tbuckley/cabot-search huggingface dataset:
LGG-24. TEMPORAL GENOMIC HETEROGENEITY IN PEDIATRIC LOW-GRADE GLIOMAS
Authors: Christine Fuller, Austin Schafer, Daniel Boue, Diana Osorio, Jonathan Finlay, Sarah Rush, Erin Wright, Lindsey Hoffman, Nancy Yanez-Escorza, Jamie Reuss, Trent Hummel, Ralph Salloum, Lionel M L Chow, Mariko DeWire, Peter de Blank, Charles Stevenson, Rachid Drissi, Maryam Fouladi
Journal: Neuro-Oncology (2018)

Pediatric low-grade gliomas (pLGG) represent the most common brain tumors in children. Though malignant transformation is rare, these tumors pose a formidable therapeutic challenge due to anatomy-limiting surgical options and local recurrence. The temporal and therapy-driven genomic evolution in pLGG is largely unknown. To characterize the temporal genomic heterogeneity of pLGG, we performed fluorescence in situ hybridization, mutation-specific immunohistochemistry, and exome analyses on paired tumor samples from primary diagnostic and subsequent surgeries of 27 pLGG patients. 59 tumor samples were available for review and included pilocytic / pilomyxoid astrocytoma (PA) (67%), low grade astrocytoma (19%), ganglioglioma (11%), and pleomorphic xanthoastrocytoma (3%). BRAF duplication/rearrangement was detected in 56% of tested samples, limited to PA in all but one patient (ganglioglioma). 58% of samples harbored CDKN2A deletion, which was demonstrable across various histologies. BRAF duplication/rearrangement was found consistently conserved across primary and subsequent surgical samples, whereas CDKN2A status changed in 60% of tested temporal pairs, with deletion acquisition the most frequent finding (40%) at second surgery. Likewise, BRAF V600E mutation in one PA was lost at second surgery. Although CDKN2A status changes were seen following surgery alone, the addition of chemo-and/or radiation therapy was associated with a higher rate of temporal CDKN2A deletion acquisition (50%, versus 33% with surgery alone). Temporal genomic heterogeneity may be encountered in a significant proportion of pLGG, with some alterations potentially facilitated by therapy. Recurrence biopsy may provide improved guidance, particularly if targeted therapeutics are being considered.
Publisher Correction: Stimulation of entorhinal cortex–dentate gyrus circuitry is antidepressive
Authors: Sanghee Yun, Ryan P. Reynolds, Iraklis Petrof, Alicia White, Phillip D. Rivera, Amir Segev, Adam D. Gibson, Maiko Suarez, Matthew J. DeSalle, Naoki Ito, Shibani Mukherjee, Devon R. Richardson, Catherine E. Kang, Rebecca C. Ahrens-Nicklas, Ivan Soler, Dane M. Chetkovich, Saïd Kourrich, Douglas A. Coulter, Amelia J. Eisch
Journal: Nature Medicine (2018)
NURS-20. NURSING IMPACT ON BONE MARROW TRANSPLANT IN THE OUTPATIENT SETTING
Authors: Melissa Waters, Erin Kissell, Stacy Silverman, Molly Hemenway, Jenny Raybin
Journal: Neuro-Oncology (2018)

