tbuckley/cabot-search huggingface dataset:
Evaluation of Peer-to-Peer Support and Health Care Utilization Among Community-Dwelling Older Adults
Authors: Elizabeth A. Jacobs, Rebecca Schwei, Scott Hetzel, Jane Mahoney, Katherine Sebastian, Kali DeYoung, Jenni Frumer, Jenny Madlof, Alis Simpson, Erika Zambrano-Morales, KyungMann Kim
Journal: JAMA Network Open (2020)

The vast majority of older adults desire to age in their communities, and it is not clear what helps them be successful at aging in place.To investigate the comparative effectiveness of community-designed and community-implemented peer-to-peer (P2P) support programs vs standard community services (SCS) to promote health and wellness in at-risk older adults.This comparative effectiveness study involved a longitudinal cohort of adults aged 65 years and older conducted between 2015 and 2017. The setting was 3 communities in which community-based organizations delivered P2P services to older adults in California, Florida, and New York. Participants in the P2P group and in the SCS group were matched at enrollment into the study according to age, sex, and race/ethnicity at each site. Data analysis was performed from October 2018 to May 2020.P2P support was provided by trained older adult volunteers in the same community. They provided support targeted at the needs of the older adult they served, including transportation assistance, check-in calls, social activities, help with shopping, and trips to medical appointments.Rates of hospitalization, urgent care (UC) and emergency department (ED) use, and a composite measure of health care utilization were collected over 12 months of follow-up.A total of 503 participants were screened, 456 participants were enrolled and had baseline data (234 in the SCS group and 222 in the P2P group), and 8 participants had no follow-up data, leaving 448 participants for the main analysis (231 in the SCS group and 217 in the P2P group; 363 women [81%]; mean [SD] age, 80 [9] years). Participants in the P2P group more often lived alone, had lower incomes, and were more physically and mentally frail at baseline compared with the SCS group. After adjusting for propensity scores to account for baseline differences between the 2 groups, there was a statistically significant higher rate of hospitalization in the P2P group than in the SCS group (0.68 hospitalization per year vs 0.44 hospitalization per year; risk ratio, 1.54; 95% CI, 1.14-2.07; P = .005) during the 12 months of observation. There were no significant differences between the 2 groups in the rates of ED or UC visits or composite health care utilization over the 12 months of the study.P2P support was associated with higher rates of hospitalization but was not associated with other measures of health care utilization. Given that this is not a randomized clinical trial, it is not clear from these findings whether peer support will help older adults age in place, and the topic deserves further study.
Clinical Characteristics and Disease Severity Among Infants With SARS-CoV-2 Infection in Montreal, Quebec, Canada
Authors: Luc Panetta, Catherine Proulx, Olivier Drouin, Julie Autmizguine, Thuy M. Luu, Caroline Quach, Fatima Kakkar
Journal: JAMA Network Open (2020)

Clinical signs and disease severity among infants in our series differ from those reported in children and older adults.Our patients had a predominance of gastrointestinal tract symptoms, even in the absence of fever, and mild disease overall.Given these differences, further work should be done to understand the pathophysiological mechanisms underlying the immune response to infection in infants, as this may be a key to addressing the underlying the morbidity associated with SARS-CoV-2 infection in adults.
INNV-16. CLINICAL APPLICABILITY OF INDIVIDUALIZED DRUG RESPONSE PROFILING UTILIZING EX-VIVO TISSUE-DERIVED 3D CELL CULTURE ASSAYS IN HIGH-GRADE GLIOMA: A SINGLE INSTITUTION CASE SERIES USING 3D-PREDICT RESULTS
Authors: Lindsay Lipinski, Ajay Abad, Laszlo Mechtler, Andrew Fabiano, Ashley Smith, Teresa DesRochers, Matthew Gevaert, Cecile Rose Vibat, Robert Fenstermaker
Journal: Neuro-Oncology (2020)

Abstract Recurrent high-grade glioma is a challenging disease process, without consensus on effective second-line therapy options. Individualized, patient-specific, biologically-based data is desirable in driving therapeutic decision-making. Patients with recurrent high-grade glioma and planned surgical re-resection at our institution were prospectively enrolled into the 3D-PREDICT study. Tissue was collected at the time of surgery for ex vivo 3D cell culture assays comprising a panel of agents commonly used for high-grade glioma, including chemotherapies and targeted therapies used in other solid cancers. In all cases, therapeutic agent selection was guided by the neuro-oncologist’s clinical judgement, factoring the patient’s age, performance status, comorbidities, toxicities/side effect profile of potential agents, and drug accessibility, plus ex-vivo drug response RESULTS: We present 3 cases in which the selection of agents was influenced by the tissue-derived 3D cell culture results; treatment led to clinical response observed in terms of progression free survival, quality of life, and pharmacologic tolerability. In Case 1, a patient with recurrent anaplastic astrocytoma was treated with a BRAF inhibitor for 12 months with excellent tolerability and no radiographic progression. Case 2 demonstrates the use of combination bevacizumab and irinotecan after disease progression subsequent to standard treatment. This patient had local radiographic control for 7 months, tolerating the regimen well. In Case 3, an individual with recurrent glioblastoma was treated with combination carboplatin and etoposide based on assay response prediction to both agents; treatment has been tolerated well with radiographic stability at 6 months while maintaining good performance status. This case series represents our institutional experience of utilizing patient-specific, ex-vivo tissue-derived cell drug response profiling to guide choice of therapy for recurrent high-grade glioma patients. Using individualized, tumor-specific drug sensitivity data to guide these decisions is representative of the ongoing paradigm shift into the realm of individualized medicine to improve outcomes in cancer patients.
