Sirtuin 3 regulates astrocyte activation by reducing Notch1 signaling after status epilepticus.

Sirtuin3 (Sirt3) is a nicotinamide adenine dinucleotide enzyme that contributes to aging, cancer, and neurodegenerative diseases. Recent studies have reported that Sirt3 exerts anti-inflammatory effects in several neuropathophysiological disorders. As epilepsy is a common neurological disease, in the present study, we investigated the role of Sirt3 in astrocyte activation and inflammatory processes after epileptic seizures. We found the elevated expression of Sirt3 within reactive astrocytes as well as in the surrounding cells in the hippocampus of patients with temporal lobe epilepsy and a mouse model of pilocarpine-induced status epilepticus (SE). The upregulation of Sirt3 by treatment with adjudin, a potential Sirt3 activator, alleviated SE-induced astrocyte activation; whereas, Sirt3 deficiency exacerbated astrocyte activation in the hippocampus after SE. In addition, our results showed that Sirt3 upregulation attenuated the activation of Notch1 signaling, nuclear factor kappa B (NF-κB) activity, and the production of interleukin-1ß (IL1ß) in the hippocampus after SE. By contrast, Sirt3 deficiency enhanced the activity of Notch1/NF-κB signaling and the production of IL1ß. These findings suggest that Sirt3 regulates astrocyte activation by affecting the Notch1/NF-κB signaling pathway, which contributes to the inflammatory response after SE. Therefore, therapies targeting Sirt3 may be a worthy direction for limiting inflammatory responses following epileptic brain injury.

Revisiting prognostic factors of gliomatosis cerebri in adult-type diffuse gliomas.

PURPOSE: There is lack of comprehensive analysis evaluating the impact of clinical, molecular, imaging, and surgical data on survival of patients with gliomatosis cerebri (GC). This study aimed to investigate prognostic factors of GC in adult-type diffuse glioma patients. METHODS: Retrospective chart and imaging review was performed in 99 GC patients from adult-type diffuse glioma (among 1,211 patients; 6 oligodendroglioma, 16 IDH-mutant astrocytoma, and 77 IDH-wildtype glioblastoma) from a single institution between 2005 and 2021. Predictors of overall survival (OS) of entire patients and IDH-wildtype glioblastoma patients were determined. RESULTS: The median OS was 16.7 months (95% confidence interval [CI] 14.2-22.2) in entire patients and 14.3 months (95% CI 12.2-61.9) in IDH-wildtype glioblastoma patients. In entire patients, KPS (hazard ratio [HR] = 0.98, P = 0.004), no 1p/19q codeletion (HR = 10.75, P = 0.019), MGMTp methylation (HR = 0.54, P = 0.028), and hemorrhage (HR = 3.45, P = 0.001) were independent prognostic factors on multivariable analysis. In IDH-wildtype glioblastoma patients, KPS (HR = 2.24, P = 0.075) was the only independent prognostic factor on multivariable analysis. In subgroup of IDH-wildtype glioblastoma with CE tumors, total resection of CE tumor did not remain as a significant prognostic factor (HR = 1.13, P = 0.685). CONCLUSIONS: The prognosis of GC patients is determined by its underlying molecular type and patient performance status. Compared with diffuse glioma without GC, aggressive surgery of CE tumor in GC patients does not improve survival.

Rethinking extent of resection of contrast-enhancing and non-enhancing tumor: different survival impacts on adult-type diffuse gliomas in 2021 World Health Organization classification.

