Gliadel Wafer Implantation Combined With Standard Radiotherapy and Concurrent Followed by Adjuvant Temozolomide for Treatment of Newly Diagnosed High-Grade Glioma: A Systematic Literature Review

Since 2003, only two chemotherapeutic agents, evaluated in phase III trials, have been approved by the US Food and Drug Administration for treatment of newly diagnosed high-grade glioma (HGG): Gliadel wafers (intracranially implanted local chemotherapy) and temozolomide (TMZ) (systemic chemotherapy). Neither agent is curative, but each has been shown to improve median overall survival (OS) compared to radiotherapy (RT) alone. To date, no phase III trial has tested these agents when used in sequential combination; however, a number of smaller trials have reported favorable results. We performed a systematic literature review to evaluate the combination of Gliadel wafers with standard RT (60 Gy) plus concurrent and adjuvant TMZ (RT/TMZ) for newly diagnosed HGG. A literature search was conducted for the period of January 1995 to September 2015. Data were extracted and categorized, and means and ranges were determined. A total of 11 publications met criteria, three prospective trials and eight retrospective studies, representing 411 patients who received Gliadel plus standard RT/TMZ. Patients were similar in age, gender, and performance status. The weighted mean of median OS was 18.2 months (ten trials, n = 379, range 12.7 to 21.3 months), and the weighted mean of median progression-free survival was 9.7 months (seven trials, n = 287, range 7 to 12.9 months). The most commonly reported grade 3 and 4 adverse events were myelosuppression (10.22 %), neurologic deficit (7.8 %), and healing abnormalities (4.3 %). Adverse events reflected the distinct independent safety profiles of Gliadel wafers and RT/TMZ, with little evidence of enhanced toxicity from their use in sequential combination. In the 11 identified trials, an increased benefit from sequentially combining Gliadel wafers with RT/TMZ was strongly suggested. Median OS tended to be improved by 3 to 4 months beyond that observed for Gliadel wafers or TMZ when used alone in the respective phase III trials. Larger prospective trials of Gliadel plus RT/TMZ are warranted

Gliadel Wafer Implantation Combined With Standard Radiotherapy and Concurrent Followed by Adjuvant Temozolomide for Treatment of Newly Diagnosed High-Grade Glioma: A Systematic Literature Review

Since 2003, only two chemotherapeutic agents, evaluated in phase III trials, have been approved by the US Food and Drug Administration for treatment of newly diagnosed high-grade glioma (HGG): Gliadel wafers (intracranially implanted local chemotherapy) and temozolomide (TMZ) (systemic chemotherapy). Neither agent is curative, but each has been shown to improve median overall survival (OS) compared to radiotherapy (RT) alone. To date, no phase III trial has tested these agents when used in sequential combination; however, a number of smaller trials have reported favorable results. We performed a systematic literature review to evaluate the combination of Gliadel wafers with standard RT (60 Gy) plus concurrent and adjuvant TMZ (RT/TMZ) for newly diagnosed HGG. A literature search was conducted for the period of January 1995 to September 2015. Data were extracted and categorized, and means and ranges were determined. A total of 11 publications met criteria, three prospective trials and eight retrospective studies, representing 411 patients who received Gliadel plus standard RT/TMZ. Patients were similar in age, gender, and performance status. The weighted mean of median OS was 18.2 months (ten trials, n = 379, range 12.7 to 21.3 months), and the weighted mean of median progression-free survival was 9.7 months (seven trials, n = 287, range 7 to 12.9 months). The most commonly reported grade 3 and 4 adverse events were myelosuppression (10.22 %), neurologic deficit (7.8 %), and healing abnormalities (4.3 %). Adverse events reflected the distinct independent safety profiles of Gliadel wafers and RT/TMZ, with little evidence of enhanced toxicity from their use in sequential combination. In the 11 identified trials, an increased benefit from sequentially combining Gliadel wafers with RT/TMZ was strongly suggested. Median OS tended to be improved by 3 to 4 months beyond that observed for Gliadel wafers or TMZ when used alone in the respective phase III trials. Larger prospective trials of Gliadel plus RT/TMZ are warranted

