tbuckley/cabot-search huggingface dataset:
RARE-54. MOLECULAR ANALYSIS OF ROSETTE-FORMING GLIONEURONAL TUMOR AT MIDBRAIN; REPORT OF TWO CASES
Authors: Hajime Handa
Journal: Neuro-Oncology (2020)

Abstract Rosette-forming glioneuronal tumor (RGNT) is a tumor that primarily arises at posterior fossa. We experienced two rare cases of RGNT located at midbrain and investigated their molecular features. Case 1 is a 23-year-old female, and Case 2 is an 18-year-old male. Both cases were surgically removed by the occipital transtentorial approach. Histological analysis demonstrated a biphasic pattern of neurocytic and glial components. The former consisted of neurocytic rosettes and perivascular pseudorosettes, and the latter was GFAP positive, corresponding to the diagnosis of RGNT. Both cases have an excellent clinical course without receiving chemotherapy or radiation therapy. Small residual tumors of both cases shrunk and maintained for 27 and 12 months, respectively. Case 1 underwent DNA methylation array and a subsequent DNA methylation-based classifier, indicating that the case matched RGNT with a 0.99 calibrated score. Also, we identified FGFR1 K656 mutation. Pyrosequence analysis of other genes such as IDH1 R132, IDH2 R172, BRAF T599, BRAF V600, H3F3A K27, H3F3A G34, HIST1H3B K27, TERT C228, FGFR1 N546 had no mutations. RT-PCR of KIAA1549-BRAF fusion was not detected. DNA methylation status of Case 2 is under investigation. Pyorosequence analysis identified TERT C228 mutation but did not identify other mutations such as FGFR1 N546 and K656. Midbrain RGNT corresponds to the histological and molecular features of RGNT. RGNT needs to be differentially diagnosed in the case of a midbrain tumor.
Automatic Digital Quantification of Bone Marrow Myeloma Volume in Appendicular Skeletons — Clinical Implications and Prognostic Significance
Authors: Yuki Nishida, Shinya Kimura, Hideaki Mizobe, Junta Yamamichi, Kensuke Kojima, Atsushi Kawaguchi, Manabu Fujisawa, Kosei Matsue
Journal: Blood (2017)
Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial
Authors: Gary Wittert, Karen Bracken, Kristy P Robledo, Mathis Grossmann, Bu B Yeap, David J Handelsman, Bronwyn Stuckey, Ann Conway, Warrick Inder, Robert McLachlan, Carolyn Allan, David Jesudason, Mark Ng Tang Fui, Wendy Hague, Alicia Jenkins, Mark Daniel, Val Gebski, Anthony Keech
Journal: The Lancet Diabetes & Endocrinology (2020)
Reconceptualising treatment-resistant depression as difficult-to-treat depression
Authors: R Hamish McAllister-Williams, Celso Arango, Pierre Blier, Koen Demyttenaere, Peter Falkai, Philip Gorwood, Malcolm Hopwood, Afzal Javed, Siegfried Kasper, Gurjhinder S Malhi, Jair C Soares, Eduard Vieta, Allan H Young, Andreas Papadopoulos, Augustus J Rush
Journal: The Lancet Psychiatry (2020)
NCOG-21. INTERIM RESULTS OF THREE COGNITIVE REHABILITATION STRATEGIES IN PATIENTS WITH LOWER GRADE GLIOMAS
Authors: Jennie Taylor, Christina Weyer-Jamora, Melissa Brie, Paige Bracci, Ellen Smith, Tracy Luks, Steve Braunstein, Javier Villanueva-Meyer, Karin Gehring, Adrian Aguilera, Nancy Ann Oberheim Bush, Jennifer Clarke, Nicholas Butowski, Susan Chang, Shawn Hervey-Jumper
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Patients with lower grade (2 and 3) gliomas (LrGG) are living longer, but often with cognitive impairments from their tumor and treatments. However, cognitive assessments and access to cognitive rehabilitation are not a standard part of care. We present preliminary results of a pilot study investigating feasibility and efficacy of three cognitive rehabilitation strategies for stable LrGG patients – in-person manualized cognitive rehabilitation; iPad based cognitive rehabilitation program of retraining and compensation strategies (ReMind); or daily instructional text messages (Healthy SMS). METHODS