RESUMEN
Increasing age is an important prognostic variable in glioblastoma (GBM). We have defined the proteomic response in GBM samples from 7 young patients (mean age 36 years) compared to peritumoural-control samples from 10 young patients (mean age 32 years). 2-Dimensional-gel-electrophoresis, image analysis, and protein identification (LC/MS) were performed. 68 proteins were significantly altered in young GBM samples with 29 proteins upregulated and 39 proteins downregulated. Over 50 proteins are described as altered in GBM for the first time. In a parallel analysis in old GBM (mean age 67 years), an excellent correlation could be demonstrated between the proteomic profile in young GBM and that in old GBM patients (r(2) = 0.95) with only 5 proteins altered significantly (p < 0.01). The proteomic response in young GBM patients highlighted alterations in protein-protein interactions in the immunoproteosome, NFkB signalling, and mitochondrial function and the same systems participated in the responses in old GBM patients.
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Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Mitocondrias/metabolismo , Adulto , Factores de Edad , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Glioblastoma/mortalidad , Glioblastoma/patología , Humanos , Espectrometría de Masas , Persona de Mediana Edad , Mitocondrias/patología , Pronóstico , Proteómica , Tasa de SupervivenciaRESUMEN
Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥ 2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein-protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology.
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Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Proteínas Mitocondriales/metabolismo , Adulto , Anciano , Encéfalo/metabolismo , Encéfalo/cirugía , Encéfalo/ultraestructura , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/ultraestructura , Estudios de Cohortes , Femenino , Glioblastoma/cirugía , Glioblastoma/ultraestructura , Humanos , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Proteómica , Adulto JovenRESUMEN
PURPOSE: Brain tumour patients may struggle to express their concerns in the outpatient clinic, creating a physician-focused rather than a shared agenda. We created a simple, practical brain-tumour-specific holistic needs assessment (HNA) tool for use in the neuro-oncology outpatient clinic. METHODS: We posted the brain tumour Patient Concerns Inventory (PCI) to a consecutive sample of adult brain tumour attendees to a neuro-oncology outpatient clinic. Participants brought the completed PCI to their clinic consultation. Patients and staff provided feedback. RESULTS: Seventy seven patients were eligible and 53 participated (response rate = 68%). The PCI captured many problems absent from general cancer checklists. The five most frequent concerns were fatigue, fear of tumour coming back, memory, concentration, and low mood. Respondents used the PCI to formulate 105 specific questions, usually about the meaning of physical or psychological symptoms. Patients and staff found the PCI to be useful, and satisfaction with the instrument was high. CONCLUSIONS: This study demonstrates the clinical utility of the brain tumour PCI in a neuro-oncology clinic. The combination of a brain-tumour-specific concerns checklist and an intervention to focus patient agenda creates a simple and efficient HNA tool.
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Neoplasias Encefálicas/psicología , Evaluación de Necesidades , Adolescente , Adulto , Instituciones de Atención Ambulatoria , Neoplasias Encefálicas/enfermería , Miedo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Derivación y Consulta , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The cerebellar cognitive affective syndrome (CCAS) was first described by Schmahmann and Sherman as a constellation of symptoms including dysexecutive syndrome, spatial cognitive deficit, linguistic deficits and behavioural abnormalities in patients with a lesion in the cerebellum with otherwise normal brain. Neurosurgical patients with cerebellar tumours constitute one of the cohorts in which the CCAS has been described. In this paper, we present a critical review of the literature of this syndrome in neurosurgical patients. Thereafter, we present a prospective clinical study of 10 patients who underwent posterior fossa tumour resection and had a detailed post-operative neuropsychological, neuropsychiatric and neuroradiological assessment. Because our findings revealed a large number of perioperative neuroradiological confounding variables, we reviewed the neuroimaging of a further 20 patients to determine their prevalence. Our literature review revealed that study design, methodological quality and sometimes both diagnostic criteria and findings were inconsistent. The neuroimaging study (pre-operative, n = 10; post-operative, n = 10) showed very frequent neuroradiological confounding complications (e.g. hydrocephalus; brainstem compression; supratentorial lesions and post-operative subdural hygroma); the impact of such features had largely been ignored in the literature. Findings from our clinical study showed various degree of deficits in neuropsychological testing (n = 1, memory; n = 3, verbal fluency; n = 3, attention; n = 2, spatial cognition deficits; and n = 1, behavioural changes), but no patient had full-blown features of CCAS. Our study, although limited, finds no robust evidence of the CCAS following surgery. This and our literature review highlight a need for guidelines regarding study design and methodology when attempting to evaluate neurosurgical cases with regard to the potential CCAS.