OBJECTIVES: Extent of resection (EOR) of contrast-enhancing (CE) and non-enhancing (NE) tumors may have different impacts on survival according to types of adult-type diffuse gliomas in the molecular era. This study aimed to evaluate the impact of EOR of CE and NE tumors in glioma according to the 2021 World Health Organization classification. METHODS: This retrospective study included 1193 adult-type diffuse glioma patients diagnosed between 2001 and 2021 (183 oligodendroglioma, 211 isocitrate dehydrogenase [IDH]-mutant astrocytoma, and 799 IDH-wildtype glioblastoma patients) from a single institution. Patients had complete information on IDH mutation, 1p/19q codeletion, and O6-methylguanine-methyltransferase (MGMT) status. Cox survival analyses were performed within each glioma type to assess predictors of overall survival, including clinical, imaging data, histological grade, MGMT status, adjuvant treatment, and EOR of CE and NE tumors. Subgroup analyses were performed in patients with CE tumor. RESULTS: Among 1193 patients, 935 (78.4%) patients had CE tumors. In entire oligodendrogliomas, gross total resection (GTR) of NE tumor was not associated with survival (HR = 0.56, p = 0.223). In 86 (47.0%) oligodendroglioma patients with CE tumor, GTR of CE tumor was the only independent predictor of survival (HR = 0.16, p = 0.004) in multivariable analysis. GTR of CE and NE tumors was independently associated with better survival in IDH-mutant astrocytoma and IDH-wildtype glioblastoma (all ps < 0.05). CONCLUSIONS: GTR of both CE and NE tumors may significantly improve survival within IDH-mutant astrocytomas and IDH-wildtype glioblastomas. In oligodendrogliomas, the EOR of CE tumor may be crucial in survival; aggressive GTR of NE tumor may be unnecessary, whereas GTR of the CE tumor is recommended. CLINICAL RELEVANCE STATEMENT: Surgical strategies on contrast-enhancing (CE) and non-enhancing (NE) tumors should be reassessed considering the different survival outcomes after gross total resection depending on CE and NE tumors in the 2021 World Health Organization classification of adult-type diffuse gliomas. KEY POINTS: The survival impact of extent of resection of contrast-enhancing (CE) and non-enhancing (NE) tumors was evaluated in adult-type diffuse gliomas. Gross total resection of both CE and NE tumors may improve survival in isocitrate dehydrogenase (IDH)-mutant astrocytomas and IDH-wildtype glioblastomas, while only gross total resection of the CE tumor improves survival in oligodendrogliomas. Surgical strategies should be reconsidered according to types in adult-type diffuse gliomas.

Human glioblastoma arises from subventricular zone cells with low-level driver mutations.

Glioblastoma (GBM) is a devastating and incurable brain tumour, with a median overall survival of fifteen months1,2. Identifying the cell of origin that harbours mutations that drive GBM could provide a fundamental basis for understanding disease progression and developing new treatments. Given that the accumulation of somatic mutations has been implicated in gliomagenesis, studies have suggested that neural stem cells (NSCs), with their self-renewal and proliferative capacities, in the subventricular zone (SVZ) of the adult human brain may be the cells from which GBM originates3-5. However, there is a lack of direct genetic evidence from human patients with GBM4,6-10. Here we describe direct molecular genetic evidence from patient brain tissue and genome-edited mouse models that show astrocyte-like NSCs in the SVZ to be the cell of origin that contains the driver mutations of human GBM. First, we performed deep sequencing of triple-matched tissues, consisting of (i) normal SVZ tissue away from the tumour mass, (ii) tumour tissue, and (iii) normal cortical tissue (or blood), from 28 patients with isocitrate dehydrogenase (IDH) wild-type GBM or other types of brain tumour. We found that normal SVZ tissue away from the tumour in 56.3% of patients with wild-type IDH GBM contained low-level GBM driver mutations (down to approximately 1% of the mutational burden) that were observed at high levels in their matching tumours. Moreover, by single-cell sequencing and laser microdissection analysis of patient brain tissue and genome editing of a mouse model, we found that astrocyte-like NSCs that carry driver mutations migrate from the SVZ and lead to the development of high-grade malignant gliomas in distant brain regions. Together, our results show that NSCs in human SVZ tissue are the cells of origin that contain the driver mutations of GBM.

The 2021 WHO Classification for Gliomas and Implications on Imaging Diagnosis: Part 2-Summary of Imaging Findings on Pediatric-Type Diffuse High-Grade Gliomas, Pediatric-Type Diffuse Low-Grade Gliomas, and Circumscribed Astrocytic Gliomas.

