tbuckley/cabot-search huggingface dataset:
EPID-36. ANTIDEPRESSANT DRUG USE IN GLIOBLASTOMA PATIENTS: AN EPIDEMIOLOGICAL VIEW
Authors: Dorothee Gramatzki, James Rogers, Marian Neidert, Caroline Hertler, Emilie Le Rhun, Patrick Roth, Michael Weller
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Antidepressant drugs have shown anti-tumor activity in preclinical glioblastoma studies. Antidepressant drug use, as well as its association with survival, in glioblastoma patients has not been well characterized on a population level. METHODS Patient characteristics, including the frequency of antidepressant drug use, were assessed in a glioblastoma cohort diagnosed in a 10-year time-frame between 2005 and 2014 in the Canton of Zurich, Switzerland. Cox proportional hazards regression models were applied for multivariate analysis. Kaplan-Meier survival curves were used to estimate overall survival data and the log-rank test was performed for comparisons. RESULTS Four hundred four patients with isocitrate dehydrogenase (IDH) wildtype glioblastoma were included in this study. Sixty-five patients (16.1%) took antidepressant drugs at some point during the disease course. Patients were most commonly prescribed selective serotonin reuptake inhibitors at any time (N=46, 70.8%). Nineteen patients (29.2%) were on antidepressant drugs at the time of their tumor diagnosis. No differences were observed in overall survival between those patients who had taken antidepressants at some point in their disease course and those who had not (p=0.356). These data were confirmed in a multivariate analysis including age, Karnofsky performance status, gender, extent of resection, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and first-line treatment as cofounders (p=0.315). Also, there was no association of use of drugs modulating voltage-dependent potassium channels (citalopram; escitalopram) with survival (p=0.639). CONCLUSIONS This signal-seeking study does not support the hypothesis that antidepressants have antitumor efficacy in glioblastoma on a population level.
Abstract P113: Increased Incidence of Atrial Fibrillation During Periods of High Influenza Activity
Authors: Payam Safavi-Naeini, Mehdi Razavi, Abdi Rasekh, Mohammad Madjid
Journal: Circulation (2020)

Introduction: Influenza is an important inflammatory illness which results in 3 to 5 million cases of severe illness, and 290,000 to 650,000 deaths per year, worldwide. Influenza’s role in triggering acute coronary syndromes is well established, but influenza’s impact on cardiac arrhythmias has yet to be investigated. Hypothesis: We investigated the effect of influenza on triggering atrial fibrillation (AFib) episodes. Methods: This retrospective observational study included de-identified data from patients who had a Zio patch (iRhythm Technologies, San Francisco), a wearable continuous cardiac monitoring device. Data were available from October 2012 to September 2017. The “influenza activity” was defined as the percentage of positive respiratory specimens that tested for influenza virus during each influenza season reported by the Centers for Disease Control and Prevention (CDC). We included all cases with AFib burden &lt;=90% from the weeks with the highest and lowest influenza activity up to two consecutive weeks after them. An independent-samples t-test was used to compare the burden of AFib in weeks with the highest and lowest influenza activity. Results: We reviewed the records of 825,869 patients (mean age= 61.1 ± 15.3 years; 48.8% male) who had a Zio patch from October 2012 to September 2017. Of these patients, 47,106 met the pre-defined inclusion criteria for our study. There was a significant difference in the AFib burden in high influenza activity (Mean=1.19, SD=0.69) and low influenza activity (Mean=1.03, SD=0.63) conditions; t (47104) = -2.6, p =0.009. The incidence of AFib was 15% higher in high influenzas activity weeks (OR=1.15, 95%CI, 1.03-1.19, p=0.009). The higher burden of AFib in high influenza activity weeks was significant for each influenza season and a similar trend was observed consistently in each individual influenza season. Conclusions: High seasonal influenza activity is associated with increased odds of AFib. Prospective studies are needed to determine the clinical implications of this finding.
