Background The current standard of care for the management of patients with newly diagnosed glioblastoma (GBM) includes maximal safe resection followed by radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). While it is well established that TMZ has better efficacy in patients with MGMT promoter methylation, it remains an area of debate whether TMZ should be omitted when treating GBM patients with unmethylated MGMT. Methods We conducted a systematic review and meta-analysis to provide separate estimates of median overall survival (OS) and progression-free survival (PFS) for patients with methylated and unmethylated GBM treated with RT with or without TMZ. We searched multiple databases from inception to January 13, 2020. Results The median OS for patients with unmethylated GBM treated with RT/TMZ pooled from 5 phase III studies (N = 655) was 14.11 months (95% confidence interval [CI], 13.18–15.04) with a median PFS of 4.99 months (95% CI, 4.25–5.72). In contrast, the median OS for patients with methylated GBM pooled from 6 studies (N = 753) was 24.59 months (95% CI, 22.19–26.99) with a median PFS pooled from 7 studies (N = 805) of 9.51 months (95% CI, 7.41–11.61). There is a paucity of prospective data pertaining to OS/PFS in unmethylated patients treated with RT only and therefore a direct comparison was not possible. Conclusions This meta-analysis provides estimates of survival for patients with MGMT methylated or unmethylated GBM treated with RT/TMZ. Further research is needed to delineate whether TMZ should be withheld for patients with unmethylated GBM outside of the setting of clinical trials.

Background Hyperinsulinaemia is considered as a major risk factor for the development of a myriad of chronic diseases. We examined the association between the dietary insulinaemic potential and the odds of non‐alcoholic fatty liver disease (NAFLD) among Iranian adults. Methods After being subjected to a liver ultrasound, 166 patients with NAFLD and 200 controls were included in the study. The dietary intakes and the physical activity levels of the participants were evaluated using a validated semi‐quantitative food frequency questionnaire and the International Physical Activity Questionnaire (short IPAQ), respectively. The insulinaemic potential of the diet was assessed by computing the scores of the Empirical Dietary Index for Hyperinsulinemia (EDIH) and the Empirical Dietary Index for Insulin Resistance (EDIR). Results Compared with the control subjects, patients with NAFLD were significantly older; had higher values for body mass index, fasting blood sugar, triglycerides, low‐density lipoprotein cholesterol, total cholesterol and alanine transaminase; and were more likely to smoke. Moreover, NAFLD patients had significant lower levels of high‐density lipoprotein cholesterol and were less likely to perform physical activity. The risk of NAFLD was higher in the individuals in the highest tertile of the EDIH (odds ratio [OR] = 2.79; 95% confidence interval [CI] = 1.32–5.90; p value for trend < 0.05) and EDIR (OR = 2.42; 95% CI = 1.22‐4.79; p value for trend < 0.05) compared to those in the lowest tertile of these scores. Conclusions Our study indicates that a higher dietary insulinaemic potential is associated with an increased risk of NAFLD.

ally representative estimates. Of the baseline sample, 75.7% were retained at wave IV and 0.1% of data were missing for exposure or outcome. The P value level of significance was .05, and all P values were 2-sided. Results | The sample consisted of 14 786 young adults, with mean (SE) age 28.1 (0.1) years, 49.3% female sex, and 65.6% non-Hispanic white race/ethnicity (Table; all means and percentages were calculated with weighted data to reflect the representative proportion in the target US population). Overall, 11% of young adults were food insecure. The prevalence of migraine was higher among food-insecure vs food-secure young adults (23.9% vs 13.6%; P < .001; Figure). Food-insecure young adults had greater odds of migraine in unadjusted (odds ratio, 2.00; 95% CI, 1.68-2.38; P < .