The fifth edition of the World Health Organization (WHO) classification of central nervous system tumors published in 2021 advances the role of molecular diagnostics in the classification of gliomas by emphasizing integrated diagnoses based on histopathology and molecular information and grouping tumors based on genetic alterations. This Part 2 review focuses on the molecular diagnostics and imaging findings of pediatric-type diffuse high-grade gliomas, pediatric-type diffuse low-grade gliomas, and circumscribed astrocytic gliomas. Each tumor type in pediatric-type diffuse high-grade glioma mostly harbors a distinct molecular marker. On the other hand, in pediatric-type diffuse low-grade gliomas and circumscribed astrocytic gliomas, molecular diagnostics may be extremely complicated at a glance in the 2021 WHO classification. It is crucial for radiologists to understand the molecular diagnostics and imaging findings and leverage the knowledge in clinical practice. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

The 2021 WHO Classification for Gliomas and Implications on Imaging Diagnosis: Part 1-Key Points of the Fifth Edition and Summary of Imaging Findings on Adult-Type Diffuse Gliomas.

The fifth edition of the World Health Organization (WHO) classification of central nervous system tumors published in 2021 advances the role of molecular diagnostics in the classification of gliomas by emphasizing integrated diagnoses based on histopathology and molecular information and grouping tumors based on genetic alterations. Importantly, molecular biomarkers that provide important prognostic information are now a parameter for establishing tumor grades in gliomas. Understanding the 2021 WHO classification is crucial for radiologists for daily imaging interpretation as well as communication with clinicians. Although imaging features are not included in the 2021 WHO classification, imaging can serve as a powerful tool to impact the clinical practice not only prior to tissue confirmation but beyond. This review represents the first of a three-installment review series on the 2021 WHO classification for gliomas, glioneuronal tumors, and neuronal tumors and implications on imaging diagnosis. This Part 1 Review focuses on the major changes to the classification of gliomas and imaging findings on adult-type diffuse gliomas. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.

The 2021 WHO Classification for Gliomas and Implications on Imaging Diagnosis: Part 3-Summary of Imaging Findings on Glioneuronal and Neuronal Tumors.

The fifth edition of the World Health Organization classification of central nervous system tumors published in 2021 reflects the current transitional state between traditional classification system based on histopathology and the state-of-the-art molecular diagnostics. This Part 3 Review focuses on the molecular diagnostics and imaging findings of glioneuronal and neuronal tumors. Histological and molecular features in glioneuronal and neuronal tumors often overlap with pediatric-type diffuse low-grade gliomas and circumscribed astrocytic gliomas (discussed in the Part 2 Review). Due to this overlap, in several tumor types of glioneuronal and neuronal tumors the diagnosis may be inconclusive with histopathology and genetic alterations, and imaging features may be helpful to distinguish difficult cases. Thus, it is crucial for radiologists to understand the underlying molecular diagnostics as well as imaging findings for application on clinical practice. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Dynamic contrast-enhanced MRI radiomics model predicts epidermal growth factor receptor amplification in glioblastoma, IDH-wildtype.

PURPOSE: To develop and validate a dynamic contrast-enhanced (DCE) MRI-based radiomics model to predict epidermal growth factor receptor (EGFR) amplification in patients with glioblastoma, isocitrate dehydrogenase (IDH) wildtype. METHODS: Patients with pathologically confirmed glioblastoma, IDH wildtype, from January 2015 to December 2020, with an EGFR amplification status, were included. Patients who did not undergo DCE or conventional brain MRI were excluded. Patients were categorized into training and test sets by a ratio of 7:3. DCE MRI data were used to generate volume transfer constant (Ktrans) and extracellular volume fraction (Ve) maps. Ktrans, Ve, and conventional MRI were then used to extract the radiomics features, from which the prediction models for EGFR amplification status were developed and validated. RESULTS: A total of 190 patients (mean age, 59.9; male, 55.3%), divided into training (n = 133) and test (n = 57) sets, were enrolled. In the test set, the radiomics model using the Ktrans map exhibited the highest area under the receiver operating characteristic curve (AUROC), 0.80 (95% confidence interval [CI], 0.65-0.95). The AUROC for the Ve map-based and conventional MRI-based models were 0.74 (95% CI, 0.58-0.90) and 0.76 (95% CI, 0.61-0.91). CONCLUSION: The DCE MRI-based radiomics model that predicts EGFR amplification in glioblastoma, IDH wildtype, was developed and validated. The MRI-based radiomics model using the Ktrans map has higher AUROC than conventional MRI.

