tbuckley/cabot-search huggingface dataset:
Responsiveness to Parenteral Corticosteroids and Lung Function Trajectory in Adults with Moderate-to-Severe Asthma
Authors: Loren C. Denlinger, Brenda R. Phillips, Ronald L. Sorkness, Eugene R. Bleecker, Mario Castro, Mark D. DeBoer, Anne M. Fitzpatrick, Annette T. Hastie, Jonathan M. Gaffin, Wendy C. Moore, Michael C. Peters, Stephen P. Peters, Wanda Phipatanakul, Juan Carlos Cardet, Serpil C. Erzurum, John V. Fahy, Merritt L. Fajt, Benjamin Gaston, Bruce D. Levy, Deborah A. Meyers, Kristie Ross, W. Gerald Teague, Sally E. Wenzel, Prescott G. Woodruff, Joe Zein, Nizar N. Jarjour, David T. Mauger, Elliot Israel
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: It is unclear why select patients with moderate-to-severe asthma continue to lose lung function despite therapy. We hypothesized that participants with the smallest responses to parenteral corticosteroids have the greatest risk of undergoing a severe decline in lung function.Objectives: To evaluate corticosteroid-response phenotypes as longitudinal predictors of lung decline.Methods: Adults within the NHLBI SARP III (Severe Asthma Research Program III) who had undergone a course of intramuscular triamcinolone at baseline and at ≥2 annual follow-up visits were evaluated. Longitudinal slopes were calculated for each participant's post-bronchodilator FEV1% predicted. Categories of participant FEV1 slope were defined: severe decline, >2% loss/yr; mild decline, >0.5-2.0% loss/yr; no change, 0.5% loss/yr to <1% gain/yr; and improvement, ≥1% gain/yr. Regression models were used to develop predictors of severe decline.Measurements and Main Results: Of 396 participants, 78 had severe decline, 91 had mild decline, 114 had no change, and 113 showed improvement. The triamcinolone-induced difference in the post-bronchodilator FEV1% predicted (derived by baseline subtraction) was related to the 4-year change in lung function or slope category in univariable models (P < 0.001). For each 5% decrement in the triamcinolone-induced difference the FEV1% predicted, there was a 50% increase in the odds of being in the severe decline group (odds ratio, 1.5; 95% confidence interval, 1.3-1.8), when adjusted for baseline FEV1, exacerbation history, blood eosinophils and body mass index.Conclusions: Failure to improve the post-bronchodilator FEV1 after a challenge with parenteral corticosteroids is an evoked biomarker for patients at risk for a severe decline in lung function.
Changes in Preterm Birth Phenotypes and Stillbirth at 2 Philadelphia Hospitals During the SARS-CoV-2 Pandemic, March-June 2020
Authors: Sara C. Handley, Anne M. Mullin, Michal A. Elovitz, Kristin D. Gerson, Diana Montoya-Williams, Scott A. Lorch, Heather H. Burris
Journal: JAMA (2020)

This study uses data from the GeoBirth pregnancy cohort of all births in 2 hospitals in Philadelphia to examine whether rates of preterm birth, spontaneous preterm birth, medically indicated preterm birth, and stillbirth have changed during the SARS-CoV-2 pandemic compared with prepandemic rates.
