tbuckley/cabot-search huggingface dataset:
INNV-04. CONGENITAL SPINAL GLIOBLASTOMA WITH SUSTAINED RESPONSE TO TROPOMYOSIN RECEPTOR KINASE (TRK) INHIBITION: A CASE REPORT
Authors: Christina Coleman Abadi, Peter Sun, Caroline Hastings
Journal: Neuro-Oncology (2020)

Abstract Large scale genomic efforts have shown that a significant percentage of infant high-grade gliomas (HGG) carry targetable gene fusions. Given the rarity of congenital spinal HGGs, little is known about the molecular features of these tumors and their response to treatment. We describe a case of a patient with congenital spinal glioblastoma. A full-term female infant with symmetric IUGR was noted to have weakness with little movement of her upper extremities. MRI of the spine showed an infiltrative and hemorrhagic intraspinal cervicothoracic neoplasm with a large hemorrhagic intramedullary component. A biopsy was done and revealed a high-grade glial neoplasm with pan-TRK expression. Next generation sequencing (NGS) confirmed a MEF2D-NTRK1 gene fusion. Prior to the result of her molecular testing, the patient clinically deteriorated with decreased movement and increased apneic episodes despite steroid treatment. She was then started on treatment with carboplatin and etoposide per Macy et al 1. After one cycle of chemotherapy and given the results of NGS, targeted therapy with larotrectinib was added to her treatment. The patient showed a response (clinical and imaging) following cycle 1 with chemotherapy, and a marked response following cycle 2 with both chemotherapy and targeted TRK inhibition. The patient completed six cycles of chemotherapy and has continued on daily oral larotrectinib. She continues to tolerate the targeted therapy well and currently is 8 months old, growing and developing well. She has regained much of her movement and is eating and growing with apparent normal development. This case provides an example of a patient with congenital glioblastoma with TRK gene fusion that showed an impressive response to targeted therapy combined with more conventional chemotherapy. 1Macy M, et al. Clinical and molecular characteristics of congenital glioblastoma. Neuro Oncol. Jul;14 (7) 931–941, 2012).
SURG-04. THE APPLICATION OF EN BLOC RESECTION IN THE OPERATION OF PEDIATRIC POSTERIOR FOSSA TUMOR
Authors: Ma Jie, Weiwei Mao, Shuaiwei Tian, Baocheng Wang, Yang Zhao
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE To explore the efficacy and safety of en bloc resection therapy on posterior fossa tumor in children. METHODS A retrospective analysis was conducted on the clinical data of 94 patients with posterior fossa tumor admitted to Department of Pediatric Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School Of Medicine from January 2018 to December 2019. Among them, 35 cases were treated with traditional resection (control group) and 59 cases with en bloc resection (observation group). We counted the amount of blood loss and the time during tumor resection, We compare the symptoms and signs between the two groups and determine a extent of tumor resection based on microscopic observation and preoperative and postoperative imaging comparison. RESULT: The total tumor resection rate of the observation group (88.1%, 52 / 59) was significantly higher than that of the control group (62.85%, 22 / 35, P &amp;lt; 0.05). The average bleeding volume of 90.8ml in the observation group was significantly smaller than that of the control group (113.3ml, P &amp;lt; 0.05), and the average operation time of 38.6min in the observation group was shorter than that of the control group (57.4min, P &amp;lt; 0.05) only for tumor resection procedure. CONCLUSION En bloc resection technique can effectively accelerate the resection time, reduce intraoperative bleeding and improve the total resection rate of tumors in children’s posterior cranial fossa.