Revisiting prognostic factors in glioma with leptomeningeal metastases: a comprehensive analysis of clinical and molecular factors and treatment modalities.

PURPOSE: To comprehensively investigate prognostic factors, including clinical and molecular factors and treatment modalities, in adult glioma patients with leptomeningeal metastases (LM). METHODS: Total 226 patients with LM (from 2001 to 2021 among 1495 grade 2 to 4 glioma patients, 88.5% of LM patients being IDH-wildtype) with complete information on IDH mutation, 1p/19q codeletion, and MGMT promoter methylation status were enrolled. Predictors of overall survival (OS) of entire patients were determined by time-dependent Cox analysis, including clinical, molecular, and treatment data. Subgroup analyses were performed for patients with LM at initial diagnosis and LM diagnosed at recurrence (herein, initial and recurrent LM). Identical analyses were performed in IDH-wildtype glioblastoma patients. RESULTS: Median OS was 17.0 (IQR 9.7-67.1) months, with shorter median OS in initial LM than recurrent LM patients (12.2 vs 20.6 months, P < 0.001). In entire patients, chemotherapy and antiangiogenic therapy were predictors of longer OS, while male sex and initial LM were predictors of shorter OS. In initial LM, higher KPS, chemotherapy, and antiangiogenic therapy were predictors of longer OS, while male sex was a predictor of shorter OS. In recurrent LM, chemotherapy and longer interval between initial glioma and LM diagnoses were predictors of longer OS, while male sex was a predictor of shorter OS. A similar trend was observed in IDH-wildtype glioblastoma. CONCLUSION: Active chemotherapy and antiangiogenic therapy demonstrated survival benefit in glioma patients with LM. There is consistent female survival advantage, whereas longer interval between initial glioma diagnosis and LM development suggests longer OS in recurrent LM.

Clinical infection of Brucella canis in a companion dog with discospondylitis in the Republic of Korea.

A 2-year-old, spayed female, Bichon Frise dog was presented with reluctance to exercise, back pain, and frequent sitting down. Multiple osteolysis, periosteal proliferation, and sclerosis of the vertebral endplates of T11-13 were observed in the radiography, computed tomography, and magnetic resonance imaging. The bacterial culture of the urine specimen, the polymerase chain reaction (PCR) of the blood, and the antibody tests were positive for Brucella canis. Accordingly, discospondylitis caused by B. canis was diagnosed and doxycycline was administered. The clinical signs resolved and the culture and PCR results were negative afterwards. Doxycycline was discontinued after 6 months. The clinical signs recurred 2 weeks later, and the combination treatment of doxycycline and enrofloxacin was initiated. Though no clinical signs were observed after 9 months and the bacterial cultures and PCR were negative, the antibody titre remained at 1 : 200 or more. The dog will continue taking antibiotics until the antibody titre drops. To the best of our knowledge, this is the first case report of a clinical infection of B. canis associated with canine discospondylitis in the Republic of Korea. Although the clinical signs of brucellosis might improve with antibiotic treatment, the disease cannot be cured due to Brucella's various strategies to evade host immune systems. Specifically, it can proliferate and replicate within the host cells, resulting in an environment that makes treatment less effective. Furthermore, owing to its zoonotic potential, owners and veterinarians should consider lifelong management or euthanasia.

Anaplastic ganglioglioma-A diagnosis comprising several distinct tumour types.