STEM-24. RADIATION-INDUCED EXTRACELLULAR VESICLE (EV) RELEASE OF miR-603 PROMOTES IGF1-MEDIATED STEM CALL STATE IN GLIOBLASTOMAS
Authors: Valya Ramakrishnan, Beibei Xu, Johnny Akers, Thien Nguyen, Jun Ma, Sanjay Dhawan, Jianfang Ning, Ying Mao, Wei Hua, Efrosini Kokkoli, Frank Furnari, Bob Carter, Clark Chen
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Release of exosomes and extracellular vesicles (EV) by glioblastomas plays key roles in modulating the tumor microenvironment and therapeutic response. Studies to date have largely focused on the impact of EV and exosomes on the recipient cell. Here, we demonstrate that EV-mediated export of a master-regulatory miRNA has fate-determining impacts on the cell releasing the EVs. METHODS microRNA (miRNA) profiling was performed using clinical glioblastoma specimens from the same patients derived pre- and post-standard of care treatment. Mechanism mediating altered miRNA homeostasis were assessed. RESULTS While the levels of nearly all miRNAs remained unchanged after standard-of-care treatment, decreased levels of few, select miRNAs were observed, including miR-603. In response to ionizing radiation (IR), but not temozolomide (TMZ), glioblastoma cell lines exhibited a time-dependent decrease in miR-603 levels. While miR-603 biogenesis and degradation remained unchanged after IR, IR induced an increase in EV-mediated export of miR-603. Profiling of miR-603 targets revealed that miR-603 repressed the insulin-like growth factor 1 (IGF1) and IGF1 receptor (IGF1R), genes required to maintain the cancer stem cell (CSC) state, as well as MGMT, the gene encoding a DNA repair protein that detoxifies temozolomide (TMZ) induced DNA damages. IR induced export of miR-603 de-repress IGF1/IGF1R to promote radiation resistance and de-repress MGMT to promote cross-resistance to TMZ and CCNU. Ectopic miR-603 expression overwhelmed cellular capacity for miR-603 export and synergized with the tumoricidal effects of IR and temozolomide (TMZ). CONCLUSIONS Radiation stimulated EV-mediated export of miR-603 to facilitate acquired resistance to IR and cross-resistance to DNA alkylating agents.
TBIO-02. IMMUNE PROFILING OF RARE EMBRYONAL BRAIN TUMORS REVEAL EVIDENCE OF DYSREGULATED INTERFERON SIGNALLING AS A POTENTIAL DETERMINANT OF IMMUNOLOGICAL HETEROGENEITY
Authors: Dean Popovski, Fupan Yao, Andrew Bondoc, Salma Al-Karmi, Ben Ho, Holly Lindsay, Xiao-Nan Li, James Rutka, Annie Huang
Journal: Neuro-Oncology (2020)

Abstract Embryonal brain tumors (EBTs) remain the most common malignant pediatric brain tumors. Despite recent advances and improved understanding of the molecular biology of EBTs, clinical outcomes remain poor for rare EBTs. Previous large-scale genomic studies of rare EBTs have shed light on distinct genomic, transcriptomic and epigenomic profiles. Interestingly, these studies have revealed prominent tumor heterogeneity that provides opportunity to develop novel treatment strategies to improve patient outcomes. To examine the tumor microenvironment and identify tumor- specific biological dependencies, we performed deconvolution analysis of bulk gene expression (171 RNA-seq, 236 microarrays) and 586 methylation arrays, which revealed significant intra and inter-tumoral heterogeneity and implicated interferon (IFN)-mediated signalling as a determinant of a distinct immunological profile in rare EBTs. To further elucidate the importance of IFN signalling, we performed scRNA-seq on 20 primary samples, which provided evidence of a spectrum of IFN-immunological responses that vary from immunosuppressive to immunologically exhaustive that occur in a host dependent manner. To further validate our findings, we utilised a genetically engineered murine model of Atypical Teratoid Rhabdoid Tumor and primary xenografts in humanised mice to corroborate our in-silico profiles in vivo. Through amalgamation of our in-silico data with our in vivo data, we have identified evidence that dysregulated IFN responses represent a core element of the immunological heterogeneity present within subsets of rare EBTs. An improved understanding of the immune milieu in rare EBTs will provide avenues to develop specific onco-immune targets to address this clinical need.
