tbuckley/cabot-search huggingface dataset:
Outcome of Allogeneic Haematopoietic Stem Cell Transplantation in Myeloproliferative Neoplasms-Unclassifiable: A Retrospective Study By the Chronic Malignancies Working Party of EBMT
Authors: Donal P. McLornan, Vittoria Malpassuti, Simona Iacobelli, Anne Lippinkhof-Kozijn, Linda Koster, Marie Robin, Yves Chalandon, Donald Bunjes, Dietrich W. Beelen, Victoria Potter, Henrik Sengeloev, Aleksandar Radujkovic, Jakob R. Passweg, Nicolaus Kröger, Gerald Wulf, Jan Erik Johansson, Fabio Ciceri, Martin Bornhäuser, Ernst Holler, Yves Beguin, Bruno Lioure, Sonja Martin, Dragana Milojkovic, Patrick Hayden, Juan Carlos Hernandez Boluda, Tomasz Czerw, Ibrahim yakoub-Agha
Journal: Blood (2019)
Assessments of cancer-free lymph nodes for the prediction of disease progression
Authors: A. Grigoriadis, N. Kurian, S. Ankathi, T. Hardiman, N. Woodman, J. Owens, S. Paharia, S. Meena, A.C. Coolen, S. Ranes, C. Gillett, S. Pinder, A. Sethi
Journal: Annals of Oncology (2019)
A Phase IIa, Open-Label, Multicenter Study of Single-Agent Tafasitamab (MOR208), an Fc-Optimized Anti-CD19 Antibody, in Patients with Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma: Long-Term Follow-up, Final Analysis
Authors: Wojciech Jurczak, Pier Luigi Zinzani, Georg Hess, Gianluca Gaidano, Mariano Provencio, Zsolt Nagy, Tadeusz Robak, Kami J. Maddocks, Christian Buske, Sumeet Ambarkhane, Wolfram Brugger, Maren Dirnberger-Hertweck, Sascha Tillmanns, Johannes Weirather, Kristie Blum
Journal: Blood (2019)
Treatment Patterns and Outcomes in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Experience from a Single UK Centre
Authors: John Radford, Ellie White, Felipe A. Castro, Anshuman Chaturvedi, Nathalie Spielewoy, Adam Gibb, Andy Surinach, Kim Linton, Aijing Shang, Michael Wenger
Journal: Blood (2019)
Elevated interferon-gamma levels during pregnancy are associated with adverse maternofetal outcomes in IBD
Authors: Humberto Jijon, Aito Ueno, Nastaran Sharifi, Yvette Leung, Subrata Ghosh, Cynthia H Seow
Journal: Gut (2019)

We read with interest van der Giessen’s observations of pregnancy-associated fluctuations in peripheral blood cytokines and stool microbiota in the setting of IBD.1 In this study, the authors profiled preconception and pregnancy-associated cytokine levels and demonstrated a significant decrease in proinflammatory cytokines (interleukin (IL)-6, IL-8, IL-12, IL-17 and tumour necrosis factor-α) during pregnancy in women with IBD.

We had undertaken a similar cytokine analysis of pregnant women with IBD at the University of Calgary but sought to relate preconception and second-trimester cytokine levels with adverse maternal–fetal outcomes, including preterm birth, emergency caesarean delivery and neonatal intensive care unit (NICU) admission. Sera from 28 women with IBD, including 19 with Crohn’s disease (CD) and 9 with UC who completed a pregnancy between 2013 and 2015, were analysed. Eighteen of these patients were on biological therapy preconception (infliximab n (CD)=7, n (UC)=4; adalimumab n (CD)=7). Disease activity was prospectively evaluated using validated disease activity indices, physician global assessment and C-reactive protein. Faecal calprotectin results were not available. Only one patient (with CD) had active disease at the time of preconception blood sampling, while three women (1 with …
SCIDOT-16. T2-WEIGHTED IMAGING MAY BE INDICATIVE OF DRUG DISTRIBUTION IN GLIOBLASTOMA PATIENTS
Authors: Pamela Jackson, Minjee Kim, Andrea Hawkins-Daarud, Kyle Singleton, Afroz Mohammad, Terence Burns, Ian Parney, Leland Hu, Timothy Kaufmann, William Elmquist, Jann Sarkaria, Kristin Swanson
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVES Dogma suggests that for brain tumors, regions of enhancement on T1-weighted gadolinium contrast enhanced (T1Gd) magnetic resonance imaging (MRI) correlate with intravenously delivered drug distribution as enhancement indicates a compromised blood-brain barrier (BBB). However, poor response to intravenous therapies highlights the importance of the diffuse disease beyond enhancing regions. This study investigated whether imaging features can provide an accurate prediction of drug distribution. METHODS Eight brain tumor patients (7 gliomas and 1 metastatic adenocarcinoma) were included in this Phase 0 trial. Presurgery T1-weighted, T1Gd, T2-weighted gadolinium contrast enhanced (T2Gd), and T2-weighted Fluid Attenuated Inversion Recovery (T2FLAIR) MRIs were acquired. All images underwent bias correction