis according to clinical and genetic factors such as specific combinations of chromosomal imbalances. METHODS: Molecular karyotyping data from a national neuroblastic tumor database of 155 NB samples were analyzed and related to clinical data. RESULTS: Segmental chromosomal alterations (SCA) were detected in 102 NB, whereas 45 only displayed numerical alterations. Incidence of SCA was higher in stage M (92%) and MYCN amplified (MNA) NB (96%). Presence of SCA was associated with older age, especially 1q gain and 3p deletion. 96% of the deaths were observed in the SCA group and 85% of the relapsed NB contained SCA. The alteration most commonly associated with a higher number of other segmental rearrangements was 11q deletion, followed by 4p deletion. Whole-chromosome 19 gain was associated with lower stages, absence of SCA and better outcome. CONCLUSIONS: SCA are not randomly distributed and are concentrated on recurrent chromosomes. The most frequently affected chromosomes identify prognostic factors in specific risk groups. SCA are associated with older age and MNA. We have identified a small subset of patients with better outcome that share whole-chromosome 19 numeric gain, suggesting its use as a prognostic biomarker in NB.
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Aberraciones Cromosómicas , Neuroblastoma/genética , Adolescente , Adulto , Niño , Preescolar , Humanos , Lactante , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: There is rising concern on the impact of new strategies, such as high-dose chemotherapy (HDC) and immunotherapy, on the pattern of relapse in high-risk neuroblastoma (HR-NBL). Our aim is to evaluate the incidence and identify risk factors for first recurrence in the central nervous system (CNS) in HR-NBL. PATIENTS AND METHODS: Data from patients with stage 4V HR-NBL included from February 2002 to June 2015 in the prospective HR-NBL trial of the European International Society of Pediatric Oncology Neuroblastoma Group were analysed. Characteristics at diagnosis, treatment and the pattern of first relapse were studied. CNS imaging at relapse was centrally reviewed. RESULTS: The 1977 included patients had a median age of 3 years (1 day-20 years); 1163 were boys. Among the 1161 first relapses, 53 were in the CNS, with an overall incidence of 2.7%, representing 6.2% of all metastatic relapses. One- and three-year post-relapse overall survival was 25 ± 6% and 8 ± 4%, respectively. Higher risk of CNS recurrence was associated with female sex (hazard ratio [HR] = 2.0 [95% confidence interval {CI}: 1.1-3.5]; P = 0.016), MYCN-amplification (HR = 2.4 [95% CI: 1.2-4.4]; P = 0.008), liver (HR = 2.5 [95% CI: 1.2-5.1]; P = 0.01) or >1 metastatic compartment involvement (HR = 7.1 [95% CI: 1.0-48.4]; P = 0.047) at diagnosis. Neither HDC nor immunotherapy was associated with higher risk of CNS recurrence. Stable incidence of CNS relapse was reported over time. CONCLUSIONS: The risk of CNS recurrence is linked to both patient and disease characteristics, with neither impact of HDC nor immunotherapy. These findings support the current treatment strategy and do not justify a CNS prophylactic treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Primarias Secundarias/tratamiento farmacológico , Neuroblastoma/tratamiento farmacológico , Adolescente , Adulto , Neoplasias del Sistema Nervioso Central/patología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Recurrencia Local de Neoplasia/patología , Neoplasias Primarias Secundarias/patología , Neuroblastoma/patología , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
PURPOSE: Early phase trials are crucial in developing innovative effective agents for childhood malignancies. We report the activity in early phase paediatric oncology trials in Spain from its beginning to the present time and incorporate longitudinal data to evaluate the trends in trial characteristics and recruitment rates. METHODS: Members of SEHOP were contacted to obtain information about the open trials at their institutions. The study period was split into two equal periods for analysis: 2007-2013 and 2014-2020. RESULTS: Eighty-one trials and two molecular platforms have been initiated. The number of trials has increased over the time of the study for all tumour types, with a predominance of trials available for solid tumours (66%). The number of trials addressed to tumours harbouring specific molecular alterations has doubled during the second period. The proportion of industry-sponsored compared to academic trials has increased over the same years. A total of 565 children and adolescents were included, with an increasing trend over the study period. For international trials, the median time between the first country study approval and the Spanish competent authority approval was 2 months (IQR 0-6.5). Fourteen out of 81 trials were sponsored by Spanish academic institutions. CONCLUSIONS: The number of available trials, and the number of participating patients, has increased in Spain from 2007. Studies focused on molecular-specific targets are now being implemented. Barriers to accessing new drugs for all ranges of age and cancer diseases remain. Additionally, opportunities to improve academic research are still required in Spain.
