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Journal of Neuro-oncology Nov 2020These recommendations apply to adult patients with newly diagnosed or suspected glioblastoma.
Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of emerging developments in the management of newly diagnosed glioblastoma.
TARGET POPULATION
These recommendations apply to adult patients with newly diagnosed or suspected glioblastoma.
IMAGING
Question What imaging modalities are in development that may be able to provide improvements in diagnosis, and therapeutic guidance for individuals with newly diagnosed glioblastoma?
RECOMMENDATION
Level III: It is suggested that techniques utilizing magnetic resonance imaging for diffusion weighted imaging, and to measure cerebral blood and magnetic spectroscopic resonance imaging of N-acetyl aspartate, choline and the choline to N-acetyl aspartate index to assist in diagnosis and treatment planning in patients with newly diagnosed or suspected glioblastoma.
SURGERY
Question What new surgical techniques can be used to provide improved tumor definition and resectability to yield better tumor control and prognosis for individuals with newly diagnosed glioblastoma?
RECOMMENDATIONS
Level II: The use of 5-aminolevulinic acid is recommended to improve extent of tumor resection in patients with newly diagnosed glioblastoma. Level II: The use of 5-aminolevulinic acid is recommended to improve median survival and 2 year survival in newly diagnosed glioblastoma patients with clinical characteristics suggesting poor prognosis. Level III: It is suggested that, when available, patients be enrolled in properly designed clinical trials assessing the value of diffusion tensor imaging in improving the safety of patients with newly diagnosed glioblastoma undergoing surgery.
NEUROPATHOLOGY
Question What new pathology techniques and measurement of biomarkers in tumor tissue can be used to provide improved diagnostic ability, and determination of therapeutic responsiveness and prognosis for patients with newly diagnosed glioblastomas?
RECOMMENDATIONS
Level II: Assessment of tumor MGMT promoter methylation status is recommended as a significant predictor of a longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level II: Measurement of tumor expression of neuron-glia-2, neurofilament protein, glutamine synthetase and phosphorylated STAT3 is recommended as a predictor of overall survival in patients with newly diagnosed with glioblastoma. Level III: Assessment of tumor IDH1 mutation status is suggested as a predictor of longer progression free survival and overall survival in patients with newly diagnosed with glioblastoma. Level III: Evaluation of tumor expression of Phosphorylated Mitogen-Activated Protein Kinase protein, EGFR protein, and Insulin-like Growth Factor-Binding Protein-3 is suggested as a predictor of overall survival in patients with newly diagnosed with glioblastoma.
RADIATION
Question What radiation therapy techniques are in development that may be used to provide improved tumor control and prognosis for individuals with newly diagnosed glioblastomas?
RECOMMENDATIONS
Level III: It is suggested that patients with newly diagnosed glioblastoma undergo pretreatment radio-labeled amino acid tracer positron emission tomography to assess areas at risk for tumor recurrence to assist in radiation treatment planning. Level III: It is suggested that, when available, patients be with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of radiation dose escalation, altered fractionation, or new radiation delivery techniques.
CHEMOTHERAPY
Question What emerging chemotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas?
RECOMMENDATION
Level III: As no emerging chemotherapeutic agents or techniques were identified in this review that improved tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of chemotherapy.
MOLECULAR AND TARGETED THERAPY
Question What new targeted therapy agents are available to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas?
RECOMMENDATION
Level III: As no new molecular and targeted therapies have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of molecular and targeted therapies IMMUNOTHERAPY: Question What emerging immunotherapeutic agents or techniques are available to provide better tumor control and prognosis for patients with newly diagnosed glioblastomas?
RECOMMENDATION
Level III: As no immunotherapeutic agents have clearly provided better tumor control and prognosis it is suggested that, when available, patients with newly diagnosed glioblastomas be enrolled in properly designed clinical trials of immunologically-based therapies.
NOVEL THERAPIES
Question What novel therapies or techniques are in development to provide better tumor control and prognosis for individuals with newly diagnosed glioblastomas?
RECOMMENDATIONS
Level II: The use of tumor-treating fields is recommended for patients with newly diagnosed glioblastoma who have undergone surgical debulking and completed concurrent chemoradiation without progression of disease at the time of tumor-treating field therapy initiation. Level II: It is suggested that, when available, enrollment in properly designed studies of vector containing herpes simplex thymidine kinase gene and prodrug therapies be considered in patients with newly diagnosed glioblastoma.
