tbuckley/cabot-search huggingface dataset:
NIMG-30. PET IMAGING OF ANDROGEN RECEPTOR EXPRESSION IN PATIENTS WITH GBM USING [18F]-FDHT
Authors: Anat Mordechai, Ofer Shamni, Nomi Zalcman, Samuel Moscovici, Alexandre Chicheportiche, Yigal Shoshan, Tal Shahar, Hanna Charbit, Mijal Guterman, Iddo Paldor, Eyal Mishani, Alexander Lossos, Marina Orevi, Iris Lavon
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND GBM is associated with poor overall survival partly due to lack of effective treatment. Recently we showed that androgen receptor (AR) protein is overexpressed in 56% of GBM specimens and that AR antagonists induced dose-dependent death in several glioblastoma cell lines. Treatment of mice implanted with human GBM with AR antagonists significantly reduced the growth of the tumor and prolonged the lifespan of the mice. 18f-fluorine-radiolabeled Dihidrotestosteron (DHT), a natural ligand of AR, [16β-18F-fluoro-5α-dihydrotestosterone ([18F]-FDHT)] is one of the PET tracers used to detect AR expression in metastatic prostate cancer. The aim of this study was to identify AR-expressing GBM tumors in real time using PET-CT scan with [18F]-FDHT. MATERIALS AND METHODS Twelve patients with GBM underwent a dynamic (first 30 min) and whole body static (later 60-80 min) [18F]-FDHT PET/CT (296-370 MBq) scans 2-4 days prior to the surgery or biopsy. Protein was extracted from the tumor and subjected to western blot analysis. AR Protein fold change of each tumor sample was calculated by densitometry analysis compared with that of normal brain, following normalization to GAPDH. RESULTS At ~60 min after injection, 6 of the 12 patients showed significantly higher tumor accumulation of [18F]-FDHT, compared to reference tissue (SUV/Control)mean: 1.33-2.63 fold, (SUV/control)max: 1.4-3.43 fold. The patient who had higher tumor accumulation of [18F]-FDHT, demonstrated also high (1.6-2.27 fold/normal brain) AR protein expression within the tumor. Pearson-correlation-coefficient analysis for the (SUV/Control)mean at ~60 min after the injection versus AR protein expression, was positive and significant (R=0.841;p=0.0024). CONCLUSION This study demonstrated for the first time that [18F]-FDHT PET can identify AR-positive-GBM-tumors (with sensitivity and specificity at 100%) and may therefore be a powerful tool to select patients eligible for treatment with AR antagonists. It could possibly be employed also to monitor treatment response and/or progression during the course of therapy.
Abstract 17413: Determination of Etiology of Left Ventricular Ejection Fracture Decline in Chemotherapy Related Cardiac Dysfunction
Authors: Jay B Patel, Muzna Hussain, Rohit Moudgil, Feixiong Cheng, Patrick Collier
Journal: Circulation (2020)

Introduction: Chemotherapy related cardiac dysfunction (CTRCD) is an undesired complication of anticancer treatment, roughly affecting 10% of patients undergoing therapy. The American Society of Echocardiography (ASE) and the European Association of Cardiovascular imaging (EACVI) defines CTRCD as a decrease in left ventricular ejection fraction (LVEF) greater than 10% from the lower limit of normal. Using this definition, several patients are diagnosed with CTRCD. Our study aims to understand the context of LVEF decline to help delineate the etiology of LVEF dysfunction in these patients. Methods: A retrospective descriptive study was conducted on registry of adult cancer patients (N=6754) referred to cardio-oncology clinic at the Cleveland Clinic between January 2011 and June 2018. The context of each LVEF decline event was independently adjudicated into one of nine categories: Chemotherapy induced, Valvular Heart Disease, Arrhythmia, Ischemia, Acute Hospitalization, Infiltrative disease, Misdiagnosed, Undifferentiated, or Other. Results: A cohort of patients (N=616) were identified to have CTRCD based on the ASE/EACVI definition. This cohort was 54% female and 80% Caucasian, with a median age of 58 years. In terms of therapy, 50% were exposed to anthracyclines, 15% exposed to HER2 neu inhibitors, 24% exposed to VEGF inhibitors. Upon adjudication of LVEF decline events, 31% of patients had isolated chemotherapy related decline, 24% caused by acute hospitalizations. 13% of events were multifactorial/undifferentiated and 11% of reported events were misdiagnosed. Conclusion: Our findings suggest left ventricular dysfunction in patients undergoing anticancer therapies can be multifaceted. Moreover, only a small proportion of reported CTRCD events were solely due to chemotherapy.