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Ensayos Clínicos como Asunto/estadística & datos numéricos , Oncología Médica/tendencias , Neoplasias/terapia , Pediatría/tendencias , Adolescente , Adulto , Niño , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Neoplasias/patología , Sociedades Médicas , Adulto JovenRESUMEN
Ewing sarcoma is a rare tumor that arises in bones of children and teenagers but, in 15% of the patients it is presented as a primary soft tissue tumor. Balanced reciprocal chimeric translocation t(11;22)(q24;q12), which encodes an oncogenic protein fusion (EWSR1/FLI1), is the most generalized and characteristic molecular event. Using conventional treatments, (chemotherapy, surgery and radiotherapy) long-term overall survival rate is 30% for patients with disseminated disease and 65-75% for patients with localized tumors. Urgent new effective drug development is a challenge. This review summarizes the preclinical and clinical investigational knowledge about prognostic and targetable biomarkers in Ewing sarcoma, finally suggesting a workflow for precision medicine committees.
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Neoplasias Óseas/terapia , Medicina de Precisión/métodos , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Genómica/métodos , Humanos , Terapia Molecular Dirigida , Proteínas de Fusión Oncogénica/genética , Pronóstico , Sarcoma de Ewing/genética , Sarcoma de Ewing/patología , Sarcoma de Ewing/terapiaRESUMEN
Clinical variability is commonly seen in Li-Fraumeni syndrome. Phenotypic heterogeneity is present among different families affected by the same pathogenic variant in TP53 gene and among members of the same family. However, causes of this huge clinical spectrum have not been studied in depth. TP53 type mutation, polymorphic variants in TP53 gene or in TP53-related genes, copy number variations in particular regions, and/or epigenetic deregulation of TP53 expression might be responsible for clinical heterogeneity. In this review, recent advances in the understanding of genetic and epigenetic aspects influencing Li-Fraumeni phenotype are discussed.
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Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/fisiopatología , Proteína p53 Supresora de Tumor/genética , Anticipación Genética , Variaciones en el Número de Copia de ADN , Epigénesis Genética , Interacción Gen-Ambiente , Humanos , Mutación , Estrés Oxidativo , Fenotipo , Polimorfismo Genético , Proteínas Proto-Oncogénicas c-mdm2/genética , Telómero/metabolismoRESUMEN
Astrocytic neoplasms are genetically heterogeneous; however a low frequency of genomic changes has been found in juvenile pilocytic astrocytoma (PA) in molecular studies. Concerning pleomorphic xanthoastrocytomas (PXA), recent studies have given heterogeneous results for chromosomal alterations. We studied the subtelomeric regions of 19 primary astrocytoma tumors. Results were near normality for the PA group with relative scarcity of chromosomal imbalances, except for the duplication of 3pter in 4/15 and deletion of 21qter in 5/15 of them. In contrast, a specific profile was observed in the 4 PXA tumoral samples. This involved 3pter, 14qter and 19pter duplication and 4qter, 6qter, 9qter, 13cen, 17pter, 18qter and 21qter deletion. Our results indicate that the chromosomal and genetic aberrations in PXAs differed from those typically associated with the diffusely infiltrating astrocytic and oligodendroglial gliomas. These genetic differences would likely contribute to the more favorable behavior of PXAs and may be helpful for molecular differential diagnosis of pediatric cerebral tumors.