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Enfermedades Cerebelosas/diagnóstico , Trastornos del Conocimiento/diagnóstico , Neoplasias Infratentoriales/cirugía , Complicaciones Posoperatorias/diagnóstico , Adulto , Anciano , Enfermedades Cerebelosas/etiología , Trastornos del Conocimiento/etiología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Infratentoriales/complicaciones , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Adulto JovenRESUMEN
While the fMRI test-retest reliability has been mainly investigated from the point of view of group level studies, here we present analyses and results for single-subject test-retest reliability. One important aspect of group level reliability is that not only does it depend on between-session variance (test-retest), but also on between-subject variance. This has partly led to a debate regarding which reliability metric to use and how different sources of noise contribute to between-session variance. Focusing on single subject reliability allows considering between-session only. In this study, we measured test-retest reliability in four behavioural tasks (motor mapping, covert verb generation, overt word repetition, and a landmark identification task) to ensure generalisation of the results and at three levels of data processing (time-series correlation, t value variance, and overlap of thresholded maps) to understand how each step influences the other and how confounding factors influence reliability at each of these steps. The contributions of confounding factors (scanner noise, subject motion, and coregistration) were investigated using multiple regression and relative importance analyses at each step. Finally, to achieve a fuller picture of what constitutes a reliable task, we introduced a bootstrap technique of within- vs. between-subject variance. Our results show that (i) scanner noise and coregistration errors have little contribution to between-session variance (ii) subject motion (especially correlated with the stimuli) can have detrimental effects on reliability (iii) different tasks lead to different reliability results. This suggests that between-session variance in fMRI is mostly caused by the variability of underlying cognitive processes and motion correlated with the stimuli rather than technical limitations of data processing.
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Mapeo Encefálico/métodos , Encéfalo/fisiología , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los Resultados , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Gross total removal of glioma is limited by proximity to eloquent brain. Awake surgery allows for intraoperative monitoring to safely identify eloquent regions. However, data on adverse psychological effects induced in these patients is limited. OBJECTIVE: This study explored patients' perception of awake surgery for glioma, with special focus on intraoperative pain and anxiety. METHODS: This study was conducted at five neurosurgical centers within the European Low Grade Glioma Network. Patients underwent awake surgery for glioma according to the protocol of the individual center. Pain and discomfort were measured during the awake phase. Postoperatively, patients answered a questionnaire on aspects of their operation. RESULTS: One hundred five patients were enrolled. Pain levels on a 10-cm visual analogue scale were 1.3 cm at the beginning, 1.9 cm the middle, and 2.1 cm at the end of awake phase. Levels of anxiety were 2.2 cm, 2.5 cm and 2.6 cm, respectively. Women and patients younger than 60 years exhibited highest mean anxiety levels. The patient questionnaire revealed that the majority of patients feel comfortable with the procedure. Discomfort resulted from head fixation or positioning on the operating table. CONCLUSIONS: We demonstrate that awake surgery is well tolerated, as neither intraoperative nor postoperative assessment revealed major disadvantages. Concerning practical lessons learned from this study, we emphasize the importance of minimizing pain and preparing patients thoroughly to reduce anxiety and maximize cooperation. Awake surgery is an excellent treatment modality for brain tumors with very positive perception by patients.
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Neoplasias Encefálicas/cirugía , Glioma/cirugía , Monitoreo Intraoperatorio , Vigilia/fisiología , Adolescente , Adulto , Anciano , Mapeo Encefálico/métodos , Neoplasias Encefálicas/patología , Craneotomía/métodos , Femenino , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio/métodos , Clasificación del Tumor , Estudios Prospectivos , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto JovenRESUMEN
Patient anxiety and fear about an awake craniotomy can affect the patient's choice about having an operation despite comprehensive pre-operative counselling. We report three cases in which a family member came into theatre during the procedure to support the patient during surgery. All three cases, which involved intra-operative cortical and subcortical stimulations and intra-operative patient testing, were successfully completed with major tumour resections and no post-operative complications. We suggest that family support should be considered in patients who have extreme fear and anxiety about awake surgery.
