Incorporating Supramaximal Resection into Survival Stratification of IDH-Wildtype Glioblastoma: A Refined Multi-institutional Recursive Partitioning Analysis.

PURPOSE: To propose a novel recursive partitioning analysis (RPA) classification model in patients with IDH-wildtype glioblastomas that incorporates the recently expanded conception of the extent of resection (EOR) in terms of both supramaximal and total resections. EXPERIMENTAL DESIGN: This multicenter cohort study included a developmental cohort of 622 patients with IDH-wildtype glioblastomas from a single institution (Severance Hospital) and validation cohorts of 536 patients from three institutions (Seoul National University Hospital, Asan Medical Center, and Heidelberg University Hospital). All patients completed standard treatment including concurrent chemoradiotherapy and underwent testing to determine their IDH mutation and MGMTp methylation status. EORs were categorized into either supramaximal, total, or non-total resections. A novel RPA model was then developed and compared to a previous RTOG RPA model. RESULTS: In the developmental cohort, the RPA model included age, MGMTp methylation status, KPS, and EOR. Younger patients with MGMTp methylation and supramaximal resections showed a more favorable prognosis (class I: median overall survival [OS] 57.3 months), while low-performing patients with non-total resections and without MGMTp methylation showed the worst prognosis (class IV: median OS 14.3 months). The prognostic significance of the RPA was subsequently confirmed in the validation cohorts, which revealed a greater separation between prognostic classes for all cohorts compared to the previous RTOG RPA model. CONCLUSIONS: The proposed RPA model highlights the impact of supramaximal versus total resections and incorporates clinical and molecular factors into survival stratification. The RPA model may improve the accuracy of assessing prognostic groups.

Absorption, Fluorescence, and Two-Photon Excitation Ability of 5-Phenylisolidolo[2,1-a]quinolines.

We report on the absorption, fluorescence, and two-photon excitation spectra of a series of 5-phenylisoindolo[2,1-a]quinoline dyes. Depending on the substituents, we observed increasing two-photon absorption cross sections, with values up to 56 GM@973 nm, which are similar to those of the enhanced green fluorescent protein and fluorescein, common fluorescent chromophores.

Spanish society of laboratory medicine external quality assurance programmes: evolution of the analytical performance of clinical laboratories over 30 years and comparison with other programmes.

The purpose of this study is to understand the evolution of the analytical performance of the laboratories participating in the Spanish society of laboratory medicine (SEQCML) external quality assurance (EQA) programmes during its 30 years of operation and to compare it with the performance of other EQA programmes to establish whether the results are similar. The results obtained during this period are evaluated by applying the biological variability (BV) and state of the art-derived quality specifications. In addition, the results are compared with those obtained by other EQA programme organisations. It is noted that the laboratories participating in the EQA-SEQCML programmes have improved their performance over 30 years of experience and that the specifications derived from biological variation are achievable. It is difficult to compare EQA programmes, due to lack of accessibility and the differences in the design of these programmes (control materials, calculations used and analytical specifications established). The data from this study show that for some biological magnitudes the results obtained by the programmes are not yet harmonised, although efforts are being made to achieve this. Organisers of EQA programmes should also join the harmonisation effort by providing information on their results to enable comparison.

State-of-the-art Approach to Goal Setting.

Four external quality assurance programs combined their data to calculate the minimum acceptable quality specifications for laboratory testing. Other sources of quality specifications may be too stringent for the current market, or too lenient given the clinical demands on the test result, but these state-of-the-art goals may be practical and useful. Two main approaches were used: (1) defining the 95% percentile and comparing with other quality specifications, and (2) using an iterative approach to increase the quality specification until 90% of laboratories could achieve 75% of their results within the specification. 72 out of 82 analytes followed procedure 2.

Biologically aggressive regions within glioblastoma identified by spin-lock contrast T1 relaxation in the rotating frame (T1ρ) MRI.