Facilitation, competition and parasitic facilitation amongst invasive and native liana seedlings and a native tree seedling

Lianas are prevalent in gaps and edges of forests where they compete intensely with trees, reducing growth and recruitment. Invasive lianas have the potential to be particularly harmful as the competitive advantage of the liana life history may be coupled with the more competitive qualities of invasiveness. However, in early stages of growth of lianas and native tree seedlings, facilitatory interactions or competitive interactions associated with soil nutrients may be more prevalent. We investigated interactions at the early stages of growth between native and invasive lianas with a common rainforest tree of temperate Australian rainforests under different light conditions. Invasive lianas, as a group, were not more competitive than native lianas in reducing growth of a native rainforest seedling. At this stage in the life cycle most lianas were as competitive as a conspecific seedling. However, one invasive liana, Anredera cordifolia, was particularly competitive and reduced biomass of tree seedlings. Light had little effect on growth of lianas nor on the impact of competition, however, specific leaf area differed between low and medium light conditions. Moderate light did improve growth in the rainforest tree seedling. When lianas were grown with a rainforest tree, three liana species overyielded, while one species was unaffected by growing with the tree seedling. Overyielding suggests a strong positive interaction with the neighbouring plant, mediated through belowground processes. We discuss the potential for these interactions to be facilitative, parasitic or competitive. We therefore show that interactions early in the life of rainforest species can be complex mixtures of interactions which are likely to influence the ability of lianas to dominate rainforests

Gender Differences in Human Single Neuron Responses to Male Emotional Faces

Well-documented differences in the psychology and behavior of men and women have spurred extensive exploration of gender€™s role within the brain, particularly regarding emotional processing. While neuroanatomical studies clearly show differences between the sexes, the functional effects of these differences are less understood. Neuroimaging studies have shown inconsistent locations and magnitudes of gender differences in brain hemodynamic responses to emotion. To better understand the neurophysiology of these gender differences, we analyzed recordings of single neuron activity in the human brain as subjects of both genders viewed emotional expressions. This study included recordings of single-neuron activity of 14 (6 male) epileptic patients in four brain areas: amygdala (236 neurons), hippocampus (n = 270), anterior cingulate cortex (n = 256), and ventromedial prefrontal cortex (n = 174). Neural activity was recorded while participants viewed a series of avatar male faces portraying positive, negative or neutral expressions. Significant gender differences were found in the left amygdala, where 23% (n = 15/66) of neurons in men were significantly affected by facial emotion, vs. 8% (n = 6/76) of neurons in women. A Fisher€™s exact test comparing the two ratios found a highly significant difference between the two (p \u3c 0.01). These results show specific differences between genders at the single-neuron level in the human amygdala. These differences may reflect gender-based distinctions in evolved capacities for emotional processing and also demonstrate the importance of including subject gender as an independent factor in future studies of emotional processing by single neurons in the human amygdala

Neuropsychological outcome following minimal access subtemporal selective amygdalohippocampectomy.

PURPOSE: The present study provides a detailed account of neurocognitive outcome following minimal access subtemporal selective amygdalohippocampectomy (SAH) and establishes rates of neurocognitive decline in the largest sample to date. Use of a subtemporal surgical approach to SAH has been proposed to possibly reduce the risk for postoperative neurocognitive decline since lateral neocortical tissues is not resected and the temporal stem is preserved. The current study extends prior research with subtemporal SAH patients to include not only group level analyses but also analyses based on reliable change data. METHODS: Neurocognitive comparisons are made between 47 patients that underwent subtemporal SAH. Statistical comparisons were made between neurocognitive performance at the group level and with use of reliable change scores. RESULTS: Approximately 75% of patients were seizure free postoperatively. At the group level, there were no significant postoperative changes. For the left SAH patients, reliable change scores demonstrated a decline in approximately one third of patients for memory, verbal intellect, and naming. Right SAH patients showed decline primarily in memory. CONCLUSIONS: These results indicated good seizure control following subtemporal SAH with greatest risk for neurocognitive decline following dominant SAH and best cognitive outcome following non-dominant SAH. Findings demonstrated the importance of reliable change analyses that make individual based comparisons and take into account measurement error. Despite preservation of the lateral neocortical tissue and the temporal stem, subtemporal SAH presents a risk for cognitive decline in a notable portion of patients

