Glioblastoma (GBM) is the most common primary malignant brain tumor that nearly always results in a bad prognosis. Temozolomide plus radiotherapy (TEM+RAD) is the most common treatment for newly diagnosed GBM. With the development of molecularly targeted drugs, several clinical trials were reported; however, the efficacy of the treatment remains controversial. So we attempted to measure the dose of the molecularly targeted drug that could improve the prognosis of those patients. The appropriate electronic databases (PubMed, MEDLINE, EMBASE, and the Cochrane Library) were searched for relevant studies. A meta-analysis was performed after determining which studies met the inclusion criteria. Six randomized, controlled trials (RCTs) were identified for this meta-analysis, comprising 2,637 GBM patients. The benefit of overall survival (OS) was hazard ratio (HZ), 0.936 [95% confidence interval (CI), 0.852-1.028]. The benefit with respect to progression-free survival (PFS) rate was HZ of 0.796 (95% CI, 0.701-0.903). OS benefit of cilengitide was HZ of 0.792 (95% CI, 0.642-0.977). The adverse effects higher than grade 3 were 57.7% in the experimental group and 44.1% in the placebo group (odds ratio, 1.679; 95% CI, 1.434-1.967). The addition of molecularly targeted drugs to TEM + RAD did not improve the OS of patients with GBM; however, it did improve PFS in patients treated by cilengitide who could not get improvement in OS. The rate of adverse effects was higher in the experimental group than in the placebo group.
Rationale: H7N9 infection causes acute respiratory distress syndrome with high mortality. The use of glucocorticoids in the acute phase lessened inflammatory responses. Some case reports suggested that secondary organizing pneumonia (SOP) could occur at the recovery stage of the influenza virus infection, and the treatment with glucocorticoid was effective. However, the reports of organizing pneumonia after H7N9 infection are lacking. This study reported a patient with H7N9 virus infection who presented a suspected SOP during the recovery stage. Patient concern: A 68-year-old woman who was diagnosed with H7N9 viral pneumonia. After standard antiviral treatment, venous-venous extracorporeal membranous oxygenation (VV-ECMO) and other supportive treatment, the antigen in the alveolar lavage fluid turned negative, and the shadow in the lung was partially absorbed. However, the imaging manifestations were deteriorated at 3 weeks after disease onset, presented as exudation and consolidation shadow distributed under the pleura and along the bronchial vascular bundles. The oxygenation could not be improved. Repeated sputum, alveolar lavage fluid, and blood pathogen examinations showed negative results. Broad-spectrum anti-infective treatment was ineffective. However, the autoantibodies (ANA, anti-SSA/Ro60, anti-SSA/Ro52) were detected. Diagnosis: SOP was considered. Interventions: Glucocorticoid treatment begun at week 4 from the disease onset. The regimen was methylprednisolone at an initial dose of 40 mg twice a day for 1 week, tapering within 70 days until total withdrawal. Outcomes: The oxygenation was rapidly improved after initiation of methylprednisolone. The shadow in the lung gradually resolved, and the patient was discharged after improvement of the disease condition. The clinical disease course, imaging findings, and treatment effects in the previous cases of SOP after influenza virus infection were similar to those in this case, suggesting the occurrence of SOP after H7N9 virus infection. Lessons: Organizing pneumonia might occur during the recovery stage of influenza virus infection. When the clinical symptoms do not improve and the shadow in the lung shows no obvious absorption after elimination of the H7N9 influenza virus, or the clinical symptoms are aggravated again after improvement, the probability of transforming into the organizing pneumonia should be taken into consideration.
Background: N6-methyladenosine (m6A) RNA methylation regulators play crucial role in tumorigenicity and progression. However, their biological significance in primary glioblastomas (GBM) has not been fully elucidated.Methods: In the present study, we evaluated the 22 m6A RNA regulators using the integrated data of primary GBM samples from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. The different m6A modification patterns and m6A-related gene signature in primary GBM were distinguished by using principal component analysis. Single-sample gene set enrichment analysis was introduced to assess the relative level of immune infiltration. Gene set variation analysis was performed to calculate the enrichment score of the signaling pathways for different clusters. An m6A scoring scheme was established to evaluate the m6A modification pattern in individual tumors in order to predict prognosis and evaluate tumor microenvironment (TME) cell infiltration, immune response, and chemotherapy effect in primary GBM.Results: Two distinct m6A modification subgroups associated with different clinical features and biological pathways were identified among the 371 primary GBM. Based on 132 prognostic m6A phenotype-related differentially expressed genes (DEGs) between 2 m6A cluster subgroups, an m6A scoring model was constructed to assess the m6A modification pattern in individual tumors. The high-m6A score group was associated with better prognosis and immune response and worse chemotherapy effect. Conclusions:The findings of the present study indicate the potential role of m6A modification in primary GBM, which will help enhance our understanding of TME characteristics, predict clinical prognosis, and provide important insight into effective immunotherapy and chemotherapy.
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