IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection

Background

IDH1 gene mutations identify gliomas with a distinct molecular evolutionary origin. We sought to determine the impact of surgical resection on survival after controlling for IDH1 status in malignant astrocytomas—World Health Organization grade III anaplastic astrocytomas and grade IV glioblastoma.

Methods

Clinical parameters including volumetric assessment of preoperative and postoperative MRI were recorded prospectively on 335 malignant astrocytoma patients: n = 128 anaplastic astrocytomas and n = 207 glioblastoma. IDH1 status was assessed by sequencing and immunohistochemistry.

Results

IDH1 mutation was independently associated with complete resection of enhancing disease (93% complete resections among mutants vs 67% among wild-type, P < .001), indicating IDH1 mutant gliomas were more amenable to resection. The impact of residual tumor on survival differed between IDH1 wild-type and mutant tumors. Complete resection of enhancing disease among IDH1 wild-type tumors was associated with a median survival of 19.6 months versus 10.7 months for incomplete resection; however, no survival benefit was observed in association with further resection of nonenhancing disease (minimization of total tumor volume). In contrast, IDH1 mutants displayed an additional survival benefit associated with maximal resection of total tumor volume (median survival 9.75 y for >5 cc residual vs not reached for <5 cc, P = .025).

Conclusions

The survival benefit associated with surgical resection differs based on IDH1 genotype in malignant astrocytic gliomas. Therapeutic benefit from maximal surgical resection, including both enhancing and nonenhancing tumor, may contribute to the better prognosis observed in the IDH1 mutant subgroup. Thus, individualized surgical strategies for malignant astrocytoma may be considered based on IDH1 status.     

Electronic,Structural, and Optical Properties of Mono-Doped and Co-Doped (210) TiO2 Brookite Surfaces for Application in Dye-Sensitized Solar Cells—A First Principles Study

Titanium dioxide (TiO₂) polymorphs have recently gained a lot of attention in dye-sensitized solar cells (DSSCs). The brookite polymorph, among other TiO₂ polymorphs, is now becoming the focus of research in DSSC applications, despite the difficulties in obtaining it as a pure phase experimentally. The current theoretical study used different nonmetals (C, S and N) and (C-S, C-N and S-N) as dopants and co-dopants, respectively, to investigate the effects of mono-doping and co-doping on the electronic, structural, and optical structure properties of (210) TiO₂ brookite surfaces, which is the most exposed surface of brookite. The results show that due to the narrowing of the band gap and the presence of impurity levels in the band gap, all mono-doped and co-doped TiO₂ brookite (210) surfaces exhibit some redshift. In particular, the C-doped, and C-N co-doped TiO₂ brookite (210) surfaces exhibit better absorption in the visible region of the electromagnetic spectrum in comparison to the pure, S-doped, N-doped, C-S co-doped and N-S co-doped TiO₂ brookite (210) surfaces.     

Nonvirally engineered porcine adipose tissue-derived stem cells: use in posterior spinal fusion

Multiple factors alter intervertebral disc volume, structure, shape, composition, and biomechanical properties, often leading to low back pain. Spinal fusion is frequently performed to treat this problem. We recently published results of our investigation of a novel system of in vivo bone formation, in which we used nonvirally nucleofected human mesenchymal stem cells that overexpress a bone morphogenetic protein gene. We hypothesized that primary porcine adipose tissue-derived stem cells (ASCs) nucleofected with plasmid containing recombinant human bone morphogenetic protein-6 (rhBMP-6) could induce bone formation and achieve spinal fusion in vivo. Primary ASCs were isolated from freshly harvested porcine adipose tissue. Overexpression of rhBMP-6 was achieved ex vivo by using a nucleofection technique. Transfection efficiency was monitored by assessing a parallel transfection involving an enhanced green fluorescent protein reporter gene and flow cytometry analysis. rhBMP-6 protein secreted by the cells was measured by performing an enzyme-linked immunosorbent assay. Genetically engineered cells were injected into the lumbar paravertebral muscle in immunodeficient mice. In vivo bone formation was monitored by a quantitative microcomputed tomography (muCT). The animals were euthanized 5 weeks postinjection, and spinal fusion was evaluated using in vitro muCT and histological analysis. We found formation of a large bone mass adjacent to the lumbar area, which produced posterior spinal fusion of two to four vertebrae. Our data demonstrate that efficient bone formation and spinal fusion can be achieved using ex vivo, nonvirally transfected primary ASCs. These results could pave the way to a novel biological solution for spine treatment.     

The natural history of EGFR and EGFRvIII in glioblastoma patients

Background  

The epidermal growth factor receptor (EGFR) is over expressed in approximately 50–60% of glioblastoma (GBM) tumors, and the most common EGFR mutant, EGFRvIII, is expressed in 24–67% of cases. This study was designed to address whether over expressed EGFR or EGFRvIII is an actual independent prognostic indicator of overall survival in a uniform body of patients in whom gross total surgical resection (GTR; ≥ 95% resection) was not attempted or achieved.     