AIMS: Anaplastic ganglioglioma is a rare tumour, and diagnosis has been based on histological criteria. The 5th edition of the World Health Organization Classification of Tumours of the Central Nervous System (CNS WHO) does not list anaplastic ganglioglioma as a distinct diagnosis due to lack of molecular data in previous publications. We retrospectively compiled a cohort of 54 histologically diagnosed anaplastic gangliogliomas to explore whether the molecular profiles of these tumours represent a separate type or resolve into other entities. METHODS: Samples were subjected to histological review, desoxyribonucleic acid (DNA) methylation profiling and next-generation sequencing. Morphological and molecular data were summarised to an integrated diagnosis. RESULTS: The majority of tumours designated as anaplastic gangliogliomas resolved into other CNS WHO diagnoses, most commonly pleomorphic xanthoastrocytoma (16/54), glioblastoma, isocitrate dehydrogenase protein (IDH) wild type and diffuse paediatric-type high-grade glioma, H3 wild type and IDH wild type (11 and 2/54), followed by low-grade glial or glioneuronal tumours including pilocytic astrocytoma, dysembryoplastic neuroepithelial tumour and diffuse leptomeningeal glioneuronal tumour (5/54), IDH mutant astrocytoma (4/54) and others (6/54). A subset of tumours (10/54) was not assignable to a CNS WHO diagnosis, and common molecular profiles pointing to a separate entity were not evident. CONCLUSIONS: In summary, we show that tumours histologically diagnosed as anaplastic ganglioglioma comprise a wide spectrum of CNS WHO tumour types with different prognostic and therapeutic implications. We therefore suggest assigning this designation with caution and recommend comprehensive molecular workup.

Lung and lymph node metastases from hepatocellular carcinoma: Comparison of pathological aspects.

BACKGROUND & AIMS: Extrahepatic metastasis from hepatocellular carcinoma (HCC) is a catastrophic event, yet organ-specific pathological characteristics of metastatic HCC remain unclear. We aimed to characterize the pathological aspects of HCC metastases to various organs. METHODS: We collected intrahepatic HCC (cohort 1, n = 322) and extrahepatic metastatic HCC (cohort 2, n = 130) samples. Clinicopathological evaluation and immunostaining for K19, CD34, αSMA, fibroblast-associated protein (FAP), CAIX, VEGF, PD-L1, CD3, CD8, Foxp3, CD163 and epithelial-mesenchymal transition (EMT)-related markers were performed. RESULTS: Independent factors for extrahepatic metastasis included BCLC stage B-C, microvascular invasion (MVI), vessels encapsulating tumour clusters (VETC)-HCC, K19 and FAP expression, and CD163+ macrophage infiltration (cohort 1, P < .05 for all). Lung metastases (n = 63) had the highest proportion of VETC-HCC and macrotrabecular-massive (MTM)-HCC. Lymph node metastases (n = 19) showed significantly high rates of EMT-high features, K19 expression, fibrous tumour stroma with αSMA and FAP expression, high immune cell infiltration, PD-L1 expression (combined positive score), CD3+, CD8+, Foxp3+ T cell and CD163+ macrophage infiltration (adjusted P < .05 for all). In both cohorts, EMT-high HCCs showed higher rates of K19 expression, fibrous tumour stroma, high immune cell infiltration, PD-L1 expression and CD3+ T cell infiltration, whereas EMT-low HCCs were more frequent among VETC-HCCs (P < .05 for all). Overall phenotypic features were not significantly different between paired primary-metastatic HCCs (n = 32). CONCLUSIONS: Metastatic HCCs to various organs showed different pathological features. VETC and MTM subtypes were related to lung metastasis, whereas K19 expression, EMT-high features with fibrous tumour stroma and high immune cell infiltration were related to lymph node metastasis.

A novel biguanide (IM1761065) inhibits bioenergetics of glioblastoma tumorspheres.

PURPOSE: Glioblastoma (GBM) is a rapidly growing tumor in the central nervous system with altered metabolism. Depleting the bioenergetics of tumors with biguanides have been suggested as an effective therapeutic approach for treating GBMs. The purpose of this study was to determine the effects of IM1761065, a novel biguanide with improved pharmacokinetics, on GBM-tumorspheres (TSs). METHODS: The biological activities of IM1761065 on GBM-TSs, including their effects on viability, ATP levels, cell cycle, stemness, invasive properties, and transcriptomes were examined. The in vivo efficacy of IM1761065 was tested in a mouse orthotopic xenograft model. RESULTS: IM1761065 decreased the viability and ATP levels of GBM-TSs in a dose-dependent manner, and reduced basal and spare respiratory capacity in patient-derived GBM-TS, as measured by the oxygen consumption rate. Sphere formation, expression of stemness-related proteins, and invasive capacity of GBM-TSs were also significantly suppressed by IM1761065. A gene-ontology comparison of IM1761065-treated groups showed that the expression levels of stemness-related, epithelial mesenchymal transition-related, and mitochondrial complex I genes were also significantly downregulated by IM1761065. An orthotopic xenograft mouse model showed decreased bioluminescence in IM1761065-treated cell-injected mice at 5 weeks. IM1761065-treated group showed longer survival than the control group (P = 0.0289, log-rank test). CONCLUSION: IM1761065 is a potent inhibitor of oxidative phosphorylation. The inhibitory effect of IM1761065 on the bioenergetics of GBM-TS suggests that this novel compound could be used as a new drug for the treatment of GBM.