OTHR-09. CENTRAL DIABETES INSIPIDUS: A RARE UNREPORTED SIDE EFFECT OF TEMOZOLOMIDE IN PEDIATRICS
Authors: Christopher Kuo, Kaaren Waters, Clement Cheung, Ashley Margol
Journal: Neuro-Oncology (2020)

Abstract Temozolomide is a chemotherapeutic agent commonly used in the treatment of central nervous system tumors. While there are case reports of temozolomide associated central diabetes insipidus (CDI) in adults, this has not been reported in children. We describe the first case of temozolomide associated CDI in a pediatric patient. The patient was a previously healthy 12yr old male diagnosed with anaplastic astroblastoma. He underwent gross total resection of the lesion and was subsequently treated with focal radiation therapy and concurrent temozolomide. On day 21 of therapy he developed thrombocytopenia, severe polyuria and polydipsia. Temozolomide was held and he underwent a preliminary evaluation for CDI. Initial laboratory findings were concerning for CDI, and he was admitted for further work-up and to assess the need for desmopressin. Additional laboratory tests demonstrated normal anterior pituitary function and his serum sodium normalized when allowed to drink to thirst, mitigating the need for desmopressin. Temozolomide was not restarted and the symptoms of polyuria and polydipsia resolved and did not recur. Upon review, the tumor did not involve the pituitary or hypothalamus. Additionally, these areas were not involved in the irradiation field. CDI is a rare but clinically significant side effect of temozolomide, reported in adults. Given this is the first report of CDI secondary to temozolomide in a pediatric patient, we speculate that this is likely under-recognized in children. Prompt recognition and treatment is necessary to prevent severe sequelae of hypernatremia.
Myocardial Regeneration by Stem Cells: Seeing the Unseeable⁎⁎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: James S. Forrester, Prediman K. Shah, Raj R. Makkar
Journal: Journal of the American College of Cardiology (2006)
From Diagnosis to Prognosis: Revisiting the Meaning of Muscle <i>ISG15</i> Overexpression in Juvenile Inflammatory Myopathies
Authors: Cyrielle Hou, Chloé Durrleman, Baptiste Periou, Christine Barnerias, Christine Bodemer, Isabelle Desguerre, Pierre Quartier, Isabelle Melki, Gillian I. Rice, Mathieu P. Rodero, Jean‐Luc Charuel, Fréderic Relaix, Brigitte Bader‐Meunier, FrançoisJérôme Authier, Cyril Gitiaux
Journal: Arthritis & Rheumatology (2020)

Juvenile idiopathic inflammatory/immune myopathies (IIMs) constitute a highly heterogeneous group of disorders with diagnostic difficulties and prognostic uncertainties. Circulating myositis-specific autoantibodies (MSAs) have been recognized as reliable tools for patient substratification. Considering the key role of type I interferon (IFN) up-regulation in juvenile IIM, we undertook the present study to investigate whether IFN-induced 15-kd protein (ISG-15) could be a reliable biomarker for stratification and diagnosis and to better elucidate its role in juvenile IIM pathophysiology.The study included 56 patients: 24 with juvenile dermatomyositis (DM), 12 with juvenile overlap myositis (OM), 10 with Duchenne muscular dystrophy, and 10 with congenital myopathies. Muscle biopsy samples were assessed by immunohistochemistry, immunoblotting, and real-time quantitative polymerase chain reaction. Negative regulators of type I IFN (ISG15 and USP18) and positive regulators of type I IFN (DDX58 and IFIH1) were analyzed.ISG15 expression discriminated patients with juvenile IIM from those with nonimmune myopathies and, among patients with juvenile IIM, discriminated those with DM from those with OM. Among patients with juvenile DM, up-regulation of the type I IFN positive regulators DDX58 and IFIH1 was similar regardless of MSA status. In contrast, the highest levels of the type I IFN negative regulator ISG15 were observed in patients who were positive for melanoma differentiation-associated gene 5 (MDA-5). Finally, ISG15 levels were inversely correlated with the severity of muscle histologic abnormalities and positively correlated with motor performance as evaluated by the Childhood Myositis Assessment Scale and by manual muscle strength testing.Muscle ISG15 expression is strongly associated with juvenile DM, with patients exhibiting a different ISG-15 muscle signature according to their MSA class. Patients with juvenile DM who are positive for MDA-5 have higher expression of ISG15 in both gene form and protein form compared to the other subgroups. Moreover, our data show that negative regulation of type I IFN correlates with milder muscle involvement.
