Prognostic Stratification of GBMs Using Combinatorial Assessment of IDH1 Mutation, MGMT Promoter Methylation, and TERT Mutation Status: Experience from a Tertiary Care Center in India

AbstractThis study aims to establish the best and simplified panel of molecular markers for prognostic stratification of glioblastomas (GBMs). One hundred fourteen cases of GBMs were studied for IDH1, TP53, and TERT mutation by Sanger sequencing; EGFR and PDGFRA amplification by fluorescence in situ hybridization; NF1expression by quantitative real time polymerase chain reaction (qRT-PCR); and MGMT promoter methylation by methylation-specific PCR. IDH1 mutant cases had significantly longer progression-free survival (PFS) and overall survival (OS) as compared to IDH1 wild-type cases. Combinatorial assessment of MGMT and TERT emerged as independent prognostic markers, especially in the IDH1 wild-type GBMs. Thus, within the IDH1 wild-type group, cases with only MGMT methylation (group 1) had the best outcome (median PFS: 83.3 weeks; OS: not reached), whereas GBMs with only TERT mutation (group 3) had the worst outcome (PFS: 19.7 weeks; OS: 32.8 weeks). Cases with both or none of these alterations (group 2) had intermediate prognosis (PFS: 47.6 weeks; OS: 89.2 weeks). Majority of the IDH1 mutant GBMs belonged to group 1 (75%), whereas only 18.7% and 6.2% showed group 2 and 3 signatures, respectively. Interestingly, none of the other genetic alterations were significantly associated with survival in IDH1 mutant or wild-type GBMs.Based on above findings, we recommend assessment of three markers, viz., IDH1, MGMT, and TERT, for GBM prognostication in routine practice. We show for the first time that IDH1 wild-type GBMs which constitute majority of the GBMs can be effectively stratified into three distinct prognostic subgroups based on MGMT and TERT status, irrespective of other genetic alterations

Altered Nasal Microbiome in Atrophic Rhinitis: A Novel Theory of Etiopathogenesis and Therapy

Background: Atrophic rhinitis (AtR) is a chronic nasal condition with polygenic and polybacterial etiology. We investigated the clinical outcomes of honey therapy and the associated nasal microbiome in AtR. Methods: For eight weeks, a nonrandomized control trial using a nasal spray of 10% manuka honey and saline on the right and left sides of the nose was conducted on 19 primary AtR patients. A nasal endoscopy was performed and a mucosal biopsy were taken before and after the intervention. Five of the nineteen patients were selected for microbiome and GPR43 expression studies. Results: We used manuka honey to describe an effective prebiotic treatment for atrophic rhinitis. There were nine males and ten females with an average (±SD) age of 33.8 (±10.7) years. Endoscopic scores and clinical symptoms improved in honey-treated nasal cavities (p < 0.003). There was a significant decrease in inflammation, restoration of mucus glands, and increased expression of GPR43 in the nasal cavities with honey therapy. The nasal microbiome composition before and after treatment was documented. Particularly, short chain fatty acid (SCFA) producers were positively enriched after honey therapy and correlated with improved clinical outcomes like nasal crusting, congestion, and discharge. Conclusion: Our approach to treating AtR patients with manuka honey illustrated effective clinical outcomes such as (1) decreased fetid smell, (2) thickening of the mucosa, (3) decreased inflammation with healed mucosal ulcers, (4) increased concentration of the mucosal glands, (5) altered nasal microbiome, and (6) increased expression of SCFA receptors. These changes are consequent to resetting the nasal microbiome due to honey therapy