tbuckley/cabot-search huggingface dataset:
Functional electrical stimulation in-bed cycle ergometry in mechanically ventilated patients: a multicentre randomised controlled trial
Authors: Sue Berney, Ramona O Hopkins, Joleen Wyn Rose, Rene Koopman, Zudin Puthucheary, Amy Pastva, Ian Gordon, Elizabeth Colantuoni, Selina M Parry, Dale M Needham, Linda Denehy
Journal: Thorax (2020)

Purpose To investigate the effect of functional electrical stimulation-assisted cycle ergometry (FES-cycling) on muscle strength, cognitive impairment and related outcomes. Methods Mechanically ventilated patients aged ≥18 years with sepsis or systemic inflammatory response syndrome were randomised to either 60 min of FES-cycling &gt; 5 days/week while in the intensive care unit (ICU) plus usual care rehabilitation versus usual care rehabilitation alone, with evaluation of two primary outcomes: (1) muscle strength at hospital discharge and (2) cognitive impairment at 6-month follow-up. Results We enrolled 162 participants, across four study sites experienced in ICU rehabilitation in Australia and the USA, to FES-cycling (n=80; mean age±SD 59±15) versus control (n=82; 56±14). Intervention participants received a median (IQR) of 5 (3–9) FES-cycling sessions with duration of 56 (34–63) min/day plus 15 (10–23) min/day of usual care rehabilitation. The control group received 15 (8–15) min/day of usual care rehabilitation. In the intervention versus control group, there was no significant differences for muscle strength at hospital discharge (mean difference (95% CI) 3.3 (−5.0 to 12.1) Nm), prevalence of cognitive impairment at 6 months (OR 1.1 (95% CI 0.30 to 3.8)) or secondary outcomes measured in-hospital and at 6 and 12 months follow-up. Conclusion In this randomised controlled trial, undertaken at four centres with established rehabilitation programmes, the addition of FES-cycling to usual care rehabilitation did not substantially increase muscle strength at hospital discharge. At 6 months, the incidence of cognitive impairment was almost identical between groups, but potential benefit or harm of the intervention on cognition cannot be excluded due to imprecision of the estimated effect. Trial registration number ACTRN 12612000528853, NCT02214823 .
RADT-35. POSTOPERATIVE RADIOTHERAPY FOR WHO GRADE II–III INTRACRANIAL EPENDYMOMA IN ADULTS: AN INTERGROUP COLLABORATIVE STUDY (KROG 18-06/KNOG 18-01)
Authors: Chan Woo Wee, Il Han Kim, Chul-Kee Park, Do Hoon Lim, Do-Hyun Nam, Hong In Yoon, Chang-Ok Suh, Jong Hee Chang, Woong-Ki Chung, Tae-Young Jung, Shin-Hyung Park, Chae-Yong Kim, Young Zoon Kim, Ho Shin Gwak, Kwan Ho Cho, Jin Hee Kim, Jung Ho Im, Woo Chul Kim, Sung-Hwan Kim, In Ah Kim
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND To evaluate the impact of adjuvant postoperative radiotherapy (PORT) in adult WHO grade II–III intracranial ependymoma (IEPN). METHODS A total of 172 pathologically confirmed adult grade II–III IEPN patients from 12 institutions were eligible. Of them, 106 (61.6%) and 66 (38.4%) patients were grade II and III, respectively. For grade II and III IEPNs, 51 (48.1%) and 59 (89.4%) patients received PORT, respectively. The median dose to the primary tumor bed was 54.0 Gy and 59.4 Gy for grade II and III patients, respectively. The prognostic impact of sex, age, performance, WHO grade, location, size, surgical extent, and PORT on local control (LC), progression-free survival (PFS), and overall survival (OS) were evaluated by univariate and multivariate analysis. RESULTS The median follow-up period for survivors was 88.1 months. The 5-/10-year LC, PFS, and OS rates were 64.8%/54.0%, 56.4%/44.8%, and 76.6%/71.0%, respectively. On multivariate analysis, adjuvant PORT significantly improved LC (P=0.002), PFS (P=0.002), and OS (P=0.043). Older age (P&amp;lt; 0.001), WHO grade III (P&amp;lt; 0.001), larger tumor size (P=0.004), and lesser surgical extent (P&amp;lt; 0.001) were also negative factors for OS. Adjuvant PORT also improved LC (P=0.010), PFS (P=0.007), and OS (P=0.069) on multivariate analysis for grade II IEPNs. CONCLUSION This multicenter retrospective study supports the role of adjuvant PORT in terms of disease control and survival in adult grade II–III IEPNs. Prospective randomized trials focused on individualized treatment based on molecular subtypes is warranted.