Spin-lattice relaxation in the rotating frame magnetic resonance imaging allows for the quantitative assessment of spin-lock contrast within tissues. We describe the utility of spin-lattice relaxation in the rotating frame metrics in characterizing glioblastoma biological heterogeneity. A 84-year-old man presented to our institution with a right frontal temporal mass. Prior tissue sampling from a peripheral nonenhancing lesion was nondiagnostic. Stereotactic image-guided tissue sampling of the nonenhancing T2-fluid-attenuated inversion recovery hyperintense region involving the anterior cingulate gyrus with elevated spin-lattice relaxation in the rotating frame metrics provided a pathologic diagnosis of glioblastoma. This case illustrates the utility of spin-lattice relaxation in the rotating frame magnetic resonance imaging in identifying biologically aggressive regions within glioblastoma.

Metastasis in Adult Brain Tumors.

Metastatic cancer to the central nervous system is primarily deposited by hematogenous spread in various anatomically distinct regions: calvarial, pachymeningeal, leptomeningeal, and brain parenchyma. A patient's overall clinical status and the information needed to make treatment decisions are the primary considerations in initial imaging modality selection. Contrast-enhanced MR imaging is the preferred imaging modality. Morphologic MR imaging is limited to delineating anatomic deraignment of tissues. Dynamic susceptibility contrast-enhanced perfusion and diffusion-weighted physiology-based MR imaging sequences have been developed that complement morphologic MR imaging by providing additional diagnostic information.

PASMet: a web-based platform for prediction, modelling and analyses of metabolic systems.

PASMet (Prediction, Analysis and Simulation of Metabolic networks) is a web-based platform for proposing and verifying mathematical models to understand the dynamics of metabolism. The advantages of PASMet include user-friendliness and accessibility, which enable biologists and biochemists to easily perform mathematical modelling. PASMet offers a series of user-functions to handle the time-series data of metabolite concentrations. The functions are organised into four steps: (i) Prediction of a probable metabolic pathway and its regulation; (ii) Construction of mathematical models; (iii) Simulation of metabolic behaviours; and (iv) Analysis of metabolic system characteristics. Each function contains various statistical and mathematical methods that can be used independently. Users who may not have enough knowledge of computing or programming can easily and quickly analyse their local data without software downloads, updates or installations. Users only need to upload their files in comma-separated values (CSV) format or enter their model equations directly into the website. Once the time-series data or mathematical equations are uploaded, PASMet automatically performs computation on server-side. Then, users can interactively view their results and directly download them to their local computers. PASMet is freely available with no login requirement at http://pasmet.riken.jp/ from major web browsers on Windows, Mac and Linux operating systems.

Metastatic Diffuse Intrinsic Pontine Glioma to the Peritoneal Cavity Via Ventriculoperitoneal Shunt: Case Report and Literature Review.

Extraneural metastatic disease resulting from a primary central nervous system neoplasm is a rare clinical finding in the pediatric population. We report a case of peritoneal glioblastoma carcinomatosis following placement of a ventriculoperitoneal shunt and chemoradiotherapy in a 6-year-old female patient who initially presented with diffuse intrinsic pontine glioma. This case demonstrates the importance of evaluation of extraspinal structures when imaging for extension of disease. Additionally, this report highlights the cross-sectional imaging characteristics of glioblastoma peritoneal carcinomatosis and presents additional information that will facilitate the timely diagnosis of extraneural metastases of primary high-grade glial neoplasms in the pediatric population.

Benefits of dynamic susceptibility-weighted contrast-enhanced perfusion MRI for glioma diagnosis and therapy.

Glioma are the most common supra-tentorial brain tumor in the USA with an estimated annual incidence of 17,000 new cases per year. Dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion MRI noninvasively characterizes tumor biology allowing for the diagnosis and therapeutic monitoring of glioma. This MRI technique utilizes the rapid changes in signal intensity caused by a rapid intravascular bolus of paramagnetic contrast agent to calculate physiologic perfusion metrics. DSC perfusion MRI has increasingly become an integrated part of glioma imaging. The specific aim of this article is to review the benefits of DSC perfusion MRI in the therapy of glioma.

Metabolomic Characterization of Knockout Mutants in Arabidopsis: Development of a Metabolite Profiling Database for Knockout Mutants in Arabidopsis.

