tbuckley/cabot-search huggingface dataset:
Emerging Therapeutic Options in Acute Lymphoblastic Leukemia
Authors: Patrick A. Brown
Journal: Journal of the National Comprehensive Cancer Network (2020)

Immunotherapies have dramatically increased response rates in the relapsed/refractory setting of acute lymphoblastic leukemia. These emerging therapeutic options include blinatumomab, a bispecific T-cell engager construct; inotuzumab, an antibody–drug conjugate; and CAR T cells. Despite significantly improved rates of response, however, CAR T-cell therapy is the only approach associated with durable survival in a significant proportion of patients. Immunotherapies come with characteristic toxicity profiles. Inotuzumab is associated with hepatotoxicity, and blinatumomab and CAR T cells are associated with both cytokine release syndrome and neurotoxicity. Furthermore, immunotherapy is not always successful. Several mechanisms of failure exist, including failure to manufacture the CAR product, failure to engraft or lack of persistence of CAR T cells, endogenous T cell or CAR T-cell exhaustion, and antigen escape.
Intense Hypermetabolic Tumefactive Demyelination on 18F-FDG PET and MRI Related to Multiple Sclerosis Relapse After Fingolimod Suspension
Authors: Gabriela Almeida Pimentel, Artur Martins Coutinho, Luis Filipe de Souza Godoy, Luiz Guilherme Cernaglia A. de Lima, Daniel Ciampi de Andrade
Journal: Clinical Nuclear Medicine (2020)

A 57-year-old woman with a history of multiple sclerosis presented with a 5-day history of progressive headache and confusion, followed by left hemiparesis. The patient had stopped her previous fingolimod usage during the last 8 weeks. Brain MRI and 18F-FDG PET showed a subcortical tumefactive lesion with an intense peripheric rim of hypermetabolism and central hypometabolism, with central hyperintensity, thin isointense rim, and peripheral finger-like "tentacles" of edema with an irregular and thick border enhancement on postcontrast T2-weighted MRI. Brain biopsy showed features suggestive of relapsing MS. The patient improved after methylprednisone and plasma exchange.
Carbon Nanotubes: Optimizing Bifurcated Channels within an Anisotropic Scaffold for Engineering Vascularized Oriented Tissues (Adv. Healthcare Mater. 24/2020)
Authors: Yongcong Fang, Liliang Ouyang, Ting Zhang, Chengjin Wang, Bingchuan Lu, Wei Sun
Journal: Advanced Healthcare Materials (2020)

In article number 2000782 by Ting Zhang and co-workers, a facile approach is developed to optimize bifurcated channels in anisotropic scaffolds. The bifurcated channel network governed by biomimetic principles is designed based on Murray's Law and further optimized by oxygen transport simulation and biological experiments. This numerical model–based strategy provides a practical guide to optimizing vascular channels for oriented tissue engineering.
Scaling up the in-hospital hepatitis C virus care cascade in Taiwan
Authors: Chung-Feng Huang, Pey-Fang Wu, Ming-Lun Yeh, Ching-I Huang, Po-Cheng Liang, Cheng-Ting Hsu, Po-Yao Hsu, Hung-Yin Liu, Ying-Chou Huang, Zu-Yau Lin, Shinn-Cherng Chen, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Chuang, Ming-Lung Yu
Journal: Clinical and Molecular Hepatology (2020)

Background/Aims: Obstacles exist in facilitating hepatitis C virus (HCV) care cascade. To increase timely and accurate diagnosis, disease awareness and accessibility, in-hospital HCV reflex testing followed by automatic appointments and a late call-back strategy (R.N.A. model) was applied. We aimed to compare the HCV treatment rate of patients treated with this strategy compared to those without.Methods: One hundred and twenty-five anti-HCV seropositive patients who adopted the R.N.A. model in 2020 and another 1,396 controls treated in 2019 were enrolled to compare the gaps in accurate HCV RNA diagnosis to final treatment allocation.Results: The HCV RNA testing rate was significantly higher in patients who received reflex testing than in those without reflex testing (100% vs. 84.8%, &lt;i&gt;P&lt;/i&gt;&lt;0.001). When patients were stratified according to the referring outpatient department, a significant improvement in the HCV RNA testing rate was particularly noted in patients from non-hepatology departments (100% vs. 23.3%, &lt;i&gt;P&lt;/i&gt;&lt;0.001). The treatment rate in HCV RNA seropositive patients was 83% (83/100) after the adoption of the R.N.A. model, among whom 96.1% and 73.9% of patients were from the hepatology and non-hepatology departments, respectively. Compared to subjects without R.N.A. model application, a significant improvement in the treatment rate was observed for patients from non-hepatology departments (73.9% vs. 27.8%, &lt;i&gt;P&lt;/i&gt;=0.001). The application of the R.N.A. model significantly increased the in-hospital HCV treatment uptake from 6.4% to 73.9% for patients from non-hepatology departments (&lt;i&gt;P&lt;/i&gt;&lt;0.001).Conclusions: The care cascade increased the treatment uptake and set up a model for enhancing in-hospital HCV elimination.