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Introduction: Nonconvulsive seizures (NCSs) are common in critically ill adult patients with acute neurologic conditions. However, the effect of NCSs on patient outcome remains unclear. In this study, we aimed to determine the effect of NCSs on short-term outcome and to assess the clinical and EEG factors associated with NCSs. Methods: We retrospectively identified 219 adult patients from the EEG reporting system who underwent continuous EEG (cEEG) monitoring between January 2018 and June 2018. Patients with anoxic brain injury were excluded from the study. Clinical, laboratory, and EEG data were reviewed to determine potentially predictive factors of NCSs. The impact of NCSs on in-hospital mortality, length of stay, and disability on discharge was measured; an modified Rankin scale of three or greater was considered disabled. Results: Of the 219 patients included in our study, a total of 14% (n = 31) had NCSs on continuous EEG, of which 42% (n = 13) had their first seizure discharge recorded during the first hour of continuous EEG monitoring. The presence of clinical seizures before continuous EEG (odds ratio = 1.787; 95% confidence interval = 1.197–2.667, P = 0.0045), history of epilepsy (odds ratio = 1.508; 95% confidence interval = 1.027–2.215, P = 0.035), and comatose state (29 vs. 16%; P = 0.0006) were associated with NCSs. Among EEG characteristics, the presence of interictal epileptiform discharges (P < 0.0001), lateralized rhythmic delta activity (P = 0.02), and lateralized periodic discharges (P < 0.0001) were associated with NCSs. Nonconvulsive seizures were significantly associated with longer in-hospital stay (23.68 ± 24.84 vs. 17.14 ± 20.52; P = 0.036) and disability on discharge (87% [n = 27] vs. 13% [n = 4], P = 0.02). However, there was no significant association between NCS and in-hospital mortality (9.6% [n = 3] vs. 10.6% [n = 20]; P = 0.1). Conclusions: Nonconvulsive seizures are associated with longer in-hospital stay and disability on discharge but not with in-hospital mortality in adult patients.

Molecular heterogeneity has confounded attempts to target individual pathways in brain tumors. However, gliomas with BRAF mutations have been identified as being uniquely vulnerable to targeted therapies. Such mutations are predominantly seen in brain tumors of the adolescent and young adult population. Given that accurate and timely identification of such mutations is essential for offering appropriate treatment, treatment centers should offer both immunohistochemical and sequencing methods for detection of these mutations to guide treatment. Additional studies of these tumors at recurrence would also allow identification of breakthrough resistance mechanisms that may also be targetable for treatment. Due to the relative rarity of these tumors, multicenter collaborative studies will be essential in achieving long term control of these tumors.

Background Glioblastoma remains a deadly brain cancer with dismal prognosis. Genetic alterations, including IDH mutations, 1p19q co-deletion status and MGMT promoter methylation have been proven to be prognostic and predictive to response to treatment in gliomas. In this manuscript, we aimed to correlate other mutations and genetic alterations with various clinical endpoints in patients with IDH-wild-type (IDHwt) glioblastoma. Methods We compiled a comprehensive clinically annotated database of IDHwt GBM patients treated at the Ohio State University Wexner Medical Center for whom we had mutational data through a CLIA-certified genomic laboratory. We then added data that is publicly available from Memorial Sloan Kettering Cancer Center through cBioPortal. Each of the genetic alterations (mutations, deletions and amplifications) served as a variable in univariate and multivariate Cox proportional hazard models. Results A total of 175 IDHwt GBM patients with available MGMT promoter methylation data from both cohorts were included in the analysis. As expected, MGMT promoter methylation was significantly associated with improved overall survival (OS). Median OS for MGMT promoter methylated and unmethylated GBM was 26.5 and 18 months, respectively (HR 0.45; p=0.003). Moreover, EGFR/ERBB alterations were associated with favorable outcome (HR of 0.37 (p=0.003), but only in MGMT promoter unmethylated GBM. We further found that patients with EGFR/ERBB alterations who also harbored PDGFRA amplification had a significantly worse outcome (HR 7.89; p=0.025). Conclusions Our data provides further insight into the impact of genetic alterations on various clinical outcomes in IDHwt GBM in two cohorts of patients with detailed clinical information and inspire new therapeutic strategies for IDHwt GBM.

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