Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice.

BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated. METHODS: C57BL/6 mice were used to establish the ICH model by injection of collagenase into mice striatum. The Mas receptor agonist AVE0991 was administered intranasally (0.9 mg/kg) after ICH. Using a combination of behavioral tests, Western blots, immunofluorescence staining, hematoma volume, brain edema, quantitative-PCR, TUNEL staining, Fluoro-Jade C staining, Nissl staining, and pharmacological methods, we examined the impact of intranasal application of AVE0991 on hematoma absorption and neurological outcomes following ICH and investigated the underlying mechanism. RESULTS: Mas receptor was found to be significantly expressed in activated microglia/macrophages, and the peak expression of Mas receptor in microglia/macrophages was observed at approximately 3-5 days, followed by a subsequent decline. Activation of Mas by AVE0991 post-treatment promoted hematoma absorption, reduced brain edema, and improved both short- and long-term neurological functions in ICH mice. Moreover, AVE0991 treatment effectively attenuated neuronal apoptosis, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines in perihematomal areas after ICH. Mechanistically, AVE0991 post-treatment significantly promoted the transformation of microglia/macrophages towards an anti-inflammatory, phagocytic, and reparative phenotype, and this functional phenotypic transition of microglia/macrophages by Mas activation was abolished by both Mas inhibitor A779 and Nrf2 inhibitor ML385. Furthermore, hematoma clearance and neuroprotective effects of AVE0991 treatment were reversed after microglia depletion in ICH. CONCLUSIONS: Mas activation can promote hematoma absorption, ameliorate neurological deficits, alleviate neuron apoptosis, reduced neuroinflammation, and regulate the function and phenotype of microglia/macrophages via Akt/Nrf2 signaling pathway after ICH. Thus, intranasal application of Mas agonist ACE0991 may provide promising strategy for clinical treatment of ICH patients.

Engineered Extracellular Vesicle-Delivered CRISPR/CasRx as a Novel RNA Editing Tool.

Engineered extracellular vesicles (EVs) are considered excellent delivery vehicles for a variety of therapeutic agents, including nucleic acids, proteins, drugs, and nanomaterials. Recently, several studies have indicated that clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) delivered by EVs enable efficient DNA editing. However, an RNA editing tool delivered by EVs is still unavailable. Here, a signal peptide-optimized and EVs-delivered guide RNA (gRNA) and CRISPR/CasRx (Cas13d) system capable of rapidly inhibiting the expression of targeted genes with quick catabolism after performing their functions is developed. EVs with CRISPR/CasRx and tandem gRNAs targeting pivotal cytokines are further packed whose levels increase substantially over the course of acute inflammatory diseases and find that these engineered EVs inhibit macrophage activation in vitro. More importantly, this system attenuates lipopolysaccharide (LPS)-triggered acute lung injury and sepsis in the acute phase, mitigating organ damage and improving the prognosis in vivo. In summary, a potent tool is provided for short-acting RNA editing, which could be a powerful therapeutic platform for the treatment of acute diseases.

Visible light-driven H2O2 synthesis over Au/C3N4: medium-sized Au nanoparticles exhibiting suitable built-in electric fields and inhibiting reverse H2O2 decomposition.

Visible light-driven H2O2 production presents the unique merits of sustainability and environmental friendliness. The size of noble metal nanoparticles (NPs) determines their dispersion and electronic structure and greatly affects their photocatalytic activity. In this work, a series of sized Au NPs over C3N4 were modulated for H2O2 production. The results show that there is a volcanic trend in H2O2 with the decrease of Au particle size, and the highest H2O2 production rate of 1052 µmol g-1 h-1 is obtained from medium-sized Au particles (∼8.7 nm). The relationship between structure and catalytic performance is supported by experimental and theoretical methods. (1) First, medium-sized Au NPs promote photon absorption, and have a suitable built-in electric field at the heterojunction, which can be successfully tuned to achieve a more efficient h+-e- spatial separation. (2) Second, medium-sized Au NPs enhance O2 adsorption, and create selective 2e- O2 reduction reaction sites. (3) Particularly, medium-sized Au NPs promote the desorption of produced H2O2 and inhibit H2O2 decomposition, finally leading to the highest H2O2 selectivity. Excellent catalytic performance will be obtained by finely optimizing the particle size in a certain range. This work provides a new idea for preparing high efficiently photocatalysts for H2O2 production.

