Thursday, May 30, 2013

Searching for the right evidence: how to answer your clinical questions using the 6S hierarchy

Asking and answering clinical questions during daily practice can be challenging and time consuming. Knowing the resources available to answer a specific clinical question can lead to a more efficient and effective search strategy and thus, to a more applicable answer based on the levels of evidence available. This primer reviews how to search for the right evidence using a specified hierarchy and provides examples of pre-appraised resources with corresponding websites to help with your search.

Introduction

The readers of our journal most likely have busy clinical, administrative and/or teaching roles. As such, time is of the essence when thinking about answering clinical questions that arise in patient care. DiCenso and colleagues recently published a hierarchy of pre-appraised evidence called the 6S model.1 This model denotes in a pyramidal fashion the six levels of evidence available in clinical decision making. It starts with the largest resource available...






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Emerging roles of astrocytes in neural circuit development

Nature Reviews Neuroscience 14, 442 (2013). doi:10.1038/nrn3506

Author: Laura E. Clarke & Ben A. Barres

Nature Reviews Neuroscience14, 311–321 (2013)In this article, the corresponding author was listed incorrectly. The corresponding author is Laura E. Clarke, e-mail: lclarke2@stanford.edu. This has been corrected in the online version of the article.






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Basic cancer research is essential for the success of personalised medicine

Publication date: Available online 28 May 2013
Source:European Journal of Cancer
Author(s): Yosef Yarden , Carlos Caldes
The last decade has witnessed significant progress in cancer understanding and therapy: we can now identify the genetic drivers of individual tumours, and tailor drugs able to specifically intercept the driver mutations. While all agree that personalised cancer medicine is a clear outcome of the resources dedicated to cancer research over the last 50 years, some critics question the necessity for continuous investments in sub-fields other than clinical research and drug development. Herein, scientists from the European Association for Cancer Research (EACR) argue that the new ways to diagnose and treat cancer present important and hitherto unaddressed challenges for fundamental research of cancer. Allocating the resources needed for basic studies will likely fuel the next wave of achievements in the long way to conquer cancer.






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[Cancer and Society] Cancer apps

A report from the consultancy firm Research2Guidance estimated that the market in mobile health applications (apps) for smartphones and tablets will be worth US$26 billion by 2017. An estimated 40 000 medical apps are already on the market; although the exact figure depends on where you draw the line between health and lifestyle. In any event, numbers are growing fast—if you're reading this article in 2014, perhaps on The Lancet iPad app, this figure is likely to be woefully out-of-date. Small wonder regulators have found it difficult to keep up.





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Wednesday, May 29, 2013

Relationship between 6- and 9-month progression-free survival and overall survival in patients with

BACKGROUND

Use of progression-free survival (PFS) as a clinical trial endpoint in first-line treatment of patients with metastatic urothelial carcinoma (UC) is attractive, but would be enhanced by establishing a correlation between PFS and overall survival (OS).

METHODS

Data was pooled from 7 phase 2 and 3 trials evaluating cisplatin-based chemotherapy in metastatic UC. An independent cohort of patients enrolled on a phase 3 trial was used for external validation. Landmark analyses for progression at 6 and 9 months after treatment initiation were performed to minimize lead-time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS.

RESULTS

A total of 364 patients were included in the initial cohort. The median PFS was 8.21 months (95% confidence interval = 7.43, 8.39) and the median OS was 13.50 months (95% confidence interval = 11.80, 15.67). In the landmark analysis, the median OS for patients who progressed at 6 months was 3.87 months compared with 15.06 months for those patients who did not progress (P < .0001) and the median OS for patients who progressed at 9 months was 5.65 months compared with 21.39 months for those patients who did not progress (P < .0001). A Fleischer model demonstrated a statistically significant dependent correlation between PFS and OS. The findings were externally validated in an independent cohort.

CONCLUSIONS

PFS at 6 and 9 months predicted OS in this analysis of patients with metastatic UC treated with first-line cisplatin-based chemotherapy and could potentially serve as endpoints in (randomized) phase 2 trials to screen the activity of novel regimens. Cancer 2013. © 2013 American Cancer Society.