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Astrocitoma/genética , Inestabilidad Cromosómica/genética , Glioma/genética , Telómero/genética , Astrocitoma/patología , Neoplasias Encefálicas/genética , Niño , Aberraciones Cromosómicas , ADN de Neoplasias/genética , ADN de Neoplasias/aislamiento & purificación , Femenino , Glioma/patología , Humanos , Pérdida de Heterocigocidad , Masculino , Oligodendroglioma/genética , Oligodendroglioma/patología , Eliminación de Secuencia , Neoplasias de la Médula Espinal/genéticaRESUMEN
INTRODUCTION: Cancer and blood disorders in children are rare. The progressive improvement in survival over the last decades largely relies on the development of international academic clinical trials that gather the sufficient number of patients globally to elaborate solid conclusions and drive changes in clinical practice. The participation of Spain into large international academic trials has traditionally lagged behind of other European countries, mainly due to the burden of administrative tasks to open new studies, lack of financial support and limited research infrastructure in our hospitals. METHODS: The objective of ECLIM-SEHOP platform (Ensayos Clínicos Internacionales Multicéntricos-SEHOP) is to overcome these difficulties and position Spain among the European countries leading the advances in cancer and blood disorders, facilitate the access of our patients to novel diagnostic and therapeutic approaches and, most importantly, continue to improve survival and reducing long-term sequelae. ECLIM-SEHOP provides to the Spanish clinical investigators with the necessary infrastructural support to open and implement academic clinical trials and registries. RESULTS: In less than 3 years from its inception, the platform has provided support to 20 clinical trials and 8 observational studies, including 8 trials and 4 observational studies where the platform performs all trial-related tasks (integral support: trial setup, monitoring, etc.) with more than 150 patients recruited since 2017 to these studies. In this manuscript, we provide baseline metrics for academic clinical trial performance that permit future comparisons. CONCLUSIONS: ECLIM-SEHOP facilitates Spanish children and adolescents diagnosed with cancer and blood disorders to access state-of-the-art diagnostic and therapeutic strategies.
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Ensayos Clínicos como Asunto/estadística & datos numéricos , Cooperación Internacional , Estudios Multicéntricos como Asunto/estadística & datos numéricos , Estudios Observacionales como Asunto/estadística & datos numéricos , Objetivos Organizacionales , Sociedades Médicas/organización & administración , Adolescente , Supervivientes de Cáncer , Niño , Neoplasias Hematológicas/terapia , Hematología/organización & administración , Humanos , Oncología Médica/organización & administración , Neoplasias/terapia , Pediatría/organización & administración , EspañaRESUMEN
OBJECTIVES: The number of enucleations and visual sequels due to retinoblastoma is high. The aim of this study was to evaluate the different diagnostic aspects and propose strategies that might improve the clinical management of this condition. METHOD: A retrospective study was conducted on 38 patients with retinoblastoma studied genetically (29 unilateral, 9 bilateral). The evaluation included: age of onset, clinical signs, and time since onset, number of enucleations, time to diagnosis, and survival at 5 years. RESULTS: Leukocoria was the main clinical sign (present in 90% of cases). The mean diagnostic delay was 3.2 months. Among the unilateral cases, the eyes were enucleated in 76%, and 55% in the bilateral forms. Only one death was found among the 25 patients followed-up for at least 5 years. CONCLUSIONS: Retinoblastoma diagnostic and treatment strategies need to be updated. Good coordination between paediatricians and ophthalmologists is essential for this. Its management in reference centres, which have the necessary technology and experience, should contribute to increase the rate of organ preservation.
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Detección Precoz del Cáncer , Neoplasias del Ojo/diagnóstico , Retinoblastoma/diagnóstico , Edad de Inicio , Enucleación del Ojo/estadística & datos numéricos , Neoplasias del Ojo/etiología , Neoplasias del Ojo/cirugía , Neoplasias del Ojo/terapia , Humanos , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/cirugía , Utilización de Procedimientos y Técnicas/estadística & datos numéricos , Retinoblastoma/etiología , Retinoblastoma/cirugía , Retinoblastoma/terapia , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
The photo-bleaching reaction of the chemical actinometer, Aberchrome 540™, is reported for the first time in a series of ionic liquids (ILs). This fulgide in its C-form undergoes an opening reaction to yield its E-form, when it is irradiated with UV light at wavelengths >400â¯nm. The magnitude of bleaching was monitored spectrophotometrically and their kinetics evaluated, obtaining first-order rate constants (kobs). The results obtained in different ILs suggest that changes in the rate constants (kobs) of the opening reaction of Aberchrome 540™ are mainly governed by weaker interactions such as coulombic (π* parameter) and Van der Waals interactions (δH2, parameter). In addition, the photochemical fatigue resistance was also studied in ILs media and compared with conventional solvents (benzene, toluene, etc.). In particular, we found that three different tendencies dependent on the ILs used exist. The first group of ILs where the reversibility of the fulgide is favored (for example, [Bmim][BF4], [Bmim][PF6] and [Bmim][OTf]), behaviour similar to conventional solvents. The second group corresponds to ILs where photo reversibility is partial; and finally, other group of ILs that prevented photo reversibility. It is proposed that depending on the ILs used, the stabilization of different forms of the fulgide can be controlled, thus resulting important in terms of choosing the appropriate ILs for a specific photochemical reaction.
