tbuckley/cabot-search huggingface dataset:
CRAN-21. PHASE II STUDY OF PEGINTERFERON ALFA-2b (PEGINTRON)/SYLATRON FOR PEDIATRIC PATIENTS WITH PROGRESSIVE OR RECURRENT CRANIOPHARYNGIOMA FOLLOWING RADIOTHERAPY: A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY (PBTC-039)
Authors: Stewart Goldman, Ian Pollack, Larry Kun, Catherine Billups, Alberto Broniscer, Giles Robinson, Girish Dhall, Nathan Robison, Ashok Panigrahy, Tina Young Poussaint, Adekunle Adesina, Arzu Onar-Thomas, Reggie Jakacki, Ira Dunkel, Maryam Fouladi
Journal: Neuro-Oncology (2018)

Despite complete resection, 20% -50% of pediatric craniopharyngiomas experience recurrence. Subtotal resection followed by radiation achieves comparable results. More effective therapies are needed. In tumor cell lines, prolonged exposure to interferon optimizes the anti-proliferative and anti-angiogenic effect. Conjugating proteins with poly-ethylene-glycol (PEG) lengthens the plasma half-life by reducing sensitivity to proteolysis, providing protracted activity. Stratum II of the PBTC-039 study proposed to estimate the sustained objective response rate (ORR=CR + PR) associated with PEGIntron/Sylatron in progressive/recurrent craniopharyngiomas post RT. Simon’s 2-stage design with 10% unacceptable and 35% desirable ORR required a total sample size of 19 (α=β=0.1). An interim analysis was planned after 11 patients and ≥2 objective responses within the first year were needed to expand accrual. 12 patients were enrolled 11, (5 males and 6 females) were eligible and evaluable. Median age at diagnosis was 7.0 years (range, 2.0–12.4) and at study entry was 20.5 years (6.1–25). Median number of cycles received was 6 (1–17). No grade 4 adverse events (AE) were reported. Grade 3 attributable AEs included decreased neutrophil count, nausea, fatigue, fever, headache and anorexia (n=1 each). No objective responses were observed. With a median follow-up 12.9 months (3.2 - 25.7), 5/11 patients have progressed at a median of 8.2 months (2.9–19.5). Other off-treatment reasons were AE, alternative therapy/withdrawal and not meeting weight criteria. PFS estimate at 1-year was 68.2% ± 14.5%. One patient remains on treatment. Although well tolerated, stratum II was permanently closed after interim analysis due to lack of objective responses.
MBCL-13. COMBINED MULTIPLE CHEMOTHERAPY AND POSTERIOR FOSSA RADIOTHERAPY IN INFANTS WITH NONMETASTATIC MEDULLOBLASTOMA
Authors: Daniel Alderete, Lorena Baroni, Fabiana Lubieniecki, Roberto Jaimovich
Journal: Neuro-Oncology (2018)

New radiotherapy modalities, 3D-conformal radiation therapy (CRT) and IMRT allow including the radiotherapy for medulloblastoma younger than 36 months. The aim is to evaluate the results of chemotherapy plus 3D-CRT/IMRT in infants nonmetastatic medulloblastoma. From October 2002 to November 2016, 38 infants medulloblastoma patients were treated in our institution, 9 metastatic; 26 of 29 nonmetastatic patients were evaluable. After initial surgery, children received 5 cycles of induction chemotherapy, including Vincristine(0.05mg/k/d1,8,15)/Cisplatin(3.5mg/k/d1)/Cyclophosphamide(30mg/k/d2,3)/Etoposide(4mg/k/d2,3), followed by four maintenance cycles: Carboplatin(18mg/k/d1)/Vincristine(0.05mg/k/d1,28)/Cyclophosphamide(50mg/k/d28)/Etoposide(1,6mg/k/d2-14;29-43orally). Posterior fossa 3D-CRT or bed tumor IMRT with/without Temozolamide was indicated after induction or when achieved 18 months(54/55.8Gy). Median age at diagnosis was 24.8m(3.1-55.4). The histological subtypes were: 10pt classic, 15pt desmoplastic/nodular, 1pt extensive nodularity. 4pt had gross residual tumor. 23pt received 3D-CRT/IMRT. The median time from resection to radiotherapy was 5.9m(5.09-25.3). The median age of 3D-CRT/IMRT was 33.9m(18.3-60.4). 3pt did not receive CRT; 2 death on induction and 1 extensive nodularity. The median follow up was 47.7m(6.3-183). The 5 year event-free survival and overall survival probabilities were 64% and 72% respectively. 7 pt relapsed; 1 supratentorial, 1 intraventicular, 4 leptomeningeal and 1 spinal space. Median time from diagnosis to relapse was 13.9m(5.6-25). 2pt had second malignant neoplasm in irradiated area; 1 osteosarcoma(+118m) and 1 undifferentiated sarcoma(+71 m). The results obtained in this particular group of patients are very encouraging, considering to be similar to older patients with craniospinal radiotherapy. This suggests that this protocol treatment can be use as first line for patients into 3-6 years old to reduce the radiotherapy sequelae.
CRAN-17. TUMOUR COMPARTMENT TRANSCRIPTOMICS DEMONSTRATE THE ACTIVATION OF INFLAMMATORY AND ODONTOGENIC PROGRAMMES IN HUMAN ADAMANTINOMATOUS CRANIOPHARYNGIOMA AND IDENTIFY NOVEL THERAPEUTIC TARGETS
Authors: John Apps, Romaine Guiho, Ying Hong, Darren Hargrave, Paul Brogan, Thomas Jacques, Juan Pedro Martinez-Barbera
Journal: Neuro-Oncology (2018)