The neuro-oncology program at Children’s Hospital Colorado has successfully established an outpatient-based model of autologous bone marrow transplant (BMT) with the delivery of high dose chemotherapy followed by stem cell transplant since 1999. In the past seven years, nearly 30 patients have been transplanted as an outpatient. Decision to proceed outpatient is based on assessment of the family and support systems as well as the treatment team and family willingness. This model requires a multi-disciplinary effort, with nursing as an integral member of the team. Nurses are involved in all aspects of the care, including stem cell collection, delivery of therapy, and post BMT follow up. Nurses are especially active in coordination of monitoring and testing needed prior to and post-transplant, delivery of high dose chemotherapy and stem cell infusions, and ongoing teaching to prepare families to safely and effectively care for the patient at home. Teaching includes specific instructions regarding anti-emetics, unique skin care and bathing needs post-thiotepa, and common side effects related to high dose chemotherapy. Successful delivery of this therapy as an outpatient embraces the philosophy of family centered care, empowering families to advocate directly for their child. Nursing knowledge and expertise is essential for the success of this model.
Prevalence of psoriatic arthritis in patients with psoriasis: A systematic review and meta-analysis of observational and clinical studies
Authors: Farzad Alinaghi, Monika Calov, Lars Erik Kristensen, Dafna D. Gladman, Laura C. Coates, Denis Jullien, Alice B. Gottlieb, Paolo Gisondi, Jashin J. Wu, Jacob P. Thyssen, Alexander Egeberg
Journal: Journal of the American Academy of Dermatology (2018)
Abstract 20801: Coxsackievirus Infection During the First Trimester of Pregnancy Leads to Ventricular Septal Defect
Authors: Vipul Sharma, Lisa Goessling, Connor Mullen, Alma Muller, Brian Dailey, Daniel Perry, Adam Miller, Horacio Carvajal, Anoop Brar, Pirooz Eghtesady
Journal: Circulation (2017)

Purpose: Coxsackievirus B (CVB), known to be the most common cause of myocarditis, target cardiomyocytes through Coxsackie and Adenovirus Receptor, which is highly expressed in the fetal heart. We ...
LGG-03. TREATMENT STRATEGY FOR THE EXPANDING CYST OF PEDIATRIC PILOCYTIC ASTROCYTOMAS
Authors: Tomoru Miwa, Ryota Tamura, Hikaru Sasaki, Kazunari Yoshida
Journal: Neuro-Oncology (2018)

Pilocytic astrocytoma (PA) shows a good prognosis after total removal. However, if the residual tumor shows with cysts, it may increase with tumor growth, or only cyst may be enlarged. A treatment strategy for cystic expansion of PA was examined. Thirteen cases of intracranial PA cases (average: 9.4 years old) who were performed the initial operation in 2000 - 2015. Among them, nine cases with cystic components were found. Among the 9 cases, 4 cases didn’t show postoperative cyst expansion, and 5 cases showed cystic expansion of the remaining lesion. In the 5 cases, locations were 3 cases of optic pathway / hypothalamus, a case of cerebellum, and brain stem each. A case was totally removed by craniotomy, a case was performed cyst fenestration + partial removal with cauterization, a case was confirmed spontaneous regression by follow up observation. Two patients underwent chemotherapy (CDDP + VCR), among them, a case showed regression, but a case gradually increased and finally needed a fenestration. Ki-67 index of these expanded cases showed 2.1% on average, and that was lower than other groups. BRAF V600E was wild type in the two cases examined. Cystic expansion may not be associated with spontaneous regression or increased tumor body. Controlling cysts by chemotherapy including Bevacizumab is controversial. If it is asymptomatic, natural regression may be expected, but if symptomatic or expansion progression is rapid, surgical treatment is inevitable. In that cases, consider partial extraction as well as fenestration, depending on cyst contents, Ommaya reservoir is also considered.
Long-term effect of peripheral sensory neuropathy (PSN) of 3 or 6 months oxaliplatin-based adjuvant chemotherapy for stage III colon cancer: ACHIEVE as part of the IDEA collaboration
Authors: S. Takeuchi, T. Yoshino, T. Yamanaka, M. Kotaka, D. Manaka, T. Eto, J. Hasegawa, A. Takagane, M. Nakamura, T. Kato, Y. Munemoto, H. Bando, H. Taniguchi, M. Gamoh, M. Shiozawa, S. Saji, Y. Maehara, T. Mizushima, A. Ohtsu, M. Mori
Journal: Annals of Oncology (2018)