Socioeconomic deprivation and survival outcomes in primary central nervous system lymphomas.

Objective: To our knowledge, the impact of area-level socioeconomic status (SES) has not yet been described in primary central nervous system lymphomas (PCNSLs). Current study sought to explore the association of socioeconomic deprivation, measured using the Area Deprivation Index (ADI), with PCNSL outcomes. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify PCNSL patients diagnosed between 2006 and 2015 for our analyses. The impact of ADI on overall survival (OS) and cancer-specific survival (CSS) were investigated. Survival analyses were conducted using Kaplan-Meier method with log-rank tests. The Inverse Probability Weighting (IPW) analysis and multivariate cox proportional hazards regression analysis were employed to make covariate adjustments. Multiple mediation analysis (MMA) was performed to estimate the mediating effects. Results: A total of 3159 PCNSL patients classified into low and high ADI subgroups according to the median ADI score were studied. The Kaplan-Meier analyses showed that low ADI was significantly associated with higher OS rates (HR 1.15, 95%CI 1.06-1.26, P<0.01) and CSS rates (HR 1.15, 95%CI 1.05-1.27, P<0.01). Similar results were observed in analyses adjusted via IPW and multivariate cox methods. Subgroup analyses revealed that ADI could remain a prognostic indictor among different subsets. MMA revealed that several factors including chemotherapy and HIV status making up about 40% of the overall effect, mediated PCNSL survival disparities related to the ADI. Finally, multivariable logistic regression analysis showed that ADI as well as several other factors were independently related to receipt of chemotherapy. Conclusions: Our study highlights the role of area-level SES in prognosis of PCNSLs. And several factors including chemotherapy and HIV status of PCNSL patents contributed to the CSS disparities between ADI subgroups were uncovered by MMA. Such relationships would highlight the importance of policies development to enhance healthcare delivery and promote awareness of HIV prevention and treatment in low-resource neighborhoods.

A B7-CD28 Family-Based Signature Demonstrates Significantly Different Prognosis and Immunological Characteristics in Diffuse Gliomas.

The B7-CD28 gene family plays a crucial role in modulating immune functions and has served as potential targets for immunotherapeutic strategies. Therefore, we systematically analyzed B7-CD28 family gene expression profiles and constructed a B7-CD28 family-based prognostic signature to predict survival and immune host status in diffuse gliomas. The TCGA dataset was used as a training cohort, and three CGGA datasets (mRNAseq_325, mRNAseq_693 and mRNA-array) were employed as validation cohorts to intensify the findings that we have revealed in TCGA dataset. Ultimately, we developed a B7-CD28 family-based signature that consisted of CD276, CD274, PDCD1LG2 and CD80 using LASSO Cox analysis. This gene signature was validated to have significant prognostic value, and could be used as a biomarker to distinguish pathological grade and IDH mutation status in diffuse glioma. Additionally, we found that the gene signature was significantly related to intensity of immune response and immune cell population, as well as several other important immune checkpoint genes, holding a great potential to be a predictive immune marker for immunotherapy and tumor microenvironment. Finally, a B7-CD28 family-based nomogram was established to predict patient life expectancy contributing to facilitate personalizing therapy for tumor sufferers. In summary, this is the first mathematical model based on this gene family with the aim of providing novel insights into immunotherapy for diffuse glioma.

PS-NPs Induced Neurotoxic Effects in SHSY-5Y Cells via Autophagy Activation and Mitochondrial Dysfunction.