Cardiac Magnetic Resonance Imaging Identification of Myocardial Fibrosis: The Need for Standardization and Therapies**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Christopher M. Kramer
Journal: Journal of the American College of Cardiology (2010)
Flavonoids in Bone Erosive Diseases: Perspectives in Osteoporosis Treatment
Authors: Daniele Bellavia, Eufrosina Dimarco, Viviana Costa, Valeria Carina, Angela De Luca, Lavinia Raimondi, Milena Fini, Carla Gentile, Fabio Caradonna, Gianluca Giavaresi
Journal: Trends in Endocrinology and Metabolism (2020)
Lipid nanoparticles loaded with ribonucleoprotein–oligonucleotide complexes synthesized using a microfluidic device exhibit robust genome editing and hepatitis B virus inhibition
Authors: Yuichi Suzuki, Haruno Onuma, Risa Sato, Yusuke Sato, Akari Hashiba, Masatoshi Maeki, Manabu Tokeshi, Mohammad Enamul Hoque Kayesh, Michinori Kohara, Kyoko Tsukiyama-Kohara, Hideyoshi Harashima
Journal: Journal of Controlled Release (2020)
QOL-02. PERCEPTIONS OF LATE EFFECTS CARE NEEDS AMONG SURVIVORS OF PEDIATRIC BRAIN TUMOURS
Authors: Chantel Cacciotti, Adam Fleming, Hanna Tseitlin, JoAnn Duckworth, Stacey Marjerrison
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVES Pediatric brain tumour survivors are at risk of long-term consequences of therapy. Comprehensive late effects care may mitigate these risks, but the best care model is unclear. We sought to describe the care experience and quality of life (QOL) of pediatric brain tumour survivors at the McMaster Children’s Hospital joint adult/pediatric Neuro-Oncology clinic. METHODS Cross-sectional survey data were collected. Care needs were assessed with the Cancer Care Experience Questionnaire (CCEQ), Cancer Worry Scale (CWS), and Self-Management Skills Scale (SMSS). Quality of life was measured utilizing the PedsQL Brain Tumor Module. Data were analyzed descriptively. RESULTS Thirty-two childhood brain tumor survivors and/or their parents participated. Their malignancies included embryonal tumors (medulloblastoma/ATRT) (62%), ependymoma (22%), and germ cell tumours (16%). Among 77%, therapy included chemotherapy, surgery and radiation. Most respondents reported high quality cancer care, although some could not recall discussions of late effects risks and health promotion. Mean cancer worry scores were low (71.8 (± 28.4)). Survivors reported limited self-management skills (58.5 (±18.2)), with support required in clinic visits, arranging medical appointments, filling prescriptions and tasks of daily living. Overall median QOL scores were in the ‘good’ range (parental report 72.3 (±17.7), survivor 68.2 (±16.6)). CONCLUSION In comparison to other childhood cancer survivor cohorts, this group of long-term brain tumour survivors appear to have similar QOL, fewer cancer worries, and increased need for aid with self-management. Given this, along with the positive care experience reported, this clinic model of care appears to meet the needs of this population.
First‐line treatment of double‐hit and triple‐hit lymphomas: Survival and tolerance data from a retrospective multicenter French study
Authors: Marie‐Charlotte Laude, Laure Lebras, Pierre Sesques, Herve Ghesquieres, Simon Favre, Krimo Bouabdallah, Carolyne Croizier, Romain Guieze, Laurianne Drieu La Rochelle, Emmanuel Gyan, Roza Chin, Thérèse Aurran‐Schleinitz, Amira Marouf, Bénédicte Deau‐Fischer, Paul Coppo, Sandrine Malot, Xavier Roussel, Adrien Chauchet, Marianne Schwarz, Charles Bescond, Thierry Lamy de la Chapelle, Lucile Bussot, Sylvain Carras, Bénédicte Burlet, Cédric Rossi, Adrien Daniel, Franck Morschhauser, Fabien Subtil, Anne‐Sophie Michallet
Journal: American Journal of Hematology (2020)

Historically, double or triple hit lymphoma (DHL and THL) have poor outcomes with conventional chemotherapy, but there is currently no guideline. We report the French experience in managing DHL and THL in first line using collective data on both survival and tolerance. All consecutive patients with newly diagnosis of large B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements, as determined by FISH between January 2013 and April 2019 were included. Based on the eligibility criteria, 160 patients were selected among the 184 patients identified. With a median follow-up of 32 months, 2- and 4-year progression free survival (PFS) rates were 40% and 28% with R-CHOP compared with 57% and 52% with intensive chemotherapy (P = .063). There was no difference in overall survival (OS). For advanced stages, PFS was significantly longer with intensive chemotherapy than with R-CHOP (P = .029). There was no impact of autologous stem cell transplantation among patient in remission. For patients with central nervous system (CNS) involvement, the 2-year PFS and OS rate was 21% and 39%, vs 57% and 75% without CNS disease (P = .007 and P < .001). By multivariate analysis, elevated IPI score and CNS disease were strongly and independently associated with a poorer survival, whereas treatment was not significantly associated with OS. This is the largest series reporting the treatment of DHL and THL in Europe. The PFS was significantly longer with an intensive regimen for advanced stage, but no difference in OS, supporting the need for a prospective randomized trial.