Introduction: ACHIEVE, a part of the IDEA collaboration, was a multicenter study randomizing patients with stage III resected colon cancer to either 3 or 6 months of mFOLFOX6/CAPOX. Previous our report showed that the frequency of PSN during the treatment was markedly lower in the 3 months arm. As many patients undergoing adjuvant chemotherapy are cured and will survive long-term, irreversible PSN is a significant issue. The present study thus aimed to evaluate the frequency of long-lasting PSN in the 3 months arm as compared to the 6 months arm. Methods: ACHIEVE enrolled 1313 patients in Japan from August 2012 through June 2014 and, of those, 1291 pts received the study treatment (modified ITT population). The hazard ratio of disease-free survival between 3 versus 6 months arm was previously reported to be 0.95 (95%CI, 0.76—1.20), implying an equivalent efficacy between the two arms. The frequency of PSN was evaluated every 3 months after the study treatment up to three years. The grade of PSN was assessed using CTCAE ver 4.0. Results: During the study treatment, PSN of grade 2/3 was observed more frequently in the 6 months arm (30%/6%) than in the 3 months arm (13%/1%). At two years after the treatment, PSN of grade 1/2/3 lasted in 31.6%/2.6%/0.5% of pts in the 6 months arm whereas 13.7%/0.2%/0.0% of patients in the 3 months arm. At three years after the treatment, PSN of grade 1/2/3 lasted in 21.5%/2.5%/0.3% of patients in the 6 months arm whereas 9.7%/0.0%/0.0% of patients in the 3 months arm. The peak neurotoxicity in the 6-month arm occurs at 6 months, and in the 3-month arm occurs at 3 months. Conclusion: In the 3-month arm, grade 2 or greater PSN was not observed at 3 years after the treatment. The frequency of grade 1 PSN lasting for three years was decreased to about a half (21.5% -> 9.7%) in the 3rd month as compared to the 6-month arm. The 3 months oxaliplatin-based adjuvant chemotherapy can bring a substantial reduction in long-term neuropathy and potential improvement in quality of life to patients without undermining the efficacy.
Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto Extracellular Vesicles
Authors: Reka Agnes Haraszti, Rachael Miller, Marie-Cecile Didiot, Annabelle Biscans, Julia F. Alterman, Matthew R. Hassler, Loic Roux, Dimas Echeverria, Ellen Sapp, Marian DiFiglia, Neil Aronin, Anastasia Khvorova
Journal: Molecular Therapy (2018)

Extracellular vesicles are promising delivery vesicles for therapeutic RNAs. Small interfering RNA (siRNA) conjugation to cholesterol enables efficient and reproducible loading of extracellular vesicles with the therapeutic cargo. siRNAs are typically chemically modified to fit an application. However, siRNA chemical modification pattern has not been specifically optimized for extracellular vesicle-mediated delivery. Here we used cholesterol-conjugated, hydrophobically modified asymmetric siRNAs (hsiRNAs) to evaluate the effect of backbone, 5'-phosphate, and linker chemical modifications on productive hsiRNA loading onto extracellular vesicles. hsiRNAs with a combination of 5'-(E)-vinylphosphonate and alternating 2'-fluoro and 2'-O-methyl backbone modifications outperformed previously used partially modified siRNAs in extracellular vesicle-mediated Huntingtin silencing in neurons. Between two commercially available linkers (triethyl glycol [TEG] and 2-aminobutyl-1-3-propanediol [C7]) widely used to attach cholesterol to siRNAs, TEG is preferred compared to C7 for productive exosomal loading. Destabilization of the linker completely abolished silencing activity of loaded extracellular vesicles. The loading of cholesterol-conjugated siRNAs was saturated at ∼3,000 siRNA copies per extracellular vesicle. Overloading impaired the silencing activity of extracellular vesicles. The data reported here provide an optimization scheme for the successful use of hydrophobic modification as a strategy for productive loading of RNA cargo onto extracellular vesicles.
DIPG-22. A PHASE 1 TRIAL OF THE HISTONE DEACETYLASE INHIBITOR PANOBINOSTAT IN PEDIATRIC PATIENTS WITH RECURRENT OR REFRACTORY DIFFUSE INTRINSIC PONTINE GLIOMA: A PEDIATRIC BRAIN TUMOR CONSORTIUM (PBTC) STUDY
Authors: Tabitha Cooney, Arzu Onar-Thomas, Jie Huang, Rishi Lulla, Jason Fangusaro, Kim Kramer, Patricia Baxter, Maryam Fouladi, Ira J Dunkel, Katherine E Warren, Michelle Monje
Journal: Neuro-Oncology (2018)

Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood cancer with a median overall survival (OS) of 10 months and a post-progression survival (PPS) of 2–3 months. Panobinostat (LBH589) is a multi-histone deacetylase inhibitor with activity against preclinical models of DIPG. The aim of this study is to determine the safety, tolerability, maximum tolerated dose (MTD), toxicity profile and pharmacokinetics of panobinostat in children with DIPG. In the initial cohort, panobinostat was administered orally three days per week for three weeks on, one week off to children with progressive DIPG. The starting dose was 10mg/m2/dose with dose escalation following a two-stage continual reassessment method. Nineteen eligible subjects were enrolled, of whom 17 were evaluable for toxicity. Dose-limiting toxicities were observed at dose level 2 (16 mg/m2/dose) and included thrombocytopenia (Grade 3, n=1; Grade 4, n=1), and neutropenia (Grade 4, n=1). Grade 3 posterior reversible encephalopathy syndrome was reported in one patient. Subjects received a median of 2 courses (range, 1–5). Several subjects remain alive at the time of abstract submission; the median survival from initiation of treatment at the time of progression (PPS) is 5.1 months (range 0.7 – 11.4 months). The MTD of panobinostat administered to children with progressive DIPG on a schedule of 3 weeks on, 1 week off, was 10mg/m2/dose. Dose-limiting toxicities (DLTs) are hematological, with thrombocytopenia the most common DLT. This trial was amended to evaluate the MTD of panobinostat in children with non-progressive DIPG, treated on alternate weeks, and is on-going.
GERM-10. EARLY DETECTION OF CNS GERMINOMA IN PITUITARY STALK THICKENING USING NON-INVASIVE microRNA TESTING
Authors: Matthew Murray, Lorena Verduci, Victoria Kyle, Dawn Ward, James Nicholson, Cinzia Scarpini, Nicholas Coleman
Journal: Neuro-Oncology (2018)

Patients presenting with diabetes insipidus (DI) and subtle pituitary-stalk thickening on MRI represent a management challenge. LCH and germinoma work-up (including serum/CSF AFP/HCG) is usually negative, given the poor sensitivity of these tests. Risks of neurosurgical biopsy in such cases often outweigh perceived benefits. Consequently, biopsy is often only performed for radiological progression. This suboptimal approach may cause diagnostic delay and inferior outcomes. Non-invasive diagnostic microRNA testing for malignant germ cell tumours (MGCTs) has shown substantial promise. Here, we highlight the potential for microRNAs to facilitate earlier diagnosis of CNS germinoma. Using qRT-PCR, we quantified CSF miR-371a-3p levels at presentation in two patients (one 15yo male, PIT#1; one 12yo female, PIT#2), both with DI and 5mm pituitary-stalk thickening, and compared levels with those at diagnosis from six CNS-MGCT patients and two controls (one CNS neuroblastoma, one low-grade-glioma). One patient (PIT#1) had elevated CSF miR-371a-3p levels consistent with those seen in CNS-MGCT patients; the other (PIT#2) had levels similar to those seen in controls. Over a two year period of surveillance (2015-2017), and consistent with the abnormally elevated CSF-miR-371a-3p level, the PIT#1 case showed clear radiological progression and after further negative serum/CSF AFP/HCG work-up, biopsy confirmed germinoma. Conversely, the PIT#2 patient showed no change in pituitary-stalk thickening, but other radiological changes suggestive of neurodegenerative LCH. CSF microRNAs show potential for screening individuals presenting with DI and pituitary-stalk thickening to identify those who might benefit from early biopsy. Ultimately, completely non-invasive CNS-MGCT diagnosis may be feasible.
DEV-09. ST. JUDE GLOBAL ACADEMY NEURO-ONCOLOGY SEMINAR: THE CREATION OF A TARGETED CURRICULUM FOR GLOBAL NEURO-ONCOLOGY
Authors: Daniel Moreira, Carlos Rodriguez-Galindo, Ibrahim Qaddoumi
Journal: Neuro-Oncology (2018)