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Tuesday, May 28, 2013

APP FREE Epilepsy App (iOS iPhone) English and Português #medicine #medicina

Epilepsy App (iOS iPhone) – CLICK HERE

https://itunes.apple.com/app/id589429873

Captura de Tela 2013-01-22 às 12.06.06

Description

The best treatment for epilepsy is the precise monitoring of the epileptic crises. Since the objective of the treatment is the control of the seizures. And it`s what the Epilepsy App offers to you. With that app it`s possible to register day and time of the seizures, the symptoms that follows, remedies that you are taking and even alarm to remember the time to do it.
The information is saved on the cloud so you take chances losing your data. Making it possible to check your notes at any Apple® device connected to internet.
All of this turn the information at a condensed report to help your doctor identify with precision the root of the problem and prescribe the ideal treatment.
Functionality
✓ Seizures video record
✓ Registry of the medicine used
✓ Alarm to remember the medicine time
✓ Registry of seizures
✓ Synchronized data on cloud (except video)
✓ Seizure list
✓ Share the information with your doctor
The application is signed by:
★ Dr. Júlio Leonardo Barbosa Pereira – Neurosurgery Blog
★ Dr. Mauro Cruz Machado Borgo – Neurosurgery Blog
★ Dr. Lucas Alverne F. Albuquerque – Neurosurgery Blog
★ Dr. Gervásio Teles Cardoso de Carvalho – Neurosurgery Assistant da Santa Casa de Belo Horizonte e Faculdade de Ciências Médicas de MG
★ Dr. Marcello Penholate Faria – Neurosurgery Assistant da Santa Casa de Belo Horizonte
★ Dr. Bruno Silva Costa – Centro de referência de cirurgia da Epilepsia e Neurosurgery Assistant da Santa Casa de Belo Horizonte

What’s New in Version 1.01

Adding support for english language

iPhone Screenshots

iPhone Screenshot 1
iPhone Screenshot 2
iPhone Screenshot 3
iPhone Screenshot 4
iPhone Screenshot 5
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Monday, May 27, 2013

Informal caregiving for cancer patients

According to the recent worldwide estimation by the GLOBOCAN project, in total, 12.7 million new cancer cases and 7.6 million cancer deaths occurred in 2008. The worldwide number of cancer survivors within 5 years of diagnosis has been estimated at be almost 28.8 million. Informal caregivers, such as family members and close friends, provide essential support to cancer patients. The authors of this report provide an overview of issues in the study of informal caregivers for cancer patients and long-term survivors in the United States and Europe, characterizing the caregivers commonly studied; the resources currently available to them; and their unmet needs, their psychosocial outcomes, and the psychosocial interventions tailored to their special circumstances. A broad overview of the state of research and knowledge, both in Europe and the United States, and observations on the directions for future research are provided. Cancer 2013;119(11 suppl):2160-9. © 2013 American Cancer Society.






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Predicting Survival in Patients With Brain Metastases Treated With Radiosurgery Using Artificial Neu

imageBACKGROUND: Artificial neural networks (ANNs) excel at analyzing challenging data sets and can be exceptional tools for decision support in clinical environments. The present study pilots the use of ANNs for determining prognosis in neuro-oncology patients. OBJECTIVE: To determine whether ANNs perform better at predicting 1-year survival in a group of patients with brain metastasis compared with traditional predictive tools. METHODS: ANNs were trained on a multi-institutional data set of radiosurgery patients to predict 1-year survival on the basis of several input factors. A single ANN, an ensemble of 5 ANNs, and logistic regression analyses were compared for efficacy. Sensitivity analysis was used to identify important variables in the ANN model. RESULTS: A total of 196 patients were divided up into training, testing, and validation data sets consisting of 98, 49, and 49 patients, respectively. Patients surviving at 1 year tended to be female (P = .001) and of good performance status (P = .01) and to have favorable primary tumor histology (P = .001). The pooled voting of 5 ANNs performed significantly better than the multivariate logistic regression model (P = .02), with areas under the curve of 84% and 75%, respectively. The ensemble also significantly outperformed 2 commonly used prognostic indexes. Primary tumor subtype and performance status were identified on sensitivity analysis to be the most important variables for the ANN. CONCLUSION: ANNs outperform traditional statistical tools and scoring indexes for predicting individual patient prognosis. Their facile implementation, robustness in the presence of missing data, and ability to continuously learn make them excellent choices for use in complicated clinical environments. ABBREVIATIONS: ANN, artificial neural network AUC, area under the curve GPA, Graded Prognostic Assessment GGS, Golden Grading Scale MLP, multilayer perceptron NPV, negative predictive value PPV, positive predictive value ROC, receiver-operating characteristic WBRT, whole-brain radiation therapy





