Prognostic nomogram for glioblastoma (GBM) patients presenting with distant extension: a seer-based study.

BACKGROUND: Glioblastoma (GBM) with distant extension is rarely reported. We retrieved the data of GBM patients from the SEER database to identify the prognostic factors of GBM with distant extension and constructed a nomogram to predict the overall survival (OS) of these patients. METHODS: The data of GBM patients between 2003 and 2018 were retrieved from the SEER Database. 181 GBM patients with distant extension were randomly divided into the training cohort (n = 129) and the validation cohort (n = 52) at a ratio of 7:3. The prognostic factors associated with the OS of the GBM patients were identified through univariate and multivariate cox analyses. A nomogram was constructed based on the training cohort to predict OS, and its clinical value was verified using the validation cohort data. RESULTS: Kaplan-Meier curves showed that the prognosis was significantly worse for GBM patients with distant extension than GBM patients without distant extension. Stage (GBM patients with distant extension) was independent prognostic factor of survival. Multivariate Cox analyses demonstrated that age, surgery, radiotherapy and chemotherapy were independent risk factors for OS of GBM patients presenting with distant extension. The C-indexes of the nomogram for predicting OS were 0.755 (95% CI 0.713-0.797) and 0.757 (95% CI 0.703-0.811) for the training and validation cohorts, respectively. The calibration curves of both cohorts showed good consistency. The area under the curve (AUC) for predicting 0.25-year, 0.5-year and 1-year OS in the training cohort were 0.793, 0.864 and 0.867, respectively, and that in the validation cohort were 0.845, 0.828 and 0.803, respectively. The decision curve analysis (DCA) curves showed that the model to predict the 0.25-year, 0.5-year and 1-year OS probabilities was good. CONCLUSION: Stage (GBM patients with distant extension) is independent prognostic factor for GBM patients. Age, surgery, radiotherapy and chemotherapy are independent prognostic factors for GBM patients presenting with distant extension, and the nomogram based on these factors can accurately predict the 0.25-year, 0.5-year and 1-year OS of these patients.

Manifestation of the malignant progression of glioma following initial intracerebral hemorrhage: A case report.

BACKGROUND: Intracranial hemorrhage is extremely rare during the initial stages of glioma. Here, we report a case of glioma with unclassified pathology and intracranial bleeding. CASE SUMMARY: After the second surgery for intracerebral hemorrhage, the patient experienced weakness in the left arm and leg, but could walk unassisted. One month after discharge, the weakness in the left limbs had exacerbated and the patient also suffered from headaches and dizziness. A third surgery was ineffective against the rapidly growing tumor. Intracerebral hemorrhage may be the initial symptom of glioma in some rare cases, and atypical perihematomal edema can be used for diagnosis during an emergency. Certain histological and molecular features seen in our case were similar to that of glioblastoma with a primitive neuronal component, which is termed diffuse glioneuronal tumor with features similar to oligodendroglioma and nuclear clusters (DGONC). The patient underwent three surgeries to remove the tumor. The first tumor resection had been performed when the patient was 14-years-old. Resection of the hemorrhage and bone disc decompression were performed when the patient was 39-years-old. One month after the last discharge, the patient underwent neuronavigation-assisted resection of the right frontotemporal parietal lesion plus extended flap decompression. On the 50th d after the third operation, computed tomography imaging showed rapid tumor growth accompanied by brain hernia. The patient was discharged and died 3 d later. CONCLUSION: Glioma can present as bleeding in the initial stage and should be considered in such a setting. We have reported a case of DGONC, which is a rare molecular subtype of glioma with a unique methylation profile.

Selective activation of TWIK-related acid-sensitive K+ 3 subunit-containing channels is analgesic in rodent models.

The paucity of selective agonists for TWIK-related acid-sensitive K+ 3 (TASK-3) channel, a member of two-pore domain K+ (K2P) channels, has contributed to our limited understanding of its biological functions. By targeting a druggable transmembrane cavity using a structure-based drug design approach, we discovered a biguanide compound, CHET3, as a highly selective allosteric activator for TASK-3-containing K2P channels, including TASK-3 homomers and TASK-3/TASK-1 heteromers. CHET3 displayed potent analgesic effects in vivo in a variety of acute and chronic pain models in rodents that could be abolished pharmacologically or by genetic ablation of TASK-3. We further found that TASK-3-containing channels anatomically define a unique population of small-sized, transient receptor potential cation channel subfamily M member 8 (TRPM8)-, transient receptor potential cation channel subfamily V member 1 (TRPV1)-, or tyrosine hydroxylase (TH)-positive nociceptive sensory neurons and functionally regulate their membrane excitability, supporting CHET3 analgesic effects in thermal hyperalgesia and mechanical allodynia under chronic pain. Overall, our proof-of-concept study reveals TASK-3-containing K2P channels as a druggable target for treating pain.