CTNI-20. PCV CHEMOTHERAPY ALONE IS ASSOCIATED WITH BETTER CLINICAL COURSE IN OLIGODENDROGLIOMA WHO GRADE II
Authors: Jonathan Weller, Sophie Katzendobler, Philipp Karschnia, Stefanie Lietke, Rupert Egensperger, Niklas Thon, Michael Weller, Friedrich-Wilhelm Kreth, Bogdana Suchorska, Joerg-Christian Tonn
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Current treatment guidelines for oligodendrogliomas (OD) recommend watch-and-wait strategies after gross total resection and radiation with subsequent chemotherapy (procarbazine, CCNU and vincristine (PCV)) after incomplete resection. The value of chemotherapy alone as an option to delay the risk of late cognitive deficits is not well defined yet. Here, we retrospectively investigated long-term outcome in OD WHO II with respect to initial therapy and tumor volume in magnetic resonance imaging (MRI). METHODS A total of 142 patients with OD WHO (World Health Organization) II according to WHO 2016 were retrospectively included. Patients either had watch and wait (W&amp;W) after histological sampling through stereotactic biopsy (n=59) or tumor resection (n=27) or else stereotactic biopsy with subsequent temozolomide (TMZ) (n=26) or PCV (n=30). Pre- and post-therapeutic T2 tumor volumes were obtained. Progression-free survival (PFS), post-recurrence PFS (PR-PFS) and rate of secondary malignization after 10 years (MR-10yrs) were correlated with clinical and volumetric data. RESULTS PFS was significantly longer in the PCV cohort compared to TMZ (9.1 vs. 3.6 years, p = 0.04), even after matching patients according to age and initial tumor volume (9.1 vs 4.7 yrs, p = 0.03). PFS in the W&amp;W cohort was 5.1 years and 4.4 years in those receiving tumor resection only. MR-10yrs was 4% in PCV cohort, 18% in the W&amp;W cohort and 52% in the resection only cohort (p = 0.01). In the W&amp;W cohort, patients treated with PCV at first relapse had a longer PR-PFS than those treated with TMZ (in years, 7.2 vs 4.0, p = 0.04). Multivariate analysis confirmed initial PCV therapy (p = 0.01) and initial T2 tumor volume (p = 0.02) to be prognostic. CONCLUSION In oligodendrogliomas WHO II PCV chemotherapy alone is superior in terms of PFS and rate of secondary malignization compared to TMZ chemotherapy alone or tumor resection only.