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Prognostic Value of Residual Fluorescent Tissue in Glioblastoma Patients After Gross Total Resection

imageBACKGROUND: There is evidence in the literature supporting that fluorescent tissue signal in fluorescence-guided surgery extends farther than tissue highlighted in gadolinium in T1 sequence magnetic resonance imaging (MRI), which is the standard to quantify the extent of resection. OBJECTIVE: To study whether the presence of residual fluorescent tissue after surgery carries a different prognosis for glioblastoma (GBM) cases with complete resection confirmed by MRI. METHODS: A retrospective review in our center found 118 consecutive patients with high-grade gliomas operated on with the use of fluorescence-guided surgery with 5-aminolevulinic acid. Within that series, the 52 patients with newly diagnosed GBM and complete resection of enhancing tumor (CRET) in early MRI were selected for analysis. We studied the influence of residual fluorescence in the surgical field on overall survival and neurological complication rate. Multivariate analysis included potential relevant factors: age, Karnofsky Performance Scale, O6-methylguanine methyltransferase methylation promoter status, tumor eloquent location, preoperative tumor volume, and adjuvant therapy. RESULTS: The median overall survival was 27.0 months (confidence interval = 22.4-31.6) in patients with nonresidual fluorescence (n = 25) and 17.5 months (confidence interval = 12.5-22.5) for the group with residual fluorescence (n = 27) (P = .015). The influence of residual fluorescence was maintained in the multivariate analysis with all covariables, hazard ratio = 2.5 (P = .041). The neurological complication rate was 18.5% in patients with nonresidual fluorescence and 8% for the group with residual fluorescence (P = .267). CONCLUSION: GBM patients with CRET in early MRI and no fluorescent residual tissue had longer overall survival than patients with CRET and residual fluorescent tissue. ABBREVIATIONS: 5-ALA, 5-aminolevulinic acid CRET, complete resection of enhancing tumor DC, dendritic cell EOR, extent of resection FGS, fluorescence-guided surgery GBM, glioblastoma GTR, gross total resection KPS, Karnofsky Performance Scale MGMT, O6-methylguanine methyltransferase OS, overall survival T1Gd, gadolinium in T1 sequence





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Hemangioblastomas and Neurogenic Polyglobulia

imageBACKGROUND: Neurogenic polyglobulia occurs with central nervous system hemangioblastomas. Among the suggested mechanisms are extramedullary hematopoiesis in the tumor tissue and germline mutations of the von Hippel-Lindau (VHL) tumor suppressor gene. OBJECTIVE: To determine the frequency and driving mechanisms of polyglobulia in central nervous system hemangioblastomas. METHODS: We performed a retrospective analysis of pre- and postoperative (at 3 and 12 months) hemoglobin levels in a consecutive series of patients with hemangioblastomas operated on in our institution from 1996 to 2009. We performed molecular genetic analyses for mutations of the VHL tumor suppressor gene. RESULTS: Preoperative hemoglobin levels were available from 164 patients. The average hemoglobin level (15.2 g/dL in males and 13.1 g/dL in females) was within normal range according to our standards. Of 22 patients with increased preoperative hemoglobin levels (>17 g/dL in males and >15 g/dL in females), 8 presented with pathological hemoglobin (>18.5 g/dL in males and >16.5 g/dL in females) according to World Health Organization criteria. Surgical removal of the hemangioblastoma resulted in a permanent cure of polyglobulia in all patients. Six of the 8 patients with pathological hemoglobin elevation carried a germline mutation of the VHL tumor suppressor gene. CONCLUSION: Neurogenic polyglobulia occurs in a subset of patients with hemangioblastomas. This phenomenon is mostly observed in VHL mutation carriers, but also occurs in patients with sporadic hemangioblastomas. Removal of the tumor results in the permanent cure of polyglobulia. Our observations suggest that polyglobulia is an effect by the tumor itself, either due to paraneoplasia or extramedullary hematopoiesis. ABBREVIATIONS: CNS, central nervous system COPD, chronic obstructive pulmonary disease Hb, hemoglobin VHL, von Hippel-Lindau WHO, World Health Organization





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Diagnostic Value and Safety of Stereotactic Biopsy for Brainstem Tumors: A Systematic Review and Me