Sex as a prognostic factor in adult-type diffuse gliomas: an integrated clinical and molecular analysis according to the 2021 WHO classification.

PURPOSE: To investigate whether type-specific sex differences in survival exist independently of clinical and molecular factors in adult-type diffuse gliomas according to the 2021 World Health Organization (WHO) classification. METHODS: A retrospective chart and imaging review of 1325 patients (mean age, 54 ± 15 years; 569 females) with adult-type diffuse gliomas (oligodendroglioma, IDH-mutant, and 1p/19q-codeleted, n = 183; astrocytoma, IDH-mutant, n = 211; glioblastoma, IDH-wildtype, n = 800; IDH-wildtype diffuse glioma, NOS, n = 131) was performed. The demographic information, extent of resection, imaging data, and molecular data including O6-methylguanine-methyltransferase promoter methylation (MGMT) promotor methylation were collected. Sex differences in survival were analyzed using Cox analysis. RESULTS: In patients with glioblastoma, IDH-wildtype, female sex remained as an independent predictor of better overall survival (hazard ratio = 0.91, P = 0.031), along with age, histological grade 4, MGMT promoter methylation status, and gross total resection. Female sex showed a higher prevalence of MGMT promoter methylation (40.2% vs 32.0%, P = 0.017) but there was no interaction effect between female sex and MGMT promoter methylation status (P-interaction = 0.194), indicating independent role of female sex. The median OS for females were 19.2 months (12.3-35.0) and 16.2 months (10.5-30.6) for males. No sex difference in survival was seen in other types of adult-type diffuse gliomas. CONCLUSION: There was a female survival advantage in glioblastoma, IDH-wildtype, independently of clinical data or MGMT promoter methylation status. There was no sex difference in survival in other types of adult-type diffuse gliomas, suggesting type-specific sex effects solely in glioblastoma, IDH-wildtype.

Adding radiomics to the 2021 WHO updates may improve prognostic prediction for current IDH-wildtype histological lower-grade gliomas with known EGFR amplification and TERT promoter mutation status.

OBJECTIVES: To assess whether radiomic features could improve the accuracy of survival predictions of IDH-wildtype (IDHwt) histological lower-grade gliomas (LGGs) over clinicopathological features. METHODS: Preoperative MRI data of 61 patients with IDHwt histological LGGs were included as the institutional training set. The test set consisted of 32 patients from The Cancer Genome Atlas. Radiomic features (n = 186) were extracted using conventional MRIs. The radiomics risk score (RRS) for overall survival (OS) was derived from the elastic net. Multivariable Cox regression analyses with clinicopathological features (including epidermal growth factor receptor [EGFR] amplification and telomerase reverse transcriptase promoter [TERTp] mutation status) and the RRS were performed. The integrated area under the receiver operating curves (iAUCs) from the models with and without the RRS were compared. The net reclassification index (NRI) for 1-year OS was also calculated. The prognostic value of the RRS was evaluated using the external validation set. RESULTS: The RRS independently predicted OS (hazard ratio = 48.08; p = 0.001). Compared with the clinicopathological model alone, adding the RRS had a better OS prediction performance (iAUCs 0.775 vs. 0.910), which was internally validated (iAUCs 0.726 vs. 0.884, 1-year OS NRI = 0.497), and a similar trend was found on external validation (iAUCs 0.683 vs. 0.705, 1-year OS NRI = 0.733). The prognostic significance of the RRS was confirmed in the external validation set (p = 0.001). CONCLUSIONS: Integrating radiomics with clinicopathological features (including EGFR amplification and TERTp mutation status) can improve survival prediction in patients with IDHwt LGGs. KEY POINTS: • Radiomics risk score has the potential to improve survival prediction when added to clinicopathological features (iAUCs increased from 0.775 to 0.910). • NRIs for 1-year OS showed that the radiomics risk score had incremental value over the clinicopathological model. • The prognostic significance of the radiomics risk score was confirmed in the external validation set (p = 0.001).