Cross-Site Concordance Evaluation of Tumor DNA and RNA Sequencing Platforms for the CIMAC-CIDC Network
Authors: Zexian Zeng, Jingxin Fu, Carrie Cibulskis, Aashna Jhaveri, Curtis Gumbs, Biswajit Das, Beatriz Sanchez-Espiridion, Sylvie Janssens, Len Taing, Jin Wang, James Lindsay, Tomas Vilimas, Jianhua Zhang, Collin Tokheim, Avinash Sahu, Peng Jiang, Chunhua Yan, Dzifa Yawa Duose, Ethan Cerami, Li Chen, David Cohen, Qingrong Chen, Rebecca Enos, Xin Huang, Jack J. Lee, Yang Liu, Donna S. Neuberg, Cu Nguyen, Candace Patterson, Sharmistha Sarkar, Sachet Shukla, Ming Tang, Junko Tsuji, Mohamed Uduman, Xiaoman Wang, Jason L. Weirather, Jijun Yu, Joyce Yu, Jianjun Zhang, Jiexin Zhang, Daoud Meerzaman, Magdalena Thurin, Andrew Futreal, Chris Karlovich, Stacey B. Gabriel, Ignacio Ivan Wistuba, X. Shirley Liu, Catherine J. Wu
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Whole-exome (WES) and RNA sequencing (RNA-seq) are key components of cancer immunogenomic analyses. To evaluate the consistency of tumor WES and RNA-seq profiling platforms across different centers, the Cancer Immune Monitoring and Analysis Centers (CIMAC) and the Cancer Immunologic Data Commons (CIDC) conducted a systematic harmonization study. Experimental Design: DNA and RNA were centrally extracted from fresh frozen and formalin-fixed paraffin-embedded non–small cell lung carcinoma tumors and distributed to three centers for WES and RNA-seq profiling. In addition, two 10-plex HapMap cell line pools with known mutations were used to evaluate the accuracy of the WES platforms. Results: The WES platforms achieved high precision (&amp;gt; 0.98) and recall (&amp;gt; 0.87) on the HapMap pools when evaluated on loci using &amp;gt; 50× common coverage. Nonsynonymous mutations clustered by tumor sample, achieving an index of specific agreement above 0.67 among replicates, centers, and sample processing. A DV200 &amp;gt; 24% for RNA, as a putative presequencing RNA quality control (QC) metric, was found to be a reliable threshold for generating consistent expression readouts in RNA-seq and NanoString data. MedTIN &amp;gt; 30 was likewise assessed as a reliable RNA-seq QC metric, above which samples from the same tumor across replicates, centers, and sample processing runs could be robustly clustered and HLA typing, immune infiltration, and immune repertoire inference could be performed. Conclusions: The CIMAC collaborating laboratory platforms effectively generated consistent WES and RNA-seq data and enable robust cross-trial comparisons and meta-analyses of highly complex immuno-oncology biomarker data across the NCI CIMAC-CIDC Network.