RADT-43. TREATMENT OF RETROPERITONEAL LEIOMYOSARCOMA BRAIN METASTASES WITH STEREOTACTIC RADIOSURGERY
Authors: Shearwood McClelland, Ulysses Gardner, Mark Langer, Kevin Shiue
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Retroperitoneal leiomyosarcoma is a relatively rare disease, with infrequent metastatic spread to the CNS. We present the first report of radiosurgical treatment of this disease. METHODS A 49-year-old woman developed leiomyosarcoma of the inferior vena cava and retroperitoneum with lung metastases on diagnosis. Following multiple courses of systemic and operative treatment, she developed a tender ulcerating mass in the left upper maxillary incisor associated with numbness along the upper gum, lip, and premaxillary area. CT revealed a 3.0 cm left posterior alveolar ridge gum lesion with bone invasion, for which she elected to undergo palliative radiation therapy (30 Gy in 10 fractions). Due to potential maxillary nerve involvement altering the intended radiation therapy treatment fields, an orbit/face MRI was performed to better delineate the lesion. On this MRI, two frontal lobe lesions were visualized; subsequent dedicated brain MRI revealed a total of five metastases (0.9 cm right superior frontal gyrus, 0.9 cm left middle frontal gyrus, 0.9 cm right postcentral gyrus, 0.7 cm right occipital, and 1.6 cm left occipital). Consequently, the decision was made to treat the brain metastases with linear accelerator (LINAC) stereotactic radiosurgery (SRS) to allow simultaneous treatment of the maxillary lesion and brain metastases. RESULTS A single CT simulation was performed for her intracranial and extracranial disease, using the Encompass face mask to allow for simultaneous head immobilization and optimal SRS targeting accuracy. LINAC SRS was delivered simultaneously during maxillary lesion radiation therapy to all five lesions (22 Gy to the 80% isodose line) in a single fraction with a 0.2 cm planning target volume (PTV) margin for each lesion. CONCLUSIONS The first reported case of metastatic retroperitoneal leiomyosarcoma brain metastases treated with SRS demonstrates the flexibility of LINAC (rather than Gamma Knife) SRS in allowing for simultaneous treatment of intracranial and extracranial metastatic disease.
Abstract 15102: Benign Cardiac Neoplasms in the United States - A Thirteen-year Review
Authors: Neiberg Lima, Kristina Byers-Spencer, Kamil Cwikla, Cuyler Huffman, Mireya Diaz, Thomas Melgar, Nicholas Helmstetter
Journal: Circulation (2020)

Introduction: Benign cardiac neoplasms (BCN) are rare; with varying reported incidence and a paucity of epidemiologic studies. The purpose of our review was to add to the small body of literature describing the characteristics and trends of BCN in the US. Methods: This study is a retrospective review of data from the HCUP-NIS Database from 2002-2014. Inclusion criteria consisted of the presence of indication for BCN. Additionally, we queried the database for BCN-associated comorbidities. SAS studio was utilized for analysis. Results: The data consisted of 482,872,274 weighted discharges. There were 45,568 weighted discharges that had BCN. Sixty four percent were women. Median cost per admission was 51,799 USD, five times higher than the national average. A total of 1,267 (2.78%) patients died during the admission. Stroke and arterial embolization were reported in 6730 (14.76%) and 573 (1.26%) weighted discharges. Weight loss, fever and endocarditis were reported in 311 (0.68%), 383 (0.84%) and 869 (1.91%) patients, respectively. Pulmonary hypertension co-occurred in 3440 (7.55%) patients. Episodes of atrial tachyarrhythmias, ventricular arrhythmias, syncope and cardiac arrest were reported in 13,184 (28.93%), 1,471 (3.23%), 1,055 (2.32%) and 393 (0.86%) cases. Sinus node dysfunction, severe AV nodal block co-occurred in 1,005 (2.21%) and 930 (2.04%) patients. Conclusions: We identified a low incidence of BCN in the US over the 13-year study period. Since the prevalence for BCN is low, clinicians must maintain a high index of suspicion due to the high morbidity and mortality.
Novel role of circRSU1 in the progression of osteoarthritis by adjusting oxidative stress
Authors: Yute Yang, Panyang Shen, Teng Yao, Jun Ma, Zizheng Chen, Jinjin Zhu, Zhe Gong, Shuying Shen, Xiangqian Fang
Journal: Theranostics (2020)

Osteoarthritis (OA), characterized as an end-stage syndrome caused by risk factors accumulated with age, significantly impacts quality of life in the elderly. Circular RNAs (circRNAs) are receiving increasing attention regarding their role in OA progression and development; however, their role in the regulation of age-induced and oxidative stress-related OA remains unclear. Methods: Herein, we explored oxidative stress in articular cartilage obtained from patients of different ages. The presence of circRSU1 was detected using RNA sequencing of H2O2-stimulated primary human articular chondrocytes (HCs), and validated in articular cartilage and HCs using fluorescence in situ hybridization (FISH) staining. miR-93-5p and mitogen-activated protein kinase kinase kinase 8 (MAP3K8) were identified as interactive circRSU1 partners based on annotation and target prediction databases, and their associations were identified through dual-luciferase reporter analysis. The effect of the circRSU1-miR-93-5p-MAP3K8 axis on HCs was confirmed using western blot, quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and reactive oxygen species (ROS) analyses. CircRSU1 and its mutant were ectopically expressed in mice to assess their effects in destabilization of the medial meniscus (DMM) in mice. Results: We found a marked upregulation of circRSU1 in H2O2-treated HCs and OA articular cartilage from elderly individuals. circRSU1 was induced by IL-1β and H2O2 stimulation, and it subsequently regulated oxidative stress-triggered inflammation and extracellular matrix (ECM) maintenance in HCs, by modulating the MEK/ERK1/2 and NF-κB cascades. Ectopic expression of circRSU1 in mouse joints promoted the production of ROS and loss of ECM, which was rescued by mutation of the mir-93-5p target sequence in circRSU1. Conclusion: We identified a circRSU1-miR-93-5p-MAP3K8 axis that modulates the progression of OA via oxidative stress regulation, which could serve as a potential target for OA therapy.