Massive Young Stellar Objects in the Galactic Center. I. Spectroscopic Identification from Spitzer/IRS Observations

We present results from our spectroscopic study, using the Infrared Spectrograph (IRS) onboard the Spitzer Space Telescope, designed to identify massive young stellar objects (YSOs) in the Galactic Center (GC). Our sample of 107 YSO candidates was selected based on IRAC colors from the high spatial resolution, high sensitivity Spitzer/IRAC images in the Central Molecular Zone (CMZ), which spans the central ~300 pc region of the Milky Way Galaxy. We obtained IRS spectra over 5um to 35um using both high- and low-resolution IRS modules. We spectroscopically identify massive YSOs by the presence of a 15.4um shoulder on the absorption profile of 15um CO2 ice, suggestive of CO2 ice mixed with CH3OH ice on grains. This 15.4um shoulder is clearly observed in 16 sources and possibly observed in an additional 19 sources. We show that 9 massive YSOs also reveal molecular gas-phase absorption from CO2, C2H2, and/or HCN, which traces warm and dense gas in YSOs. Our results provide the first spectroscopic census of the massive YSO population in the GC. We fit YSO models to the observed spectral energy distributions and find YSO masses of 8 - 23 Msun, which generally agree with the masses derived from observed radio continuum emission. We find that about 50% of photometrically identified YSOs are confirmed with our spectroscopic study. This implies a preliminary star formation rate of ~0.07 Msun/yr at the GC.Comment: Accepted for publication in Ap

Cooling abolishes neuronal network synchronization in rat hippocampal slices.

PURPOSE: We sought to determine whether cooling brain tissue from 34 to 21 degrees C could abolish tetany-induced neuronal network synchronization (gamma oscillations) without blocking normal synaptic transmission. METHODS: Intracellular and extracellular electrodes recorded activity in transverse hippocampal slices (450-500 microm) from Sprague-Dawley male rats, maintained in an air-fluid interface chamber. Gamma oscillations were evoked by afferent stimulation at 100 Hz for 200 ms. Baseline temperature in the recording chamber was 34 degrees C, reduced to 21 degrees C within 20 min. RESULTS: Suprathreshold tetanic stimuli evoked membrane potential oscillations in the 40-Hz frequency range (n = 21). Gamma oscillations induced by tetanic stimulation were blocked by bicuculline, a gamma-aminobutyric acid (GABA)A-receptor antagonist. Cooling from 34 to 21 degrees C reversibly abolished gamma oscillations in all slices tested. Short, low-frequency discharges persisted after cooling in six of 14 slices. Single-pulse-evoked potentials, however, were preserved after cooling in all cases. Latency between stimulus and onset of gamma oscillation was increased with cooling. Frequency of oscillation was correlated with chamber cooling temperature (r = 0.77). Tetanic stimulation at high intensity elicited not only gamma oscillation, but also epileptiform bursts. Cooling dramatically attenuated gamma oscillation and abolished epileptiform bursts in a reversible manner. CONCLUSIONS: Tetany-induced neuronal network synchronization by GABAA-sensitive gamma oscillations is abolished reversibly by cooling to temperatures that do not block excitatory synaptic transmission. Cooling also suppresses transition from gamma oscillation to ictal bursting at higher stimulus intensities. These findings suggest that cooling may disrupt network synchrony necessary for epileptiform activity

Long-term outcome data from 121 patients treated with Gamma Knife stereotactic radiosurgery as salvage therapy for focally recurrent high-grade gliomas.