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Ansiedad/prevención & control , Neoplasias Encefálicas/psicología , Sedación Consciente/psicología , Craneotomía/psicología , Miedo , Adulto , Neoplasias Encefálicas/cirugía , Craneotomía/métodos , Femenino , Humanos , Imagen por Resonancia Magnética , Convulsiones/etiología , Resultado del Tratamiento , VigiliaRESUMEN
AIM: To describe experience using general practitioners (GPs), with an extended role (GPwER) in spinal medicine, to expedite assessment, triage, and management of patients referred from primary care for specialist spinal surgical opinion. BACKGROUND: Low back and neck pain are common conditions in primary care. Indiscriminate or inappropriate referral to a spinal surgeon contributes to long waiting times. Previous attempts at triaging patients who really require a surgical opinion have used practice nurses, physiotherapists, clinical algorithms, and interdisciplinary screening clinics. METHODS: Within the setting of an independent spinal care centre, we have used GPs specially trained in spinal practice to expedite the assessment and triage of new referrals between 2015 and 2021. We reviewed feedback from a Patient Satisfaction Questionnaire and the postgraduate backgrounds, training, practice with regard to triage of new referrals, and experiences of the GPs who were recruited. FINDINGS: Six GPwER had a mean of 26 years of postgraduate experience before appointment (range 10-44 years). The first four GPwER, appointed between 2015 and 2018, underwent an ad hoc in-house, interdisciplinary training programme and saw 2994 new patients between 2016 and 2020. After GPwER, assessment in only 18.9% (range 12.6 to 22.7%) of these patients was a spinal surgical opinion deemed necessary. Waiting times to see the spinal surgeon remained at 6-8 weeks despite a three-fold annual increase (from 340 to 1058) in new referrals. A Patient Satisfaction Questionnaire revealed high levels of satisfaction with the performances of the GPwER across seven dimensions. A dedicated training programme was designed in 2020, and the last two appointees underwent 20 h of clinical teaching prior to practice. Initial experience using GPwER, here termed 'Spinal Clinicians', suggests they are efficient at screening for patients needing spinal surgical referral. Establishing a recognised training programme, assessment, and certification for these practitioners are the next challenges.
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Médicos Generales , Cirujanos , Humanos , Derivación y ConsultaRESUMEN
Introduction Low back pain (LBP) is common and a significant cause of morbidity. Many patients receive inappropriate imaging for LBP in primary care. Aim To explore the incidence and type of spinal imaging conducted for LBP patients referred from general practice for specialist surgical opinion, and evaluate whether imaging conformed to clinical guidelines. Methods Audit of a sequential cohort (n = 100) of new LBP patients referred from primary care for specialist opinion at a suburban Australian capital city independent Spinal Centre. Results In the 6 months before referral, 90% (95% CI 83-95%) of patients underwent spinal imaging. Imaging was performed in 95% of those who did and 79% of those who did not meet guidelines for radiological investigation. 35% of patients were inappropriately imaged and 3% inappropriately not imaged. Spinal computed tomography (CT) imaging was used in 52% of patients, magnetic resonance imaging (MRI) in 42% and image-guided lumbar spinal interventional procedures in 28%. Discussion Most patients with LBP referred for surgical opinion have diagnostic radiological investigations whether or not it is indicated by clinical guidelines. The more frequent use of spinal CT compared to MRI may be due to idiosyncrasies of the Australian Medicare Benefits Schedule (MBS) rebate system. The findings of this pilot study provide support for the changes recommended by the 2016 MBS Review Taskforce on LBP that permit GP access to subsidised lumbar MRI, while constraining access to lumbar CT, and provide novel data about spinal imaging and practice in this cohort of patients.