Abstract 12772: Evaluation of a Tummy Time Intervention to Improve Motor Skill Development in Infants After Cardiac Surgery
Authors: Karen Uzark, Cynthia Smith, Sunkyung Yu, Ray Lowery, Chris Tapley, Jennifer Romano, Jennifer Butcher
Journal: Circulation (2019)

Introduction: Children who require open heart surgery in the 1st year of life are vulnerable to developmental delays and are at significantly greater risk for gross motor impairment than healthy in...
MBCL-14. A STUDY OF LOW-DOSE CRANIOSPINAL RADIATION THERAPY IN PATIENTS WITH NEWLY DIAGNOSED AVERAGE-RISK MEDULLOBLASTOMA
Authors: Aaron Mochizuki, Anna Janss, Sonia Partap, Paul Fisher, Yimei Li, Michael Fisher, Jane Minturn
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Medulloblastoma is one of the most common malignant brain tumors in children. To date, the treatment of average-risk (non-metastatic, completely resected) medulloblastoma includes craniospinal radiation therapy and adjuvant chemotherapy. Modern treatment modalities and now risk stratification of subgroups have extended the survival of these patients, exposing the long-term morbidities associated with radiation therapy. METHODS We performed a single-arm, multi-institution study, seeking to reduce the late effects of treatment in patients with average-risk medulloblastoma prior to advances in molecular subgrouping. To do so, we reduced the dose of craniospinal irradiation by 25% to 18 gray with the goal of maintaining the therapeutic efficacy as described in CCG 9892 with maintenance chemotherapy. RESULTS 28 patients aged 3–30 years were enrolled across three institutions between April 2001 and December 2010. Median age at enrollment was 9 years with a median follow-up time of 11.7 years. The 3-year relapse-free (RFS) and overall survival (OS) were 78.6% (95% CI 58.4% to 89.8%) and 92.9% (95% CI 74.4% to 98.2%), respectively. The 5-year RFS and OS were 71.4% (95% CI 50.1% to 84.6%) and 85.7% (95% CI 66.3% to 94.4%), respectively. Toxicities were similar to those seen in other studies; there were no grade 5 toxicities. CONCLUSIONS Given the known neurocognitive adverse effects associated with cranial radiation therapy, studies to evaluate the feasibility of dose reduction are needed. In this study, we demonstrate that select patients with average-risk medulloblastoma may benefit from reduced craniospinal radiation dose of 18 gray without impacting relapse-free or overall survival.