Roger Williams, CBE, 1931‐2020
Authors: William Lee
Journal: Hepatology (2020)

O ne of the towering figures in hepatology, Roger Williams, has died at age 88 after suffering a heart attack while playing tennis, a fitting passing for a giant in our field.Professor Williams' many achievements were possible because he combined incredible energy and determination to succeed, with a warm embrace of all who sought to work under his tutelage.The breadth of his vision and tireless efforts formed the largest liver unit in the world.More than 400 Fellows from his 30 years at King's College Liver Unit call themselves "King's Old Boys (and Girls)" and are part of Roger's extended family, testifying to the range of his experience and the reach of those around the world whose lives he has touched as teacher, mentor, and physician.Although many called him Professor Williams or Prof, at least as many always referred to him just as Roger and he didn't seem to mind.He demonstrated every day a passion for setting and achieving tough goals and a genuine interest in his fellow human beings.
LINC-32. REPORT OF AN INITIAL SITE VISIT TO DETERMINE FEASIBILITY AND IMPLEMENTATION OF A COMPREHENSIVE NEURO-ONCOLOGY PROGRAM IN KENYA
Authors: Beth Armstrong, Mark Mbiro, Michael Magoha, Minda Okemwa, Nimrod Mwang’ombe, Scott Coven
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Pediatric central nervous system (CNS) tumors are the leading solid tumors in the United States, but vastly under-reported in the African population. There’s limited data on childhood brain tumors as well as the histopathological distribution in Kenya. This report surveys as an initial site visit to determine the feasibility of a comprehensive neuro-oncology program at Kenyatta National Hospital (KNH) in Nairobi, Kenya. DESIGN: This collaboration began with a visit from the director of neuropathology at KNH to our neuro-Oncology program at Riley Hospital for Children at Indiana University Health in May 2019. This report includes recommendations from the May 2019 trip, as well as a reciprocal site visit to Kenya in January 2020. RESULTS Building off the May 2019 trip, a brain tumor registry has been initiated and maintained. Additionally, the KNH program has many necessary components to forming a comprehensive neuro-oncology program, including capable neurosurgeons with a neurosurgical training program, radiology, intensive care unit, oncology ward, rehab, skilled nursing, and radiation oncology services. Currently, neurosurgery, radiology, and pathology meet weekly to review challenging cases. CONCLUSION Kenyatta National Hospital has the expertise to build a comprehensive neuro-oncology program. The program currently lacks a dedicated nurse coordinator and “specialist” in neuro-oncology. Ongoing discussions with local stakeholders are aimed to galvanize national support to improve awareness for children with brain tumors and to plan a multidisciplinary neuro-oncology symposium in 2021. In the meantime, telemedicine efforts can support nursing education and reiterate the multidisciplinary needs for children with brain tumors.