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Dolor de la Región Lumbar , Humanos , Anciano , Dolor de la Región Lumbar/diagnóstico por imagen , Dolor de la Región Lumbar/epidemiología , Estudios Transversales , Incidencia , Proyectos Piloto , Australia/epidemiología , Programas Nacionales de Salud , Tomografía Computarizada por Rayos X , Atención Primaria de SaludRESUMEN
BACKGROUND: Large cerebral infarction has a high case fatality. Despite the use of conventional medical treatments such as hyperventilation, mannitol, diuretics, corticosteroids and barbiturates, the outcome of this condition remains poor. Decompressive surgery to relieve intracranial pressure is performed in some cases, although evidence of any clinical benefits has not been available until recently. This is an update of a Cochrane review first published in 2002. OBJECTIVES: To examine the effects of decompressive surgery in patients with massive acute ischaemic stroke complicated with cerebral oedema, and to judge whether decompressive surgery is effective in improving survival or survival free of severe disability. SEARCH METHODS: We searched the Cochrane Stroke Group's Trials Register (last searched October 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 7), MEDLINE (1966 to October 2010), EMBASE (1980 to October 2010) and Science Citation Index (October 2010). We also searched the reference lists of all relevant articles. SELECTION CRITERIA: Randomised controlled studies of decompressive surgery plus medical treatment versus medical treatment alone in patients with clinically and radiologically confirmed cerebral infarcts complicated with cerebral oedema. DATA COLLECTION AND ANALYSIS: One author assessed the titles and retrieved the relevant studies. The same author extracted data, with discussion among all authors for clarification. Outcomes were death at the end of follow-up, death or disability defined as the modified Rankin Scale (mRS) > 3 at the end of follow-up, death or severe disability defined as mRS > 4 at 12 months and disability defined as mRS 4 or 5 at 12 months. The results are given using the Peto odds ratio (Peto OR) with 95% confidence intervals (CIs). MAIN RESULTS: We included three trials in this review, involving 134 patients who were 60 years of age or younger. The time window for the intervention was 30 hours from stroke onset in two studies and 96 hours in one study. All trials were stopped early. Surgical decompression reduced the risk of death at the end of follow-up (OR 0.19, 95% CI 0.09 to 0.37) and the risk of death or disability defined as mRS > 4 at 12 months (OR 0.26, 95% CI 0.13 to 0.51). Death or disability defined as mRS > 3 at the end of follow-up was no different between the treatment arms (OR 0.56, 95% CI 0.27 to 1.15). AUTHORS' CONCLUSIONS: Surgical decompression lowers the risk of death and death or severe disability defined as mRS > 4 in selected patients 60 years of age or younger with a massive hemispheric infarction and oedema. Optimum criteria for patient selection and for timing of decompressive surgery are yet to be defined. Since survival may be at the expense of substantial disability, surgery should be the treatment of choice only when it can be assumed, based on their preferences, that it is in the best interest of patients. Since all the trials were stopped early, an overestimation of the effect size cannot be excluded.
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Edema Encefálico/cirugía , Infarto Cerebral/complicaciones , Descompresión Quirúrgica , Humanos , Persona de Mediana Edad , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de TiempoRESUMEN
BACKGROUND: This study compared prospectively the quality of life (QoL), function and mood of patients about to undergo surgery for either an intracranial supratentorial tumour or a spinal degenerative condition. The QoL scores were also compared to that of cohorts with a range of extracranial cancers. MATERIAL AND METHODS: The study took place in a Scottish NHS Neurosurgical Unit. Patients were assessed on the day prior to surgery for their QoL (European Organisation for Research and Treatment of Cancer (EORTC)-QLQ C30), mood status (Hospital Anxiety and Depression Score), Performance status (Karnosky Score, timed 10-m walk) and disability (Barthel Disability Index). All tests were performed by a single trained psychologist. RESULTS: Between 2007 and 2009, 101 patients with intracranial tumours, 75 age- and gender-matched patients with degenerative spinal disorders and 80 healthy adults were evaluated. There was no difference in the mood or disability scores between the two patient cohorts, but mood was significantly worse than a matched healthy cohort. The spinal cohort had significantly worse scores on the Karnovsky Scale, timed 10-m walk and for Global Health than those of the brain tumour cohort. They also had worse mean scores on all five functional scales, as well as six of the nine symptom/single-item scales, of the EORTC QLQ C30. SUMMARY: Patients with degenerative spinal disorders awaiting surgery on the NHS have significantly impaired QoL in multiple domains as well as other functional and mood disorders. Not only are their scores worse than a brain tumour cohort but they are also worse than many cancer cohorts described in the literature using the EORTC QLQ C30. These findings suggest that preoperative care, assessment and management of NHS patients with degenerative spinal disorders could be improved and that the EORTC QLQ C30 may be a useful tool for audit purposes in this cohort.
