H3K27M, IDH1, and ATRX expression in pediatric GBM and their clinical and prognostic significance.

PURPOSE: Pediatric glioblastoma (pGBM) tumors have been identified as an entity distinct and different from the adult variety of GBM not only with respect to pathogenesis, genetics, and molecular alterations but also in clinical outcomes and overall survival. This study aims to evaluate the immunohistochemical profile of molecular markers in pediatric GBM and correlate them with clinical features and prognosis. MATERIALS AND METHODS: We retrospectively analyzed 29 pGBMs (age range 3 to 18 years), operated at our institute between 2009 and 2014, and evaluated their clinical and histopathological features along with the immunohistochemical expression of clinically relevant molecular markers: H3K27M, p53, ATRX, and IDH1 (R132H), and correlated their expression with clinical features. We further assessed the prognostic value of these markers in our cohort of patients. RESULTS: The median overall survival (OS) of the cohort was 6.00 ± 0.882 months. The mean overall survival was 7.571 ± 1.118 months which was lower than in most studies. Preoperative Karnofsky Performance Score (KPS), extent of surgical resection, and adjuvant radiotherapy were found to be the clinical factors strongly influencing median survival (p < 0.05). Loss of ATRX expression was predominantly noted in hemispheric tumors (84%), while p53 staining was maximum in thalamic tumors (8 out of 9 cases). H3K27M mutant protein expression was noted in 8/9 thalamic tumors and 5/7 tumors in the brain stem-cerebellar-peduncular region. Patients with tumors showing H3K27M immunopositivity had the worst prognosis with a mean OS of 5 months ± 0.832 months, as against patients with H3K27M-immunonegative tumors, which was 10.143 ± 1.866 months(p = 0.006). Other markers like p53, ATRX, and IDH1 did not influence the prognosis in this patient cohort. ATRX loss of expression was associated with a better OS, with a trend to significance, and such an association has not been reported earlier. CONCLUSIONS: Ours is one among the few studies from India describing the clinical parameters and evaluating the key immunohistochemical markers in pGBM and deriving their prognostic significance. The study reiterates the poor prognostic significance of H3K27M immunopositivity.

UDAY: A comprehensive diabetes and hypertension prevention and management program in India.

INTRODUCTION: Diabetes and hypertension are two leading non-communicable conditions, which are suboptimally managed in India. Thus, innovative comprehensive approaches that can concomitantly improve their detection, prevention and control are warranted. METHODS AND ANALYSIS: UDAY, a 5-year initiative, aims to reduce the risk of diabetes and hypertension and improve management by implementing a comprehensive intervention programme in the two selected study sites, Sonipat and Visakhapatnam (Vizag). It has a pre-post evaluation design with representative cross-sectional surveys before and after intervention. Within these two sites, urban and rural subsites each with a total population of approximately 100 000 people each were selected and a baseline and postintervention assessment was conducted deploying five surveys [among general population (including body measurements or biosamples), patients, healthcare providers including physicians and pharmacists, health facilities], which will determine the knowledge levels about diabetes and hypertension, the proportion treated and controlled; the patient knowledge and self-management skills; healthcare providers' management practices; the level of access and barriers to obtaining care.The interventions will include: tailored health promotion for improving public knowledge; screening of adults aged ≥ 30 years for identifying those at high risk of diabetes and/or hypertension for linkage to the healthcare system; patient education using technology enabled community health workers, geographic information system (GIS) based mapping of the communities, healthcare provider training on management guidelines, community based diabetes registry and; advocacy to improve access to healthcare. The baseline surveys have been completed, the study areas mapped using GIS and the interventions are being implemented. UDAY is expected to increase over baseline the levels of: public knowledge about diabetes and hypertension; those treated and controlled; patient self-management skills; the use of guideline based management by providers and; access to healthcare, leading to improved health outcomes and inform development of a India relevant chronic care model. ETHICS AND DISSEMINATION: Ethical clearance for conduct of the study was obtained from the Institutional Ethics Committee (IEC) of the Public Health Foundation of India. The findings will be targeted primarily at public health policymakers and advocates, but will be disseminated widely through other mechanisms including conference presentations and peer-reviewed publications, as well as to the participating communities.