Hodgkin's lymphoma,nephrotic syndrome,and echinococcosis cysts: an unusual association and literature review

We present a 5-year-old female with minimal change nephrotic syndrome (MCNS). Within several months, she became steroid-dependent with progression of edema and ascites. Imaging studies revealed abnormal solid mass and liver cysts and she was diagnosed with both abdominal Hodgkin's lymphoma (cHD) and large hepatic cystic echinococcosis (CE). Association between MCNS and cHL or with CE has been described in the literature in adults and rarely in the pediatric population. We report, for the first time, a simultaneous occurrence of all three: MCNS, cHL, and CE. Literature review and suggested pathophysiologic mechanisms underlying this phenomenon are presented.     

Beyond the Bayley: Neurocognitive Assessments of Development During Infancy and Toddlerhood

The use of global, standardized instruments is conventional among clinicians and researchers interested in assessing neurocognitive development. Exclusively relying on these tests for evaluating effects may underestimate or miss specific effects on early cognition. The goal of this review is to identify alternative measures for possible inclusion in future clinical trials and interventions evaluating early neurocognitive development. The domains included for consideration are attention, memory, executive function, language, and socioemotional development. Although domain-based tests are limited, as psychometric properties have not yet been well-established, this review includes tasks and paradigms that have been reliably used across various developmental psychology laboratories.     

White Matter Alterations in Early Stages of Schizophrenia: A Systematic Review of Diffusion Tensor Imaging Studies

Several lines of evidence suggest that the normal integration of cerebral communication may be compromised in schizophrenia, with white matter (WM) abnormalities being integral to these functional deficits. Diffusion tensor imaging (DTI) is a neuroimaging technique which has increasingly been used to study WM through quantitative indices of its structural and orientational characteristics. Identifying the WM differences early in the course of schizophrenia may assist in prevention, early diagnosis and identification of treatment targets. In that respect, the aims of the present study were to (a) systematically review WM integrity in the early stages of schizophrenia as inferred by DTI and (b) specifically examine parameters that may affect WM: age, duration of illness and treatment. In summary, DTI studies in early schizophrenia suggest that structural dysconnectivity may be already present in recent‐onset and drug‐naïve patients, as well as in individuals clinically at high risk for developing schizophrenia. Although the pattern of WM differences is not totally consistent frontal, fronto‐temporal and fronto‐limbic connections, with tracts including the superior longitudinal fasciculus, cingulum bundle, uncinate fasciculus and corpus callosum seem to be affected. These differences may depend on the developmental stage of the subjects, the duration of illness and exposure to antipsychotic medication.     

Chronic Avulsion Lesion at the Brachialis Muscle Insertion

Teaching Point: Humeral splints or brachialis insertion avulsion syndrome is a distinct type of stress injury at the insertion of the brachialis muscle on the lateral surface of the humeral diaphysis.     

Responses of cortical noradrenergic and somatostinergic fibres and terminals to adjacent strokes and subsequent treatment with NGF and/or the ganglioside GM1

The occurrence of sprouting by fibre systems in the neocortex following lesion is still a controversial issue. In previous studies, we showed a nerve growth factor (NGF)-induced sprouting and hypertrophy of presynaptic terminals in the cholinergic fibres of the rat neocortex following stroke-type lesions, effects that were potentiated by the monosialoganglioside GM1. The present study investigated whether exogenous NGF and/or GM1 treatment could also affect the noradrenergic and somatostinergic systems in the neocortex. Immediately following unilateral vascular decortication, adult rats received, via minipump, a 7-day infusion of vehicle, NGF (12 μg/day) and/or GM1 (1.5 mg/day) into the cerebroventricular space. Thirty days postlesion, the animals were perfused with histological fixatives, the brains were removed, and relevant sections were processed for dopamine β-hydroxylase and somatostatin immunocytochemistry at the light and electron microscopic levels. A Quantimet 920 image analysis system was used for the quantification of fibre length and size of presynaptic boutons. The lesion caused a reduction in the dopamine β-hydroxylase-immunoreactive fibre length, which was not attenuated by either NGF or GM1 treatment or both. The somatostatin-immunoreactive network, in contrast, was unaffected by the lesion, and there was no sprouting of somatostatin fibres following trophic factor therapy. We also found no significant differences in the size and number of synapses of both the dopamine β-hydroxylase-immunoreactive and somatostatin-immunoreactive boutons following lesion and drug treatments. These results indicate that NGF and/or GM1 therapies do not cause regrowth in the noradrenergic and somatostatinergic cortical fibre networks or their presynaptic elements following a cortical devascularizing lesion. J. Neurosci. Res. 50:627–642, 1997. © 1997 Wiley-Liss, Inc.