Eligible patients were adults with clinically and radiologically stable LrGG, &amp;gt; 6 months from last treatment, and ≥1 standard deviation (SD) below normal on ≥ 2 domains of neuropsychological assessments. Patients were first offered in-person cognitive rehabilitation or randomized to ReMind or Healthy SMS if unable to attend in-person. Interventions lasted 3 months. Neuropsychological and HRQOL assessments, using PROMIS NeuroQOL, were conducted at baseline, 3, and 6 months post-intervention. Feasibility was defined as attending ≥80% of in-person sessions; completing ≥80% of ReMind tasks; or not opting out of Healthy SMS texts. RESULTS To date 23/60 patients have enrolled: 11 in-person and 12 randomized to ReMind (5) or Healthy SMS (7). Demographic and clinical characteristics were similar between cohorts. Median age at testing was 46 years, with 65% female, and 78% having received prior radiation (median 4.1 years, range 3.2 – 11.5). At baseline, processing speed was the most common domain of impairment with 43% ≥ 1.5 SD below normal and 36% patients reporting subjective cognitive impairment on HROQL assessment. Feasibility was 71% for in-person rehabilitation; 50% for ReMind; and 100% for Health SMS. CONCLUSION These preliminary results demonstrate that stable LrGG patients with subjective and objective cognitive impairments can reasonably engage in cognitive rehabilitation interventions. Updated data including post-intervention neuropsychological and HROQL related changes will be presented.
The Month After: A Novel Tale on Eplerenone, But With a Different Ending⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Michele Emdin, Luigi Emilio Pastormerlo, Claudio Passino
Journal: Journal of the American College of Cardiology (2011)
COVD-09. INVESTIGATION AND SUMMARY OF DIAGNOSIS AND TREATMENT OF NEUROLOGICAL TUMORS DURING COVID-19 IN CHINA
Authors: Zhen Liang, Yuanjun Hu, Zhong-ping Chen
Journal: Neuro-Oncology (2020)

In order to realize the condition of diagnosis and treatment of neurological tumors in China during COVID-19, CSNO (China Anti-Cancer Association Neuro-Oncology Professional Committee) organized this questionnaire survey. The survey was conducted online from June 3rd to 16th in 2020. A total of 373 replies were received and 370 were confirmed valid questionnaires. The respondents were mainly neurosurgeons, as well as radiotherapists and pathologists in general hospitals and specialized hospitals in 29 provinces and municipalities in China. The survey results are summarized as follows. Firstly, the number of outpatient and inpatient of neurological tumors significantly declined during the epidemic compared with the same period last year in more than 90% of hospitals surveyed, and a few specialized hospitals even stopped treatment due to the outbreak of COVID-19. Compelled by illness was the main reason for most of the patients to go to hospital. As the epidemic prevention and controlling, the normal treatment process for each patient was tedious than that for the same period before, and the costing time also turned longer. Most patients might feel poor medical experience, but they also expressed understanding for the hospital and cooperated with the diagnosis and treatment works. Secondly, during the epidemic period, the participation in academic conferences or MDT decreased significantly for most doctors, and scientific research work even stopped in some hospitals. Online tools have risen as the primary means of communication, not only for academic communication but also for diagnosis and treatment works. More than 90% of doctors believe the style of online communication was a new mode in this special period, with advantages such as convenient and quick. It could be an effective supplement to daily work and would be utilized into work in future.