Long Term Outcome of Patients with MPN-Associated Myelofibrosis Treated with Peg-Interferon-α2a, a French Intergroup of Myeloproliferative Neoplasms (FIM) Study
Authors: Jean-Christophe Ianotto, Aurélie Chauveau, Francoise Boyer-Perrard, Emmanuel Gyan, Kamel Laribi, Pascale Cony-Makhoul, Jean-Loup Demory, Benoit De Renzis, Christine Dosquet, Jerome Rey, Lydia Roy, Brigitte Dupriez, Laurent Knoops, Laurence Legros, Mohamed Malou, Pascal Hutin, Dana Ranta, Omar Benbrahim, Valerie Ugo, Eric Lippert, Jean-Jacques Kiladjian
Journal: Blood (2017)
Transcription Strikes Back: Clinical Utility of Lung Adenocarcinoma Subtypes
Authors: Ferdinandos Skoulidis
Journal: Clinical Cancer Research (2021)

Using transcriptional profiling, three robust subtypes of nonsquamous non-small cell lung cancer were defined, independently of initiating oncogenic driver events. Subtype-specific differential sensitivity to MEK1/2 inhibitors was reported and an interaction between the mucinous subtype, STK11/LKB1 genomic alterations, and inferior clinical outcomes with atezolizumab in the OAK clinical trial was identified.See related article by Daemen et al., p. 1162.
By Releasing the Brakes With Immunotherapy, Are We Accelerating Atherosclerosis?
Authors: Lavanya Kondapalli, Wendy Bottinor, Carrie Lenneman
Journal: Circulation (2020)

In the past decade, a new paradigm in cancer therapy termed immuno-oncology has emerged.The goal of immuno-oncology is to harness innate cytotoxic T cells to treat cancer.Currently developed immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target programmed cell death protein 1 (PD-1), programmed death ligand-1 (PD-L1), or cytotoxic T lymphocyte-associated antigen 4. Immune checkpoint inhibitors "remove the brakes" that tumors use to suppress native T cell activation, thus allowing the immune system to target tumor cells.Ipilimumab, a monoclonal anti-cytotoxic T lymphocyte-associated antigen 4 antibody, was the first ICI approved by the US Food and Drug Administration in 2011 for the treatment of advanced melanoma.There are now 6 additional ICIs approved: anti-PD1-nivolumab, pembrolizumab, and cemiplimab; and anti-PD-L1-atezolizumab, avelumab, and durvalumab.The list of indications for ICI therapy is rapidly expanding because of dramatic improvements in cancer prognosis and durable cancer response often observed with these agents. 1 The phenomenal success of ICIs, however, has come at the cost of potential immune-related adverse events (iRAEs).iRAEs can affect any organ of the body, although most commonly occur in the gastrointestinal tract, endocrine system, and skin. 2 Although the incidence of cardiovascular iRAEs including myocarditis, pericarditis, vasculitis, and arrhythmias remains relatively low, myocarditis in particular is associated with high patient mortality. 3Pharmcovigilance studies showed a median time to onset of 30 days for myocarditis, but timing can vary by the type of ICI and can be more common with combination therapy. 4However, because of to the presence of autoimmune clones underlying iRAEs, iRAEs may occur years after treatment. 2It is interesting that a systematic review and meta-analysis of 125 clinical trials amounting to 20 128 patients treated with single-agent PD-1 and PD-L1 inhibitors reported 82 treatment-related deaths with a 9.8% incidence of a cardiovascular cause including myocardial infarction and acute coronary syndrome, implying that ICI therapy may have contributed to coronary events. 5he groundbreaking work by Drobni et al 6 and Calabretta et al 7 in this issue of Circulation goes beyond ICI-associated myocarditis to examine the relationship between ICI therapy and atherosclerosis.Drobni et al and Calabretta et al provide evidence that ICIs promote atherosclerosis and reemphasize the critical role of the immune system in modulating risk for major adverse cardiovascular events.The study of immunologic mechanisms underlying atherosclerosis is an active area of research, and several interesting advances have been made.For example, T cells and B cells are present in atherosclerotic plaque, which may mean there is an autoimmune component contributing to atherosclerosis.Cholesterol microcrystals trigger the inflammasome, which cleaves prointerleukin-1β into the active form, and prointerleukin-1β
Green Infrastructure and Health
Authors: Mark J. Nieuwenhuijsen