The majority of the burden of pediatric patients with central nervous system (CNS) tumors resides in low- and middle-income countries (LMICs). The success of the treatment of this patient population relies on an effective multidisciplinary team, with updated knowledge and skills and, most importantly, awareness of the context in which they practice. The SJGANOS seeks to change the paradigm of educational interventions in pediatric oncology, by systematically creating a curriculum with directed educational interventions that will lead to improved patient outcomes. A targeted needs assessment (TNA) survey to evaluate the care team members, team dynamic, infrastructure, and patient outcomes was designed and distributed to 20 centers around the world. This TNA will describe the current state of neuro-oncology as a field in LMICs and define high-impact educational interventions. Since interdisciplinary competencies are best gained as a group, teams that treat patients with CNS tumors, including oncologists, neurosurgeons, pathologists, radio-oncologists, and radiologists from around the world will be invited to the SGNOS to be held in the summer of 2018. The Seminar will have two components, a distance-learning course and an onsite workshop, with the goal to provide higher-cognitive skills and provide the basis for a change in behavior. Ultimately, we wish to increase knowledge and skills, increase the multidisciplinary approach to care, and measurably increase the survival and quality of life of patients with CNS tumors around the world.
Adolescent mental health in crisis
Authors: David Gunnell, Judi Kidger, Hamish Elvidge
Journal: BMJ (2018)

We need to understand the causes to inform prevention

Universities UK recently reported a fivefold increase in the number of students disclosing mental health conditions since 2007 (from 9675 in 2007-8 to 57 305 in 2017-18) and growing pressures on student mental health services, despite only a modest rise in student numbers.1 A growing number of UK and international studies show that affective disorders in young people are rising substantially, particularly among girls and young women.2 A recent UK analysis reported a 68% increase in hospital self harm presentations in 13-16 year old girls between 2011 (45.9 per 100 000) and 2014 (76.9 per 100 000).3

Causes of the escalation are uncertain. Some studies point to a rise in presentation and diagnosis rather than a true increase in incidence.4 More people self reporting problems may partly reflect greater willingness to share feelings, such as suicidal thoughts, due to better mental health literacy. If the situation reflects a real deterioration in the mental health of young people, there are several possible explanations.

The young people affected are “generation Z,” born in the mid 1990s and early …
Diabetes Technology Update: Use of Insulin Pumps and Continuous Glucose Monitoring in the Hospital
Authors: Guillermo E. Umpierrez, David C. Klonoff
Journal: Diabetes Care (2018)