Polystyrene nanoparticles (PS-NPs) are organic pollutants that are widely detected in the environment and organisms, posing potential threats to both ecosystems and human health. PS-NPs have been proven to penetrate the blood-brain barrier and increase the incidence of neurodegenerative diseases. However, information relating to the pathogenic molecular mechanism is still unclear. This study investigated the neurotoxicity and regulatory mechanisms of PS-NPs in human neuroblastoma SHSY-5Y cells. The results show that PS-NPs caused obvious mitochondrial damages, as evidenced by inhibited cell proliferation, increased lactate dehydrogenase release, stimulated oxidative stress responses, elevated Ca2+ level and apoptosis, and reduced mitochondrial membrane potential and adenosine triphosphate levels. The increased release of cytochrome c and the overexpression of apoptosis-related proteins apoptotic protease activating factor-1 (Apaf-1), cysteinyl aspartate specific proteinase-3 (caspase-3), and caspase-9 indicate the activation of the mitochondrial apoptosis pathway. In addition, the upregulation of autophagy markers light chain 3-II (LC3-II), Beclin-1, and autophagy-related protein (Atg) 5/12/16L suggests that PS-NPs could promote autophagy in SHSY-5Y cells. The RNA interference of Beclin-1 confirms the regulatory role of autophagy in PS-NP-induced neurotoxicity. The administration of antioxidant N-acetylcysteine (NAC) significantly attenuated the cytotoxicity and autophagy activation induced by PS-NP exposure. Generally, PS-NPs could induce neurotoxicity in SHSY-5Y cells via autophagy activation and mitochondria dysfunction, which was modulated by mitochondrial oxidative stress. Mitochondrial damages caused by oxidative stress could potentially be involved in the pathological mechanisms for PS-NP-induced neurodegenerative diseases.

Noncoding RNAs in pediatric brain tumors: Molecular functions and pathological implications.

Brain tumors are common solid pediatric malignancies and the main reason for cancer-related death in the pediatric setting. Recently, evidence has revealed that noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), play a critical role in brain tumor development and progression. Therefore, in this review article, we describe the functions and molecular mechanisms of ncRNAs in multiple types of cancer, including medulloblastoma, pilocytic astrocytoma, ependymoma, atypical teratoid/rhabdoid tumor, glioblastoma, diffuse intrinsic pontine glioma, and craniopharyngioma. We also mention the limitations of using ncRNAs as therapeutic targets because of the nonspecificity of ncRNA targets and the delivery methods of ncRNAs. Due to the critical role of ncRNAs in brain oncogenesis, targeting aberrantly expressed ncRNAs might be an effective strategy to improve the outcomes of pediatric patients with brain tumors.

Allicin Inhibits Proliferation by Decreasing IL-6 and IFN-ß in HCMV-Infected Glioma Cells.

PURPOSE: Allicin, an extract of garlic, has antitumor effects in multiple tumor types. However, the efficacy of allicin for treating glioblastoma has not yet been examined. This study examined the antitumor effect of allicin on human cytomegalovirus (HCMV)-infected glioblastoma multiforme (GBM) and its role in cytokine signaling. MATERIALS AND METHODS: HCMV-infected glioblastoma was modeled by transfection of U87MG glioblastoma cells with HMCV proteins. MTT assay was used to assess the effect of allicin on the proliferation of glioma cells. Western blot analysis was used to detect the effect of allicin on the expression of intermediate-early gene 2 (IE2) and p53. Reverse transcription-quantitative polymerase chain reaction was used to assess and the levels of interleukin (IL)-6 and interferon (IFN)-ß. Single cell gel electrophoresis was used to analyze changes in radiotherapy-induced DNA damage. RESULTS: Transfection of the IE2 protein led to decreased p53 expression and increased glioblastoma cell proliferation. Allicin inhibited this proliferation in a dose- and time-dependent manner. An inhibitory effect on cytokine release was observed in GBM cells treated with allicin. After treatment with allicin, p53 levels increased significantly, whereas expression of the inflammatory factors such as IL-6 and IFN-ß decreased. U87MG cells treated with allicin and 10 Gy irradiation had increased intracellular DNA damage compared to either treatment alone. CONCLUSION: Allicin inhibited proliferation of glioblastoma cells in vitro. Allicin also inhibited cytokine release, upregulated p53 activity, and increased the sensitivity of glioblastoma to radiotherapy. These results suggest that allicin is effective against HCMV-infected glioblastomas.

Identification of an immune-related signature for the prognosis of uveal melanoma.