Adamantinomatous Craniopharyngiomas (ACPs) are challenging sellar region tumours, known to be characterised by mutations in CTNNB1. ACPs are often histologically complex, with different morphological cell types and surrounded by reactive glial tissue. Murine models, generated through activating β-catenin, support a critical role for nucleo-cytoplasmic accumulating β-catenin cell clusters (‘clusters’) in driving tumorigenesis. We performed RNA-Seq, with and without laser capture microdissection, of human ACP to develop cell type specific molecular signatures. We integrate this with RNA-Seq data from two ACP mouse models to reveal that cell clusters are molecularly analogous to the enamel knot, a critical signalling centre controlling normal tooth morphogenesis. Supporting this finding, we show that human cluster cells express high levels of several members of the FGF, TGFB and BMP families of secreted factors, which signal to neighbouring cells as evidenced by immunostaining against the phosphorylated proteins pERK1/2, pSMAD3 and pSMAD1/5/9 in both human and mouse ACP. We reveal that inhibiting the MAPK/ERK pathway with a clinically approved MEK inhibitor results in the reduction of proliferation and increased apoptosis in explant cultures of human and mouse ACP. Finally, we analysed a prominent molecular signature in the glial reactive tissue to characterise the inflammatory microenvironment and uncover the activation of inflammasomes in human ACP. We validated these results by immunostaining, ELISA and proteomic analysis in both solid tumour and cystic fluid from ACP patients. Our data support a new molecular paradigm for understanding ACP tumorigenesis as an aberrant mimic of natural tooth development and opens new therapeutic opportunities.
Bariatric patients' nutritional status as a risk factor for postoperative complications, prolonged length of hospital stay and hospital readmission: A retrospective cohort study
Authors: Piotr Major, Piotr Małczak, Michał Wysocki, Grzegorz Torbicz, Natalia Gajewska, Michał Pędziwiatr, Andrzej Budzyński
Journal: International Journal of Surgery (2018)
Comment on Gordin et al. Differential Association of Microvascular Attributions With Cardiovascular Disease in Patients With Long Duration of Type 1 Diabetes. Diabetes Care 2018;41:815–822
Authors: Marie Azar, Elise Coirier, Marie-Noelle Delyfer, Jean-François Korobelnik, Kamel Mohammedi, Laurence Blanco, Laure Alexandre, Marie Monlun, Vincent Rigalleau
Journal: Diabetes Care (2018)

We were interested by the recent article from Gordin et al. (1), who showed that proliferative diabetic retinopathy (DR) was related to cardiovascular disease (CVD) in type 1 diabetes (T1D), even in patients without diabetic kidney disease (DKD) (1). DKD is an important marker of cardiovascular risk in T1D (2), but a residual risk persists for patients without kidney damage, and its association with DR seems important information.