Parent-Reported Symptoms and Medications Used Among Children With Severe Neurological Impairment
Authors: James A. Feinstein, Chris Feudtner, Allison B. Blackmer, Robert J. Valuck, Diane L. Fairclough, Jacqueline Holstein, LiseAnne Gregoire, Sadaf Samay, Allison Kempe
Journal: JAMA Network Open (2020)

Children with severe neurological impairment (SNI) often take multiple medications to treat problematic symptoms. However, for children who cannot self-report symptoms, no system exists to assess multiple symptoms and their association with medication use.To assess the prevalence of 28 distinct symptoms, test whether higher global symptom scores (GSS) were associated with use of more medications, and assess the associations between specific symptoms and medications.This cross-sectional study was conducted between April 1, 2019, and December 31, 2019, using structured parent-reported symptom data paired with clinical and pharmacy data, at a single-center, large, hospital-based special health care needs clinic. Participants included children aged 1 to 18 years with SNI and 5 or more prescribed medications. Data analysis was performed from April to June 2020.During routine clinical visits, parent-reported symptoms were collected using the validated 28-symptom Memorial Symptom Assessment Scale (MSAS) and merged with clinical and pharmacy data.Symptom prevalence, counts, and GSS (scored 0-100, with 100 being the worst) were calculated, and the association of GSS with medications was examined. To evaluate associations between symptom-medication pairs, the proportion of patients with a symptom who used a medication class or specific medication was calculated.Of 100 patients, 55.0% were boys, the median (interquartile range [IQR]) age was 9 (5-12) years, 62.0% had 3 or more complex chronic conditions, 76.0% took 10 or more medications, and none were able to complete the MSAS themselves. Parents reported a median (IQR) of 7 (4-10) concurrent active symptoms. The median (IQR) GSS was 12.1 (5.4-20.8) (range, 0.0-41.2) and the GSS was 9.8 points (95% CI, 5.5-14.1 points) higher for those with worse recent health than usual. Irritability (65.0%), insomnia (55.0%), and pain (54.0%) were the most prevalent symptoms. Each 10-point GSS increase was associated with 12% (95% CI, 4%-19%) higher medication counts, adjusted for age and complex chronic condition count. Among the 54.0% of children with reported pain, 61.0% were prescribed an analgesic.These findings suggest that children with SNI reportedly experience substantial symptom burdens and that higher symptom scores are associated with increased medication use. Paired symptom-medication data may help clinicians identify targets for personalized symptom management, including underrecognized or undertreated symptoms.
Exome Sequencing as Part of a Multidisciplinary Approach to Diagnosis
Authors: Alice Doreille, Laure Raymond, Laurent Mesnard
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
EPID-04. MORBIDITY IN PAEDIATRIC BRAIN TUMOURS: 17 YEARS’ EXPERIENCE IN A TERTIARY NEUROSURGICAL UNIT
Authors: Chun Peng Goh, Vincent Diong Weng Nga, Cindy Wei Li Ho
Journal: Neuro-Oncology (2020)

Abstract The treatment of paediatric brain tumours has shown significant improvement over the last 2 decades. The aim of our study is to evaluate the prevalence of various effects among this population within our institution. 102 patients diagnosed with a brain tumour at the age of 0–18 years between 2002 and 2018 were identified within a single paediatric institution. Data was collected retrospectively based on electronic medical records. Medulloblastoma (20.6%) was the most common subtype followed by pilocytic astrocytoma (18.6%) and craniopharyngioma (11.8%). Overall, the 5-years survival rate was approximately 77%. Endocrine dysfunction was reported in 36% of the population, mainly due to tumour located in suprasellar region and irradiation causing progressive pituitary dysfunction. Neurological disorders such as epilepsy, weakness, cranial nerves palsy, visual and hearing impairment were present in 46% of the population. Importantly, 20.4% of patients who received chemotherapy had some degree of sensorineural hearing loss. 16% of the population suffered from impaired neurocognition which is likely an underestimation as screening could not be performed on all patients. Other significant complications are infections (12%) and ventriculoperitoneal shunt dysfunction (7%). Most of these effects can be attributed to direct injury to the developing brain caused by the tumour or related to its treatment during surgical excision and the long term side effects of chemotherapy and radiation therapy. Morbidities in various domains can pose significant challenges to survivors of paediatric brain tumours. Active screening and surveillance of these effects can help improve the health outcomes of survivors of paediatric brain tumours.