EXTH-38. ORTHOGONAL IN VIVO MODELS WERE THE SOLE PRECLINICAL PREDICTOR OF CLINICAL EFFICACY IN PHASE 1 TRIALS OF TARGETED THERAPIES FOR GLIOBLASTOMA: RESULTS OF A SYSTEMATIC REVIEW
Authors: Ashray Gunjur, Adithya Balasubramanian, Umbreen Hafeez, Siddharth Menon, Lawrence Cher, Sagun Parakh, Hui Gan
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION No drug has improved survival in recurrent glioblastoma despite encouraging activity preclinically. We undertook a systematic review of matched preclinical and Phase 1 trials (P1Ts) of targeted agents to investigate potential preclinical predictors of clinical efficacy. METHODS We identified all adult glioblastoma monotherapy P1Ts of targeted agents &amp; preceding preclinical data published between 2006–2019 via structured searches of EMBASE/MEDLINE/PUBMED. For preclinical studies, data regarding in vitro models, in vivo models (species, implantation site, cell-line type) and efficacy (growth inhibition, regression rate, survival) were extracted. For P1T, response rate (RR) data were collected as absolute (%) and categorical (RR&amp;lt; 5% vs. RR≥ 5%) variables. Associations were compared by chi-square/Fisher’s exact test, Kruskal-Wallis or Mann-Whitney U testing as appropriate with 2-sided p-values. RESULTS We found 28 P1Ts with median RR 2.9% (range 0.0–33.3%) and mOS 8.0mo (range 4.6–13.0mo). Seven (25%) had ‘minimal’ published pre-clinical data (5 missing entirely; 2 in vitro only); 12 (43%) utilised one cell line in vivo (‘single model’ group); and 9 (32%) used 2+ biologically distinct in vivo models (‘orthogonal’ group). There was strong reliance on U87-based cell lines (14/21 (71%)) in the latter groups. None of the variables tested were associated with RR except for use of ‘orthogonal models’. Compared to the ‘orthogonal’ group, the P1T RR rate was lower in ‘single’ and ‘minimal’ groups (6.8% vs 1.2%, p= 0.043 and 6.8% vs 0.0%, p= 0.026 respectively). The frequency of P1T with a RR &amp;gt; 5% was also higher in the ‘orthogonal’ compared to the same two groups (78% vs 20%, p= 0.042 and 78% vs 17%, p= 0.041). CONCLUSION The availability of good quality pre-clinical data, especially the use of orthogonal models in vivo, was significantly associated with P1T response rates and warrants further investigation as a minimal threshold of evidence in future drug development.
TAMI-27. RADIATION THERAPY REPROGRAMS THE TUMOR METABOLISM TO PROMOTE SURVIVAL AND IMMUNOSUPPRESSION IN GLIOBLASTOMA
Authors: Mara De Martino, Camille Daviaud, Claire Vanpouille-Box
Journal: Neuro-Oncology (2020)

Abstract Immune checkpoint blockade has re-stimulated the interest of immunotherapeutic strategies for glioblastoma (GBM). However, PD-1 blockade in recurrent GBM patients failed to meet the primary endpoint of superior survival (NCT02017717) highlighting the need to identify mechanisms of GBM immune evasion. One possibility is the metabolic landscape that cancer cells generate to promote survival and prevent immune responses. Radiation therapy (RT), a standard of care for GBM, is well-documented to reprogram the metabolism of the tumor microenvironment (TME). Therefore, we hypothesize that RT generates a metabolic shift in the TME to support GBM survival and immunosuppression. To address this question, we first defined RT-induced metabolic changes by Seahorse assay. We observed that mitochondrial respiration and ATP production were significantly increased in 10 gray (Gy)-irradiated GL261 cells after 24hr. Metabolomic profiling of 10Gy-irradiated GL261 cells showed a strong increase in metabolic pathways related to nucleotide, amino acids and lipid metabolism. We next ask whether RT was modulating the fatty acid synthase (FASN), a key lipogenic enzyme. Western blot analysis indicated upregulation of FASN expression in irradiated GL261 cells. Interestingly, flow cytometry of orthotopically implanted GL261 tumors not only confirmed FASN upregulation in cancer cells in vivo, but also revealed a marked FASN expression in tissue-resident microglia after 10Gy focal irradiation. Moreover, flow cytometry analysis showed increased expression of the immunosuppressive markers PD-L1 and CSF-1R in macrophages co-cultured with irradiated GL261. Finally, targeting FASN using shRNA or pharmacological inhibition, significantly reduced the proliferation of GL261 cells. Altogether, our data indicate that RT is rewiring the energy supply of GBM to presumably foster its growth and immunosuppression of the TME by promoting lipid biosynthesis. While much work remains to be done to confirm this hypothesis, our data propose FASN as a novel therapeutic target to overcome RT resistance and reduce immunosuppression in GBM.