AIM: To construct an immune-related prognostic signature (IPS) that can distinguish and predict prognosis in uveal melanoma (UM). METHODS: The transcriptomic data and clinicopathological information of 80 UM patients were extracted from the TCGA database. These patients were randomly assigned to a training and a testing set. RESULTS: Lasso Cox analysis was performed for the prognostic immune-related genes to develop an IPS for UM in the training set. The signature was validated in both the testing set and entire cohort. We confirmed the prognostic value of our IPS in distinct subgroups and found its association with the T stage and basal diameter of the tumor. Tumor Immune Estimation Resource database analysis revealed that the IPS was negatively correlated with the infiltration of neutrophils and dendritic cells, but positively correlated with the infiltration level of CD8+ T cells. In addition, we demonstrated that immune checkpoints containing PD-1, CTLA-4, IDO, and TIGIT were moderately associated with the IPS. CONCLUSION: This is the first study to develop and validate an immune-related signature with the ability of predicting prognosis for UM patients. Further studies are needed to validate its prediction accuracy.

Incidence, Treatment, and Survival in Primary Central Nervous System Neuroblastoma.

BACKGROUND: Primary central nervous system neuroblastoma (PCNSN) is a rare disease, and its incidence, treatment modalities, and survival remain poorly understood. METHODS: The SEER (Surveillance Epidemiology and End Results) database was used to identify patients diagnosed with PCNSN from 1973 to 2013. The incidence and survival rates were examined. Clinical features, treatment modalities, and prognosis were also assessed. RESULTS: A total of 280 patients with PCNSN were identified, with annual age-adjusted incidence being 0.37 per 1,000,000 persons in 1973 and decreasing to 0.12 in 2013. Neuroblastoma (NBL) (ganglioneuroblastoma vs. NBL; odds ratio [OR], 25.01; P = 0.008) and tumor with distant metastasis (OR, 0.17; P = 0.002) were more likely to receive conservative treatment over surgery, whereas older age (OR, 1.02; P = 0.011) and tumors located in the brain (other nervous system vs. brain: OR, 0.31; P = 0.001) increased the likelihood of receiving combined surgery and radiotherapy over surgery alone. In addition, younger age, ganglioneuroblastoma, and surgery treatment were significantly associated with improved outcomes (all P < 0.05). Furthermore, a nomogram model was established to effectively estimate survival for patients with PCNSN. CONCLUSIONS: We updated epidemiologic information of PCNSN and showed that age, histologic type, tumor extension, and surgery were independent prognostic factors. Moreover, treatment modalities of these tumors are influenced by patient and tumor characteristics.

Profiles of immune-related genes and immune cell infiltration in the tumor microenvironment of diffuse lower-grade gliomas.

The tumor microenvironment is highly correlated with tumor occurrence, progress, and prognosis. We aimed to investigate the immune-related gene (IRG) expression and immune infiltration pattern in the tumor microenvironment of lower-grade glioma (LGG). We employed the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm to calculate immune and stromal scores and identify prognostic IRG based on The Cancer Genome Atlas data set. The potential molecular functions of these genes were explored with the help of functional enrichment analysis and the protein-protein interaction network. Remarkably, three cohorts that were downloaded from the Chinese Glioma Genome Atlas database were analyzed to further verify the prognostic values of these genes. Moreover, the Tumor IMmune Estimation Resource (TIMER) algorithm was used to estimate the abundance of infiltrating immune cells and explore the immune infiltration pattern in LGG. And unsupervised cluster analysis determined three clusters of the immune infiltration pattern and indicated that CD8+ T cells and macrophages were significantly associated with LGG outcomes. Altogether, our study identified a list of prognostic IRGs and provided a perspective to explore the immune infiltration pattern in LGG.

Real-World Impact of Surgical Excision on Overall Survival in Primary Central Nervous System Lymphoma.