Despite recent intensive research efforts in functional genomics, the functions of only a limited number of Arabidopsis (Arabidopsis thaliana) genes have been determined experimentally, and improving gene annotation remains a major challenge in plant science. As metabolite profiling can characterize the metabolomic phenotype of a genetic perturbation in the plant metabolism, it provides clues to the function(s) of genes of interest. We chose 50 Arabidopsis mutants, including a set of characterized and uncharacterized mutants, that resemble wild-type plants. We performed metabolite profiling of the plants using gas chromatography-mass spectrometry. To make the data set available as an efficient public functional genomics tool for hypothesis generation, we developed the Metabolite Profiling Database for Knock-Out Mutants in Arabidopsis (MeKO). It allows the evaluation of whether a mutation affects metabolism during normal plant growth and contains images of mutants, data on differences in metabolite accumulation, and interactive analysis tools. Nonprocessed data, including chromatograms, mass spectra, and experimental metadata, follow the guidelines set by the Metabolomics Standards Initiative and are freely downloadable. Proof-of-concept analysis suggests that MeKO is highly useful for the generation of hypotheses for genes of interest and for improving gene annotation. MeKO is publicly available at http://prime.psc.riken.jp/meko/.

Imaging diagnosis of brain metastasis.

Hematogeneous spread of primary neoplasm can result in central nervous system (CNS) disease burden in various anatomically distinct regions; calvarial, pachymeningeal, leptomeningeal, and intraparenchymal. The choice of imaging modality is dependent on the individual clinical situation, but, largely depends on the patients overall clinical status and the information needed to make treatment decisions. Contrast-enhanced magnetic resonance (MR) imaging is the preferred imaging modality of choice; however, computed tomography (CT) is often utilized as the first-pass screening modality for CNS disease. Despite the superior soft tissue resolution, multiplanar capability, and noninvasive nature of MR imaging, T(1)- and T(2)-weighted sequences are limited to delineating morphologic anatomical deraignment of tissues by tumor. Several physiology based MR imaging sequences have been developed which compliment anatomic MR imaging. Proton magnetic resonance spectroscopic and dynamic susceptibility contrast-enhanced perfusion-weighted imaging are two physiologic sequences which add additional diagnostic information allowing for improved tumor characterization. Common pitfalls in evaluating for metastatic disease burden include the misidentification of non-neoplastic hematomas, remote microvascular ischemia, and acute onset of ischemic stroke. In the pediatric population, CNS metastases are rare; however, the onset of acute neurological symptoms in a child with known primary tumor should prompt imaging of the neuroaxis.

Minimum analytical quality specifications of inter-laboratory comparisons: agreement among Spanish EQAP organizers.

BACKGROUND: Four Spanish scientific societies organizing external quality assessment programs (EQAP) formed a working group to promote the use of common minimum quality specifications for clinical tests. Laboratories that do not meet the minimum specifications are encouraged to make immediate review of the analytical procedure affected and to implement corrective actions if necessary. METHODS: The philosophy was to use the 95th percentile of results sent to EQAP (expressed in terms of percentage deviation from the target value) obtained for all results (except the outliers) during a cycle of 1 year. The target value for a number of analytes of the basic biochemistry program was established as the overall mean. However, because of the substantial discrepancies between routine methods for basic hematology, hormones, proteins, therapeutic drugs and tumor markers, the target in these cases was the peer group mean. RESULTS: The resulting specifications were quite similar to those established in the US (CLIA), and Germany (Richtlinie). CONCLUSIONS: The proposed specifications stand for the minimum level of quality to be attained for laboratories, to assure harmonized service performance. They have nothing to do with satisfying clinical requirements, which are the final level of quality to be reached, and that is strongly recommended in our organizations by means of documents, courses, symposiums and all types of educational activities.

Anaphylaxis in Latin America: a report of the online Latin American survey on anaphylaxis (OLASA).