Topics: Biomarkers, Tumor; Combined Modality Therapy; Disease Management; Evidence-Based Practice; Glioblastoma; Humans; Multimodal Imaging; Practice Guidelines as Topic
PubMed: 33215345
DOI: 10.1007/s11060-020-03607-4 -
Journal of Psychopharmacology (Oxford,... Apr 2019Multiple N-methyl-d-aspartate (NMDA)-receptor-enhancing agents have demonstrated promising effects for cognition in schizophrenia. However, the results of studies have... (Meta-Analysis)
Meta-Analysis
Effect of N-methyl-D-aspartate-receptor-enhancing agents on cognition in patients with schizophrenia: A systematic review and meta-analysis of double-blind randomised controlled trials.
BACKGROUND
Multiple N-methyl-d-aspartate (NMDA)-receptor-enhancing agents have demonstrated promising effects for cognition in schizophrenia. However, the results of studies have been conflicting. This updated meta-analysis explored the effect of NMDA-receptor-enhancing agents on cognitive function.
METHODS
We searched PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials and Cochrane Systematic Reviews for studies on the effect of NMDA-receptor-enhancing agents on cognitive function in patients with schizophrenia up to September 2018. Double-blind randomised placebo trials with cognition rating scales were included. We pooled studies by using a random-effect model for comparisons with add-on NMDA-receptor-enhancing agents. Cognitive function scores were compared between baseline and subsequent levels, and NMDA-receptor-positive modulators were assessed using the standardised mean difference (SMD) with 95% confidence intervals (CIs). We evaluated statistical heterogeneity through visual inspection of funnel plots and by using the I statistic.
RESULTS
We identified 25 trials with 1951 participants meeting the inclusion criteria. NMDA-receptor-enhancing agents had a small but nonsignificant effect compared with the placebo on overall cognitive function (SMD = 0.068, CI = -0.056 to 0.193, P = 0.283). We identified trials enrolling patients aged between 30 and 39 years old, which reported significant positive effects (SMD: 0.163, 95% CI: 0.016-0.310, P = 0.030). Men were associated with a smaller effect of NMDA-receptor-positive modulators on overall cognitive function. Moreover, subgroup meta-analysis of cognitive domains revealed that N-acetyl cysteine (NAC) had a significant effect on working memory ( P-value for interaction = 0.038; SMD = 0.679, CI = 0.397-0.961, P < 0.001).
CONCLUSIONS
Our meta-analysis revealed no significant effect of NMDA-enhancing agents on overall cognition. However, subgroup analysis suggested that NMDAR-enhancing agents may benefit young patients with schizophrenia, and NAC may have an effect on working memory. Additional trials with larger samples are suggested to evaluate these cognitive domains and ascertain the possible mechanisms.
Topics: Age Factors; Cognition; Excitatory Amino Acid Agonists; Humans; Randomized Controlled Trials as Topic; Receptors, N-Methyl-D-Aspartate; Schizophrenia; Sex Factors
PubMed: 30730250
DOI: 10.1177/0269881118822157 -
Pharmacological Research Aug 2019Excessive adiposity in an obese state is known to drive the onset of metabolic dysregulations, mostly involving chronic immune activation and oxidative stress. Prolonged...
Excessive adiposity in an obese state is known to drive the onset of metabolic dysregulations, mostly involving chronic immune activation and oxidative stress. Prolonged inflammation and oxidative stress have been linked to impaired adipose tissue function and the development of the metabolic syndrome. Currently available therapies offer minimal prophylactic effects, while substantial experimental evidence supports the ameliorative effects of N-acetylcysteine (NAC) against various metabolic complications associated with obesity. The current review provides a comprehensive synthesis of studies published in major search engines such as PubMed, Cochrane library, Embase, and Google Scholar assessing the therapeutic effect of NAC against obesity associated complications. Overwhelming literature included in this review supports the ameliorative effects of NAC against such complications in both in vitro and in vivo models of obesity. In addition to attenuating an abnormal pro-inflammatory response and limiting oxidative damage, NAC could inhibit lipid accumulation by targeting adipogenic transcription factors such as peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein beta (C/EBPβ), and improve insulin sensitivity through augmenting phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. Although necessary evidence informing on its optimal dose and its comparative effect with other well-studied pharmacological compounds is demonstrated, it is clear that future investigations are required to confirm the therapeutic effect of NAC in obese human subjects.
Topics: Acetylcysteine; Animals; Humans; Inflammation; Obesity; Oxidative Stress; Transcription Factors
PubMed: 31254666
DOI: 10.1016/j.phrs.2019.104332