EPID-15. RACIAL AND SOCIOECONOMIC DISPARITIES DIFFERENTIALLY AFFECT OVERALL AND CAUSE-SPECIFIC SURVIVAL IN GLIOBLASTOMA
Authors: Elisa Liu, Sharon Yu, Erik Sulman, Sylvia Kurz
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The prognostic role of racial and socioeconomic factors in patients with glioblastoma is controversially debated. We aimed to evaluate how these factors may affect survival outcomes in an overall and cause-specific manner using large, national cancer registry cohort data in the temozolomide chemoradiation era. METHODS The National Cancer Institute’s Surveillance, Epidemiology, and End Results database was queried for patients diagnosed with glioblastoma between 2005 and 2016. Overall survival was assessed using Cox proportional hazard models using disease intrinsic and extrinsic factors. Cause-specific mortality was assessed using cumulative incidence curves and modeled using multivariate cumulative risk regression. RESULTS A total of 28,954 patients met the prespecified inclusion criteria and were included in this analysis. The following factors were associated with all-cause mortality: age, calendar year of diagnosis, sex, treatment receipt, tumor size, tumor location, extent of resection, median household income, and race. Asian/Pacific Islanders and Hispanic Whites had lower mortality compared to Non-Hispanic Whites. Cause-specific mortality was associated with both racial and socioeconomic groups. After adjusting for treatment and tumor-related factors, Asian/Pacific and black patients had lower glioblastoma-specific mortality. However, lower median household income and black race were associated with significantly higher non-glioblastoma mortality. CONCLUSION Despite the aggressive nature of glioblastoma, racial and socioeconomic factors influence glioblastoma-specific and non-glioblastoma associated mortality. Our study shows that patient race has an impact on glioblastoma-associated mortality independently of tumor and treatment related factors. Importantly, socioeconomic and racial differences largely contribute to non-glioblastoma mortality, including death from other cancers, cardio- and cerebrovascular events.
Neurodegeneration in Hepatic and Neurologic Wilson’s Disease
Authors: André Viveiros, Vincent Beliveau, Marlene Panzer, Benedikt Schaefer, Bernhard Glodny, Benjamin Henninger, Herbert Tilg, Heinz Zoller, Christoph Scherfler
Journal: Hepatology (2020)

Clinical presentation of Wilson disease (WD) includes hepatic and neurologic manifestations. This study compares subcortical brain regions by magnetic resonance imaging in patients with WD and without neurological symptoms. Distinct atrophy affecting the basal ganglia, accumbens, and hippocampus was present in neurological WD. Cerebellar atrophy was observed in hepatic WD without neurological symptoms.
URATE OFFSETS MANGANESE-INDUCED IRON DYSHOMEOSTASIS AND NEURONAL DEGENERATION
Authors: Rachit Bakshi, Vivek Venkataramani, Sanghamitra Bandyopadhyay, Yadong Huang, Yanyan Liu, Xudong Huang, Ashley Bush, Catherine Cahill, Debomoy Lahiri, Hong Jiang, Fudi Wang, Ann Smith, Jack Rogers
Journal: American Journal of Hematology (2017)
CTNI-33. DEBIO1347, AN ORAL FGFR INHIBITOR: RESULTS FROM A SINGLE CENTER STUDY IN PEDIATRIC PATIENTS WITH RECURRENT/REFRACTORY FGFR ALTERED GLIOMAS
Authors: Sameer Farouk Sait, Marc Rosenblum, Tejus Bale, Sofia Haque, Stephen Gilheeney, Krisoula Spatz, Daniel Prince, Katarzyna Ibanez, Ira Dunkel, Matthias Karajannis
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Oncogenic driver alterations in fibroblast growth factor receptors (FGFRs) are present in a subset of pediatric gliomas. Debio1347 is an orally available, highly selective FGFR 1–3 inhibitor with a favorable safety profile and encouraging preliminary clinical activity in an adult phase 1 study. METHODS We treated five children with progressive/refractory CNS tumors harboring an FGFR gene alteration with Debio1347 on single patient use protocols. Patients were treated using the 20 mg tablet formulation at the adult recommended phase 2 dose (80 mg/1.73 m2 ′ BSA once daily). RESULTS All adverse events (AEs) were grade 1–2. Most common treatment-related AEs were hyperphosphatemia, ALT elevation and hypoalbuminemia. Two patients met criteria for partial response and two patients had stable disease. A 13-month-old patient with a spinal cord high-grade glioma harboring two FGFR1 mutations had tumor reduction of 96.3% maintained for 11 months. A 26 month-old patient with a pilomyxoid astrocytoma harboring an FGFR1-TACC1 fusion had a tumor reduction of 74.5% maintained for 9 months. Prolonged disease stabilization and clinically significant improvement in visual function was noted in an eight year-old patient with metastatic suprasellar pilomyxoid astrocytoma harboring two FGFR1 mutations (14 months overall and sustained for 6 months off therapy) and in a 14 year-old patient with posterior fossa glioneuronal tumor harboring an FGFR3-TACC3 fusion (26 months and ongoing). CONCLUSIONS FGFR targeted therapy with Debio1347 demonstrated tolerable toxicity and promising anti-tumor efficacy in pediatric patients with recurrent/refractory FGFR altered gliomas. Further studies in this population are warranted.