Journal: Annual Review of Public Health (2020)

The health benefits of green space are well known, but the health effects of green infrastructure less so. Green infrastructure goes well beyond the presence of green space and refers more to a strategically planned network of natural and seminatural areas, with other environmental features designed and managed to deliver a wide range of ecosystem services and possibly to improve human health. In this narrative review, we found that small green infrastructure, such as green roofs and walls, has the potential to mitigate urban flooding, attenuate indoor temperatures and heat islands, improve air quality, and muffle noise, among other benefits, but these effects have not been linked directly to health. Larger green infrastructure has been associated with reduced temperatures, air pollution, and crimes and violence, but less so with health, although some evidence suggests that it may be beneficial for health (e.g., good health, decreased mortality). Finally, parks and street trees show many health benefits, but it is not clear if they can always be considered green infrastructure.
A Data-Driven Rationale for High-Throughput SARS-CoV-2 Mass Screening Programs
Authors: Christopher D. Pilcher
Journal: JAMA Network Open (2020)

Christopher R. Polage, MD, MAS; Mark J. Lee, PhD; Christopher Hubbard, PhD; Catherine Rehder, PhD; Diana Cardona, MD; Thomas Denny, MSc, MPhil; Michael B. Datto, MD, PhD
Author Correction: A guiding map for inflammation
Authors: Mihai G. Netea, Frances Balkwill, Michel Chonchol, Fabio Cominelli, Marc Y. Donath, Evangelos J. Giamarellos-Bourboulis, Douglas Golenbock, Mark S. Gresnigt, Michael T. Heneka, Hal M. Hoffman, Richard Hotchkiss, Leo A. B. Joosten, Daniel L. Kastner, Martin Korte, Eicke Latz, Peter Libby, Thomas Mandrup-Poulsen, Alberto Mantovani, Kingston H. G. Mills, Kristen L. Nowak, Luke A. O’Neill, Peter Pickkers, Tom van der Poll, Paul M. Ridker, Joost Schalkwijk, David A. Schwartz, Britta Siegmund, Clifford J. Steer, Herbert Tilg, Jos W. M. van der Meer, Frank L. van de Veerdonk, Charles A. Dinarello
Journal: Nature Immunology (2020)
STEM-06. THE ROLE OF IFITMs IN MAINTAINING GLIOMA STEM CELLS
Authors: Erisa Nita, Marta Nekulova, Paul M Brennan, Kathryn Ball
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma, one of the most lethal and heterogeneous primary brain tumours, contains cellular hierarchies with both quiescent and self-renewing glioblastoma stem cells (GSCs). GSCs contribute to a lack of progress in patient survival as they appear to have an innate resistance to both chemotherapy and radiotherapy. The aim of this study is to elucidate how constitutive expression of interferons (IFNs) and their downstream signalling pathways maintain GSCs thereby supporting treatment resistance and tumour reoccurrence. To understand the mechanism of action of a subset of IFN regulated genes, originally characterized as a signature for radiation and chemotherapy resistance (IRDS), a panel of patient derived GSCs was generated and manipulated using CRISPR/Cas9 gene-editing. Phenotypic changes in growth, viability and drug resistance were characterised and linked to molecular level events using transcriptomic and proteomic techniques. Using this approach, in conjunction with patient tissue analysis, signalling under basal as well as IFN-activated conditions was studied in the context of GSC status. Immunohistopathology of a glioma tissue micro-array identified an increased expression of IFN induced transmembrane receptors (IFITMs), which co-localised with Nestin, around the blood vessels suggesting that IFITM positive cells were in the stem cell niche. Further analysis showed the presence of IFITM1 and IFITM3 in GSCs and established that loss of IFITMs function impacted on growth rate and cell cycle progression as well as treatment sensitivity. By using wild-type and gene-edited GSC to focus on the relationship between IFITM1 and IFITM3, we have compelling phenotypic and molecular evidence that IFN-induced changes in the localisation of IFITMs impact on the ability of stem cells to ‘escape’ normal growth control mechanisms. Taking into consideration the constitutive expression of interferons in the tumour microenvironment, our study provides evidence that IFITMs regulate GSC self-renewal and are involved in maintaining a quiescent population which can escape chemotherapy.