In Bordeaux we followed a cohort of patients with T1D since 2009, and we have recently shown that DR could predict their later fast renal decline (3). The article from Gordin et al. prompted us to test whether their initial …
Combined physiologic and excisional therapies improve cancer‐related lymphedema outcomes
Authors: Mike Fillon
Journal: CA A Cancer Journal for Clinicians (2018)

Key Points Treating lymphedema with VLNT followed by SAL may be more effective than using either procedure alone. Prior to treatment, patients reported an average of 1.8 infectious episodes but only 1 patient had a single episode after VLNT and prior to SAL. In addition to the near‐complete reduction in the excess limb size and the absence of infections after the second stage of the treatment, patients were able to maintain these favorable outcomes at an average follow‐up of 23.5 months.
Management of patients with unresectable HCC: A simulation-based assessment of medical oncologists’ practice choices
Authors: T. Herrmann, A. Carothers, G. Littman, M. Warters, C. Cason, T. Bekaii-Saab
Journal: Annals of Oncology (2018)

Introduction: For the first time in a decade the hepatocellular carcinoma (HCC) treatment algorithm is undergoing significant change, challenging oncologists to assimilate evidence into practice. Methods: A CME certified virtual patient simulation (VPS) was made available via a website dedicated to professional development. The VPS consisted of 2 cases presented in a platform that allows oncologists to assess the patients and choose from an extensive database of diagnostic and treatment possibilities matching the scope and depth of actual practice. Clinical decisions were analyzed using a sophisticated decision engine, and instantaneous clinical guidance (CG) employing evidence-base and faculty recommendations was provided after each decision. Oncologists were allowed to revise each decision point post-CG, if desired. Rationales for clinical decisions were also collected in real time. Data were collected between 11/27/2017 and 2/21/2018. Results: At the time of initial assessment, 76 oncologists, 76% of whom practiced in the community setting, fulfilled the participation criteria for completing the simulation. Assessment of their practice choices revealed: In a patient with newly diagnosed unresectable HCC, only 52% ordered an appropriate regimen. CG led to a 26% increase in evidence-based treatment orders (P = 0.004). Sorafenib remained the systemic treatment of choice, with only 10% choosing a different regimen. In a patient whose disease has progressed on sorafenib after 6 months of therapy, only 36% of oncologists prescribed an appropriate regimen. CG resulted in a 36% improvement in evidence-based treatment orders (P < 0.001). The primary rationale for the selected treatment differed based on the chosen regimen, disease characteristics (22%) with use of nivolumab to better efficacy for this patient profile (33%) for regorafenib. Less than 50% of oncologists initially ordered side effect counseling in each case. CG resulted in a 14% (P = 0.091) and 25% (P = 0.013) improvement in case 1 and case 2, respectively. Conclusion: This study, using an immersive VPS, provides access to unique insights into oncologists' real world clinical practices in an evolving HCC treatment landscape and identifies a lack of clarity about identification of the most appropriate regimen for these patients. Our findings demonstrate a continued need to educate oncologists about how to select and prescribe the most appropriate regimen for a patient with HCC.
CRAN-14. ASTROBLASTOMA – A REPORT FROM 3 CASES
Authors: Monika Drogosiewicz, Iwona Filipek, Marta Perek-Polnik, Ewa Swieszkowska, Iwona Kosciesza, Wieslawa Grajkowska, Bozenna Dembowska-Baginska
Journal: Neuro-Oncology (2018)

Astroblastoma is a rare CNS tumor of glial origin distinguished from other gliomas in the recent International Classification of Tumors of the Central Nervous System proposed by the World Health Organization. We present our experience with 3 astroblastoma patients. Between 2003–2017 among 978 patients with tumors of glial origin treated at our Institution 3 patients (0,3 %) were diagnosed with astroblastoma. There were 2 girls and 1 boy aged 2.5, 3, 5.5 years. Two patients had supratentorial tumors, one tumor was located infratentorially. All patients underwent subtotal tumor resection received pre-irradiation chemotherapy, local irradiation (54Gy) and maintenance chemotherapy. All patients are alive 1, 5 yrs 8 m, 13 yrs2m from diagnosis. Our results as of other authors confirm favorable prognosis and rarity of astroblastoma in pediatric population.
Abstract 19140: Quantification of Mitochondrial Structure for the First Time in Intact Arteries
Authors: Matthew J Durand, Karima Ait Aissa, David D Gutterman, Andreas M Beyer
Journal: Circulation (2016)