QOLP-10. MONITORING TRENDS IN PATIENT DISTRESS IN GLIOBLASTOMA USING THE PHQ4 QUESTIONNAIRE
Authors: Anh Huan Vo, Connor Hambelton, Lauren Popp, Verda Dew, Maria Turchan, Sofia Gallamore, Rochelle Fu, Edward Neuwelt, Prakash Ambady
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE To identify the trend of distress over time and whether palliative care (PC) referral and visit affected distress level in glioblastoma (GBM) patients. BACKGROUND GBM patients experience significant distress due to their prognosis and neurologic involvement. All subjects in the neuro-oncology clinic at our institution routinely receive the Patient Health Questionnaire-4 (PHQ4) which is a validated screening tool that comprises a section for generalized anxiety disorder (GAD2) and a depression screen (PHQ2). DESIGN This prospective study was approved by the institutional review board. GBM patients who started radiation therapy on 1/1/2019 or later were included. Patients with a GAD2 or PHQ2 of 3 or above were categorized as present for anxiety or depression. A logistic mixed-effects model was used to test the trend of anxiety or depression over time and the impact of PC referral and visit. RESULT 131 PHQ4 questionnaires from 39 newly diagnosed GBM patients (mean age: 59.9yrs ± 15.0; 23M/16F) at the pre-radiation, post radiation and at least every 2 months thereafter were reviewed. Before radiation, 54.8% of patients reported anxiety, higher than at 1-month post radiation (23.5%), 2-3 months (41.4%), 4-6 months (20.0%), and after 6 months (25.0%). This temporal trend is significant (P = 0.0385) after adjusting for patient characteristics such as age, gender and performance status. The proportions of anxiety were not different among visits without PC referral (23.7%), with PC referral and no PC visit (42.4%), and with PC visit (32.4%, P = 0.64). We did not identify a similar temporal trend in depression. CONCLUSION Our data suggests that anxiety is more prevalent than depression in this cohort. This study identifies subjects to be at a greatest likelihood of experiencing anxiety at the pre-radiation time point. Focused interventions at this time point may help improve the patient’s overall quality of life.
BIOM-42. ASSOCIATION OF NEUTROPHIL-LYMPHOCYTE RATIO WITH GLIOMA GRADING AND SURVIVAL
Authors: Rusdy Ghazali Malueka, Ery Kus Dwianingsih, Maria Alethea, Ibnu Widya Argo, Aulia Fitri Ramadhani, Sabillal Saleh, Adiguno Suryo Wicaksono, Kusumo Dananjoyo, Ahmad Asmedi, Rachmat Andi Hartanto
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Gliomas are the most common primary central nervous system tumor. Inflammatory responses are thought to play an important role in cancer progression. Neutrophil-lymphocyte ratio (NLR) is a simple, low cost and easy to measure inflammation marker that has been shown to be a poor prognostic factor in many solid tumors. The preoperative NLR has been shown to be associated with histopathological grading of glioblastoma. This study aimed to find the association of NLR with glioma grading and overall survival in Indonesian patients. METHODS The patients were enrolled from Dr. Sardjito General Hospital, Yogyakarta Province, Indonesia. Neutrophil and lymphocyte counts were extracted from the complete blood count test before surgery. NLR was calculated as neutrophil count divided by lymphocyte count using standard units. Detailed demographic and clinical data were collected from medical records. RESULT A total of 79 patients were included in this study, consisting of 48 (60.8%) males and 31(39.2%) females. Most patients were diagnosed as WHO grade IV gliomas (43%), followed by grade II (26%), grade III (13%), and grade I (7.6%). In multivariate analysis, NLR ≥ 5.01 was significantly associated with high grade glioma (HR 5.50, 95%CI 1.96–15.44, p=0.001). We also found that patients with NLR ≥ 10.5 have significantly shorter median overall survival compared with patients with NLR &amp;lt; 10.5 (4.6 months and 27.2 months respectively, HR 2.13, 95%CI 1.03–4.40, p=0.041). Multivariate analysis using Cox Regression method showed that higher NLR (≥ 10.5) and IDH1 wild type were independent predictors for worse outcome. CONCLUSION In conclusion, NLR is associated with grading and overall survival of glioma patients in Indonesia.