PATH-16. CORRELATION OF PATHOLOGICAL AND RADIOGRAPHICAL DIAGNOSES FOR CHILDREN WITH BRAIN TUMORS AT TWO MAJOR HOSPITAL IN KENYA
Authors: Dr Minda Okemwa, Dr Simon Omouk, Prof Nimrod Mwangombe, Dr Benson Macharia
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Central nervous system (CNS) tumors are the leading solid tumors in the childhood population but vastly underreported in the African population. There’s limited data on childhood brain tumors as well as the histopathological distribution in Kenya. Our study aimed at assessing the spectrum as well as the level of correlation with imaging in diagnosis of brain tumors within two major hospital settings. DESIGN: This was a cross-sectional retrospective descriptive study conducted at the two major hospitals in Kenya: Kenyatta National Hospital (KNH) and Moi Teaching and Referral Hospital (MTRH). Children who underwent treatment for brain tumors between 2015 and 2017 and whose tissue biopsies were available at the laboratory archives were included. RESULTS 87 cases were available for review, and the majority of the affected population were of ages 5–9 years. The most affected site was infratentorial compartment (48.3%) with gliomas and medulloblastoma being equally distributed. Majority of the gliomas were low grade (69%) with pilocytic astrocytoma being the most common subtype (42.9%). The overall sensitivity for the diagnosis of brain tumors through radiology was 69.4%. The level of correlation of histopathological to radiological diagnosis was statistically insignificant with P and kappa values of 0.814 and -0.024 respectively. CONCLUSION Gliomas and medulloblastomas were the commonest tumors at both centers. Histopathological diagnoses have a high concordance of agreement among various morphologists. The level of correlation between histopathological and radiological diagnosis was high. Next steps include standardizing clinical, radiological and pathological details within Kenya.
EPEN-03. LONG-TERM FOLLOW-UP OF AIEOP 2ND SERIES OF CHILDREN AND ADOLESCENT WITH PRIMARY INTRACRANIAL (ST:SUPRATENTORIAL; PF: POSTERIOR FOSSA) EPENDYMOMA AND METHYLATION GROUPS RE-ANALYSES
Authors: Maura Massimino, Francesca Romana Buttarelli, Hendrik Witt, Pascal Johann, Simone Minasi, Stefan M Pfister, Kristian W Pajtler, Manila Antonelli, Francesco Barretta, Piergiorgio Modena, Lorenza Gandola, Maria Luisa Garrè, Daniele Bertin, Angela Mastronuzzi, Maurizio Mascarin, Lucia Quaglietta, Elisabetta Viscardi, Iacopo Sardi, Antonio Ruggiero, Bianca Pollo, Annamaria Buccoliero, Luna Boschetti, Veronica Biassoni, Elisabetta Schiavello, Luisa Chiapparini, Alessandra Erbetta, Felice Giangaspero
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND This 2002–2014 Italian prospective study stratified 160 patients by surgical resection (complete=NED/incomplete=ED) and centrally-reviewed grade. Grade2/NED patients received focal radiotherapy (RT) up to 59.4Gy, Grade3/NED received 4 courses of VEC(vincristine,etoposide,cyclophosphamide) after RT.ED patients received 1–4 VEC courses, second-look surgery, 59.4 Gy+8Gy boost on measurable residue. METHODS We re-analyzed data at 115 months follow-up including methylation profile on available samples. RESULTS Global PFS/OS at 5/10 years were 66/59% and 80/74%, respectively. Of the 64 relapsers at median 20 months, 53 died at median 37/18 months after diagnosis/relapse, respectively.10/64 relapsed after 5 years (66–126 months); 4 died, relapse was local in 8/10, metastatic 1, combined 1;5/10 patients were below age 3, 5 females, 8 PF tumors. Their survival post-relapse was not longer than earlier relapsers’. At univariable analysis, age over 3 years, female sex, complete surgery, grade 2, no shunt confirmed better PFS/OS. 66/95 analyzed tumors received a score &amp;gt;0.80 through the DNA methylation-based central nervous system tumor classifier: 41/8 as PFA/PFB, respectively,14/17 ST as RELA-positive (3 scored for other molecular entities i.e. anaplastic PXA, LGG MYB, HGNET). Prognostic factors were equally distributed among PFA/PFB groups,1 only group B patient relapsed locally at 96 months. CONCLUSIONS Already published prognostic factors remained at long-term follow-up;6.2% patients had late relapses. OS after relapse was not better in late relapsers. Group B confirmed better prognosis but all patients had received «at least» adjuvant RT. Modern ependymoma trials need long follow-up to draw firm conclusions.