Substantial controversy still exists regarding the use of surgical excision in the treatment of primary central nervous system lymphoma (PCNSL). This study was aimed to evaluate the survival benefit of surgical excision in PCNSL patients based on a US population. Using the Surveillance, Epidemiology, and End Results (SEER) Program database, a total of 3,543 PCNSL patients were identified from 2000 to 2014 for analysis. Surgical excision was accessed via Kaplan-Meier and multivariate Cox regression survival analyses. Coarsened exact matching (CEM) analysis was additionally employed to intensify our findings. Finally, we found that surgical excision was significantly associated with increased survival over no surgery/biopsy (P < 0.001), and its survival benefit was also independent of baseline prognostic factors. The survival benefit of surgery was also validated in clinically important subsets. CEM analysis further validated the survival advantage of surgery (P < 0.001). Moreover, a novel prediction model with excellent performance was established to estimate the potential benefit from surgical excision of the lesion with respect to the end point of overall survival. The current study supports the favorable impact of surgical excision on clinical outcome in patients with PCNSL. Although further randomized controlled trials are warranted, currently available evidence should be considered in the clinical management of this disease.

Personalizing age-specific survival prediction and risk stratification in intracranial grade II/III ependymoma.

BACKGROUND: Models for estimation of survival rates of patients with intracranial grade II/III ependymoma (EPN) are scarce. Considering the heterogeneity in prognostic factors between pediatric and adult patients, we aimed to develop age-specific nomograms for predicting 3-, 5-, and 8-year survival for these patients. METHODS: A total of 1390 cases (667 children; 723 adults) of intracranial grade II/III EPNs diagnosed between 1988 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database for our study. Univariable and multivariable Cox analyses were employed to identify independent prognostic predictors. Age-specific nomograms were developed based on the results of multivariate Cox analyses. We also evaluated the performance of these predictive models by concordance index, calibration curves, time-dependent receiver operating characteristic curves, and decision curve analyses. RESULTS: Considerable heterogeneity in prognostic factors was highlighted between pediatric and adult patients. Age, sex, tumor grade, surgery treatment and radiotherapy were identified as significant predictors of overall survival for children, and age, tumor grade, tumor size, surgery treatment, and marital status for adult. Based on these factors, age-specific nomogram models were established and internally validated. These models exhibited favorable discrimination and calibration characteristics. Nomogram-based risk classification systems were also constructed to facilitate risk stratification in EPNs for optimization of clinical management. CONCLUSIONS: We developed the first nomograms and corresponding risk classification systems for predicting survival in patients with intracranial grade II/III EPN. These easily used tools can assist oncologists in making accurate survival evaluation.

Development and Validation of an IDH1-Associated Immune Prognostic Signature for Diffuse Lower-Grade Glioma.

A mutation in the isocitrate dehydrogenase 1 (IDH1) gene is the most common mutation in diffuse lower-grade gliomas (LGGs), and it is significantly related to the prognosis of LGGs. We aimed to explore the influence of the IDH1 mutation on the immune microenvironment and develop an IDH1-associated immune prognostic signature (IPS) for predicting prognosis in LGGs. IDH1 mutation status and RNA expression were investigated in two different public cohorts. To develop an IPS, LASSO Cox analysis was conducted for immune-related genes that were differentially expressed between IDH1wt and IDH1mut LGG patients. Then, we systematically analyzed the influence of the IPS on the immune microenvironment. A total of 41 immune prognostic genes were identified based on the IDH1 mutation status. A four-gene IPS was established and LGG patients were effectively stratified into low- and high-risk groups in both the training and validation sets. Stratification analysis and multivariate Cox analysis revealed that the IPS was an independent prognostic factor. We also found that high-risk LGG patients had higher levels of infiltrating B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages and dendritic cells, and expressed higher levels of CTLA-4, PD-1 and TIM-3. Moreover, a novel nomogram model was established to estimate the overall survival in LGG patients. The current study provides novel insights into the LGG immune microenvironment and potential immunotherapies. The proposed IPS is a clinically promising biomarker that can be used to classify LGG patients into subgroups with distinct outcomes and immunophenotypes, with the potential to facilitate individualized management and improve prognosis.

FGF21 augments autophagy in random-pattern skin flaps via AMPK signaling pathways and improves tissue survival.