Cyclin A2 maintains colon homeostasis and is a prognostic factor in colorectal cancer
Authors: Yuchen Guo, Monica Gabola, Rossano Lattanzio, Conception Paul, Valérie Pinet, Ruizhi Tang, Hulya Turali, Julie Bremond, Ciro Longobardi, Chloé Maurizy, Quentin Da Costa, Pascal Finetti, Florence Boissière-Michot, Benjamin Rivière, Céline Lemmers, Séverine Garnier, François Bertucci, Inti Zlobec, Karim Chebli, Jamal Tazi, Rania Azar, Jean-Marie Blanchard, Peter Sicinski, Emilie Mamessier, Bénédicte Lemmers, Michael Hahne
Journal: Journal of Clinical Investigation (2020)

To clarify the function of cyclin A2 in colon homeostasis and colorectal cancer (CRC), we generated mice deficient for cyclin A2 in colonic epithelial cells (CECs). Colons of these mice displayed architectural changes in the mucosa and signs of inflammation, as well as increased proliferation of CECs associated with the appearance of low- and high-grade dysplasias. The main initial events triggering those alterations in cyclin A2–deficient CECs appeared to be abnormal mitoses and DNA damage. Cyclin A2 deletion in CECs promoted the development of dysplasia and adenocarcinomas in a murine colitis–associated cancer model. We next explored the status of cyclin A2 expression in clinical CRC samples at the mRNA and protein levels and found higher expression in tumors of patients with stage 1 or 2 CRC compared with those of patients with stage 3 or 4 CRC. A meta-analysis of 11 transcriptome data sets comprising 2239 primary CRC tumors revealed different expression levels of CCNA2 (the mRNA coding for cyclin A2) among the CRC tumor subtypes, with the highest expression detected in consensus molecular subtype 1 (CMS1) and the lowest in CMS4 tumors. Moreover, we found high expression of CCNA2 to be a new, independent prognosis factor for CRC tumors.
COVD-30. A SNAPSHOT OF THE IMPACT OF COVID-19 ON PATIENTS WITH NERVOUS SYSTEM TUMORS
Authors: Ashley Aaroe, Rebecca Harrison, Nazanin Majd, Barbara O’Brien, Shiao-Pei Weathers, Monica Loghin, Carlos Kamiya-Matsuoka, W K Alfred Yung, John de Groot, Karin Woodman
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The impact of COVID-19 on patients with nervous system tumors is not known. This population is often immunosuppressed, susceptible to neurological complications, and requiring of frequent cancer care, all of which may confer vulnerability to poorer outcomes after infection. METHODS Clinical data were obtained from structured electronic medical record elements, clinical note text and laboratory RESULTS: Each source was identified, integrated and analyzed using the Palantir Foundry platform (Syntropy), part of the Context Engine Data Management System through the MD Anderson Cancer Center (MDACC) IRB approved D3CODE initiative. The population of interest was patients diagnosed with COVID-19 who had been seen at the Brain and Spine Center for nervous system tumors. RESULTS 8,177 ambulatory patients were seen at the Brain and Spine Center from 3/1/20–9/1/20. COVID status was known for 1,753 (21%). Sixty-one (0.7%) were COVID-19 positive. Of these, 17 had primary nervous system tumors. Seven (41%) were treated in the emergency department or hospital for infection. Two were symptomatic but did not require further care. Eight were asymptomatic. Nine (53%) had alterations in cancer management within one week of COVID-19 diagnosis – delayed surgery (3), delayed/interrupted chemotherapy (2), delayed/interrupted radiation (2), cancer treatment discontinued (2). Eight patients (47%) had no clear impact of infection on their cancer treatment, three were on surveillance. Three (18%) unique patients had neurological symptoms attributed to/exacerbated by COVID-19 – encephalopathy (2), seizure (2), stroke (1). CONCLUSION No deleterious effects of alterations in cancer management after COVID-19 infection have been identified thus far, though longitudinal follow up is warranted. Our results suggest that COVID-19 infection frequently incurs medical complications or alterations in cancer treatment. The potential impacts of COVID-19 on our vulnerable neuro-oncology patient population should be further explored, and attention to these potential implications for our patients is warranted by treating clinicians.