imageBACKGROUND: The feasibility and safety of stereotactic biopsy for brainstem tumors (BSTs) are controversial. Although magnetic resonance imaging (MRI) has been reported as the preferred diagnostic tool, histopathological analysis is frequently necessary to establish a definitive diagnosis. Recent advances in molecular characterization of brainstem gliomas—accounting for the majority of BSTs—have revealed several potential targets for molecular-based therapies. Hence, a molecular stereotactic biopsy that combines histopathological diagnosis with molecular-genetic analysis will become increasingly important for patients with BSTs. OBJECTIVE: We conducted a systemic review and meta-analysis to determine the risks and benefits of stereotactic biopsy for BSTs. METHODS: A systematic search in PubMed, Embase, and the Web of Science yielded 3766 potentially eligible abstracts. Meta-analysis was conducted on 38 studies describing 1480 biopsy procedures for BSTs. Primary outcome measures were diagnostic success and procedure-related complications. Data were analyzed according to standard meta-analytic techniques. RESULTS: The weighted average proportions across the analyzed studies were: 96.2% (95% confidence interval [CI]: 94.5%-97.6%) for diagnostic success, 7.8% (95% CI: 5.6%-10.2%) for overall morbidity, 1.7% (95% CI: 0.9%-2.7%) for permanent morbidity, and 0.9% (95% CI: 0.5%-1.4%) for mortality. Meta-regression revealed a significant correlation between diagnostic success rates and the number of biopsy procedures performed annually in each center (P = .011). Other factors did not affect the outcome measures. CONCLUSION: Stereotactic biopsy of BSTs is safe. It allows exact histopathological diagnosis as a prerequisite for adequate treatment and opens new perspectives for the molecular characterization of these tumors as a crucial first step toward more individualized treatment concepts. ABBREVIATIONS: BST, brainstem tumor CI, confidence interval D-BSG, diffuse brainstem glioma HGG, high-grade glioma LGG, low-grade gliomas TC, transcerebellar TF, transfrontal





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Sunday, May 26, 2013

Oncology Scan—Improvements in Dose Calculation, Deformable Registration, and MR-Guided Radiation Del

The Physics Editorial Team for the International Journal of Radiation Oncology Biology Physics (IJROBP) includes 7 associate editors and 1 senior editor. It comprises physicists having diverse expertise from North America and Europe, and from small and large academic centers . The Physics Team by far receives the most manuscripts among the 9 broad editorial categories within IJROBP, which includes 7 clinical sites, biology, and physics. This, unfortunately, leads to a high rate of manuscripts that must be declined or rejected.





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Internet exec talks cancer gene

Jackie MacDougall, executive editor of TheRickilakeshow.com talks about her own decision to have a double mastectomy.





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CT Scans May Increase Cancer Risk in Children, Adolescents

An Australian study has found higher cancer incidence but relatively low absolute risk in children and adolescents who undergo CT scans.
Medscape Medical News





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Wednesday, May 22, 2013

Pathologic and gene expression features of metastatic melanomas to the brain

BACKGROUND

The prognosis of metastatic melanomas to the brain (MBM) is variable with prolonged survival in a subset. It is unclear whether MBM differ from extracranial metastases (EcM) and primary melanomas (PrM).

METHODS

To study the biology of MBM, histopathologic analysis of tumor blocks from patients' craniotomy samples and whole-genome expression profiling (WGEP) with confirmatory immunohistochemistry were performed.

RESULTS

High mononuclear infiltrate and low intratumoral hemorrhage were associated with prolonged overall survival (OS). Pathway analysis of WGEP data from 29 such craniotomy tumor blocks demonstrated that several immune-related BioCarta gene sets were associated with prolonged OS. WGEP analysis of MBM in comparison with same-patient EcM and PrM showed that MBM and EcM were similar, but both differ significantly from PrM. Immunohistochemical analysis revealed that peritumoral CD3+ and CD8+ cells were associated with prolonged OS.

CONCLUSIONS

MBMs are more similar to EcM compared with PrM. Immune infiltrate is a favorable prognostic factor for MBM. Cancer 2013. © 2013 American Cancer Society.






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1p/19q codeletion and IDH1/2 mutation identified a subtype of anaplastic oligoastrocytomas with prog

Background

Anaplastic astrocytoma (AA), anaplastic oligoastrocytoma (AOA), and anaplastic oligodendroglioma (AO) are the major histological subtypes of World Health Organization grade III gliomas. More evidence suggests that AOA is unlikely to be a distinct entity, and re-evaluation of this issue has been recommended. In this study, we divided AOA into 2 subgroups, according to molecular biomarkers, and compared the survivals between them.

Methods

One hundred nine patients with histological diagnosis of anaplastic gliomas enrolled in the study. Molecular biomarkers evaluated included 1p/19q codeletion and IDH1/2 mutation. Kaplan-Meier plots were compared by log-rank method.

Results

There was no significant difference between AA and AOA with regard to the frequencies of biomarkers and survival plots. According to the status of biomarkers, AOA was classified into 2 subgroups (AOA1 and AOA2), for which Kaplan-Meier plots were significantly different (P = .001 for both progression-free survival [PFS] and overall survival [OS]). AOA1 with 1p/19q codeletion and/or IDH1/2 mutation showed similar Kaplan-Meier plots with AO (P = .169 for PFS and P = .523 for OS). AOA2 without either biomarker showed similar Kaplan-Meier plots with AA (P = .369 for PFS and P = .271 for OS). In addition, patients with AO and AOA1 had significantly longer PFS and OS than did patients with AA and AOA2 (P < .001 for both PFS and OS).