Independent Observational Analysis of Ulcer Outcomes for SINBAD and University of Texas Ulcer Scoring Systems
Authors: Graham P. Leese, Enrique Soto-Pedre, Christopher Schofield
Journal: Diabetes Care (2020)

OBJECTIVE The aim of this study was to compare the University of Texas (UT) and Site, Ischemia, Neuropathy, Bacterial Infection, and Depth (SINBAD) foot ulcer scores in predicting ulcer outcome within a routine diabetes foot clinic. RESEARCH DESIGN AND METHODS From 2006 to 2018, data were collected from all patients attending an outpatient diabetes foot clinic with an active ulcer not healed within 4 weeks. UT and SINBAD were compared in predicting ulcer outcome. A unified numerical score for UT was constructed and compared with UT grade (depth) and stage scores. Outcomes included death, a healed ulcer, or a nonhealed ulcer, which included major or minor amputation and nonhealing chronic ulcers. RESULTS Outcomes were available from 1,645 ulcer outcomes in 1,068 patients (mean [SD] age 65.4 [4] years, 72% male), of which 1,108 (67%) healed. With exclusion of death as an adverse outcome, the c-statistic (area under operator curve) was 0.67 (95% CI 0.65–0.71) for UT grade/depth and 0.64 (0.61–0.67) for UT stage. The new unified UT score had an improved c-statistic of 0.71 (0.68–0.74). The c-statistic was 0.72 (0.69–0.75) for SINBAD. There was a stepwise decrease in the proportion of ulcers healed for each increased score on ulcer grading for both grading schemes. CONCLUSIONS This large and independent observational comparison, in a real-world clinical setting, demonstrated that the UT and SINBAD diabetes foot ulcer grading schemes had similar prognostic ability for predicting foot ulcer outcomes. We have devised and validated a unified numerical scoring system for UT.
Bone marrow niche ATP levels determine leukemia-initiating cell activity via P2X7 in leukemic models
Authors: Xiaoxiao He, Jiangbo Wan, Xiaona Yang, Xiuze Zhang, Dan Huang, Xie Li, Yejun Zou, Chiqi Chen, Zhuo Yu, Li Xie, Yaping Zhang, Ligen Liu, Shangang Li, Yuzheng Zhao, Hongfang Shao, Ye Yu, Junke Zheng
Journal: Journal of Clinical Investigation (2020)

How particular bone marrow niche factors contribute to the leukemogenic activities of leukemia-initiating cells (LICs) remains largely unknown. Here, we showed that ATP levels were markedly increased in the bone marrow niches of mice with acute myeloid leukemia (AML), and LICs preferentially localized to the endosteal niche with relatively high ATP levels, as indicated by a sensitive ATP indicator. ATP could efficiently induce the influx of ions into LICs in an MLL-AF9–induced murine AML model via the ligand-gated ion channel P2X7. P2x7 deletion led to notably impaired homing and self-renewal capacities of LICs and contributed to an approximately 5-fold decrease in the number of functional LICs but had no effect on normal hematopoiesis. ATP/P2X7 signaling enhanced the calcium flux–mediated phosphorylation of CREB, which further transactivated phosphoglycerate dehydrogenase (Phgdh) expression to maintain serine metabolism and LIC fates. P2X7 knockdown resulted in a markedly extended survival of recipients transplanted with either human AML cell lines or primary leukemia cells. Blockade of ATP/P2X7 signaling could efficiently inhibit leukemogenesis. Here, we provide a perspective for understanding how ATP/P2X7 signaling sustains LIC activities, which may benefit the development of specific strategies for targeting LICs or other types of cancer stem cells.