LGG-27. TARGETED THERAPY FOR PEDIATRIC LOW-GRADE GLIOMAS AND PLEXIFORM NEUROFIBROMAS WITH TRAMETINIB
Authors: Tiffany Nguyen, Kathleen McMahon, Molly Hemenway, Jean Mulcahy Levy, Nicholas Foreman, Kathleen Dorris
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Targeted therapy aimed at modulating the RAS/RAF/MEK/ERK pathway is of increasing interest for patients with plexiform neurofibromas and low-grade gliomas. Trametinib is an FDA-approved MEK inhibitor that has little published pediatric experience to date. METHODS A retrospective chart review of patients treated with trametinib for low-grade gliomas (LGG) and/or plexiform neurofibromas (PN) between 2015–2018 was conducted at Children’s Hospital Colorado. Data collected included patient demographics, lesion location, Neurofibromatosis type 1 (NF1) status, best response of PN/LGG to trametinib, duration of trametinib therapy, and reported toxicities at least possibly attributed to trametinib. RESULTS Thirty (57% male; 73% NF1) patients were identified. Sixteen (53%) patients had PN only, 12 (40%) had LGG only, and two (7%) patients had both PN and LGG. The most common LGG location was the optic pathway/hypothalamus (72%). The most common location of PN was the face (63%). Two-thirds (8/12) of patients with LGG had a BRAF alteration or NF1 mutation. The median age at start of trametinib therapy was 9.9 years (range, 2.0 – 18.8 years). The median duration of trametinib therapy was 0.8 years (range 0.1 – 2.9 years). The most commonly reported adverse event was rash. No patients developed retinal toxicity or cardiotoxicity. Only two (7%) patients discontinued for toxicity and one (3%) for progressive disease. CONCLUSIONS Trametinib can be administered without significant toxicity to children with PN or LGG. Clinical benefit is noted in this cohort; however, prospective clinical trials are necessary to characterize efficacy formally.
NIMG-44. INTEGRATING AUTOMATED LESION SEGMENTATIONS FROM SINGLE-IMAGES INTO ROUTINE CLINICAL WORKFLOW FOR VOLUMETRIC RESPONSE ASSESSMENT
Authors: Javier Villanueva-Meyer, Pablo Damasceno, Marisa LaFontaine, James Hawkins, Tracy Luks, Jason Crane, Janine Lupo
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Volume calculations have not been adopted into glioma response assessment due to lengthy times for manual definition and unreliable measures provided by automated algorithms. Relatively new artificial intelligence approaches such as convolutional neural networks have significantly improved lesion segmentation with performance accuracies &amp;gt;90%. However, their adoption into routine practice remains limited due to poor generalizability and failure rates approaching 25% when incorporated into clinical workflow. The latter can be attributed to 1) the requirement of four different types of anatomic images (T2, T2-FLAIR, T1 pre- and post-contrast); 2) cumbersome preprocessing including alignment, reformatting, and skull removal; and 3) the lack of a well-integrated clinical deployment system. The goal of this study was to demonstrate how simple modifications to a robust network coupled with an integrated workflow can provide reliable measures of tumor volume for real-time use in the reading room. METHODS Leveraging NVIDIA’s Clara-Train software and a molecularly diverse dataset of 400 labeled images for training, we modified a top-performing ensembled 2D-U-Net to require a single image-volume input (T2-FLAIR or post-contrast T1 for the T2-hyperintense or contrast-enhancing lesions) and deployed the results in the clinic to provide quantitative volumetrics. Inference was performed on a mix of image orientations without any reformatting or skull-stripping. RESULTS Training on only 115 of our 400 datasets, we achieved Dice Coefficients of 90% and 81% overlap of our auto-segmented T2 and contrast-enhancing lesions with manual labels in our 25-patient validation cohort (11 enhancing), compared to 91% and 83% overlap with the original model that required four anatomic images to segment each lesion. Radiologists can view segmentations directly from PACS as contours or overlays and provide numerical feedback for model refinement. The workflow has been applied on 50 cases to date without any failures and can be easily shared for deployment on any clinical PACS.