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine
Authors: Fernando P Polack, Stephen J Thomas, Nicholas Kitchin, Judith Absalon, Alejandra Gurtman, Stephen Lockhart, John L Perez, Gonzalo Pérez Marc, Edson D Moreira, Cristiano Zerbini, Ruth Bailey, Kena A Swanson, Satrajit Roychoudhury, Kenneth Koury, Ping Li, Warren V Kalina, David Cooper, Robert W Frenck, Laura L Hammitt, Özlem Türeci, Haylene Nell, Axel Schaefer, Serhat Ünal, Dina B Tresnan, Susan Mather, Philip R Dormitzer, Uğur Şahin, Kathrin U Jansen, William C Gruber
Journal: New England Journal of Medicine (2020)

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a worldwide pandemic. Safe and effective vaccines are needed urgently.MethodsIn an ongoing multinational, placebo-controlled, observer-blinded, pivotal efficacy trial, we randomly assigned persons 16 years of age or older in a 1:1 ratio to receive two doses, 21 days apart, of either placebo or the BNT162b2 vaccine candidate (30 μg per dose). BNT162b2 is a lipid nanoparticle–formulated, nucleoside-modified RNA vaccine that encodes a prefusion stabilized, membrane-anchored SARS-CoV-2 full-length spike protein. The primary end points were efficacy of the vaccine against laboratory-confirmed Covid-19 and safety.Download a PDF of the Research Summary.ResultsA total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo; BNT162b2 was 95% effective in preventing Covid-19 (95% credible interval, 90.3 to 97.6). Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions. Among 10 cases of severe Covid-19 with onset after the first dose, 9 occurred in placebo recipients and 1 in a BNT162b2 recipient. The safety profile of BNT162b2 was characterized by short-term, mild-to-moderate pain at the injection site, fatigue, and headache. The incidence of serious adverse events was low and was similar in the vaccine and placebo groups.ConclusionsA two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older. Safety over a median of 2 months was similar to that of other viral vaccines. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.) Quick Take Safety and Efficacy of the BNT162b2 Covid-19 Vaccine 3m 0s
NURS-10. IMPROVEMENTS IN A BEHAVIORAL TRAINING AND PHARMACOLOGICAL ANXIOLYSIS ALGORITHM FOR INCREASED COMPLIANCE IN PEDIATRIC PATIENTS IN PREPARATION FOR RADIATION THERAPY: A RETROSPECTIVE ANALYSIS
Authors: Judy Tran, Jennifer Holt, Danielle Crump, Anita Shea, Lin Whetzel, Andrea Lattimore, Rebecca Carson, Roberta Anderson
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND In the pediatric population, the probability of compliance with radiation involves multifactorial elements. Younger pediatric patients often require anesthesia to ensure accurate delivery of radiotherapy. The purpose of this analysis was to refine our algorithm in pediatric patients to better identify children who would benefit from behavioral training and/or anxiolyxis intervention with the goal of minimizing anesthesia use. METHOD Retrospective data was collected from electronic medical records from 150 pediatric oncology patients &amp;lt;18 years old, treated with photon and proton radiation at our center from August 2016 to December 2019. We identified potential socio-developmental treatment factors thought to impact behavioral compliance and categorized risk factors based on an algorithm to determine risk for noncompliance with radiotherapy. RESULTS Six categories demonstrated statistical significance (p&amp;lt;0.05) in their influence on behavioral compliance during radiotherapy: age category (specifically age &amp;lt;7: Odds ratio [OR] 3.0, 95% Confidence Interval [CI] 1.0, 9.1), need for sedation with prior imaging studies (p&amp;lt;0.001), parental premonition of requiring anesthesia for successful treatment (p&amp;lt;0.001), duration of treatment, primary language (p&amp;lt;0.001), and use of total body irradiation (OR 3.1, 95% CI 1.1, 9.3). CONCLUSION Identification of pre-radiation risk factors allowed for better recognition of patients at risk for treatment non-compliance and for requiring daily sedation. Future studies should focus on implementing the algorithm prospectively in an effort to identify and direct early intervention with behavioral training and/or anxiolytics to minimize the need for sedation.