Respectful language in intrapartum and newborn care
Authors: Claudia Ravaldi, Alfredo Vannacci, Caroline Homer
Journal: The Lancet Global Health (2020)

Dilys Walker and colleagues (August, 2020)1 describe the efficacy of a quality improvement package for intrapartum and immediate newborn care. It was encouraging to see that such a package reduced the risk of intrapartum stillbirth and neonatal mortality among preterm and low-birthweight babies in Kenya and Uganda, saving hundreds of babies' lives.
The influence of proton pump inhibitor therapy on the outcome of infliximab therapy in inflammatory bowel disease: a patient-level meta-analysis of randomised controlled studies
Authors: Thomas X Lu, Matthew Dapas, Erika Lin, Trevor Peters, Atsushi Sakuraba
Journal: Gut (2020)

Objective In treating patients with inflammatory bowel disease (IBD), how concomitant medications influence the response to infliximab is largely unexplored. We aim to evaluate whether proton pump inhibitors (PPIs) affect the response to infliximab therapy in patients with IBD. Design Patient-level data of adult patients with moderate-to-severe IBD treated with infliximab were obtained from the Yale Open Data Access Framework. Multivariable analysis and propensity score-matched analysis were performed to assess week 30 remission rates, week 54 remission rates and hospitalisation rates in patients on infliximab therapy with and without PPI exposure. Results Among the five randomised controlled studies, there were 147 and 889 patients on infliximab with and without PPI therapy, respectively. Patients on PPI were older, more likely to be Caucasian and were less likely to be on immunomodulator therapy. Patients on PPI were significantly less likely to achieve week 30 remission on multivariable analysis (OR 0.45, p&lt;0.001). Following propensity score matching adjusting for baseline difference in patient characteristics, the week 30 remission rates were 30% and 49% in patients with and without PPI therapy, respectively (p&lt;0.001). Analysing separately for disease, the findings remained statistically significant in Crohn’s disease but did not reach significance in UC. Similar results were seen with week 54 remission rates. Patients on PPI were also more likely to be hospitalised (15% vs 8%, p=0.007). Rates of adverse events such as gastroenteritis were not different between the two groups. Conclusion In this patient-level meta-analysis of randomised controlled studies, we found that patients with IBD taking PPI were less likely to achieve remission while on infliximab therapy. The results of our study warrant further investigation into the effect of PPI on IBD outcomes and therapies.
Covid-19: Oxford vaccine could be 59% effective against asymptomatic infections, analysis shows
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: Oxford vaccine could be 59% effective against asymptomatic infections, analysis shows Elisabeth MahaseThe Oxford and AstraZeneca covid-19 vaccine prevented some asymptomatic covid-19 infections in phase III trials, but the effect was mainly seen in the group who received a half dose first, followed by a full dose, the peer reviewed efficacy results have shown. 11
98P Low prognostic nutritional index is independently associated with poorer survival in patients receiving immune checkpoint inhibitors
Authors: D.C. Guven, O.H. Aktepe, H. Taban, B.Y. Aktas, G. Guner, H.C. Yildirim, T.K. Sahin, M.S. Aksun, O. Dizdar, S. Aksoy, M. Erman, S. Yalcin, S. Kilickap
Journal: Annals of Oncology (2020)
DDEL-03. LONG-TERM INTRAVENTRICULAR THERAPY ALTERNATING ETOPOSIDE AND LIPOSOMAL CYTARABINE: EXPERIENCE IN 75 CHILDREN AND ADOLESCENTS WITH MALIGNANT BRAIN TUMORS
Authors: Natalia Stepien, Andreas Peyrl, Amedeo Azizi, Johannes Gojo, Lisa Mayr, Dominik Reisinger, Christine Haberler, Thomas Czech, Irene Slavc