An electroporation strategy to synthesize the membrane-coated nanoparticles for enhanced anti-inflammation therapy in bone infection
Authors: Miusi Shi, Kailun Shen, Bin Yang, Peng Zhang, Kangle Lv, Haoning Qi, Yunxiao Wang, Mei Li, Quan Yuan, Yufeng Zhang
Journal: Theranostics (2020)

The cell membrane-coated nanoparticles (MNPs) showed great potential in treating infectious disease due to their superior biofunctions in improving biocompatibility of nanoparticles and neutralization of pathogen or toxins. However, bone infection is accompanied with severe inflammation and bone loss, which also requires anti-inflammatory and osteoconductive treatment. The conventional membrane coating method has to undergo ultrasonication and extrusion procedures, which reduces the functionality of cell membrane and limits the choice of nanoparticles. In this study, we proposed an electroporation-based membrane coating strategy to facilitate the synthesis of MNPs to tackle those problems.
Abstract P139: Clinical Classifiers To Identify Prevalent Aortopathy In Patients With Bicuspid Versus Tricuspid Aortic Valves
Authors: Bamba Gaye, Maxime Vignac, Gådin Jesper, Xavier Jouven, Anders Franco-Cereceda, Eriksson Per
Journal: Circulation (2020)

Background and Aims: The mechanisms underlying bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) ascending aortic aneurysm are still unknown. We sought to identify predictors of aortopathy in BAV and TAV patients, respectively, and determine the genetic contribution to the valve phenotype. Methods: This study included BAV (n=545) and TAV (n=496) patients with aortic valve disease and/or ascending aorta dilatation but devoid of coronary artery disease. We applied machine learning algorithms and classic logistic regression models using multiple variable selection methodologies to predict individuals of high risk of aneurysm. Analyses included comprehensive multidimensional data (i.e., valve morphology, plasma analyses, genetic- and clinical data, family history of cardiovascular diseases, prevalent diseases, demographic, lifestyle and medication). The genetic impact on phenotype was estimated in a genome-wide complex trait analysis using a variance components model. Results: BAV patients were younger (60.4±12.3 years) than TAV patients (70.2±9.5 years), and had a higher frequency of aortic dilatation (45.1% and 29% for BAV and TAV, respectively. P&lt;0.001). The unadjusted aneurysm prediction model showed a mean AUC of 0.8 for TAV patients, with absence of aortic stenosis (AS) being the main predictor, followed by diabetes and hsCRP. Using the same clinical measures in our prediction model for BAV patients resulted in a AUC of only 0.6 which cannot be considered a good predictor of aortic dilatation. Instead, genetic estimation showed higher genetic impact on BAV patients for both ascending aortic dimensions (sinotubular junction, sinus valsalva and aortic root) (genetic impact of 0.8 and 0.3 on BAV and TAV, respectively) and plasma profiles of 455 proteins (BAV: 0.8 vs. TAV: 0.3, for both dimensions and protein levels). Conclusions: The predictive classifier of TAV patients is clinically relevant and potentially offers important implications for better targeting TAV individual at high risk of developing aneurysm. Cardiovascular risk profiles appear to be more predictive of aortopathy than valve morphology and genetic data in TAV patients, whereas in BAV patients, the genetic contribution exceeds environmental factors.