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BACKGROUND: Under the ExPO-r-NeT project (European Expert Paediatric Oncology Reference Network for Diagnostics and Treatment), we aimed to identify paediatric oncology tumour boards in Europe to investigate the kind of technologies and logistics that are in place in different countries and to explore current differences between regions. METHODS: A 20-question survey regarding several features of tumor boards was designed. Data collected included infrastructure, organization, and clinical decision-making information from the centres. The survey was distributed to the National Paediatric Haematology and Oncology Societies that forwarded the survey to the sites. For comparative analysis, respondents were grouped into four geographical regions. RESULTS: The questionnaire was distributed amongst 30 countries. Response was obtained from 23 (77%) that altogether have 212 paediatric oncology treating centres. A total of 121 institutions answered (57%). Ninety-one percent of the centres hold multidisciplinary boards; however, international second consultations are performed in 36% and only 15% participate on virtual tumor boards. Videoconferencing facilities and standard operational procedures (SOPs) are available in 49 and 43% of the centres, respectively. There were statistically significant differences between European regions concerning meeting infrastructure and organization/logistics: specific room, projecting equipment, access to medical records, videoconferencing facilities, and existence of SOPs. CONCLUSION: Paediatric tumor boards are a common feature in Europe. To reduce inequalities and have equal access to healthcare, a virtual network is needed. Important differences on the functioning and access to technology between regions in Europe have been observed and need to be addressed.
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Atención a la Salud/normas , Accesibilidad a los Servicios de Salud/normas , Oncología Médica/normas , Neoplasias/terapia , Grupo de Atención al Paciente/normas , Pediatría/normas , Niño , Atención a la Salud/organización & administración , Europa (Continente) , Humanos , Oncología Médica/organización & administración , Neoplasias/diagnóstico , Grupo de Atención al Paciente/organización & administración , Pediatría/organización & administración , Encuestas y CuestionariosRESUMEN
BACKGROUND: Arthropathy is a prevalent and invalidating complication of acromegaly with a characteristic radiographic phenotype. We aimed to further characterize cartilage and bone abnormalities associated with acromegalic arthropathy using magnetic resonance imaging (MRI). METHODS: Twenty-six patients (23% women, mean age 56.8 ± 13.4 years), with active (n = 10) and controlled acromegaly (n = 16) underwent a 3.0 T MRI of the right knee. Osteophytes, cartilage defects, bone marrow lesions and subchondral cysts were assessed by the Knee Osteoarthritis Scoring System (KOSS) method. Cartilage thickness and cartilage T2 relaxation times, in which higher values reflect increased water content and/or structural changes, were measured. Twenty-five controls (52% women, mean age: 59.6 ± 8.0 years) with primary knee OA were included for comparison. RESULTS: Both in active and controlled acromegaly, structural OA defects were highly prevalent, with thickest cartilage and highest cartilage T2 relaxation times in the active patients. When compared to primary OA subjects, patients with acromegaly seem to have less cysts (12% vs 48%, P = 0.001) and bone marrow lesions (15% vs 80%, P = 0.006), but comparable prevalence of osteophytosis and cartilage defects. Patients with acromegaly had 31% thicker total joint cartilage (P < 0.001) with higher cartilage T2 relaxation times at all measured sites than primary OA subjects (P < 0.01). CONCLUSIONS: Patients with active acromegaly have a high prevalence of structural OA abnormalities in combination with thick joint cartilage. In addition, T2 relaxation times of cartilage are high in active patients, indicating unhealthy cartilage with increased water content, which is (partially) reversible by adequate treatment. Patients with acromegaly have a different distribution of structural OA abnormalities visualized by MRI than primary OA subjects, especially of cartilage defects.