Body mass index change and incident asthma in adults: A nationwide cohort study
Authors: Hyun Lee, Hayoung Choi, Hyewon Nam, Bumhee Yang, Bin Hwangbo, Sun‐Young Kong, Sung Jun Chung, Yoomi Yeo, Tai Sun Park, Dong Won Park, Ji‐Yong Moon, Tae‐Hyung Kim, Jang Won Sohn, Ho Joo Yoon, Sang‐Heon Kim
Journal: Allergy (2020)

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Dose intense schedules of temozolomide (SCH 52365) achieve better efficacy than continuous low dose schedules in human brain cancer and melanoma models
Authors: Lianzhu Liang, Lissette Nale, Linda James, Suining Lee, Lori Hollis, Paul Kirschmeier, W. Robert Bishop, Ming Liu
Journal: Cancer Research (2007)

3195  Temozolomide (TMZ) is an alkylating agent indicated for use in adult patients with newly diagnosed glioblastoma multiforme and refractory anaplastic astrocytoma. In the current studies, we evaluated the effects of temozolomide treatment schedule and dose on antitumor efficacy and MGMT activity in models of human brain cancer (Daoy) and melanoma (LOX, A375). The objective of these studies was to compare a compressed dose intense schedule of TMZ to a continuous low dose schedule in which the same total dose of TMZ is administered over a longer period of time. For in vitro studies, the same total dose of TMZ was administered as constant daily dosing, single pulse, or intermittent pulse. For in vivo studies the same total cumulative dose of TMZ was administered either on a continuous schedule (e.g., day 1 through day 15 in a 15 day cycle), on a compressed schedule (day 1 through day 5), or intermittently on day 1, 4, 7, 10, 13.  MGMT (O6-methyl guanine methyl transferase) is the enzyme responsible for repair of the O6-methyl guanine lesion induced by TMZ. MGMT protein level, activity, and promoter methylation were measured in tumor cells or xenograft tumors following TMZ treatment. Different tumor models tested in the study have different levels of MGMT, which in turn correlates with sensitivity to TMZ. Treatment with TMZ depleted MGMT in a dose dependent fashion and reduction of MGMT levels correlated with TMZ activity both in-vitro and in-vivo.  MGMT activity and tumor growth inhibition were reduced in a dose-dependent fashion regardless of treatment schedule in both in vitro and in vivo systems. However, the compressed scheduled appeared to have greater efficacy in terms of growth inhibition and decreased MGMT activity at a given cumulative dose. This difference was most pronounced in models with higher MGMT levels and higher resistance to TMZ. These data suggest that compressed high intensity dose schedules with higher doses may be superior to continuous low doses when treating higher MGMT cancers with TMZ.