A fully automatic multiparametric radiomics model for differentiation of adult pilocytic astrocytomas from high-grade gliomas.

OBJECTIVES: To develop a fully automatic radiomics model to differentiate adult pilocytic astrocytomas (PA) from high-grade gliomas (HGGs). METHODS: This retrospective study included 302 adult patients with PA (n = 62) or HGG (n = 240). The patients were randomly divided into training (n = 211) and test (n = 91) sets. Clinical data were obtained, and radiomic features (n = 372) were extracted from multiparametric MRI with automatic tumour segmentation. After feature selection with F-score, a Light Gradient Boosting Machine classifier with subsampling was trained to develop three models: (1) clinical model, (2) radiomics model, and (3) combined clinical and radiomics model. Human performance was also assessed. The performance of the classifier was validated in the test set. SHapley Additive exPlanations (SHAP) was applied to explore the interpretability of the model. RESULTS: A total of 15 radiomic features were selected. In the test set, the combined clinical and radiomics model (area under the curve [AUC], 0.93) showed a significantly higher performance than the clinical model (AUC, 0.79, p = 0.037) and had a similar performance to the radiomics model (AUC, 0.92, p = 0.828). The combined clinical and radiomics model also showed a significantly higher performance than humans (AUC, 0.76-0.81, p < 0.05). The model explanation by SHAP suggested that lower intratumoural heterogeneity from T2-weighted images was highly associated with PA diagnosis. CONCLUSIONS: The fully automatic combined clinical and radiomics model may be helpful for differentiating adult PAs from HGGs. KEY POINTS: • Differentiating adult PAs from HGGs is challenging because PAs may manifest a large spectrum of imaging presentations, often including aggressive imaging features. • The fully automatic combined clinical and radiomics model showed a significantly higher performance than the clinical model or humans. • The model explanation by SHAP suggested that second-order features from T2-weighted imaging were important in diagnosis and might reflect the underlying pathophysiology that PAs have lesser tissue heterogeneity than HGGs.

Intramedullary parasite eggs, latent for three decades, mimicking acute transverse myelitis.

BACKGROUND: Intramedullary parasitic infection is extremely uncommon, and clinical presentation of Brown-Sequard syndrome is even rarer. CASE PRESENTATION: The authors report a case involving a 57-year-old woman with Brown-Sequard syndrome, in whom magnetic resonance imaging and clinical and epidemiological features were similar to those of acute transverse myelitis. Myelotomy suggested inflammation caused by latent parasite eggs in the spinal cord. Antiparasitic and steroid therapies were administered postoperatively. To the author's knowledge, this is the first report to describe a surgical experience for Taenia solium eggs in the spinal cord. CONCLUSION: Intramedullary parasitic infection is a diagnostic challenge that requires careful discrimination from other diseases. If parasite infection is suspected in a progressively deteriorating patient, myelotomy should be considered for rapid and accurate treatment.

Asian-specific 3'UTR variant in CDKN2B associated with risk of pituitary adenoma.

BACKGROUND: Previous genomewide association studies (GWASs), single nucleotide polymorphisms (SNPs) on cyclin-dependent kinase inhibitor 2 A (CDKN2A), cyclin-dependent kinase inhibitor 2B (CDKN2B), and cyclin-dependent kinase inhibitor 2B antisense RNA1 (CDKN2B-AS1) were reported as risk loci for glioma, a subgroup of the brain tumor. To further characterize this association with the risk of brain tumors in a Korean population, we performed a fine-mapping association study of CDKN2A, CDKN2B, and CDKN2B-AS1. METHODS AND RESULTS: A total of 17 SNPs were selected and genotyped in 1,439 subjects which were comprised of 959 patients (pituitary adenoma 335; glioma 324; meningioma 300) and 480 population controls (PCs). We discovered that a 3'untranslated region (3'UTR) variant, rs181031884 of CDKN2B (Asian-specific variant), had significant association with the risk of pituitary adenoma (PA) (Odds ratio = 0.58, P = 0.00003). Also, rs181031884 appeared as an independent causal variant among the significant variants in CDKN2A and CDKN2B, and showed dose-dependent effects on PA. CONCLUSIONS: Although further studies are needed to verify the impact of this variant on PA susceptibility, our results may help to understand CDKN2B polymorphism and the risk of PA.