OBJECTIVES: The aims of the Online Latin American Survey of Anaphylaxis (OLASA) were to identify the main clinical manifestations, triggers, and treatments of severe allergic reactions in patients who were seen by allergists from July 2008 to June 2010 in 15 Latin American countries and Portugal (n =634). RESULTS: Of all patients, 68.5% were older than 18 years, 41.6% were male, and 65.4% experienced the allergic reaction at home. The etiologic agent was identified in 87.4% of cases and predominantly consisted of drugs (31.2%), foods (23.3%), and insect stings (14.9%). The main symptom categories observed during the acute episodes were cutaneous (94.0%) and respiratory (79.0%). The majority of patients (71.6%) were treated initially by a physician (office/emergency room) within the first hour after the reaction occurred (60.2%), and 43.5% recovered in the first hour after treatment. Most patients were treated in an emergency setting, but only 37.3% received parenteral epinephrine alone or associated with other medication. However, 80.5% and 70.2% were treated with corticosteroids or antihistamines (alone or in association), respectively. A total of 12.9% of the patients underwent reanimation maneuvers, and 15.2% were hospitalized. Only 5.8% of the patients returned to the emergency room after discharge, with 21.7% returning in the first 6 hours after initial treatment. CONCLUSION: The main clinical manifestations of severe allergic reactions were cutaneous. The etiologic agents that were identified as causing these acute episodes differed according to age group. Following in order: drugs (31.2%), foods (23.3% and insect stings (14.9%) in adults with foods predominance in children. Treatment provided for acute anaphylactic reactions was not appropriate. It is necessary to improve educational programs in order to enhance the knowledge on this potentially fatal emergency.

Hypebaric oxygen treatment in urology.

OBJECTIVES: Hyperbaric oxygen therapy (HBO) has been successfully used in several disorders derived from tissue hypoxia, due to the extra oxygen supply to the tissues it enables. In this manuscript we performed a systematic review including all the existing data published until 2010 about HBO in urologic disorders. METHODS: We performed a Medline search using the terms "hyperbaric oxygen", "radical cystitis", "interstitial cystitis", "hemorrhagic cystitis", "urological/pelvic fistula"and "Fournier's gangrene". The search was restricted to human clinical trials published in any language. RESULTS: We found 56 papers: 1 randomized controlled trial, 7 reviews and 48 case reports; only one of them was a prospective study. A total of 695 patients were included. Just one study used tissue oxygen measurement to define hypoxia. The number of hyperbaric oxygen therapy sessions ranged from 4 to 44 (mean 19.2 sessions/patient). CONCLUSIONS: The level of evidence from most reviewed papers is low because most of them are case series. Nevertheless, results of most of those studies regarding patient management are good or very good. So it seems that HBO can be very useful in urological diseases related to tissue hypoxia.

Anaphylaxis in Latin America: a report of the online Latin American survey on anaphylaxis (OLASA)

OBJECTIVES: The aims of the Online Latin American Survey of Anaphylaxis (OLASA) were to identify the main clinical manifestations, triggers, and treatments of severe allergic reactions in patients who were seen by allergists from July 2008 to June 2010 in 15 Latin American countries and Portugal (n =634). RESULTS: Of all patients, 68.5 percent were older than 18 years, 41.6 percent were male, and 65.4 percent experienced the allergic reaction at home. The etiologic agent was identified in 87.4 percent of cases and predominantly consisted of drugs (31.2 percent), foods (23.3 percent), and insect stings (14.9 percent). The main symptom categories observed during the acute episodes were cutaneous (94.0 percent) and respiratory (79.0 percent). The majority of patients (71.6 percent) were treated initially by a physician (office/emergency room) within the first hour after the reaction occurred (60.2 percent), and 43.5 percent recovered in the first hour after treatment. Most patients were treated in an emergency setting, but only 37.3 percent received parenteral epinephrine alone or associated with other medication. However, 80.5 percent and 70.2 percent were treated with corticosteroids or antihistamines (alone or in association), respectively. A total of 12.9 percent of the patients underwent reanimation maneuvers, and 15.2 percent were hospitalized. Only 5.8 percent of the patients returned to the emergency room after discharge, with 21.7 percent returning in the first 6 hours after initial treatment. CONCLUSION: The main clinical manifestations of severe allergic reactions were cutaneous. The etiologic agents that were identified as causing these acute episodes differed according to age group. Following in order: drugs (31.2 percent), foods (23.3 percent and insect stings (14.9 percent) in adults with foods predominance in children. Treatment provided for acute anaphylactic reactions was not appropriate. It is necessary to improve educational programs in order to enhance the knowledge on this potentially fatal emergency.