QOLP-05. OLANZAPINE FOR REFRACTORY CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING IN MALIGNANT GLIOMA PATIENTS
Authors: Mallika Patel, Katherine Peters, Eric Lipp, Justin Low, James Herndon, Gloria Broadwater, Margaret Johnson, Dina Randazzo, Jung-Young Kim, Mary Affronti
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Malignant glioma (MG) patients often experience chemotherapy-induced nausea and vomiting (CINV). Olanzapine has recently been added to national anti-emesis guidelines for patients on moderately/highly emetogenic chemotherapy. In this retrospective study, we investigated the use of olanzapine for refractory-CINV (R-CINV) in MG patients. METHODS In this chart review, we queried adult MG patients with KPS ≥ 70 who received olanzapine from January 2019-March 2020. Patients were included if they were prescribed olanzapine for CINV. Data on nausea/vomiting improvement, olanzapine dosing/schedule, number of refractory anti-emetic trials, concomitant corticosteroid use, and demographics were collected. RESULTS We identified 21 MG patients who were prescribed olanzapine, with 9 of those patients receiving olanzapine specifically for CINV. Seven patients had WHO grade IV glioma, and 2 patients had anaplastic astrocytoma (WHO grade III). Five of 9 patients (55.6%) were male, all were Caucasian and median age was 54 years. Patients tried an average of 3 anti-emetics prior to initiating olanzapine for R-CINV. Only one patient was taking concomitant corticosteroids; which is not in concordance with national anti-emesis guidelines. Four of 9 patients (44.4%) achieved control of R-CINV with olanzapine. The olanzapine dose and key biomarkers (IDH-status, MGMT promoter methylation) were similar between those experiencing R-CINV and those without symptoms. CONCLUSIONS In this study, we find that approximately half of patients with R-CINV achieved improved nausea and vomiting control with the addition of olanzapine. The lack of corticosteroid use for anti-emesis in MG continues to make this population challenging to manage. The relatively high success rate in patients that had failed, on average, 3 anti-emetics, suggests that olanzapine may be a potent addition to the anti-emetic toolkit for MG patients. These results inspire further large-scale research to validate this observation and define the optimal role for olanzapine in treating R-CINV in MG patients.
COVD-01. VINBLASTINE MONOTHERAPY INDUCTION FOR LOCALISED CNS GERMINOMA DURING THE COVID-19 PANDEMIC
Authors: Rafael Moleron, Sara Stoneham, Thankamma Ajithkumar, Justin Cross, James Nicholson, Matthew Murray
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Patients with localised CNS-germinoma have excellent survival. More recently, intensive inpatient chemotherapy (carboPEI=carboplatin/etoposide/ifosfamide in Europe) has been effectively employed to reduce radiotherapy fields and/or dose. Current research priorities focus on reducing treatment burden and long-term sequelae. Of note, outpatient-based single-agent carboplatin chemotherapy is associated with excellent outcomes in metastatic testicular seminoma (an identical pathology) [Alifrangis,EJC,2020]. Recently, successful vinblastine monotherapy was reported in localised CNS-germinoma [Murray,Neurooncol-Adv,2020]. METHODS Due to the COVID-19 pandemic, adapted UK guidelines for germ-cell-tumour management were distributed, including potential non-standard treatment options that would reduce hospital visits/admissions. A 30-year-old patient presented with a 32mmx30mmx35mm diameter solid+multi-cystic localised pineal CNS lesion, consistent radiologically with a germ-cell-tumour with prominent teratoma component. Investigation revealed negative AFP/HCG markers and biopsy-proven pure germinoma. After appropriate consent, the patient commenced 12-week induction with weekly vinblastine monotherapy (low-grade-glioma dosing [Lassaletta,JCO,2016]), with wk6&amp;12 MRI re-assessment prior to definitive radiotherapy. RESULTS Vinblastine was well-tolerated. After initial 4mg/m2 test-dosing (wk1), standard 6mg/m2 was delivered for wk2, but resulted in asymptomatic neutropenia (nadir 0.3x10^9/l) and missed dosing at wk3. Subsequent doses were 4mg/m2, with no further neutropenia. As expected, MRI showed moderate 40% tumour volume reduction by wk12. Surgical resection of the residual presumed teratoma component was undertaken prior to radiotherapy. CONCLUSION Patients with CNS-germinoma have excellent outcomes and reduction of treatment-effects remains a priority. The exquisite chemosensitivity of germinoma, excellent results from monotherapy for metastatic testicular disease, and early promise of vinblastine monotherapy lend itself to further exploration for CNS-germinoma.