Clinical factors and conventional MRI may independently predict progression-free survival and overall survival in adult pilocytic astrocytomas.

PURPOSE: Pilocytic astrocytoma (PA) is rare in adults, and only limited knowledge on the clinical course and prognosis has been available. The combination of clinical information and comprehensive imaging parameters could be used for accurate prognostic stratification in adult PA patients. This study was conducted to predict the prognostic factors from clinical information and conventional magnetic resonance imaging (MRI) features in adult PAs. METHODS: A total of 56 adult PA patients were enrolled in the institutional cohort. Clinical characteristics including age, sex, anaplastic PA, presence of neurofibromatosis type 1, Karnofsky performance status, extent of resection, and postoperative treatment were collected. MRI characteristics including major axis length, tumor location, presence of the typical 'cystic mass with enhancing mural nodule appearance', proportion of enhancing tumor, the proportion of edema, conspicuity of the nonenhancing margin, and presence of a cyst were evaluated. Univariable and multivariable Cox proportional hazard modeling were performed. RESULTS: The 5-year progression-free survival (PFS) and overall survival (OS) rates were 83.9% and 91.l%, respectively. On univariable analysis, older age, larger proportion of edema, and poor definition of nonenhancing margin were predictors of shorter PFS and OS, respectively (all Ps < .05). On multivariable analysis, older age (hazard ratio [HR] = 1.04, P = .014; HR = 1.14, P = .030) and poor definition of nonenhancing margin (HR = 3.66, P = .027; HR = 24.30, P = .024) were independent variables for shorter PFS and OS, respectively. CONCLUSION: Age and the margin of the nonenhancing part of the tumor may be useful biomarkers for predicting the outcome in adult PAs.

Red-Emitting Latex Nanoparticles by Stepwise Entrapment of ß-Diketonate Europium Complexes.

The core-shell structure of poly(St-co-MAA) nanoparticles containing ß-diketonate Eu3+ complexes were synthesized by a step-wise process. The ß-diketonate Eu3+ complexes of Eu (TFTB)2(MAA)P(Oct)3 [europium (III); 4,4,4-Trifluoro-1-(2-thienyl)-1,3-butanedione = TFTB; trioctylphosphine = (P(Oct)3); methacrylic acid = MAA] were incorporated to poly(St-co-MAA). The poly(St-co-MAA) has highly monodispersed with a size of 300 nm, and surface charges of the poly(St-co-MAA) are near to neutral. The narrow particle size distribution was due to the constant ionic strength of the polymerization medium. The activated carboxylic acid of poly(St-co-MAA) further chelated with europium complex and polymerize between acrylic groups of poly(St-co-MAA) and Eu(TFTB)2(MAA)P(Oct)3. The Em spectra of europium complexes consist of multiple bands of Em at 585, 597, 612 and 650 nm, which are assigned to 5D0→7FJ (J = 0-3) transitions of Eu3+, respectively. The maximum Em peak is at 621 nm, which indicates a strong red Em characteristic associated with the electric dipole 5D0→7F2 transition of Eu3+ complexes. The cell-specific fluorescence of Eu(TFTB)2(MAA)P(Oct)3@poly(St-co-MAA) indicated endocytosis of Eu(TFTB)2(MAA)P(Oct)3@poly(St-co-MAA). There are fewer early apoptotic, late apoptotic and necrotic cells in each sample compared with live cells, regardless of the culture period. Eu(TFTB)2(MAA)P(Oct)3@poly(St-co-MAA) synthesized in this work can be excited in the full UV range with a maximum Em at 619 nm. Moreover, these particles can substitute red luminescent organic dyes for intracellular trafficking and cellular imaging agents.