Conclusions

AOA is a heterogeneous group and can be divided into 2 subgroups with significantly different prognoses according to the status of 1p/19q and IDH1/2. This will be helpful in estimating patients' prognosis and guiding reasonable therapy for patients with anaplastic gliomas.






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Outcome and prognostic factors in adult cerebellar glioblastoma

Publication date: Available online 22 May 2013
Source:Journal of Clinical Neuroscience
Author(s): Ranjith Babu , Richa Sharma , Isaac O. Karikari , Timothy R. Owens , Allan H. Friedman , Cory Adamson
Cerebellar glioblastoma multiforme (GBM) occurs rarely in adults, accounting for 0.4–3.4% of all GBM. Current studies have all involved small patient numbers, limiting the clear identification of prognostic factors. Additionally, while few studies have compared cerebellar GBM to their supratentorial counterparts, there is conflicting data regarding their relative prognosis. To better characterize outcome and identify patient and treatment factors which affect survival, the authors analyzed cases of adult cerebellar GBM from the Surveillance, Epidemiology, and End Results database. A total of 247 adult patients with cerebellar GBM were identified, accounting for 0.67% of all adult GBM. Patients with cerebellar GBM were significantly younger than those with supratentorial tumors (56.6 versus 61.8years, p &lt;0.0001), but a larger percentage of patients with supratentorial GBM were Caucasian (91.7% versus 85.0%, p &lt;0.0001). Overall median survival did not differ between those with cerebellar and supratentorial GBM (7 versus 8months, p =0.24), with similar rates of long-term (greater than 2years) survival (13.4% versus 10.6%, p =0.21). Multivariate analysis revealed age greater than 40years (hazard ratio [HR]: 2.20; 95% confidence interval [CI]: 1.47–3.28; p =0.0001) to be associated with worse patient survival, while the use of radiotherapy (HR: 0.33; 95% CI: 0.24–0.47; p &lt;0.0001) and surgical resection (HR: 0.66; 95% CI: 0.45–0.96; p =0.028) were seen to be independent favorable prognostic factors. In conclusion, patients with cerebellar GBM have an overall poor prognosis, with radiotherapy and surgical resection significantly improving survival. As with supratentorial GBM, older age is a poor prognostic factor. The lack of differences between supratentorial and cerebellar GBM with respect to overall survival and prognostic factors suggests these tumors to be biologically similar.






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Trends in treatment and outcomes of pediatric craniopharyngioma, 1975-2011

Background

Craniopharyngioma tumors and their treatment can lead to significant long-term morbidity due to their proximity to vital structures. The optimal treatment has been debated for many years. We aimed to review the long-term outcomes of children treated for craniopharyngioma in our institution over the past decade and describe trends in treatment and outcomes over the past 3 decades.

Methods

Charts of children with craniopharyngioma treated and followed at The Hospital for Sick Children between 2001 and 2011 were reviewed. Data regarding findings at diagnosis, treatment, and long-term outcomes were analyzed. Comparison was made with previously published data from our institution.

Results

Data from 33 patients are included; mean age at treatment, 10.7 ± 4.8 years. In 18 children (55%), the initial surgical approach was tumor cyst decompression with or without adjuvant therapy, compared with only 0–2% in the preceding decades (P < .01). Diabetes insipidus occurred in 55% of children and panhypopituitarism in 58% compared with 88% (P < .01) and 86% (P < .01), respectively, in the previous 10 years. Overall, there was a 36% reduction in the number of children who developed severe obesity compared with the preceding decade. Body mass index at follow-up was associated with body mass index at diagnosis (P = .004) and tumor resection as an initial treatment approach (P = .028).

Conclusions

A shift in surgical treatment approach away from gross total resection has led to improved endocrine outcomes. This may have beneficial implications for quality of life in survivors.






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Comparative study of IDH1 mutations in gliomas by immunohistochemistry and DNA sequencing

Background

Mutations involving isocitrate dehydrogenase 1 (IDH 1) occur in a high proportion of diffuse gliomas, with implications on diagnosis and prognosis. About 90% involve exon 4 at codon 132, replacing amino acid arginine with histidine (R132H). Rarer ones include R132C, R132S, R132G, R132L, R132V, and R132P. Most authors have used DNA-based methods to assess IDH1 status. Preliminary studies comparing imunohistochemistry (IHC) with IDH1-R132H mutation-specific antibodies have shown concordance with DNA sequencing and no cross-reactivity with wild-type IDH1 or other mutant proteins. The present study compares results of IHC with DNA sequencing in diffuse gliomas.