CTIM-15. PRELIMINARY RESULTS OF A PHASE II STUDY OF NIVOLUMAB WITH HYPOFRACTIONATED RE-RADIATION AND BEVACIZUMAB FOR RECURRENT MGMT METHYLATED GLIOBLASTOMA
Authors: Christian Grommes, Minesh Mehta, Alexandra Miller, Mariza Daras, Anna Piotrowski, Adrienne Boire, Brittany Butler, Jacqueline Stone, Elena Pentsova, Rupesh Kotecha, Tara Morrison, Yazmin Odia, Ingo Mellinghoff, Kathryn Beal
Journal: Neuro-Oncology (2020)

Abstract Standard of standard of care for glioblastoma (GBM) remains unsatisfactory with universal disease recurrence and a median survival of &amp;lt; 2 years. Immune checkpoint inhibitors (ICI) have shown limited single-agent activity in GBM thus far. GBMs with methylated MGMT promoter and no baseline corticosteroid dependence may be most likely to derive benefit from ICI. The combination of ICIs with radiation has shown promising activity in other human cancers. Combining nivolumab and re-RT/bevacizumab in GBM may augment ICI activity through immunogenic effects of radiation, may reduce the risk of radiation necrosis by addition of bevacizumab at the time of radiation, and may reduce the need for corticosteroids. In this multicenter phase II study, nivolumab is combined with re-irradiation and optional concurrent bevacizumab followed by nivolumab in patients with first recurrence of IDH-wildtype and MGMT methylated glioblastoma. Primary objective is to improve 1-year overall survival (OS) from 33 (based on EORTC 26101) to 50%. Nine-three patients are required to show a significant finding with an α of 0.05 and 81% power. Thirteen of 93 patient (14%) have been enrolled with a median age of 59 (range 42–71) with a median KPS of 90 (range 70–90). Treatment has been tolerated well without any grade ≥ 4 toxicities and only one grade 3 (amylase elevation). The most common adverse events were pruritus and hypothyroidism in 3/13 (23%). The median progression-free survival (PFS) is 7 months with a 6months PFS of 55.6%. The 12months OS is 66.7%. Patients with recurrent MGMT methylated, IDH-wildtype glioblastoma tolerate trial treatment with acceptable toxicities. Clinical efficacy in the first patients enrolled shows a promising effect. Enrollment is ongoing.
NIMG-69. PERSONALIZED CONNECTOMIC SIGNATURES: BRIDGING THE GAP BETWEEN NEURO-ONCOLOGY AND CONNECTOMICS
Authors: Yusuf Osmanlioglu, Drew Parker, Steven Brem, Ali Shokoufandeh, Ragini Verma
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Connectomics has led to significant neuroscientific findings within the last two decades, eventually making impact in the clinics. Neuro-oncology can benefit immensely from connectomics in evaluating structural connectivity of brains with tumor for pre- and post-treatment planning, as a tumor connectome along with derived network measures will make it possible to determine the cognitive effects of treatment and quantify the effect of surgery on quality of life. However, generating connectomes in the presence of tumor is a challenging task. Specifically, registration of an atlas to the brain, which is essential in parcellating the brain into regions of interest, fails around the tumor due to mass effect and infiltration related distortions which are not present in the atlas that comes from a healthy brain. We aim to tackle this problem by introducing a novel atlas registration method. METHOD Although tumor deforms the geometrical shape of its surrounding regions, it does not violate the connectivity of displaced cortical voxels to the rest of the brain. Leveraging this fact, we represent the brain as an annotated graph with nodes representing ROIs encoding geometric features of regions and weighted edges representing the connectivity between regions. In encoding the surroundings of the tumor into the graph, we subsample the region into smaller patches to represent the area with multiple nodes. We then calculate many-to-one graph matching between the graphs of a tumor patient and a healthy control to associate surroundings of tumor with healthy ROIs. OUTCOME A tumor connectome showing how the connectivity is morphed around the tumor, which can further be extended to creating connectomes of recurrence. CLINICAL IMPLICATIONS Use of connectomes can revolutionize neuro-oncology by helping surgeons in estimating structural, functional, and behavioral outcomes of resection prior to surgery and in predicting recovery after the surgery, potentially suggesting subject specific treatment plans.
