716 IDH2 mutations are commonly associated with 1p/19q codeletion in diffuse adult gliomas Diffuse gliomas are classified according to the 2016 World Health Organization (WHO) Classification of ...Tumors of the Central Nervous System, 1 which combines histological and molecular features. Diagnosis requires the assessment of mutations in the isocitrate dehydrogenase genes (IDH1 and IDH2), key genetic alterations characterizing gliomas with favorable outcome. 2 Because IDH1 and IDH2 are highly similar enzymes, the WHO classification, as most of the current studies, combines these mutations into the same molecular group; however, it is unclear whether these tumors share the same characteristics. We analyzed data from 1517 patients included in the French POLA Network to investigate differences between IDH1-and IDH2-mutant gliomas. Inclusion criteria were the written consent of the patient for clinical data collection and genetic analysis and sufficient material for molecular studies allowing classification according to the 2016 WHO classification. IDH1-R132H mutational status was evaluated using automated immunohistochemistry in all cases (n = 1517). Direct sequencing 3 was performed in 978 cases and demonstrated IDH mutation in 573 cases (this includes confirmation of IDH1-R132H mutation in 468 cases, other IDH1 mutations in 61 cases, and IDH2 mutation in 44 cases). The 1p/19q codeletion status was determined based on single nucleotide polymor-phism arrays, comparative genomic hybridization arrays, and/ or microsatellite marker analysis. 3 The following data were recorded: age, sex, follow-up, and MRI features (tumor location , extension, contrast enhancement, edema). All statistical analysis was done using IBM SPSS statistics software version 23. Chi-square test was used to compare qualitative variables. Continuous variables were compared using the Mann– Whitney U-test, and the Kaplan–Meier method was used to estimate survival distributions. Among the 1517 patients, 1025 had an IDH-mutant tumor: 96% were IDH1-mutant and 4% IDH2-mutant. Integrated diagnoses are summarized in Fig. 1. The frequency of 1p/19q code-letion was higher in the IDH2-mutant group compared with the IDH1-mutant group (91% vs 48%, P < 0.001). Wang and coworkers previously reported higher frequency of 1p/19q codeletion in IDH2-mutant gliomas (9/18 samples) compared with IDH1-mutant. 4 The percentage of each category in our study does not reflect the normal distribution of glioma because of the inclusion criteria in the POLA Network (ie, high-grade glioma with oligodendroglial component). However, the higher proportion of 1p/19q codeleted glioma in the IDH2-mutant group cannot be attributed to the inclusion criteria. Because the main population of glioma associated with IDH2 mutation was 1p/19q codeleted anaplastic oligodendroglioma, we focused on this subgroup to search for differences compared with IDH1 mutation. Among these patients (n = 474), we did not observe any difference in terms of age, sex, progression free survival, or overall survival between IDH1-and IDH2-mutant tumors. However, IDH2-mutant anaplastic oli-godendrogliomas presented more frequently with multilobar extension (56% of the IDH2-mutant vs 35% of the IDH1-mutant, P = 0.015) and edema (79% vs 57%, P = 0.02). Furthermore, bifrontal location with corpus callosum involvement was more frequent in IDH2-mutant compared with IDH1-mutant tumors (41% vs 16%, P < 0.001). IDH mutation is supposed to be one of the first " hits " of gliomagenesis, 5 resulting in production of an oncome-tabolite, D-2-hydroxyglutarate (D-2HG), which impacts the α-ketoglutarate–dependent dioxygenase functions. Previous studies demonstrated that the potential for IDH-mutant enzymes to produce D-2HG depends on the mutation type. 6 Based on our observations, we could hypothesize that the higher D-2HG accumulation induced by IDH2 mutation may lead to a phenotype that is favorable to 1p/19q chromosomal loss. It may also impact distinct cellular pathways that promote a more invasive phenotype. Whether IDH1 or IDH2 mutations impact distinct glial precursor cells with differential invasive properties remains to be elucidated. In conclusion, our results illustrate that IDH2-mutant glio-mas are commonly associated with 1p/19q codeletion. Most of IDH2-mutant anaplastic oligodendroglioma 1p/19q codeleted are multilobar. Understanding the genomic events involved in these specificities may represent a step forward for therapeutic development.
•Xanthan was successfully C-6 carboxylated by TEMPO/NaOCl/NaBr media system.•A new family of polyglucuronic acid called xanthouronan was generated.•Xanthouronan was a high molecular weight ...polysaccharide with antioxidant properties.•Xanthouronan was very resistant to various enzymatic treatments.