using the N4 algorithm, standardization of intensities, and registration. Prior to incision, patients received both an antibiotic cefazolin (6% BBB penetrance) and levetiracetam (80% BBB penetrance), an anti-seizure drug. Subsequently, multiple blood samples and image-guided biopsies were taken and analyzed for drug concentration using liquid chromatography mass spectrometry. Biopsy drug levels are reported as Brain-Plasma Ratio (BPR), the ratio of biopsy concentration relative to plasma concentration. Mean image intensity was extracted from an 8x8 mm window surrounding each biopsy location. Regression analysis was performed to determine which combination of image types were linearly predictive of BPR for both drugs. Correlations were also analyzed according to the biopsy location radiographic appearance. RESULTS Regression analysis revealed that T2Gd intensity was linearly predictive of cefazolin BPR and FLAIR intensity was linearly predictive of levetiracetam BPR (p=0.009 and 0.041, respectively). Grouping samples according the the radiographic appearance revealed that levetiracetam BPR had a similar pattern of values to that of FLAIR intensities and cefazolin BPR had a similar pattern to T2, further supporting the regression analysis results. CONCLUSIONS Local concentrations of drug may be related to T2-weighted signals (T2Gd and T2FLAIR) rather than the gadolinium distribution on T1Gd images.
From the authors
Authors: A. Vazir
Journal: European Respiratory Journal (2006)

Symptom burden of sleep-disordered breathing in systolic heart failure patientsTo the Editors:We read with interest the paper by HASTINGS et al.[1] who studied the symptom burden resulting from sleep-disordered breathing in patients with congestive heart failure, which was mainly due to left ventricular systolic dysfunction.The possible presence of diastolic abnormalities was not reported to have been evaluated.
TMOD-34. A RADIOMIC SIGNATURE OF INFILTRATION IN PERITUMORAL EDEMA PREDICTS SUBSEQUENT RECURRENCE IN GLIOBLASTOMA
Authors: Saima Rathore, Gaurav Shukla, Hamed Akbari, Chiharu Sako, Michel Bilello, Suyash Mohan, Chaitra Badve, Jill Barnholtz-Sloan, Andrew Sloan, Robert Lustig, Christos Davatzikos
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The malignant parenchyma in glioblastoma extends beyond the enhancing borders of tumor on postcontrast T1-weighted magnetic resonance imaging (MRI), which is the primary target of treatment. Such non-enhancing tumor invasion into the peri-tumoral edema (PED) is, however, not usually distinguishable on conventional MRI. The aim of this study was to evaluate pre-operative MRI in the PED to assess whether areas of tumor infiltration and early recurrence can be detected. METHODS A cohort of 90 de novo glioblastoma patients from a single institution (Penn) was selected. All included patients had preoperative multi-parametric MRI (mpMRI;T1,T1Gd,T2,T2-FLAIR,ADC), underwent initial gross-total-resection followed by standard chemoradiation, and had pathologically-confirmed recurrence. An extensive panel of handcrafted features, including shape, volume, intensity distributions, texture, was extracted from mpMRI scans. Predictive modeling for estimation of PED infiltration was performed using sequential feature selection approach designed with a support vector machine classifier and through a Leave-one-out cross-validation approach in the Penn cohort. Generalizability of the model was evaluated by applying it on a cohort of 20 patients from a second institution (Case), and predicted probability distributions in PED were compared in both the cohorts. RESULTS Spatial probability maps, representing the likelihood of tumor infiltration and eventual recurrence, were binarized at 50% cutoff, and compared with actual recurrence on post-recurrence scans. The cross-validated accuracy of our model within Penn cohort was 81.35% (odds-ratio=3.62, sensitivity/specificity=78.26/81.35). The model trained on the Penn cohort, when applied on the Case cohort, produced almost similar intensity distribution in the PED, suggesting that the method has potential for robust performance across institutions. The comparison of intensity distributions revealed higher ADC and T2-FLAIR in non-recurrent regions compared to recurrent ones. CONCLUSION Multi-parametric pattern analysis of mpMRI across multiple institutions generates similar, accurate estimates of spatial extent and patterns of recurrence in PED, which may guide strategies for treatment intensification in glioblastoma.