Abstract 3553: Effect of Resolution of Metabolic Syndrome on Endothelial Function and Cardiovascular Events after Acute Coronary Syndromes
Authors: Shin-ichiro Miyazaki, Yoshikazu Hiasa, Takefumi Takahashi, Riyo Ogura, Naoki Suzuki, Shinobu Hosokawa, Koichi Kishi, Ryuji Ohtani
Journal: Circulation (2007)

Background: Metabolic syndrome (MetS) is associated with endothelial dysfunction, and recognized as a risk factor of cardiovascular events after acute coronary syndromes (ACS). We examined whether the resolution of MetS would improve endothelial function and provide a beneficial effect on clinical outcome after ACS. Methods: We studied 60 patients with MetS who underwent a percutaneous revascularization procedure for ACS. MetS was defined using modified International Diabetes Federation criteria. Brachial artery flow-mediated dilation (FMD) and several risk parameters related to metabolic disorders were assessed at baseline and at 6 months. Each patient was given basic spoken advice on lifestyle modification and optimal medications before discharge. Patients were divided into 2 groups according to whether the criteria for MetS were fulfilled at 6 months: resolved MetS (R-MetS, n=35) and persistent MetS (P-MetS, n=25). Cardiovascular events were defined as cardiac death, stroke, myocardial infarction, unstable angina, and target vessel revascularization. Results: During the 1-year follow-up, 3 patients with R-MetS (8.6%) and 14 patients with P-MetS (56%) had cardiovascular events (p=0.0002). The extent of improvement in FMD was significantly greater in patients with R-MetS than those with P-MetS (change in FMD: 1.5 vs −1.2: p=0.007; respectively). In a multivariate logistic regression analysis, P-MetS was an independent predictor of cardiovascular events (odds ratio 18.4, 95%CI 1.67–28.5, p=0.025). Conclusion: The resolution of MetS is associated with the recovery of endothelial function and prevents cardiovascular events after ACS. Multivariate logistic regression analysis
RONC-05. PRESERVING VISION IN OPTIC PATHWAY GLIOMA AMONG PATIENTS WITHOUT NEUROFIBROMATOSIS TYPE 1
Authors: Alexander Hanania, Arnold Paulino, Ethan Ludmir, Veeral Shah, Susan McGovern, David Grosshans, Fatih Okcu, Patricia Baxter, Jack Su, Murali Chintagumpala
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Sporadic optic pathway/hypothalamic gliomas (OP/HGs) represent a unique entity within pediatric low-grade glioma. Despite favorable survival, the location makes treatment difficult and local progression debilitating. We conducted longitudinal assessment of visual acuity (VA) among patients treated in the modern era with chemotherapy (CT) or early radiotherapy (RT). METHODS Clinical characteristics were abstracted for patients treated over a 15-year period (2000–2015) at a single institution. Comprehensive ophthalmologic data taken at three to six-month intervals was examined with age-appropriate VA metrics converted to LogMAR scale. Kaplan-Meir “blindness-free survival” (BFS) curves were calculated as time to bilateral functional blindness (i.e. LogMAR ≥ 0.8 in both eyes), stratified by treatment and compared using log-rank test. RESULTS Thirty-six patients with median follow-up of 7.6 years (range: 2–17) were identified. Median age at diagnosis was 2.5 years (IQR: &amp;lt;1–5). Early RT was administered as initial therapy (n=6) or first-line salvage (n=5) in a total of eleven patients (31%) at a mean age of 12 years (range: 6–17). Twenty-five patients (69%) were maintained primarily on CT with a mean age at initiation of 2.4 years (range &amp;lt;1–8). Of these, five patients received RT after ≥2 systemic therapy regimens. In terms of visual preservation, five/eight-year BFS rates were 84%/59% and 100%/100%, for CT and early RT, respectively (p=0.046). CONCLUSIONS In a contemporary cohort, early RT, defined as initial or 1st line salvage therapy for OP/HGs manifested in superior VA. Children undergoing CT are at highest risk of functional blindness following five years of treatment.