A xanthouronic acid sodium salt called xanthouronan was produced from xanthan by regioselective oxidation with NaOCl/NaBr using 2,2,6,6-tetramethylpiperidine-1-oxy radical (TEMPO) as catalyst. The efficiency of the one pot TEMPO-mediated oxidation was confirmed by HPAEC-PAD, 13C NMR, and FT-IR. The oxidation degree was close to 98% and the mass yield of this new polyglucuronic acid was higher than 90% (w/w). The macromolecular characterization of xanthouronan using SEC-MALLS showed a molecular size reduced by a third due to the oxidation treatment and the degree of polymerization (DP) of the xanthouronan form was about 665. The evaluation of the enzymatic degradation of this C-6 carboxylated xanthan by various polysaccharide hydrolases and one polysaccharide lyase showed its high resistant to biodegradation. The antioxidant activity of xanthouronan was also tested by using the 2,2′-diphenyl-1-picrylhydrazyle (DPPH) and hydroxyl radical procedures. At 1g/L, xanthouronan presented 75% of the ascorbic acid antioxidant activity.
The N=48 super(80) Ge nucleus is studied by means of beta-delayed electron-conversion spectroscopy at ALTO. The radioactive super(80) Ga beam is produced through the isotope separation on line ...photofission technique and collected on a movable tape for the measurement of gamma and e super(-) emission following beta decay. An electric monopole E 0 transition, which points to a 639(1) keV intruder 0(ProQuest: Formulae and/or non-USASCII text omitted) state, is observed for the first time. This new state is lower than the 2(ProQuest: ... denotes formulae and/or non-USASCII text omitted) level in super(80) Ge, and provides evidence of shape coexistence close to one of the most neutron-rich doubly magic nuclei discovered so far, super(78) Ni. This result is compared with theoretical estimates, helping to explain the role of monopole and quadrupole forces in the weakening of the N=50 gap at Z=32. The evolution of intruder ... states towards super(78) Ni is discussed.
Flow-diverter stents are widely used for the treatment of wide-neck intracranial aneurysms. Various parameters may influence intracranial aneurysm thrombosis, including the flow reduction induced by ...flow-diverter stent implantation, which is assumed to play a leading role. However, its actual impact remains unclear due to the lack of detailed intra-aneurysmal flow measurements. This study aimed to clarify this relationship by quantitatively measuring the intra-aneurysmal flow using 4D phase-contrast MR imaging.
We acquired prospective pre- and post-stent implantation 4D phase-contrast MR imaging data of a consecutive series of 23 patients treated with flow-diverter stents. Velocity field data were combined with the intraprocedural 3D angiogram vessel geometries for precise intracranial aneurysm extraction and partial volume correction. Intra-aneurysmal hemodynamic modifications were compared with occlusion outcomes at 6 and 12 months.
The averaged velocities at systole were lower after flow-diverter stent implantation for all patients and ranged from 21.7 ± 7.1 cm/s before to 7.2 ± 2.9 cm/s after stent placement. The velocity reduction was more important for the group of patients with aneurysm thrombosis at 6 months (68.8%) and decreased gradually from 66.2% to 55% for 12-month thrombosis and no thrombosis, respectively (
= .08).
We propose an innovative approach to measure intracranial flow changes after flow-diverter stent implantation. We identified a trend between flow reduction and thrombosis outcome that brings a new insight into current understanding of the flow-diversion treatment response.
•An automatic tool (Morpho3D) was developed to register and analyze 3D body shapes of large animals.•Correlations between Morpho3D and manual measurements on morphological traits are ...high.•Reproducibility and repeatability variation coefficients are lower than 4%.•It will offer opportunities to determine animal body volume and surface.
Monitoring the growth and body condition of cows is essential for optimal management of modern dairy farms. However, monitoring is rarely performed on commercial farms. Modern technologies based on three-dimensional (3D) shape analysis could address this problem. The objective of the present study was to test and validate tools that can record and analyze 3D body shapes of animals. On 30 Holstein dairy cows, wither height (WH), heart girth (HG), chest depth (CD), hip width (HW), backside width (BaW) and ischial width (IW) were manually measured. These manual measurements were compared to those measured with a scanner (Morpho3D) that provided 3D images of the entire cow body. Correlations between manual and Morpho3D measurements were high: 0.89 for CD, 0.82 for HW, 0.78 for HG, 0.76 for BaW, 0.63 for IW and 0.62 for WH. The mean coefficient of variation of reproducibility for Morpho3D was 2.8%. Future development can provide new opportunities for dairy herd management based on determining animal body volume and surface area.