Materials and methods

Fifty diffuse gliomas with frozen tissue samples for DNA sequencing and adequate tissue in paraffin blocks for IHC using IDH1-R132H specific antibody were assessed for IDH1 mutations.

Results

Concordance of findings between IHC and DNA sequencing was noted in 88% (44/50) cases. All 6 cases with discrepancy were immunopositive with DIA-H09 antibody. While in 3 of these 6 cases, DNA sequencing failed to reveal any mutations, R132L (arginine replaced by leucine) mutation was found in the rest 3 cases. Interestingly, of the immunopositive cases, 46.6% (14/30) showed immunostaining in only a fraction of tumor cells.

Conclusions

IHC is an easy and quick method of detecting IDH1-R132H mutations, but there may be some discrepancies between IHC and DNA sequencing. Although there were no false-negative cases, cross-reactivity with IDH1-R132L was seen in 3, a finding not reported thus far. Because of more universal availability of IHC over genetic testing, cross-reactivity and staining heterogeneity may have bearing over its use in detecting IDH1-R132H mutation in gliomas.






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Efficacy of protracted temozolomide dosing is limited in MGMT unmethylated GBM xenograft models

Background

Temozolomide (TMZ) is important chemotherapy for glioblastoma multiforme (GBM), but the optimal dosing schedule is unclear.

Methods

The efficacies of different clinically relevant dosing regimens were compared in a panel of 7 primary GBM xenografts in an intracranial therapy evaluation model.

Results

Protracted TMZ therapy (TMZ daily M–F, 3 wk every 4) provided superior survival to a placebo-treated group in 1 of 4 O6-DNA methylguanine-methyltransferase (MGMT) promoter hypermethylated lines (GBM12) and none of the 3 MGMT unmethylated lines, while standard therapy (TMZ daily M–F, 1 wk every 4) provided superior survival to the placebo-treated group in 2 of 3 MGMT unmethylated lines (GBM14 and GBM43) and none of the methylated lines. In comparing GBM12, GBM14, and GBM43 intracranial specimens, both GBM14 and GBM43 mice treated with protracted TMZ had a significant elevation in MGMT levels compared with placebo. Similarly, high MGMT was found in a second model of acquired TMZ resistance in GBM14 flank xenografts, and resistance was reversed in vitro by treatment with the MGMT inhibitor O6-benzylguanine, demonstrating a mechanistic link between MGMT overexpression and TMZ resistance in this line. Additionally, in an analysis of gene expression data, comparison of parental and TMZ-resistant GBM14 demonstrated enrichment of functional ontologies for cell cycle control within the S, G2, and M phases of the cell cycle and DNA damage checkpoints.

Conclusions

Across the 7 tumor models studied, there was no consistent difference between protracted and standard TMZ regimens. The efficacy of protracted TMZ regimens may be limited in a subset of MGMT unmethylated tumors by induction of MGMT expression.






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Saturday, May 18, 2013

Clinical features of brain metastasis from salivary gland tumors

Publication date: Available online 16 May 2013
Source:Journal of Clinical Neuroscience
Author(s): Andrew S. Venteicher , Brian P. Walcott , Sameer A. Sheth , Matija Snuderl , Anoop P. Patel , William T. Curry , Brian V. Nahed
Salivary gland tumors comprise a group of 24 tumor subtypes with a wide range of clinical behaviors and propensities for metastasis. Several prognostic factors have been identified that help predict the development of systemic metastases, most commonly to the lung, liver, or bone. Metastases to the brain are rare. To better understand the behavior of salivary gland tumors that metastasise to the brain, we performed a retrospective cohort analysis on a series of patients to highlight features of their medical and surgical management. From 2007 to 2011, a database of 4117 elective craniotomies were queried at a single institution to identify patients surgically treated for salivary gland metastases to the brain. Three patients were identified. Histologic subtypes included salivary duct carcinoma, poorly differentiated carcinoma, and papillary mucinous adenocarcinoma. They had all undergone previous treatment for their primary malignancy. The mean time to intracranial metastasis was 48months from initial diagnosis (range, 14–91months). Treatment for intracranial metastases included surgical resection, whole brain radiation, stereotactic radiosurgery, and chemotherapy. Intracranial metastases from salivary gland tumors are rare, present years after diagnosis of the primary tumor, and are treatable with multimodality therapy.






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Skin Cancer May Be Linked to Lower Risk of Alzheimer's Disease

MINNEAPOLIS – People who have skin cancer may be less likely to develop Alzheimer's disease, according to new research published in the May 15, 2013, online issue of Neurology®, the medical journal of the American Academy of Neurology. The link does not apply to melanoma, a less common but more aggressive type of skin cancer.