Introduction:  Endothelial cell (EC) mitochondrial structure has only been evaluated in cultured cells as methods to label the mitochondria in intact arteries lack proper resolution and cell-specificity for high resolution imaging. Thus, the native structure of the EC mitochondrial network in intact arteries is unknown.   Objective:  To quantify the mitochondrial structure of ECs in intact arteries vs. cultured cells.   Methods:  Cre-stop mito-Dendra2 mice, expressing the fluorescent protein Dendra2 in the mitochondrial matrix only, were used to label EC mitochondria using Cre-recombinase under the control of the VE-cadherin promoter. Aortas were either fixed immediately with paraformaldehyde or incubated in normal (NG; 5 mM) or high glucose (HG; 33 mM) media for 24 h at 37 °C, cut open, mounted on a glass slide and fluorescent images were obtained on a Nikon A1 confocal microscope (ex 488 nm; em 550 nm) at 100X magnification. ImageJ was used to calculate form factor (FF; 1/circularity) and aspect ratio (AR) of the mitochondrial segments. Mitochondrial fission ratio (MFR) was calculated by counting non-contiguous mitochondrial particles and dividing by the number of pixels which composed the mitochondrial network. Primary aortic EC cultures (48 h in culture) were also generated to compare the mitochondrial structure of cultured ECs vs. intact arteries.   Results:  Compared to cultured ECs, the mitochondrial network of ECs from the intact aorta was in a highly fragmented state (MFR: 8.09 ± 0.55 vs. 24.65 ± 2.76, respectively; p   Conclusion:  Using this novel mouse model, for the first time we were able to obtain high resolution images of EC mitochondrial structure in intact arteries. The mitochondrial network was significantly more fragmented in the intact aorta compared to ECs in culture, indicating that mitochondria assume a more elongated and branched phenotype in cultured cells.
Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B
Authors: Franziska Rinker, Christine L. Zimmer, Christoph Höner zu Siederdissen, Michael P. Manns, Anke R.M. Kraft, Heiner Wedemeyer, Niklas K. Björkström, Markus Cornberg
Journal: Journal of Hepatology (2018)
DIPG-31. TUMOR SURVEILLANCE USING LIQUID BIOME IN PEDIATRIC HIGH GRADE GLIOMAS
Authors: Erin Bonner, Eshini Panditharatna, Madhuri Kambhampati, Stefaan Van Gool, Wilfried Stuecker, Roger Packer, Javad Nazarian
Journal: Neuro-Oncology (2018)

Immunotherapy is currently being used to treat pediatric brain cancer, though its efficacy in treating patients with diffuse intrinsic pontine glioma (DIPG), the deadliest pediatric brain tumor, has not been evaluated. MRI is the gold standard for monitoring tumor response to therapy, but is limited by pseudoresponse and psuedoprogression: post-treatment, immune cells infiltrate the primary tumor causing transient tumor enlargement, which falsely resembles tumor progression on MRI. Thus, it is critical to develop more accurate approaches to monitor tumor response to immunotherapy. Here, we use a liquid biopsy platform we have already established to monitor tumor response to therapy, to assess whether this platform is sufficient to monitor response to immunotherapy. The most frequent driver mutation in DIPG is the conversion of lysine 27 to methionine in histone H3, encoded by H3 variants H3.3 (H3F3A) and H3.1 (HIST1H3B/C). Here, we report detection of H3F3A mutation allelic frequency (MAF) in circulating tumor DNA in plasma obtained from DIPG patients undergoing immunotherapy with Newcastle disease virus (NDV) vaccine. NDV selectively targets tumor cells and induces immunogenic cell death; we hypothesize that this treatment will decrease tumor burden, corresponding to lower levels of mutant H3F3A and HIST1H3B in plasma. We used our digital droplet PCR liquid biopsy platform to determine histone mutation status (H3.3, H3.1, H3 wild type) at time of diagnosis, and to monitor MAF through the course of treatment, in order to correlate MAF to tumor response. This platform allows for more sensitive, accurate monitoring of tumor response than conventional MRI.
Evolution of Sex-Biased Gene Expression and Dosage Compensation in the Eye and Brain of Heliconius Butterflies
Authors: Ana Catalán, Aide Macias-Muñoz, Adriana D Briscoe
Journal: Molecular Biology and Evolution (2018)

Differences in behavior and life history traits between females and males are the basis of divergent selective pressures between sexes. It has been suggested that a way for the two sexes to deal with different life history requirements is through sex-biased gene expression. In this study, we performed a comparative sex-biased gene expression analysis of the combined eye and brain transcriptome from five Heliconius species, H. charithonia, H. sara, H. erato, H. melpomene and H. doris, representing five of the main clades from the Heliconius phylogeny. We found that the degree of sexual dimorphism in gene expression is not conserved across Heliconius. Most of the sex-biased genes identified in each species are not sex-biased in any other, suggesting that sexual selection might have driven sexually dimorphic gene expression. Only three genes shared sex-biased expression across multiple species: ultraviolet opsin UVRh1 and orthologs of Drosophila Krüppel-homolog 1 and CG9492. We also observed that in some species female-biased genes have higher evolutionary rates, but in others, male-biased genes show the fastest rates when compared with unbiased genes, suggesting that selective forces driving sex-biased gene evolution in Heliconius act in a sex- and species-specific manner. Furthermore, we found dosage compensation in all the Heliconius tested, providing additional evidence for the conservation of dosage compensation across Lepidoptera. Finally, sex-biased genes are significantly enriched on the Z, a pattern that could be a result of sexually antagonistic selection.
Abstract 2403: Effect Of Prehospital Cath Lab Activation On Door To Balloon Time Of STEMI Patients Presenting During Normal Workday Hours <i>vs.</i> After Hours
Authors: Fouad Bachour, Stephen Smith, David Hildebrandt, Mengistu Simegn, Richard Asinger
Journal: Circulation (2007)