Random-pattern skin flap is commonly used for surgical tissue reconstruction due to its ease and lack of axial vascular limitation. However, ischemic necrosis is a common complication, especially in distal parts of skin flaps. Previous studies have shown that FGF21 can promote angiogenesis and protect against ischemic cardiovascular disease, but little is known about the effect of FGF21 on flap survival. In this study, using a rat model of random skin flaps, we found that the expression of FGF21 is significantly increased after establishment skin flaps, suggesting that FGF21 may exert a pivotal effect on flap survival. We conducted experiments to elucidate the role of FGF21 in this model. Our results showed that FGF21 directly increased the survival area of skin flaps, blood flow intensity, and mean blood vessel density through enhancing angiogenesis, inhibiting apoptosis, and reducing oxidative stress. Our studies also revealed that FGF21 administration leads to an upregulation of autophagy, and the beneficial effects of FGF21 were reversed by 3-methyladenine (3MA), which is a well-known inhibitor of autophagy, suggesting that autophagy plays a central role in FGF21's therapeutic benefit on skin flap survival. In our mechanistic investigation, we found that FGF21-induced autophagy enhancement is mediated by the dephosphorylation and nuclear translocation of TFEB; this effect was due to activation of AMPK-FoxO3a-SPK2-CARM1 and AMPK-mTOR signaling pathways. Together, our data provides novel evidence that FGF21 is a potent modulator of autophagy capable of significantly increasing random skin flap viability, and thus may serve as a promising therapy for clinical use.

Trends in intracranial meningioma incidence in the United States, 2004-2015.

BACKGROUND: Meningioma incidence was reported to have risen substantially in the United States during the first decade of the 21st century. There are few reports about subsequent incidence trends. This study provides updated data to investigate trends in meningioma incidence by demographic and tumor characteristics at diagnosis in the United states from 2004 to 2015. METHODS: Trends in meningioma incidence were analyzed using data from the Surveillance, Epidemiology, and End Results-18 (SEER-18) registry database of the National Cancer Institute. The joinpoint program was used to calculate annual percent change (APC) in incidence rates. RESULTS: The overall incidence of meningioma increased by 4.6% (95% CI, 3.4-5.9) annually in 2004-2009, but remained stable from 2009 to 2015 (APC, 0; 95% CI, -0.8 to 0.8). Females (10.66 per 100 000 person-years) and blacks (9.52 per 100 000 person-years) had significant predominance in meningioma incidence. Incidence in many subgroups increased significantly up to 2009 and then remained stable until 2015. However, meningioma incidence in young and middle-aged people increased significantly throughout the entire time period from 2004 to 2015 (APC: 3.6% for <20-year-olds; 2.5% for 20-39-year-olds; 1.8% for 40-59-year-olds). The incidence of WHO II meningioma increased during 2011-2015 (APC = 5.4%), while the incidence of WHO III meningioma decreased during 2004-2015 (APC = -5.6%). CONCLUSION: In this study, the incidence of meningioma was found to be stable in recent years. Possible reasons for this finding include changes in population characteristics, the widespread use of diagnostic techniques, and changes in tumor classification and risk factors in the US population.

Multi-reference broadband laser ranging to increase the measuring range.

Broadband laser ranging (BLR) is an appropriate method to obtain absolute distance in dynamic experiments. In this article, we first analyze the performance limit for BLR and indicate that the measuring range can be hardly increased while keeping the distance or time resolution unchanged. Then, multi-reference BLR is proposed, which can break this limit and greatly increase the measuring range. Its validity is demonstrated by an experiment with an explosively driven aluminum surface flying over 100 mm. This method would improve the capability of BLR.

Epidemiological trends, relative survival, and prognosis risk factors of WHO Grade III gliomas: A population-based study.

BACKGROUND: Population-based studies on grade III gliomas are still lacking. The purpose of our study was to investigate epidemiological characteristics, survival, and risk factors of these tumors. PATIENTS AND METHODS: All data of patients with grade III gliomas were extracted from the Surveillance, Epidemiology, and End Results database. This database provides analysis to evaluate age-adjusted incidence, incidence-based mortality, and limited-duration prevalence. The trends of incidence and mortality were modeled using Joinpoint program. Relative survival was also available in this database. Univariate and multivariate analyses were used to access the prognostic significance of risk factors on cancer-specific survival. Nomogram was constructed to predict 3-, 5-, and 10-year survival. RESULTS: Our study showed that during 2000-2013, the incidence was stable and the mortality rate dropped significantly with APC as -1.95% (95% CI: -3.35% to -0.54%). Patients aged 40-59 had the highest prevalent cases. The 1-, 3-, 5-, and 10-year relative survival rates for all patients were 74.7%, 52.8%, 44.4%, and 32.4%. And it varied by risk factors. Cox regression analysis showed older age, male, black race, divorced status, histology of AA, tumor size <3.5 cm and no surgery were associated with worse survival. CONCLUSION: Our study provides reasonable estimates of the incidence, mortality, and prevalence for patients with grade III gliomas during 2000-2013. The results of relative survival and Cox regression analysis revealed that age, race, sex, year of diagnosis, tumor site, histologic type, tumor size, and surgery were the identifiable prognostic indicators. The effects of radiotherapy still need further study. We integrated these risk factors to construct an effective clinical prediction model.