A retrospective clinical and pathological study of 4 patients who developed the syndrome of radiation induced dementia was performed. All patients fulfilled the following criteria: (1) a history of ...supratentorial irradiation; (2) no evidence of symptomatic recurrent tumor; (3) no other cause of progressive cerebral dysfunction and dementia. The clinical picture consisted of a progressive "subcortical" dementia occurring 3-12 months after a course of cerebral radiotherapy. Examination revealed early bilateral corticospinal tract involvement in all patients and dopa-resistant Parkinsonian syndrome in two. On CT scan and MRI of the brain, the main features consisted of progressive enlargement of the ventricles associated with a diffuse hypodensity/hyperintensity of the white matter best seen on T2 weighted images on MRI. The course was progressive over 8-48 months in 3 patients while one patient had stabilization of his condition for about 28 years. Treatment with corticosteroids or shunting did not produce sustained improvement and all patients eventually died. Pathological examination revealed diffuse white matter pallor with sparing of the arcuate fibers in all patients. Despite a common pattern on gross examination, microscopic studies revealed a variety of lesions that took two basic forms: (1) a diffuse axonal and myelin loss in the white matter associated with tissue necrosis, particularly multiple small foci of necrosis disseminated in the white matter which appeared different from the usual "radionecrosis"; (2) diffuse spongiosis of the white matter characterized by the presence of vacuoles that displaced the normally-stained myelin sheets and axons. Despite a rather stereotyped clinical and radiological course, the pathological substratum of radiation-induced dementia is not uniform. Whether the different types of white matter lesions represent the spectrum of a single pathological process or indicate that the pathogenesis of this syndrome is multifactorial with different target cells, remains to be seen.
Assessment of mutation status in patients with non-small cell lung cancer (NSCLC) is often required. The aim of this study was to confirm the feasibility of molecular mutation analysis in cytologic ...specimens obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).
Patients with an EBUS-TBNA positive for adenocarcinoma or NSCLC (squamous cell carcinoma excluded) were included retrospectively from January to December 2010, and prospectively from January to August 2011. Specimens were collected on liquid based preparation and processed on paraffin-embedded cell blocks after ThinPrepÒ procedure. Molecular analysis was performed by a SnaPshot assay for EGFR and by pyrosequencing for KRAS on suitable samples (>5% tumor cells).
Eighty-two patients were included (63 adenocarcinoma). Molecular analysis for EGFR was feasible in 80 (97.6%) patients and for KRAS in 78 (95.1%) patients. Molecular analysis identified EGFR and KRAS mutations in tumor samples from four (5%) and 18 (23%) patients respectively. All EGFR mutations were found in women.
Molecular analysis mutations can be performed routinely in cytologic specimens obtained by EBUS-TBNA.
Background: Paraneoplastic neurological syndromes (PNS) are defined by the presence of cancer and exclusion of other known causes of the neurological symptoms, but this criterion does not separate ...“true” PNS from neurological syndromes that are coincidental with a cancer. Objective: To provide more rigorous diagnostic criteria for PNS. Methods: An international panel of neurologists interested in PNS identified those defined as “classical” in previous studies. The panel reviewed the existing diagnostic criteria and recommended new criteria for those in whom no clinical consensus was reached in the past. The panel reviewed all reported onconeural antibodies and established the conditions to identify those that would be labelled as “well characterised”. The antibody information was obtained from published work and from unpublished data from the different laboratories involved in the study. Results: The panel suggest two levels of evidence to define a neurological syndrome as paraneoplastic: “definite” and “possible”. Each level can be reached combining a set of criteria based on the presence or absence of cancer and the definitions of “classical” syndrome and “well characterised” onconeural antibody. Conclusions: The proposed criteria should help clinicians in the classification of their patients and the prospective and retrospective analysis of PNS cases.
There is limited data about the diagnostic performance of EBUS-TBNA in patients with mediastinal lymphadenopathy and extrathoracic malignancy.
From January 2007 to July 2011, EBUS-TBNA was performed ...in 68 patients with a history of extrathoracic malignancy (current or past) and suspected mediastinal lymph node metastases.
Thirty-one patients had a final diagnosis of cancer. In nineteen patients, the same histology was identified in the mediastinal nodes as in their prior extrathoracic cancer (colorectal cancer, esophageal cancer and lymphoma). In 12, the diagnosis was not "as expected" (ten lung cancers, one colorectal cancer, one unidentified cancer). Among 37 patients without diagnosis, biopsies in 27 showed normal lymphoid material, two had non-specific inflammation and eight had no contributory results. It was noted that procedures were reported to have been more difficult in these patients.
Diagnostic performance of EBUS-TBNA in the context of extrathoracic malignancy is very variable depending on the origin of the cancer. Nevertheless, a diagnosis is concluded in almost 50% of the cases. These results underline the necessity to select carefully the indications of EBUS-TBNA in extrathoracic cancer.
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