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Afecto , Neoplasias Encefálicas/psicología , Glioma/psicología , Enfermedades Neurodegenerativas/psicología , Calidad de Vida , Estudios de Casos y Controles , Femenino , Humanos , Estado de Ejecución de Karnofsky , Masculino , Persona de Mediana Edad , Enfermedades Neurodegenerativas/cirugía , Cuidados Preoperatorios , Estudios Prospectivos , Tiempo de TratamientoRESUMEN
BACKGROUND: Multidisciplinary team (MDT) working in oncology aims to improve outcomes for patients with cancer. One role is to ensure the implementation of best practice and National Institute for Health and Clinical Excellence (NICE) guidance. In this study, we have assessed the role of MDT in implementing the TA121 appraisal of the use of carmustine wafers in high grade gliomas. METHODS: 296 patients with high-grade glioma suitable for maximal resection were recruited from 17 Neurosurgical Centres. The number of patients treated with carmustine wafers and reasons for not using this were recorded. Complications at 48 hours post-operatively and at 6 weeks post-radiotherapy were recorded. RESULTS: 94/296 (32%) of suitable patients received carmustine wafers. In 55% of cases carmustine was not used due to either surgeon preference or a lack of an MDT decision. There was no increased complication rate with carmustine use at either 48 hours post-surgery or at 6 weeks post radiotherapy. Use of carmustine wafers did not decrease access to and use of chemoradiotherapy. CONCLUSIONS: One third of patients suitable for carmustine wafers received them. Their use was neither associated with more frequent complications, nor decreased use of chemoradiotherapy. Implementation of NICE TA121 Guidance is extremely variable in different MDTs across the United Kingdom.
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Antineoplásicos Alquilantes/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Carmustina/administración & dosificación , Glioma/tratamiento farmacológico , Anciano , Antineoplásicos Alquilantes/efectos adversos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Carmustina/efectos adversos , Terapia Combinada/métodos , Femenino , Glioma/radioterapia , Glioma/cirugía , Adhesión a Directriz , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Grupo de Atención al Paciente/organización & administración , Grupo de Atención al Paciente/normas , Complicaciones Posoperatorias/etiología , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/normas , Resultado del TratamientoRESUMEN
INTRODUCTION: Chronic low back pain (CLBP) is one of the most common disorders presenting in primary healthcare. Kinematic studies of low lumbar pelvic mobility allied with surface electromyography (sEMG) may assist in the assessment and management of CLBP. However, the applicability in the use of sEMG in the clinical setting remains uncertain. In this protocol, we aim to review the clinical utility and reproducibility of the sEMG component of these kinematic studies in patients with CLBP. METHODS AND ANALYSIS: This protocol was informed by the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) and results will be reported in line with the PRISMA. Searches will be conducted on PubMed, Scopus, Web of Science, Embase, CINAHL and Google Scholar databases, along with a comprehensive review of grey literature. Two reviewers will conduct the searches and independently screen them, according to title and abstract. Two independent reviewers will then assess the full-text versions of those selected articles and assess the risk of bias using the defined protocol inclusion criteria. The risk of bias within the studies included will be assessed via the Quality Assessment of Diagnostic Accuracy Studies tool, V.2 and the Grading of Recommendations Assessment, Development and Evaluation guidelines will be used to assess certainty of evidence for recommendations based on the risk of bias findings. Meta-analysis will be conducted where appropriate on groups of studies with low heterogeneity. In instances of higher heterogeneity, meta-synthesis will instead be completed, comparing results in terms of increased or decreased clinical utility and/or reproducibility of sEMG. ETHICS AND DISSEMINATION: Ethics approval was not required for this research. It is anticipated that the results will influence the use, interpretation and further development of sEMG in management and assessment of these patients. PROSPERO REGISTRATION NUMBER: CRD42021273936.