Treatment of chronic spontaneous urticaria with benralizumab: Report of primary endpoint per‐protocol analysis and exploratory endpoints
Authors: Jonathan A. Bernstein, Umesh Singh, Marepalli B. Rao, Karen Berendts, Xiang Zhang, Diya Mutasim
Journal: Allergy (2020)

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Re: Thulium Laser Transurethral Vaporesection of the Prostate Versus Transurethral Resection of the Prostate for Men with Lower Urinary Tract Symptoms or Urinary Retention (UNBLOCS): A Randomised Controlled Trial
Authors: Francesco Montorsi, Eugenio Ventimiglia, Paolo Capogrosso, Alberto Briganti, Andrea Salonia
Journal: European Urology (2020)
Efficient homing of antibody-secreting cells to the bone marrow requires RNA-binding protein ZFP36L1
Authors: Alexander Saveliev, Sarah E. Bell, Martin Turner
Journal: The Journal of Experimental Medicine (2020)

Cell migration relies on coordinated activity of chemotactic and guidance receptors. Here, we report a specific role for the RNA-binding protein ZFP36L1 in limiting the abundance of molecules involved in the homing of antibody-secreting cells (ASCs) to the bone marrow (BM). In the absence of ZFP36L1, ASCs build up in the spleen and the liver and show diminished accumulation in the BM. ZFP36L1 facilitates migration by directly regulating G protein–coupled receptor kinase 2 (GRK2) and the integrin chains α4 and β1 in splenic ASCs. Expression of CXCR4 and of the integrins α4 and β1 is differentially regulated on ASCs produced at the early and late stages of the immune response. Consequently, deletion of the Zfp36l1 gene has a stronger effect on BM accumulation of high-affinity ASCs formed late in the response. Thus, ZFP36L1 is an integral part of the regulatory network controlling gene expression during ASC homing.
STEM-09. INTRINSIC INTERFERON SIGNALING REGULATES THE CELL DEATH OF GLIOBLASTOMA STEM CELLS
Authors: Sabbi Khan Khan, Emmanuel Martinez-Ledesma, Sandeep Mittal, Kaitlin Gandy, Kristin Alfaro-Munoz, Nazanin Majd, Veerakumar Balasubramaniyan, John de Groot
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma (GBM) is the most common, highly aggressive, and lethal primary brain tumor in adults. Interferon (IFN)-mediated signal transducer and activator of transcription 1 (STAT1) signaling contributes to various aspects of stemness, cell death, cytokine signaling in immune and non-immune cells. However, the role of IFN/STAT1 signaling in stemness, cell death and treatment resistance in GBM is unclear. This study aimed to investigate the cancer cell-intrinsic IFN/STAT1 signaling and its role in cell proliferation, stemness, and apoptosis. By using the metagene scores for type I and type II IFN-responsive genes, we evaluated basal IFN/STAT1 signaling in The Cancer Genome Atlas (TCGA) and in patient-derived cohorts of stem-like cells (GSCs) RNA expression datasets. In-silico analyses were further validated for the constitutive IFN signaling in a subset of GSCs using qPCR, WB and ELISA assays. We employed pharmacological activators and/or inhibitors of IFN/STAT1 signaling in GSCs to study its role in stemness and cell death. We found differential cell-intrinsic type I and type II IFN-signaling markers in GSCs and GBM tumors. High IFN-signaling is associated with mesenchymal phenotype and poor survival outcomes. Acute and chronic GSC exposure to recombinant IFNs reversibly activated both type I and II IFN-signaling in GSCs. IFN-β exposure induced apoptosis in intrinsically high IFN/STAT1-signaling GSCs, but not in the low IFN/STAT1-signaling GSCs. In summary, our findings demonstrate that GBM exhibit differential cell-intrinsic IFN-signaling, and basal IFN/STAT1 is a key factor for IFN-β-mediated cell death in GSCs. However, further mechanistic investigation of intrinsic IFN signaling in GBM, particularly in the stem cell compartment is needed.