Coronary Atheroma Regression From Infusions of Autologous Selectively Delipidated Preβ-HDL-Enriched Plasma in Homozygous Familial Hypercholesterolemia
Authors: Brian B. Ghoshhajra, Borek Foldyna, Daniel Gaudet, Etienne Khoury, Steven R. Sloan, Prediman K. Shah, Steven R. Jones, Ron Waksman, Ernst J. Schaefer, H. Bryan Brewer
Journal: Journal of the American College of Cardiology (2020)
Urbanized microbiota in infants, immune constitution, and later risk of atopic diseases
Authors: Jenni Lehtimäki, Jonathan Thorsen, Morten Arendt Rasmussen, Mathis Hjelmsø, Shiraz Shah, Martin S. Mortensen, Urvish Trivedi, Gisle Vestergaard, Klaus Bønnelykke, Bo Lund Chawes, Susanne Brix, Søren J. Sørensen, Hans Bisgaard, Jakob Stokholm
Journal: Journal of Allergy and Clinical Immunology (2020)
GCT-41. RESPONSE-BASED RADIATION THERAPY IN PATIENTS WITH NEWLY DIAGNOSED CENTRAL NERVOUS SYSTEM LOCALIZED GERMINOMA: A CHILDREN’S ONCOLOGY GROUP (COG) PROSPECTIVE PHASE 2 CLINICAL TRIAL
Authors: Ute Bartels, Jason Fangusaro, Dennis Shaw, Aashim Bhatia, Arzu Omar-Thomas, Shengjie Wu, Shannon MacDonald, Erin Murphy, Mark Souweidane, Maryam Fouladi, Amar Gajjar, Girish Dhall, Soumen Khatua
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The objective of stratum 2 of COG ACNS1123 was to evaluate children and young adults (3–21 years) with localized central nervous system (CNS) germinoma and investigate whether simplified pre-irradiation chemotherapy followed by response based dose-reduced whole ventricular irradiation (WVI) would maintain a high progression-free survival (PFS) while reducing long term treatment burden. METHODS Pre-irradiation chemotherapy consisted of 4 cycles of carboplatin and etoposide every 21 days followed by response-based irradiation (XRT). Patients with a complete response (CR) to pre-XRT chemotherapy received 18Gy WVI + 12Gy boost to the tumor bed. Patients with partial response (PR) but less than 1.5 cm residual proceeded to 24Gy WVI + 12Gy boost. All patients were also enrolled on COG ALTE07C1 to prospectively evaluate and longitudinally model the cognitive, social and behavioral functioning. RESULTS During a total accrual time of 45.5 months from 05/2012 to 06/2018, 137 eligible patients were enrolled. Median age was 14.09 years (4.95–21.46), 73% were male, and 45.26% had elevated βhCG in serum and/or cerebrospinal fluid. Twenty-nine patients (21.17%) did not have tissue biopsy. Eleven patients underwent second-look surgery; 7 had mature teratoma and 4 had non-viable tumor. Eighty-one patients (59.13%) had a CR. There were 4 relapses in patients receiving 18Gy WVI + boost, but no deaths. No unexpected treatment-related events were observed. The estimated 3-year PFS was 94.4 ±2.7% among 74 evaluable subjects. CONCLUSION This study shows promise in XRT reduction for patients with localized CNS germinoma and CR. Long-term survival outcomes and ALTE07C1 data are being evaluated.
69P Outcomes with durvalumab and savolitinib in metastatic papillary renal cancer (mPRC) according to international metastatic renal cell carcinoma database consortium (IMDC) risk groups
Authors: J. Choy, C. Suarez Rodriguez, J. Larkin, P. Patel, B. Perez Valderrama, A. Rodriguez-Vida, H. Glen, F. Thistlethwaite, C. Ralph, G. Srinivasan, M.J. Mendez Vidal, A. Carter, C. Tyson, A. Prendergast, K. Mousa, T.B. Powles, B.E. Szabados
Journal: Annals of Oncology (2020)