The role of postoperative radiotherapy in pediatric patients with grade II intracranial ependymomas: a population-based, propensity score-matched study.

PURPOSE: The main objectives of this study were to clarify the efficacy of postoperative radiotherapy (PORT) for pediatric intracranial grade II ependymomas (EPNs) and to explore whether various characteristics are associated with different outcomes in patients with and without PORT. PATIENTS AND METHODS: Data from patients younger than 18 years diagnosed with grade II intracranial EPNs and treated by surgery, with or without PORT, were obtained from the Surveillance, Epidemiology, and End Results (SEER) database (1973-2013 data set). Propensity score-matched analysis was conducted to balance clinical variables. Patient characteristics were stratified and analyzed. RESULTS: In total, data from 632 patients with grade II EPNs treated by cancer-directed surgery with or without PORT were obtained from the SEER database. Multivariable Cox analysis in the matched cohort suggested that undergoing PORT (overall survival [OS], P=0.020; cancer-specific survival [CSS], P=0.031), undergoing gross total resection (GTR; subtotal resection [STR] vs GTR; OS, P<0.001; CSS, P<0.001), and older age (OS, P<0.001; CSS, P<0.001) were the independent predictors of superior prognosis. Stratified analysis demonstrated that patient characteristics, including infratentorial location, younger age, and STR, were associated with benefit from PORT, while the survival advantage was not detected in patients who underwent GTR. CONCLUSION: Propensity score-matched analysis using SEER data indicates survival advantages of PORT. Given the strong prognostic associations with extent of resection and patient age, we recommend PORT for younger patients treated by STR.

The effects of tumor size and postoperative radiotherapy for patients with adult low-grade (WHO grade II) infiltrative supratentorial astrocytoma/oligodendroglioma: A population-based and propensity score matched study.

BACKGROUND: The update of 2018 NCCN guidelines (central nervous system cancers) recommended the risk classification of postoperative patients diagnosed as adult low-grade (WHO grade II) infiltrative supratentorial astrocytoma/oligodendroglioma (ALISA/O) should take tumor size into consideration. Moreover, the guidelines removed postoperative radiotherapy (PORT) for low risk patients. Our study aimed to explore the specific tumor size to divide postoperative patients into relatively low- or high risk subgroups and the effect of PORT for ALISA/O patients. METHODS: We conducted a retrospective study choosing 1277 postoperative ALISA/O patients from the Surveillance, Epidemiology, and End Results database. The X-tile analysis provided the optimal cutoff point based on tumor size. The differences between surgery alone and surgery +RT groups were balanced by propensity score-matched analysis. The multivariable analysis and the nomogram evaluated multiple prognostic factors based on cancer-specific survival (CSS) and overall survival (OS). RESULTS: X-tile plots defined 59 mm (P < 0.001) as the optimal cutoff tumor size value in terms of CSS, which was verified in multivariate analysis (P < 0.001). The Kaplan-Meier analysis showed that the surgery alone had higher CSS and OS than surgery +RT, while the low risk group had no statistical significance after propensity score match. Multivariable analysis showed that surgery +RT was independently associated with diminished OS and CSS for high risk group, which had no statistical significance for low-risk group. CONCLUSIONS: Our study suggested that tumor size of 59 mm was an optimal cutoff point to divide postoperative patients into relatively low- or high risk subgroups. PORT may not benefit patients, while the effects of PORT for low risk patients need further research.