COVD-07. THE IMPACT OF COVID-19 ON PATIENTS AND CAREGIVERS AFFECTED BY BRAIN TUMORS: THE PATIENT NAVIGATOR PERSPECTIVE
Authors: Kyle Walsh
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Preliminary evidence indicates that glioma patients are at higher risk for COVID-19 complications due to systemic immunosuppression. Interruptions in cancer care may exacerbate patient and caregiver anxiety, but surveying patients/caregivers about their COVID-19 experiences is often limited by attainable sample sizes and over-reliance upon single-institution experiences. METHODS To explore how COVID-19 is impacting brain tumor patients/caregivers across the U.S., we performed semi-structured interviews with brain tumor patient navigators employed by two different 501(c)3 nonprofit organizations. A semi-structured interview guide was used, utilizing prompts and open-ended questions to facilitate dialogue. A core set of COVID-19 topics were covered, including: financial issues, coping strategies, geographic variability, variability by tumor grade/histology, disruptions in care continuity, accessing clinical trials, psychosocial issues, and end-of-life care. Interviews were audio-recorded, transcribed, and organized by discussion topic to identify emerging themes. Inductive sub-coding was completed using the constant comparison method, within and between transcripts. RESULTS/CONCLUSIONS Ten patient navigators were interviewed between April 15th and May 8th, with interviews lasting approximately one hour (range 38-77minutes). Navigators reported having contact with 183 unique brain tumor families during the pandemic (range 7–38 families per navigator). High concordance emerged across narratives, revealing important considerations for the neuro-oncology workforce. The most prominent theme was increased caregiver burden, attributed to maintaining social distancing by reducing visits from home-health aides and friends/family. A related theme that applied to both patients and caregivers was increased social isolation due to social distancing, suspension of in-person support groups, and church/temple closures. Accessing clinical trials was a recurrent issue, exacerbated by patients’ increasing unwillingness to travel. Glioblastoma patients, especially those with recurrent tumors, expressed greater reluctance to travel. Access to standard-of-care treatment was rarely interrupted, but reduced access to supportive services – especially physical and occupational therapy – was identified as an emerging COVID-related deficiency in clinical care.
NURS-07. STAFF EDUCATION THROUGH NURSING AND PHARMACY COLLABORATION
Authors: Lauren Hancock, Whitney Pittman
Journal: Neuro-Oncology (2020)

Abstract Even within the focused field of pediatric oncology, there are healthcare providers who lack education regarding the specialized population of children with brain tumors. In order to improve staff knowledge of pediatric neuro-oncology, nursing and pharmacy developed a collaborative Lunch and Learn program to provide additional education. An eight week brain tumor curriculum was developed, and informal sessions grouped by diagnosis were held over lunch between the neuro-oncology nursing team (nurse practitioners and nurse coordinator) and a clinical pharmacy resident. A nurse practitioner provided academic literature and the pharmacy resident did further research and developed an outline for discussion. During these sessions, nursing was able to contribute academic knowledge and clinical experience, while pharmacy presented an overview of each tumor and provided education about medications. After each session, the pharmacy resident presented the information from the Lunch and Learn to all staff oncology pharmacists, which then increased their working knowledge of neuro-oncology as a whole, helping them feel better able to manage this population within their scope of practice. Because this innovative collaboration was so successful in heightening knowledge and awareness of the care and management of pediatric neuro-oncology patients for all those involved, the team now has future plans to utilize a similar model to provide neuro-oncology education to clinic and inpatient RNs.
QOL-41. CARDIAC DYSFUNCTION IN MEDULLOBLASTOMA SURVIVORS TREATED WITH PHOTON IRRADIATION
Authors: Chantel Cacciotti, Christine Chordas, Kate Valentino, Rudy Allen, Peter Manley, Natasha Pillay-Smiley
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Medulloblastoma is an aggressive central nervous system (CNS) tumor that occurs mostly in the pediatric population. Treatment includes surgical resection, craniospinal radiation (CSI) and chemotherapy. Children who receive standard photon radiation (RT) are at risk for cardiac toxicities. Potential late effects include coronary artery disease, left ventricular scarring and dysfunction, valvular damage and atherosclerosis. Current survivorship guidelines recommend routine ECHO surveillance for these patients but this comes at significant health care costs over a lifetime. We describe the experience of cardiac dysfunction in medulloblastoma survivors in a multi-institution study. METHODS A retrospective chart review of medulloblastoma patients treated between 1980 and 2010 with radiation at Lurie Children’s Hospital and Dana-Farber/ Boston Children’s Hospital who had an echocardiogram done following completion of therapy. RESULTS 168 patients were treated for medulloblastoma during the study time. Of whom, 80 patients had echocardiogram follow up and 76 received photon irradiation. The latter were included in the study. The mean age at CSI was 8.6 years (range 2.9- 20), and mean number of years post RT at echocardiogram 7.4 years (range 2–16). Mean ejection fraction (EF) was 60.03% and shortening fraction (SF) 33.8%. Four patients (5%) had abnormal results, all of which had EF&amp;lt;50%. CONCLUSION Patients who received craniospinal irradiation for medulloblastoma therapy have relatively normal echocardiograms post treatment. Although RT may result in cardiac risks, echocardiograms may not be the most cost effective or efficacious mode to evaluate the risk in these survivors long term.