Abstract 2149: Long-Term Outcomes with Drug-Eluting Stents versus Bare-Metal Stents in Diabetic Patients
Authors: Seong-Wook Park, Duk-Woo Park, Jeong-Soon Kim, Hyo-Jung Nam, Jong-Young Lee, Gyung-Jung Kim, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Myeong-Ki Hong, Jae-Joong Kim, Seung-Jung Park
Journal: Circulation (2007)

Background Recent reports shows an increased risk of mortality with the use of drug-eluting stents (DES) in diabetic patients, as compared with bare-metal stents (BMS). Methods We evaluated 1,700 c...
HGG-02. ADOLESCENT AND YOUNG ADULT (AYA) GLIOMA WITH BRAF V600E-MUTANTATION
Authors: Yui Kimura, Yukitomo Ishi, Yuko Watanabe, Yoshiko Nakano, Shigeru Yamaguchi, Yoshitaka Narita, Koichi Ichimura
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Biological features of pediatric glioma differ significantly from those of adult glioma, and limited data are available on those of AYA patients. Here, we focused on AYA patients with glioma, especially those harboring BRAF V600E mutation, and investigated their clinical and genetic features. METHOD: We retrospectively analyzed AYA patients with brain tumors harboring BRAF V600E, who were treated in two hospitals in Japan. RESULTS Clinical information was available for 14 patients. The median age at diagnosis was 25 years (range: 15–38). Five patients were diagnosed with glioblastoma (GBM), including one epithelioid type. These patients were over 25. Although one patient with GBM died of the disease 6.9 years after initial diagnosis, the remaining patients were alive. Two patients were alive without recurrence at 38 and 51 months after the treatment. The patient with epithelioid glioblastoma experienced early recurrence. The remaining nine patients (64%) were diagnosed with low-grade glioma, including ganglioglioma, pilocytic astrocytoma, diffuse astrocytoma, oligodendroglioma, pleomorphic xanthoastrocytoma, and polymorphous low-grade neuroepithelial tumor of the young. No patients died of the disease, and four patients are alive without recurrence after initial operation without adjuvant treatment. Two patients are (epithelioid glioblastoma and ganglioglioma) currently undergoing treatment with a BRAF inhibitor for recurrent tumors. DISCUSSION Although the number of this study is limited, our study suggested that the prognosis of AYA patients with BRAF-V600E positive GBM may not be as dismal as that of children or adults.
PATH-23. ADULT SPINAL CORD ASTROBLASTOMA WITH EWSR1-BEND2 FUSION
Authors: Takeyoshi Tsutsui, Yoshiki Arakawa, Yasuhide Makino, Hiroharu Kataoka, Sachiko Minamiguti, Takanori Hirose, Sumihito Nobusawa, Yoshiko Nakano, Koichi Ichimura, Susumu Miyamoto
Journal: Neuro-Oncology (2020)

Abstract The most recurrent fusion of CNS high-grade neuroepithelial tumor with MN1alteration(HGNET-MN1) is MN1- BEN Domain Containing 2(BEND2) fusion. Recently, there was a report of a 3-month-old boy with spinal astroblastoma, classified as CNS HGNET-MN1 by DKFZ methylation classification but positive for EWSR1-BEND2 fusion(Yamasaki, 2019). Here, we report a 36-year old man with a spinal cord astroblastoma with EWSR1 alternation. The patient presented with back pain, gait disorder and dysesthesia in lower extremities and trunk was referred to our hospital. MRI showed intramedullary tumor in Th3-5 level, displaying low-intensity on T1 weighted image, high-intensity on T2 weighted image, and homogeneous gadolinium enhancement. Partial removal was performed with the laminectomy. The tumor extended to extramedullary and its boundary was unclear. Histological examinations showed the epithelium-like tumor cells with eosinophilic cytoplasm with high cellularity palisade, intracellar fibrosis, and mitosis. Immunohistochemical staining showed positive for Olig2, GFAP, EMA, SSTR2, S-100, but negative for p53, PgRAE1/AE3. The tumor was diagnosed as astroblastoma, and was classified as HGNET-MN1 by the DKFZ methylation classifier. However, the MN1 alternation was not detected by fluorescence in situ hybridization, instead EWSR1 and BEND2 alternations which suggested EWSR1-BEND2 fusion were detected. After radiation therapy of 54Gy/30fr with bevacizumab and temozolomide, the residual tumor reduced the size and his symptoms improved. This case provides evidence that EWSR1-BEND2 fusion is recurrent in HGNET-MN1 and, as previously reported, suggests the importance of BEND2 in this entity. These two cases suggested that it may be the BEND2 alteration that biologically defines the HGNET-MN1 subclass rather than MN1.