Dexmedetomidine anesthesia enhances spike generation during intra-operative electrocorticography: A promising adjunct for epilepsy surgery.

BACKGROUND: Anesthetic-induced suppression of cortical electrical activity is a major concern during epilepsy surgery. Dexmedetomidine (Dex) has been recently evaluated in a few small series for its effect on the electrocorticographic spikes intra-operatively. METHODS: In this prospective study, electrocorticogram (ECoG) was monitored during dexmedetomidine infusion in 34 patients (M:F=23:11, age=29.2 ± 10.9 years; duration of epilepsy=15.3 ± 8.9 years) undergoing anterior temporal lobe resection with amygdalo-hippocampectomy for drug-resistant mesial temporal lobe epilepsy (Right: 18, Left: 16). Anesthesia was induced with thiopental/propofol and maintained with oxygen-N2O-isoflurane. ECoG was recorded for 5 min after the end tidal MAC of N2O and isoflurane were decreased to zero; anesthesia was maintained with O2:Air=50:50, vecuronium and fentanyl. ECoG was recorded using a 4-contact strip electrode for: (a) 5 min prior to dexmedetomidine (PreDEX), (b) 5 min during dexmedetomidine infusion (DEX; 1 µg/kg) and (c) 5 min after stopping dexmedetomidine (PostDEX). RESULTS: The ECoG spikes were manually counted in all the channels. The mean spike rate in the 2 channels with maximum spikes (MAX CH A and MAX CH B) was normalized to a 3-min duration. RM-ANOVA and post hoc comparison of three phases were used to compare the spike rates. The mean spike rate during Dex phase was higher compared to preDEX (MAX CH B: p=0.007 and MAX CH A: p=0.079) and PostDEX (MAX CH B: p=0.17, MAX CH A: p=0.79) phases. The spike rate increased in 67.6% patients, while 11.8% patients showed ≤ 25% reduction and 20.6% patients showed >25% reduction in spike frequency. CONCLUSION: Dexmedetomidine is useful during intra-operative ECoG recording in epilepsy surgery as it enhances or does not alter spike rate in most of the cases, without any major adverse effects.

Hemodynamic effects of dexmedetomidine during intra-operative electrocorticography for epilepsy surgery.

BACKGROUND: Dexmedetomidine, a predominant alpha-2-adrenergic agonist has been used in anesthetic practice to provide good sedation. The drug is being recently used in neuroanesthesia during awake surgery for brain tumors and in functional neurosurgery. MATERIALS AND METHODS: This prospective study analyzed the hemodynamic effects of dexmedetomidine infusion during electrocorticography in patients undergoing surgery for mesial temporal sclerosis. Dexmedetomidine infusion was administered during intra-operative electrocorticography recording, 15 minutes after the end tidal MAC of N2O and isoflurane were decreased to zero. Anesthesia was maintained with O2 : air mixture = 50:50, vecuronium and fentanyl. Heart rate (HR), mean arterial pressure (MAP) and end tidal carbon dioxide (ETCO2) were recorded across at induction, 2 min prior to dexmedetomidine (PreDEX), 5 min during dexmedetomidine infusion (DEX; 1 µg/kg), 5 min after stopping dexmedetomidine and 10 minutes after stopping dexmedetomidine. RESULTS: Forty patients with mesial temporal sclerosis (M: F = 27:13, mean age = 28.15 ± 10.9 years; duration of epilepsy = 12.0 ± 7.9 years) underwent anterior temporal lobe resection with amygdalohippocampectomy for drug-resistant epilepsy. Infusion of dexmedetomidine caused a transient fall in HR in 87.5% of patients and an increase in MAP in 62.5% of patients, which showed a tendency to revert back towards PreDEX values within 10 min after stopping the infusion. Sixty-five percent of the patients showed ≤25% reduction and 10% of them showed >25% reduction in HR. 47.5% of the patients showed ≤25% increase and 15% of them showed >25% increase in MAP. These changes were over a narrow range and within physiological limits. CONCLUSION: The infusion of dexmedetomidine for a short period causes reduction of HR and increase in MAP in patients, however the variations are within acceptable range.