Introduction: We examined patient outcomes after Gamma Knife stereotactic radiosurgery (GKSRS) salvage therapy for recurrent high-grade gliomas (HGGs) to determine whether tumor grade or lesion size affected overall survival (OS) and progression-free survival (PFS). Methods: This single-center retrospective study assessed radiographic response and clinical outcomes following GKSRS salvage treatment of recurrent malignant gliomas (January 2005-March 2014). Results: A total of 121 patients (67 female) with 132 tumors were treated. Median (range) PFS was 4.7 (3.9-5.4) months for the cohort, 6.8 (4.6-8.9) months for initial grade 2 tumors, 4.2 (1.9-6.5) months for initial grade 3 tumors, and 4.3 (3.7-4.9) months for initial grade 4 tumors. Patients with small lesions (≤6.7 cm Conclusions: GKSRS offers meaningful salvage therapy with minimal morbidity in appropriately selected patients with focally recurrent HGGs

Point Sources from a Spitzer IRAC Survey of the Galactic Center

We have obtained Spitzer/IRAC observations of the central 2.0 x 1.4 degrees (~280 x 200 pc) of the Galaxy at 3.6-8.0 microns. A point source catalog of 1,065,565 objects is presented. The catalog includes magnitudes for the point sources at 3.6, 4.5, 5.8, and 8.0 microns, as well as JHK photometry from 2MASS. The point source catalog is confusion limited with average limits of 12.4, 12.1, 11.7, and 11.2 magnitudes for [3.6], [4.5], [5.8], and [8.0], respectively. We find that the confusion limits are spatially variable because of stellar surface density, background surface brightness level, and extinction variations across the survey region. The overall distribution of point source density with Galactic latitude and longitude is essentially constant, but structure does appear when sources of different magnitude ranges are selected. Bright stars show a steep decreasing gradient with Galactic latitude, and a slow decreasing gradient with Galactic longitude, with a peak at the position of the Galactic center. From IRAC color-magnitude and color-color diagrams, we conclude that most of the point sources in our catalog have IRAC magnitudes and colors characteristic of red giant and AGB stars.Comment: 44 pages, 13 figures, ApJS in pres

Magnetic Resonance-Guided Laser Interstitial Thermal Therapy for Management of Low-Grade Gliomas and Radiation Necrosis: A Single-Institution Case Series

Background: Laser interstitial thermal therapy (LITT) has emerged as a minimally invasive treatment modality for ablation of low-grade glioma (LGG) and radiation necrosis (RN). Objective: To evaluate the efficacy, safety, and survival outcomes of patients with radiographically presumed recurrent or newly diagnosed LGG and RN treated with LITT. Methods: The neuro-oncological database of a quaternary center was reviewed for all patients who underwent LITT for management of LGG between 1 January 2013 and 31 December 2020. Clinical data including demographics, lesion characteristics, and clinical and radiographic outcomes were collected. Kaplan-Meier analyses comprised overall survival (OS) and progression-free survival (PFS). Results: Nine patients (7 men, 2 women; mean [SD] age 50 [16] years) were included. Patients underwent LITT at a mean (SD) of 11.6 (8.5) years after diagnosis. Two (22%) patients had new lesions on radiographic imaging without prior treatment. In the other 7 patients, all (78%) had surgical resection, 6 (67%) had intensity-modulated radiation therapy and chemotherapy, respectively, and 4 (44%) had stereotactic radiosurgery. Two (22%) patients had lesions that were wild-type IDH1 status. Volumetric assessment of preoperative T1-weighted contrast-enhancing and T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences yielded mean (SD) lesion volumes of 4.1 (6.5) cm(3) and 26.7 (27.9) cm(3), respectively. Three (33%) patients had evidence of radiographic progression after LITT. The pooled median (IQR) PFS for the cohort was 52 (56) months, median (IQR) OS after diagnosis was 183 (72) months, and median (IQR) OS after LITT was 52 (60) months. At the time of the study, 2 (22%) patients were deceased. Conclusions: LITT is a safe and effective treatment option for management of LGG and RN, however, there may be increased risk of permanent complications with treatment of deep-seated subcortical lesions