EPID-07. A GLOBAL PERSPECTIVE ON THE BURDEN OF PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS
Authors: Daniel Moreira, Ibrahim Qaddoumi, Nickhill Bhakta, Amar Gajjar, Carlos Rodriguez-Galindo
Journal: Neuro-Oncology (2020)

Abstract Although approximately 90% of pediatric cancer cases exist in low- and middle-income countries, the magnitude of the global burden of pediatric central nervous system (CNS) tumors remains poorly quantified. METHODS: Data from International Incidence of Childhood Cancer-3 and CONCORD-3, which include observed incidence and survival from population-based cancer registries (PBCR), and from GLOBOCAN 2018 and Global Burden of Disease 2016, which produce burden estimates from observed and modelled data, were used to analyze epidemiologic characteristics and correlations for CNS tumors globally. Data from The World Bank were used for national macroeconomic variables. RESULTS: The majority of countries are not covered by PBCR, with information on incidence and survival available for 37% and 27% of countries, respectively. Survival data is not available for any low-income country. The incidence of CNS tumors varies markedly, from 0.4 to 49 x106 person-years, the greatest variability in pediatric cancer subgroups. Modelled data suggests that approximately 40,000 incident cases and 19,000 deaths occur from CNS tumors worldwide. When country-level data are segregated based on World Bank groups, a difference in incidence and survival exists (p&amp;lt;0.05). A higher national health expenditure correlates with both an increased incidence and survival of CNS tumors, while the inverse is true for under-5 mortality (p&amp;lt;0.05). CONCLUSIONS: Scarce facts are available, but this analysis establishes a link between national income and epidemiologic parameters for CNS tumors. In this context, carefully designed initiatives, focusing on a health-systems approach are critical to meet the global challenge of pediatric CNS tumors.
PATH-06. IMAGE-BASED MACHINE LEARNING CLASSIFIER FOR PEDIATRIC POSTERIOR FOSSA TUMOR HISTOPATHOLOGY
Authors: Lydia Tam, Wasif Bala, Jonathan Lavezo, Seth Lummus, Hannes Vogel, Kristen Yeom
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Pediatric posterior fossa (PF) tumors can include astrocytomas, ependymomas, and medulloblastomas, all of which demonstrate unique histopathology. Whole slide image analyses can be time consuming and difficult. Therefore, we used machine learning to create a screenshot-based histopathology image classifier that can distinguish between types of pediatric PF tumors. METHODS We took 179 histopathology slides from Stanford University, dated from 2008–2019: 87 astrocytomas, 42 ependymomas, and 50 medulloblastomas, per pathology report. Each slide was viewed under a microscope at 20x. Then, a screenshot was taken of the region of interest representative of principal slide pathology, confirmed by a trained neuropathologist. These screenshots were used to train Resnet-18 models pre-trained on the ImageNet dataset and modified to predict three classes. Various models with different hyperparameters were trained using a random hyperparameter search method. Trained models were evaluated using 5-fold cross-validation, assigning 20% of the dataset for validation with each evaluation. Qualitative analysis of model performance was assessed by creating Class Activation Map (CAM) representations of image predictions. RESULTS The top performing Resnet-18 model achieved a cross-validation F1 of 0.967 on categorizing screenshots of tumor pathology into three types. Qualitative analysis using CAMs indicated the model was able to identify salient distinguishing features of each tumor type. CONCLUSIONS We present a PF lesion classifier capable of distinguishing between astrocytomas, ependymomas, and medulloblastomas based on a histopathology screenshot. Given its ease of use, this tool has potential as an educational tool in an academic setting.