EPCO-37. USING SINGLE-CELL RNA SEQUENCING TO IDENTIFY CELLULAR HETEROGENEITY WITHIN NON-FUNCTIONING PITUITARY ADENOMAS
Authors: Saket Jain, Husam Babikir, Karin Shamardani, Francisca CatalanSaavedra, Aaron Diaz, Manish Aghi
Journal: Neuro-Oncology (2020)

Abstract Pituitary adenomas (PA) are one of the most common primary brain tumors and comprise approximately 15% of brain neoplasms. Most PA are histologically benign but can cause significant morbidity. Previous studies utilized whole-genome and exome sequencing to identify a few somatic variants, but no recurrent mutations were observed. Further studies are warranted to identify driver mutations occurring at low frequencies. We used single-cell RNA sequencing (10X Genomics) to investigate cellular heterogeneity in three non-functioning pituitary adenomas. Our analysis identified discrete clusters of cells associated with specific functional pathways. One of these clusters corresponded to cells expressing genes related to metabolic pathways, primarily lipid metabolism. Another cluster consistent amongst the three patients comprised of cells involved in antigen presentation and processing. In addition, the copy number variation analysis highlighted distinct chromosomal alterations within our samples. Interestingly, we were able to identify clonal variations within each tumor based on chromosomal aberrations. For example, in our first patient, we observed a gain of chromosome 19 and loss of chromosome 2. Our analysis showed three different clonal populations within this tumor. All three populations harbored the loss of chromosome 2, one population exhibited gain of chromosome 19, while a third population exhibited loss of chromosome 19. These early results indicate the loss of chromosome 2 as an early event in tumorigenesis and gain/loss of chromosome 19 as late events. We are currently in a process of identifying somatic variations within these tumors by variant calling. Currently we are expanding our analysis to 20 non-functional PA. Mapping the single-cell gene expression profiles with mutational phylogeny will reveal the differences in clonal evolution within the tumor subtypes. This study will help us define the molecular fingerprint of pituitary adenomas and provide insights which could be utilized in the clinic for better management of these tumors.
Obesity Genes and Weight Loss During Lifestyle Intervention in Children With Obesity
Authors: Melanie Heitkamp, Monika Siegrist, Sophie Molnos, Stefan Brandmaier, Simone Wahl, Helmut Langhof, Harald Grallert, Martin Halle
Journal: JAMA Pediatrics (2020)

Genome-wide association studies have identified genetic loci influencing obesity risk in children. However, the importance of these loci in the associations with weight reduction through lifestyle interventions has not been investigated in large intervention trials.To evaluate the associations between various obesity susceptibility loci and changes in body weight in children during an in-hospital, lifestyle intervention program.Long-term Effects of Lifestyle Intervention in Obesity and Genetic Influence in Children (LOGIC), an interventional prospective cohort study, enrolled 1429 children with overweight or obesity to participate in an in-hospital lifestyle intervention program. Genotyping of 56 validated obesity single-nucleotide variants (SNVs) was performed, and the associations between the SNVs and body weight reduction during the intervention were evaluated using linear mixed-effects models for each SNV. The LOGIC study was conducted from January 6, 2006, to October 19, 2013; data analysis was performed from July 15, 2015, to November 6, 2016.A 4- to 6-week standardized in-hospital lifestyle intervention program (daily physical activity, calorie-restricted diet, and behavioral therapy).The association between 56 obesity-relevant SNVs and changes in body weight and body mass index.Of 1429 individuals enrolled in the LOGIC Study, 1198 individuals (mean [SD] age, 14.0 [2.2] years; 670 [56%] girls) were genotyped. A mean (SD) decrease was noted in body weight of -8.7 (3.6) kg (95% CI, -15.7 to -1.8 kg), and body mass index (calculated as weight in kilograms divided by height in meters squared) decreased by -3.3 (1.1) (95% CI, -5.4 to -1.1) (both P < .05). Five of 56 obesity SNVs were statistically significantly associated with a reduction of body weight or body mass index (all P < 8.93 × 10-4 corresponding to Bonferroni correction for 56 tests). Compared with homozygous participants without the risk allele, homozygous carriers of the rs7164727 (LOC100287559: 0.42 kg; 95% CI, 0.31-0.53 kg, P = 4.00 × 10-4) and rs12940622 (RPTOR: 0.35 kg; 95% CI, 0.18-0.52 kg; P = 1.86 × 10-5) risk alleles had a lower reduction of body weight, whereas carriers of the rs13201877 (IFNGR1: 0.65 kg; 95% CI, 0.51-0.79 kg; P = 2.39 × 10-5), rs10733682 (LMX1B: 0.45 kg; 95% CI, 0.27-0.63 kg; P = 6.37 × 10-4), and rs2836754 (ETS2: 0.56 kg; 95% CI, 0.38-0.74 kg; P = 1.51 × 10-4) risk alleles were associated with a greater reduction of body weight after adjustment for age and sex.Genes appear to play a minor role in weight reduction by lifestyle in children with overweight or obesity. The findings suggest that environmental, social, and behavioral factors are more important to consider in obesity treatment strategies.