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Hospital Variation and Temporal Trends in Palliative and End-of-Life Care in the ICU*

imageObjectives: Although studies have shown regional and interhospital variability in the intensity of end-of-life care, few data are available assessing variability in specific aspects of palliative care in the ICU across hospitals or interhospital variability in family and nurse ratings of this care. Recently, relatively high family satisfaction with ICU end-of-life care has prompted speculation that ICU palliative care has improved over time, but temporal trends have not been documented. Design/Setting: Retrospective cohort study of consecutive patients dying in the ICU in 13 Seattle-Tacoma-area hospitals between 2003 and 2008. Measurements: We examined variability over time and among hospitals in satisfaction and quality of dying assessed by family, quality of dying assessed by nurses, and chart-based indicators of palliative care. We used regression analyses adjusting for patient, family, and nurse characteristics. Main Results: Medical charts were abstracted for 3,065 of 3,246 eligible patients over a 55-month period. There were significant differences between hospitals for all chart-based indicators (p < 0.001), family satisfaction (p < 0.001), family-rated quality of dying (p = 0.03), and nurse-rated quality of dying (p = 0.003). There were few significant changes in these measures over time, although we found a significant increase in pain assessments in the last 24 hours of life (p < 0.001) as well as decreased documentation of family conferences (p < 0.001) and discussion of prognosis (p = 0.020) in the first 72 hours in the ICU. Conclusions: We found significant interhospital variation in ratings and delivery of palliative care, consistent with prior studies showing variation in intensity of care at the end of life. We did not find evidence of temporal changes in most aspects of palliative care, family satisfaction, or nurse/family ratings of the quality of dying. With the possible exception of pain assessment, there is little evidence that the quality of palliative care has improved over the time period studied.





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Thursday, May 16, 2013

Aplicativo Craniotomia (Aplicativo de Neurocirurgia )

CRANIOTOMIA APP 
 
Está disponível na App Store e no Google Play o mais novo app desenvolvido por nós, o Craniotomia App. É uma ferramenta que descreve abordagens cirúrgicas em neurocirurgia de um modo prático, simples e ilustrativo para uso de profissionais de Saúde e estudantes.

Para fazer o download, seguem os links:

App Store: http://bit.ly/16VXFXx
Google Play: http://bit.ly/17trrpD




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Tuesday, May 14, 2013

Intraparenchymal Schwannoma Involving the Brainstem in a Young Woman

Abstract: Schwannomas are tumors derived from the Schwann cells, which form the myelin sheath of the peripheral nerves. Fewer than 1% of these tumors occur within the brain parenchyma without arising from the cranial nerves. Only 55 cases have been published after the first recorded case. We report a 17-year-old girl with a 3-month history of unspecific dizziness, unsteadiness, and headache. Magnetic resonance imaging showed a heterogeneous cystic lesion involving midbrain, pons, and left cerebellar peduncle. The patient underwent a retromastoid craniotomy with complete resection of the tumor. Pathologic examination was compatible with intraparenchymal schwannoma. Since the first case of intraparenchymal schwannoma involving the brainstem was described in 1980, only seven others have been reported. Diagnosis of intraparenchymal schwannoma is almost never made preoperatively. Immunohistochemical staining is crucial in distinguishing a Schwannoma from a meningioma, glial tumor, or metastatic tumor. Pathologic findings are those typical of acoustic neurinomas. Histogenesis of intraparenchymal schwannoma remains unclear, and several theories have been proposed to explain their origin. The recognition of this curable tumor and its differentiation from brainstem glioma, which generally has a less favorable outcome, is of obvious importance.





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Teaching NeuroImages: T2 hyperintensities in neurofibromatosis type 1

A 4-year-old boy with neurofibromatosis type 1 (NF1), an asymptomatic optic glioma, and a right basal ganglia T2-hyperintense lesion (figure, A and B) developed a left hemiparesis with hyperreflexia over the course of a year. Neuroimaging revealed a cyst-like mass in the region of his previously identified T2 hyperintensity (figure, C and D). While it is often difficult to distinguish T2 hyperintensities from low-grade glioma without tissue diagnosis,1 even with advanced imaging methods,2 T2 hyperintensities typically disappear with age and do not become cystic with associated mass effect. Coupled with the development of new neurologic signs, these MRI features are worrisome for neoplasm in a patient with NF1.