Corticosteroids in patients hospitalized for COVID-19 pneumonia who require oxygen: observational comparative study using routine care data
Authors: Viet-Thi Tran, Matthieu Mahévas, Firouze Bani-Sadr, Olivier Robineau, Thomas Perpoint, Elodie Perrodeau, Laure Gallay, Philippe Ravaud, François Goehringer, François-Xavier Lescure, François-Xavier Lescure, Viet-Thi Tran, Matthieu Mahévas, Firouze Bani-Sadr, Olivier Robineau, Thomas Perpoint, Elodie Perrodeau, Laure Gallay, Philippe Ravaud, François Goehringer, François-Xavier Lescure, François-Xavier Lescure, Laure Gallay, Matthieu Mahévas, Viet-Thi Tran, Viet-Thi Tran, Elodie Perrodeau, Philippe Ravaud, Sophie Ismaël, François Goehringer, François-Xavier Lescure, Matthieu Mahévas, Thomas Perpoint, Viet-Thi Tran, François-Xavier Lescure, Cédric Laouénan, Jennifer Soulier, Oriane Puéchal, Eric D’Ortenzio, Yazdan Yazdanpanah, Laurence Maulin, Stéphanie Martinez, Diane Sanderink, Pascale Fialaire, Séverine Ansart, Lucas Perez, Anne - Laure Destrem, Chloé Moulin, Pascal Gicquel, Frédéric Rivière, Martin Martinot, Mahsa Mohseni Zadeh, Tomasz Chroboczek, Thibaut Challan Belval, Lionel Piroth, Thibault Sixt, Florian Moretto, André Cabié, Jérémie Pasquier, Ornella Cabras, Marine Morrier, Jean Reuter, Thomas Henin, Pierre Braquet, Helene Desmurs-Clavel, Arnaud Hot, Thomas Perpoint, Boris Bienvenu, Belkacem Asselate, Nicolas Vignier, Steve Nguala, Sylvain Diamantis, Guillemette Frémont, Pierre Louis Nivose, Mathilde Thiébaut, François Goehringer, Benjamin Lefevre, Hélène Auge, Paul le Turnier, Naila Benkalfate, Olivier Grossi, Samuel Pineau, Elisa Demonchy, Julie Merindol, Claire Durand, Nathalie Tieulié, Viviane Queyrel, Didier Laureillard, Paul Loubet, Ségolène Greffe, Nathalie Dournon, Youssouf Mohamed Kassim, Cyrille Gourjault, Alexandre Lahens, François-Xavier Lescure, Paul Legendre, Caroline Morbieu, Matthieu Mahevas, Giovanna Melica, Jean-Daniel Levièvre, Frédéric Schlemmer, Simone Tunesi, Claire Leblanc, Anne Bourgarit-Durand, Alexandre Bleibtreu, Gianpiero Tebano, Jérôme Pacanowski, Jean-Benoit Zabbe, Mathilde Devaux, Laurent Bellec, Marine Gosset-Woimant, Céleste Lambert, Firouze Bani-Sadr, Maxime Hentzien, Amélie Servettaz, Kevin Alexandre, Manuel Etienne, Romain Leguillon, Marion Dollat, Rémi Lefrancois, Anne Pouvaret, Yvon Ruch, Yannick Dieudonné, Guillaume Martin-Blondel, Xavier Boumaza, Margaux Lafaurie, Olivier Robineau, Macha Tetart, Adrien Lemaignen, Nicole Ferreira-Maldent, Amélie Duréault, Marie Gousseff, Claire Chantepie, Francesca Bisio, Fanny Pommeret, Emeline Colomba Blamble, Claire Ara Somohano
Journal: Clinical Microbiology and Infection (2020)
Prevalence and intensity of soil-transmitted helminth infections of children in sub-Saharan Africa, 2000–18: a geospatial analysis
Authors: Benn Sartorius, Jorge Cano, Hope Simpson, Lucy S Tusting, Laurie B Marczak, Molly K Miller-Petrie, Boniface Kinvi, Honorat Zoure, Pauline Mwinzi, Simon I Hay, Maria Rebollo, Rachel L Pullan
Journal: The Lancet Global Health (2020)

BackgroundDriven by global targets to eliminate soil-transmitted helminths as a public health problem, governments have rapidly rolled out control programmes using school and community-based platforms. To justify and target ongoing investment, quantification of impact and identification of remaining high-risk areas are needed. We aimed to assess regional progress towards these targets.MethodsWe did a continental-scale ecological analysis using a Bayesian space–time hierarchical model to estimate the effects of known environmental, socioeconomic, and control-related factors on the prevalence of soil-transmitted