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Dolor de la Región Lumbar , Electromiografía , Humanos , Dolor de la Región Lumbar/diagnóstico , Metaanálisis como Asunto , Reproducibilidad de los Resultados , Proyectos de Investigación , Literatura de Revisión como Asunto , Revisiones Sistemáticas como AsuntoRESUMEN
Thirteen proteins (identified with 2-D gels and MALDI-TOF MS) are significantly altered during staurosporine-induced apoptosis in SH-SY5Y cells. To gain further insight into the integrated cellular response to apoptosis, we have investigated whether a network can be generated of direct and indirect interactions between these 13 proteins. A network that contains 12 out of the 13 proteins was generated using Ingenuity Pathway Analysis (IPA) and this network is dominated (89%) by direct protein-protein interactions. This network scored 34 with IPA. Bootstrapping 1000 random lists of 13 proteins suggested that the frequency of this score occurring by chance was 1 in 500. We examined whether subsets of proteins such as HSPs, which were elevated after staurosporine, had a disproportionate impact on the network generated. There was no evidence that any subset of 8 from the 13 proteins contributed disproportionately to the network. Network generation, using IPA, identified common features (such as endoplasmic reticular stress protein interactions) in apoptotic studies from different laboratories. The generation of protein interaction networks clearly enhances the interpretation of proteomic data, but only when interpreted cautiously, particularly in respect of statistical analyses.
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Apoptosis/efectos de los fármacos , Mapeo de Interacción de Proteínas , Proteómica/métodos , Estaurosporina/farmacología , Apoptosis/fisiología , Línea Celular Tumoral , Electroforesis en Gel Bidimensional , Proteínas de Choque Térmico/metabolismo , Humanos , Neuroblastoma/metabolismo , Pliegue de Proteína/efectos de los fármacos , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Proteínas/efectos de los fármacos , Proteínas/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Imaging-based markers of treatment response are increasingly being used in studies of brain-tumour therapies, for evaluating novel treatments and further understanding of existing therapies. An ultimate goal of these studies is to identify pre- or early-stage treatment imaging biomarkers that enable prediction of subsequent treatment response. We hypothesised that pretreatment MRI-based measurements of tumoural perfusion may provide a suitable imaging-based biomarker for prediction of subsequent treatment response and evaluated this in a group of nine high-grade glioma patients undergoing dexamethasone treatment. A strong positive correlation was observed between tumoural blood flow (R(2)=0.90, p<0.001) and tumoural blood volume (R(2)=0.76, p=0.002), and subsequent treatment response as measured by alterations in tumour leakage properties. These preliminary results indicate that measurements of tumoural perfusion may provide useful imaging biomarkers for predicting treatment response to dexamethasone and would therefore also be worth evaluating in newer emerging therapies.
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Antiinflamatorios/uso terapéutico , Neoplasias Encefálicas/líquido cefalorraquídeo , Neoplasias Encefálicas/tratamiento farmacológico , Dexametasona/uso terapéutico , Glioblastoma/líquido cefalorraquídeo , Glioblastoma/tratamiento farmacológico , Imagen por Resonancia Magnética , Edema Encefálico/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECT: Multiparametric brain monitoring probes now make it possible to measure cerebral physiology. This prospective clinical study was designed to evaluate the pathophysiological environment of tumoural and peritumoural tissue O(2), CO(2), pH, HCO(3)- and temperature of awake patients with glioblastoma. METHODS: A Neurotrend multiparametric sensor was placed using intraoperative image guidance into glioblastoma after biopsy under general anesthetic. Postoperative monitoring was then performed in awake patients. RESULTS: Twelve patients were recruited and monitoring was performed, and well tolerated in 9 for up to 22 hrs. Mean glioblastoma tumour values were: tissue oxygen pressure (PtiO(2)) 21.0 mmHg, standard deviation +/- 7.9; PtiCO(2) 60.2 +/- 17.2 mmHg; temperature 36.9 +/- 0.4 degrees C, pH 7.08 + 0.2; and HCO(3) 17.1 +/- 3.7. Mean peritumoural brain values in 5 patients were PtiO(2) 29.1 +/- 27.6 mmHg; PtiCO(2) 48.6 +/- 7.0 mmg; temperature 36.4 +/- 0.6 degrees C; pH 7.20 +/- 0.09 and HCO(3) 19.1 +/- 3.5. There were trends for the PtiO(2) to decrease with increasing brain depth. As glioblastoma PtiCO(2) levels decreased, pH increased. There were no relationships between either tumoural PtiO(2) and pH, or PtiO(2) and PtiCO(2), however there were large intra- and inter-tumoural variation in monitoring values. There were technical problems in some patients with the Neurotrend sensor that limited its application, and that compromised aspects of data collection and interpretation, particularly of PtiO(2). CONCLUSION: This study has shown that this novel approach to monitoring glioma pathophysiology is feasible and well tolerated by patients. The data, much of which is novel, contributes to the knowledge of glioblastoma pathophysiology. However, further study and clinical exploitation awaits the development of a more reliable multiparametric sensor.