The use of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems has gained wide acceptance in diabetes care. These devices have been demonstrated to be clinically valuable, improving glycemic control and reducing risks of hypoglycemia in ambulatory patients with type 1 diabetes and type 2 diabetes. Approximately 30-40% of patients with type 1 diabetes and an increasing number of insulin-requiring patients with type 2 diabetes are using pump and sensor technology. As the popularity of these devices increases, it becomes very likely that hospital health care providers will face the need to manage the inpatient care of patients under insulin pump therapy and CGM. The American Diabetes Association advocates allowing patients who are physically and mentally able to continue to use their pumps when hospitalized. Health care institutions must have clear policies and procedures to allow the patient to continue to receive CSII treatment to maximize safety and to comply with existing regulations related to self-management of medication. Randomized controlled trials are needed to determine whether CSII therapy and CGM systems in the hospital are associated with improved clinical outcomes compared with intermittent monitoring and conventional insulin treatment or with a favorable cost-benefit ratio.
NURS-05. MULTI-INSTITUTIONAL NEURO-ONCOLOGY NURSING COLLABORATION: THE PEDIATRIC BRAIN TUMOR CONSORTIUM NURSING COMMITTEE EXPERIENCE
Authors: Lauren Hancock, Anna Evans, Elizabeth Gilger, Mary Petriccione, Megan Urban, Lindsay Chapman
Journal: Neuro-Oncology (2018)

The Pediatric Brain Tumor Consortium (PBTC) was founded in 1999 by the National Cancer Institute (NCI) to improve the treatment of primary brain tumors in children. Nurses have long played an integral role in the care of children enrolled on PBTC clinical trials; however a nursing committee was not formalized until 2013. With the support of the PBTC scientific committee and after review of the literature regarding supportive care in pediatric brain tumor patients, a nursing committee was conceptualized to begin with yearly meetings. We describe the experience of the PBTC nursing committee and the challenges and rewards of multi-institutional nursing collaboration. The creation of this nursing committee in 2013 led to more active nursing participation, having a nurse assigned to each clinical trial, and led to the development of a nursing-led quality of life protocol. The nursing care of children with brain tumors can present unique challenges. Collaboration with nurses at multiple institutions can provide innovative new approaches to supportive care, leading to improved quality of life for patients with brain tumors.
Abstract 10283: Motivational Interviewing Decreases Readmissions in Adults With Heart Failure
Authors: Barbara Riegel, Ruth Masterson Creber, Julia Hill, Michael Stawnychy, Jesse Chittams, Linda Hoke
Journal: Circulation (2015)

Introduction: In chronic heart failure (HF), 70% of patients are readmitted to the hospital within 12 months. At least 63% of these readmissions are for a condition other than HF. Hypothesis: We hypothesized that motivational interviewing (MI) would be effective in decreasing readmissions unrelated to HF in HF patients. Methods: Hospitalized adults with HF were enrolled if they were symptomatic (NYHA class II-IV), spoke and read English, lived in a setting where they could independently engage in self-care, and were cognitively intact. We enrolled 100 HF patients (mean age 60 ± 14.3 years; 57% Black, 33% female, 85% NYHA class III/IV symptoms, 64% were educated ≤ high school level) into a randomized controlled trial, using minimization to balance group assignment on NYHA class and gender. Participants in both groups received educational materials emphasizing self-care behavior change. The intervention group received MI emphasizing self-care (e.g. adherence, symptom monitoring) and tailored to individual goals. The intervention was provided by a nurse in a single home visit with 3-4 follow-up phone calls. Participants were followed for 3 months. For the primary outcome, readmission unrelated to HF, a multiple variable regression model was constructed using a backward variable elimination approach. Results: Over 3 months, 25% of the sample had a HF-readmission and 15% had a readmission unrelated to HF. There was an absolute difference of 21% (9 vs 30) in readmissions unrelated to HF between the MI intervention and control groups (p=0.006). The MI group had 94% lower odds of having a readmission unrelated to HF (p=0.001). Each additional unit of hemoglobin was associated with 48% lower odds of having a readmission unrelated to HF (p=0.006). For each additional year of age, the odds of having a readmission unrelated to HF were 7% lower. Participants with diabetes had 6.7 times the odds (p=0.012) of having a readmission unrelated to HF. Conclusion: An MI intervention emphasizing self-care and tailored to individual goals significantly reduced readmissions unrelated to HF in adults with HF, even after accounting for the influence of anemia, age, and diabetes.