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Localised thoracic sarcomas: Outcome improvement over time at a single institution

Publication date: Available online 14 May 2013
Source:European Journal of Cancer
Author(s): Leonardo Duranti , Alessandro Gronchi , Silvia Stacchiotti , Marco Fiore , Paolo G. Casali , Paola Collini , Giuseppe Pelosi , Carlotta Galeone , Ugo Pastorino
Purpose To assess changes in survival over time in patients affected by thoracic soft tissue sarcomas treated at a single institution. Patients and Methods Patients with localised adult-type deep thoracic soft tissue sarcoma surgically treated at our institution between 1980 and 2012 were retrospectively reviewed. Patients were categorised into two groups according to timing of their first operation, i.e. surgery done before or after 31st December 2001 (so called 'early years' and 'recent years' groups, respectively), since a more extended surgery was used in the second interval. Overall survival (OS) and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastases (DM) were calculated for each time period. Results Three-hundred-thirty-seven patients were identified. Median follow-up was 4.7years. Tumour size and rate of critical site involvement were larger in 'recent years', while the distribution of all other tumour- and patient-related factors was identical in the two periods. Despite this, OS and CCI of LR were significantly better in 'recent years' as compared to 'early' ones, the 5-year OS increasing from 58% to 72% and the CCI of LR dropping from 22% to 11%. CCI of DM was equal in the two periods. Conclusion Reference institutions for sarcomas may have improved their outcome in the last years. Although biases of retrospective analyses need to be discounted, it is possible that optimal exploitation of a series of subtle improvements in sarcoma treatment may make a difference in results achievable today.






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Primary stability of pedicle screws depends on the screw positioning and alignment

Publication date: Available online 14 May 2013
Source:The Spine Journal
Author(s): Francesco Costa , Tomaso Villa , Federica Anasetti , Massimo Tomei , Alessandro Ortolina , Andrea Cardia , Luigi La Barbera , Maurizio Fornari , Fabio Galbusera
Background context There is no universal consensus regarding the biomechanical aspects and relevance on the primary stability of misplaced pedicle screws. Purpose The study is aimed to the determination of the correlation between axial pullout forces of pedicle screws with the possible screw misplacement, including mild and severe cortical violations. Methods Eighty-eight monoaxial pedicle screws were implanted into 44 porcine lumbar vertebral bodies, paying attention on trying to obtain a wide range of placement accuracy. After screw implantation, all specimens underwent a spiral computed tomography scan, and the screw placements were graded following the scales of Laine et al. and Abul Kasim et al. Axial pullout tests were then performed on a servohydraulic material testing system. Results Decreasing pullout forces were determined for screws implanted with increasing cortical violation. A smaller influence of cortical violations in the medial direction with respect to the lateral direction was observed. Screws implanted with a large cortical violation and misplacement in the craniocaudal direction were found to be significantly less stable than screws having comparable cortical violation but in a centered sagittal position. Conclusions These results provide adjunctive criteria to evaluate more accurately the fate of a spine instrumentation. Particular care should be placed in the screw evaluation regarding the craniocaudal positioning and alignment.






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Monday, May 13, 2013

Uncertainty, mood states, and symptom distress in patients with primary brain tumors

BACKGROUND

Patients with primary brain tumors (PBTs) face uncertainty related to prognosis, symptoms, treatment response, and toxicity. The authors of this report examined the direct/indirect relations among patients' uncertainty, mood states, and symptoms.

METHODS

In total, 186 patients with PBTs were accrued at various points in the illness trajectory. Data-collection tools included an investigator-completed clinician checklist, a patient-completed demographic data sheet, the Mishel Uncertainty in Illness Scale-Brain Tumor Form (MUIS-BT), the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT), and the Profile of Mood States-Short Form (POMS-SF). Structural equation modeling was used to explore correlations among variables.

RESULTS

Participants were primarily white (80%) men (53%) with a variety of brain tumors. They ranged in age from 19 to 80 years (mean ± standard deviation, 44.2 ± 12.6 years). Lower functional status and earlier point in the illness trajectory were associated with greater uncertainty (P < .01 for both). Uncertainty (P < .05), except in the model of "confusion," and the 5 negative mood states measured by the POMS-SF were directly associated with symptom severity perceived by patients (P < .01 for all). The impact of uncertainty on perceived symptom severity also was mediated significantly by mood states.

CONCLUSIONS

The results from the study clearly demonstrated distinct pathways for the relations between uncertainty-mood states-symptom severity for patients with PBTs. Uncertainty in patients with PBTs is higher for those who have a poor performance status and directly impacts negative mood states, which mediate patient-perceived symptom severity. This conceptual model suggests that interventions designed to reduce uncertainty or that target mood states may help lessen patients' perception of symptom severity, which, in turn, may result in better treatment outcomes and quality of life. Cancer 2013; © 2013 American Cancer Society.






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