helminths, and we mapped the probability that implementation units had achieved moderate-to-heavy intensity infection prevalence of less than 2% among children aged 5–14 years between Jan 1, 2000, and Dec 31, 2018.FindingsWe incorporated data from 26 304 georeferenced surveys, spanning 3096 (60%) of the 5183 programmatic implementation units. Our findings suggest a reduction in the prevalence of soil-transmitted helminths in children aged 5–14 years in sub-Saharan Africa, from 44% in 2000 to 13% in 2018, driven by sustained delivery of preventive chemotherapy, improved sanitation, and economic development. Nevertheless, 1301 (25%) of 5183 implementation units still had an estimated prevalence of moderate-to-heavy intensity infection exceeding the 2% target threshold in 2018, largely concentrated in nine countries (in 1026 [79%] of 1301 implementation units): Nigeria, Democratic Republic of the Congo, Ethiopia, Cameroon, Angola, Mozambique, Madagascar, Equatorial Guinea, and Gabon.InterpretationOur estimates highlight the areas to target and strengthen interventions, and the areas where data gaps remain. If elimination of soil-transmitted helminths as a public health problem is to be achieved in sub-Saharan Africa by 2030, continued investment in treatment and prevention activities are essential to ensure that no areas are left behind.FundingBill & Melinda Gates Foundation.
GCT-20. EVALUATION OF NEURORADIOLOGICAL RESPONSE TO INDUCTION CHEMOTHERAPY FOR PATIENTS WITH LOCALISED GERMINOMA IN THE SIOP CNS GCT II TRIAL
Authors: Brigitte Bison, Giovanni Morana, Dipayan Mitra, Herve Brisse, Cecile Faure-Conter, Thankamma Ajithkumar, Claire Alapetite, Beate Timmermann, James Nicholson, Gabriele Calaminus, Matthew Murray
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION The SIOP-CNS-GCT-96 trial demonstrated excellent survival for patients with germinoma. Localised patients received either craniospinal irradiation (CSI) 24Gy plus tumour-bed-boost 16 Gy or 2xcarboPEI chemotherapy (carboplatin/etoposide alternating with etoposide/ifosfamide) and focal-radiotherapy 40 Gy. Following trial closure, whole-ventricular-irradiation (WVI) was delivered with focal-radiotherapy to avoid ventricular relapse. Accordingly, current research priorities focus on reducing treatment burden and long-term neurocognitive sequelae. METHODS SIOP-CNS-GCT-II employed national central radiological review to assess whether dropping the 16Gy boost was safe for localized germinoma in complete-remission (CR) following 2xcarboPEI: i.e. no disease on clinical/marker/radiological assessment. Any abnormal thickening/enhancement after chemotherapy was to be classified as partial-remission (PR). Patients with less than CR after chemotherapy received a boost. RESULTS Shortly before trial closure (2018), it was noted that national CR rates were discrepant across the largest recruiting countries. For German patients, CR rates were ~80%, compared with ~30–40% for UK and France. A formal neuroradiology review was therefore convened. A total of 59 cases were randomly selected (UK, n=32; France, n=14 and Germany, n=13), including those deemed to be in CR and PR. Cases included those with disease at pituitary, pineal and bifocal sites. Both diagnostic scan and scan after induction chemotherapy were used for assessment. Detailed analysis is ongoing and will be presented. CONCLUSION Residual changes at both pituitary and pineal sites of uncertain significance may remain after chemotherapy. This process should facilitate consensus to define the best response criteria allowing treatment reduction for CNS germinoma for future clinical trials.