BACKGROUND : We significantly reduced door-to-balloon-time (DBT) after instituting prehospital cath lab activation for STEMI, without EKG transmittal or MD involvement. OBJECTIVE: To study the effect of the protocol on DBT in normal workday hours (cath lab team is in-house) vs. after-hours (cath lab team is not in-house). METHODS : For all STEMI patients (pts), data are collected prospectively. Since 2001 all pts transported by our institution’s EMS, with symptoms suggesting MI, have had prehospital EKG. In April 2005, we started the following additional protocol (with no other changes in our acute MI program): if the chief complaint is Chest Pain and the Zoll® M Series Interpretive EKG (Marquette 12SL algorithm) reads ``**Acute MI**,” Paramedics call the ED unit coordinator from the scene to activate the cath lab without MD involvement. For all EMS transported pts from Jan 2004 to Jan 2007, we analyzed demographics, symptoms, Zoll interpretation, door-to-EKG-time, and DBT. We compared the time saved before and after protocol change for normal workday hours vs. after hours. Statistics were by Kruskal Wallis and the two-tailed Fisher Exact test. RESULTS: There were 104 patients with STEMI transported in the time period. 36 were excluded: 26 with no chest pain (14 cardiac arrest), 8 with a non-diagnostic Zoll EKG and 2 others. Of 68 eligible patients (65% of all STEMI), 36 had prehospital activation (20 workday, 16 after hours) and 32 did not get prehospital activation (12 Workday and 20 after hours). See table for results. Overall mean DBT was reduced from 86.0 ± 9.6 (CI) min. in the before group to 56.1 ± 7.7 min. in the prehospital activation group. CONCLUSION : Prehospital activation significantly reduces DBT in STEMI patients presenting during both normal workday hours and after hours. Significant time savings and exceptionally short DBTs (&lt; 60 min) were achieved by prehospital activation for STEMI patients presenting during normal workday hours.
DEV-04. FEASIBILITY AND TOXICITY OF DAILY CARBOPLATIN DURING CRANIOSPINAL IRRADIATION FOR HIGH RISK PEDIATRIC EMBRYONAL BRAIN TUMORS: FIRST REPORT FROM A MIDDLE INCOME COUNTRY
Authors: Carlos Leal-Cavazos, Michelle Gutierrez-Herrera, David Hernández-Barajas, Manuel De la O-Cavazos
Journal: Neuro-Oncology (2018)

Embryonal brain tumors are a highly aggressive group of tumors in children. Medulloblastoma (MB) is the most common of them in children and up to 30% are metastatic at diagnosis. Carboplatin used as a radiosensitizer during craniospinal irradiation (CSI) has shown to improve outcomes in metastatic medulloblastoma by Children’s Oncology Group. This strategy could be difficult in countries with limited resources due to restricted access to supportive care or lack of staff. The aim of this study was to demonstrate the feasibility of daily carboplatin during CSI for embryonal brain tumors in children in our hospital. We reviewed all medical records of patients treated in our institution with this protocol between 2015 and 2017. This study included 6 patients (5 metastatic MB and one localized sPNET). The median age was 6.3 years old (range 3 to 13y). The median Hb level was 10.8 g/dL (range 8.8 to 14.4g/dL). The median platelets level was 123 x109/L (range 53 to 256 x109/L). There were no episodes of febril neutropenia. No patient required transfusion (neither platelets nor RBC). From 162 scheduled treatments (carboplatin before radiation) there were 4 episodes (2.4%) where the sequence was incorrectly followed. At present 4 patients (66%) remain disease free. To our knowledge this is the first case series reported using this protocol in a middle income country. This strategy is feasible with a low risk of hematological toxicity requiring supportive care. Patients could be treated with this strategy in less developed countries.