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Neoplasias Encefálicas/fisiopatología , Corteza Cerebral/fisiopatología , Sedación Consciente/métodos , Glioblastoma/fisiopatología , Hipoxia/fisiopatología , Monitoreo Intraoperatorio/métodos , Neoplasias Encefálicas/cirugía , Corteza Cerebral/cirugía , Femenino , Glioblastoma/cirugía , Humanos , Hipoxia/etiología , Masculino , Oxígeno/metabolismo , Estudios Prospectivos , Recuperación de la Función/fisiología , Resultado del TratamientoRESUMEN
INTRODUCTION: Following Simpson Grade 1 excision of large convexity meningioma there is often a need for synthetic dural substitutes. DISCUSSION: One problem with some of these grafts is that they lack tensile strength when wet and therefore sink into the cavity left following removal of the meningioma. CONCLUSION: A simple method to prevent 'sinking' or sagging of such synthetic dural grafts is described and illustrated.
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Duramadre/cirugía , Neoplasias Meníngeas/cirugía , Meningioma/cirugía , Procedimientos Neuroquirúrgicos/métodos , Procedimientos de Cirugía Plástica/métodos , Técnicas de Sutura , Anciano , Encéfalo/patología , Encéfalo/cirugía , Duramadre/anatomía & histología , Femenino , Humanos , Imagen por Resonancia Magnética , Neoplasias Meníngeas/patología , Meningioma/patología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/prevención & control , Prótesis e Implantes , Suturas/normas , Resultado del TratamientoRESUMEN
PURPOSE: Patients who participate in questionnaire surveys, clinical studies and clinical trials can be different from patients who do not participate. The occurrence and direction of this response, participation or ascertainment bias is unpredictable, and can harm the external validity of medical research. METHODS: We compared the characteristics of patients with intracranial tumours who participated in a psychological study of inspection time with the characteristics of patients who did not participate for a number of reasons. RESULTS: Of 178 newly diagnosed adults with intracranial tumours, 136 (76%) were eligible, of whom 76 (56%) participated and 34 (25%) declined. There were no significant differences in terms of age and sex of the patients who participated and those who declined. When the participation group was combined with those who were ineligible and those who declined, the majority of patients in the combined cohort (n = 152) had a WHO grade III or IV glioma (high-grade glioma) (48.0%), and only 13.2% had a WHO grade I or II glioma (low-grade glioma). However, only 38.2% of those who participated had a WHO grade III or IV glioma, and 23.7% had a WHO grade I or II glioma. Comparisons of the participation vs. ineligible and declined groups revealed there was a significant difference (p = 0.002) between the ratio of high-grade to low-grade gliomas in the total and recruited cohorts. Comparisons of only the participation vs. declined groups approached significance (p = 0.051). WHO grade III and IV glioma patients were under-represented, and WHO grade I or II glioma patients were over-represented in the study group. CONCLUSIONS: Noninterventional, non-therapeutic applied neuropsychological studies in neuro-oncology are susceptible to bias since the spectrum of neuropathologies in recruited patients can be significantly different from that of the total cohort. These data could help anticipate recruitment rates for applied neuropsychological studies in clinical neuro-oncology and may help anticipate likely selection biases amongst those who participate.