Tobacco, cannabis, and liquorice: Hidden players altering albendazole metabolism in patients with hepatic alveolar echinococcosis
Authors: Solange Bresson-Hadni, Damien Montange, Carine Richou, Eléonore Brumpt, Aurélie Fillion, Brigitte Bartholomot, Oleg Blagosklonov, Eric Delabrousse, Frédéric Grenouillet, Dominique-Angèle Vuitton, Laurence Millon
Journal: Journal of Hepatology (2020)
Stenosis is in the eye of the observer: impact of pressure recovery on assessing aortic valve area**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: Robert A Levine, Ehud Schwammenthal
Journal: Journal of the American College of Cardiology (2003)
Variation in oral microbiome is associated with future risk of lung cancer among never-smokers
Authors: H Dean Hosgood, Qiuyin Cai, Xing Hua, Jirong Long, Jianxin Shi, Yunhu Wan, Yaohua Yang, Christian Abnet, Bryan A Bassig, Wei Hu, Bu-Tian Ji, Madelyn Klugman, Yongbing Xiang, Yu-Tang Gao, Jason YY Wong, Wei Zheng, Nathaniel Rothman, Xiao-Ou Shu, Qing Lan
Journal: Thorax (2020)

Objective To prospectively investigate whether diversity in oral microbiota is associated with risk of lung cancer among never-smokers. Design and setting A nested case–control study within two prospective cohort studies, the Shanghai Women’s Health Study (n=74 941) and the Shanghai Men’s Health Study (n=61 480). Participants Lifetime never-smokers who had no cancer at baseline. Cases were subjects who were diagnosed with incident lung cancer (n=114) and were matched 1:1 with controls on sex, age (≤2 years), date (≤30 days) and time (morning/afternoon) of sample collection, antibiotic use during the week before sample collection (yes/no) and menopausal status (for women). Main outcomes and measures Metagenomic shotgun sequencing was used to measure the community structure and abundance of the oral microbiome in pre-diagnostic oral rinse samples of each case and control. Multivariable logistic regression models were used to estimate the association of lung cancer risk with alpha diversity metrics and relative abundance of taxa. The Microbiome Regression-Based Kernel Association Test (MiRKAT) evaluated the association between risk and the microbiome beta diversity. Results Subjects with lower microbiota alpha diversity had an increased risk of lung cancer compared with those with higher microbial alpha diversity (Shannon: p trend =0.05; Simpson: p trend =0.04; Observed Species: p trend =0.64). No case–control differences were apparent for beta diversity (p MiRKAT =0.30). After accounting for multiple comparisons, a greater abundance of Spirochaetia (OR low 1.00 (reference), OR medium 0.61 (95% CI 0.32 to 1.18), OR high 0.42 (95% CI 0.21 to 0.85)) and Bacteroidetes (OR low 1.00 (reference), OR medium 0.66 (95% CI 0.35 to 1.25), OR high 0.31 (95% CI 0.15 to 0.64)) was associated with a decreased risk of lung cancer, while a greater abundance of the Bacilli class (OR low 1.00 (reference), OR medium 1.49 (95% CI 0.73 to 3.08), OR high 2.40 (95% CI 1.18 to 4.87)) and Lactobacillales order (OR low 1.00 (reference), OR medium 2.15 (95% CI 1.03 to 4.47), OR high 3.26 (95% CI 1.58 to 6.70)) was associated with an increased risk of lung cancer. Conclusions Our prospective study of never-smokers suggests that lower alpha diversity was associated with a greater risk of lung cancer and the abundance of certain specific taxa was associated with altered risk, providing further insight into the aetiology of lung cancer in the absence of active tobacco smoking.
Patterns of Ventricular Remodeling After Myocardial Infarction: Clues Toward Linkage Between Mechanism and Morbidity⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Marvin A. Konstam
Journal: JACC. Cardiovascular imaging (2008)