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Malignant brain tumors of childhood carry a high risk for leptomeningeal dissemination and tumor cells floating in the CSF are often not amenable to systemic and/or antiangiogenic chemotherapy. We report on our experience with an intraventricular therapy consisting of alternating cycles of liposomal cytarabine and etoposide. PATIENTS AND METHODS Between 2004 and 2017, 75 patients aged 0.6 to 22 years (median 11) with various malignant brain tumors received intraventricular etoposide 0.25mg (&amp;lt;1year) - 0.5mg on five consecutive days alternating with liposomal cytarabine at a dose of 25mg (&amp;lt;3 years) - 50mg via an Ommaya reservoir. RESULTS 5533 doses of etoposide (5–277/patient, median 141) corresponding to 1–56 five-day-cycles/patient alternating with 534 doses of liposomal cytarabine (1–21/patient, median 11) were administered. Treatment was given over a period of 1 – 146 months (median 73.5). Toxicities did occur but were infrequent and mostly mild. Since all patients received some sort of concurrent anti-cancer therapy, the efficacy of intrathecal therapy cannot be assessed independently. However, 29/75 patients are still alive, and none of the patients had tumor cells in the CSF at their last evaluation. CONCLUSION In conclusion, alternating intraventricular liposomal cytarabine and etoposide produced responses and proved to be an important adjunct for patients receiving drugs with a low penetrance into the CSF. Since production of liposomal cytarabine was discontinued in 2017 it remains to be determined whether substitution of the slow release formulation by aqueous cytarabine on days 1, 4, 8, and 11 may produce similar results.
SURG-35. INTRACRANIAL MYXOID MESENCHYMAL TUMOR WITH EWSR1-ATF1 GENE FUSION
Authors: Benjamin Ward, Christopher Wang, Rob Macaulay, James Liu
Journal: Neuro-Oncology (2020)

Abstract Intracranial myxoid mesenchymal tumors (IMMT) carrying an EWSR1-CREB gene family fusion are extremely rare and have only been identified in ten relatively recent reported cases. There is some question as to whether this is a novel entity, or a myxoid variant of angiomatoid fibrous histiocytoma (AFH), given certain histopathological similarities. Despite these similarities, the increasing number of cases reported appear to demonstrate clear histological differences that indicate IMMTs are a distinct and novel entity. Previous reports have focused on histological analysis but have lacked detailed long-term clinical follow-up and recommendations regarding treatment approach. In this case, we describe a 48-year-old female who presented with a left intraventricular mass that was identified histologically as an IMMT with an EWSR1-ATF1 gene fusion. Following initial resection, the tumor demonstrated local recurrence. Repeat resection was performed followed by immediate demonstration of local, as well as distant, tumor recurrence. Subsequent histological analysis of the tumor demonstrated a myxoid mesenchymal tumor clearly distinct from AFH. Fractionated stereotactic radiation therapy was administered following the second resection and tumor control was achieved at 1 year. This case is particularly remarkable as it is only the second reported IMMT case to occur in a middle-aged adult, with all other cases occurring in children or young adults. The two middle-aged adult cases share striking similarities in clinical presentation, including a history of breast cancer. Our findings indicate that an intracranial myxoid mesenchymal tumor is a novel and rare entity that may demonstrate rapid local and distant recurrence. Given the aggressive recurrence seen with the presented case, we recommend the treatment plan to be surgical resection followed by adjuvant radiation therapy to maintain tumor control.
Understanding and Measuring the Value of Peer-to-Peer Community Support Programs for Older Adults
Authors: Gabrielle Kelly, Leon Neville Geffen
Journal: JAMA Network Open (2020)

Elizabeth A. Jacobs, MD, MPP; Rebecca Schwei, MPH; Scott Hetzel, MS; Jane Mahoney, MD; Katherine Sebastian, RN, MSPH; Kali DeYoung, BA; Jenni Frumer, PhD, LCSW, MSEd; Jenny Madlof, BA; Alis Simpson, EdD; Erika Zambrano-Morales, MA; KyungMann Kim, PhD