Author Correction: c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies
Authors: Jochem H. Bernink, Yoichiro Ohne, Marcel B. M. Teunissen, Jingya Wang, Jincheng Wu, Lisette Krabbendam, Christine Guntermann, Richard Volckmann, Jan Koster, Sophie van Tol, Ivan Ramirez, Yashaswi Shrestha, Menno A. de Rie, Hergen Spits, Xavier Romero Ros, Alison A. Humbles
Journal: Nature Immunology (2019)
Multidimensional Single Cell Analysis Shows Increased T/NK Cell Subsets in Both Blood and Bone Marrow of Iberdomide (CC-220) Treated Relapsed/Refractory Multiple Myeloma Patients
Authors: Michael Amatangelo, Oliver Van Oekelen, Adeeb H Rahman, Alessandro Lagana, Sarah Gooding, Hervé Avet-Loiseau, Udo Oppermann, William E Pierceall, Anjan Thakurta, Samir Parekh
Journal: Blood (2019)
Phase III Randomized Trial of Bisphosphonates as Adjuvant Therapy in Breast Cancer: S0307
Authors: Julie R Gralow, William E Barlow, Alexander H G Paterson, Jieling L M'iao, Danika L Lew, Alison T Stopeck, Daniel F Hayes, Dawn L Hershman, Mark M Schubert, Mark Clemons, Catherine H Van Poznak, Elizabeth C Dees, James N Ingle, Carla I Falkson, Anthony D Elias, Michael J Messino, Jeffrey H Margolis, Shaker R Dakhil, Helen K Chew, Kim Z Dammann, Jeffrey S Abrams, Robert B Livingston, Gabriel N Hortobagyi
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Adjuvant bisphosphonates, when given in a low-estrogen environment, can decrease breast cancer recurrence and death. Treatment guidelines include recommendations for adjuvant bisphosphonates in postmenopausal patients. SWOG/Alliance/Canadian Cancer Trials Group/ECOG-ACRIN/NRG Oncology study S0307 compared the efficacy of three bisphosphonates in early-stage breast cancer. Methods Patients with stage I–III breast cancer were randomly assigned to 3 years of intravenous zoledronic acid, oral clodronate, or oral ibandronate. The primary endpoint was disease-free survival (DFS) with overall survival as a secondary outcome. All statistical tests were two-sided. Results A total of 6097 patients enrolled. Median age was 52.7 years. Prior to being randomly assigned, 73.2% patients indicated preference for oral vs intravenous formulation. DFS did not differ across arms in a log-rank test (P = .49); 5-year DFS was 88.3% (zoledronic acid: 95% confidence interval [CI] = 86.9% to 89.6%), 87.6% (clodronate: 95% CI = 86.1% to 88.9%), and 87.4% (ibandronate: 95% CI = 85.6% to 88.9%). Additionally, 5-year overall survival did not differ between arms (log rank P = .50) and was 92.6% (zoledronic acid: 95% CI = 91.4% to 93.6%), 92.4% (clodronate: 95% CI = 91.2% to 93.5%), and 92.9% (ibandronate: 95% CI = 91.5% to 94.1%). Bone as first site of recurrence did not differ between arms (P = .93). Analyses based on age and tumor subtypes showed no treatment differences. Grade 3/4 toxicity was 8.8% (zoledronic acid), 8.3% (clodronate), and 10.5% (ibandronate). Osteonecrosis of the jaw was highest for zoledronic acid (1.26%) compared with clodronate (0.36%) and ibandronate (0.77%). Conclusions We found no evidence of differences in efficacy by type of bisphosphonate, either in overall analysis or subgroups. Despite an increased rate of osteonecrosis of the jaw with zoledronic acid, overall toxicity grade differed little across arms. Given that patients expressed preference for oral formulation, efforts to make oral agents available in the United States should be considered.
Responsiveness to Change and Establishment of the Minimal Clinically Important Difference for the Cutaneous Sarcoidosis Activity and Morphology Instrument
Authors: Megan H. Noe, Joel M. Gelfand, Joshua S. Bryer, Sarah N. Price, Marc A. Judson, Misha Rosenbach
Journal: JAMA Dermatology (2019)

Activity and Morphology InstrumentThe Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) is a reliable and valid instrument to objectively measure disease activity in cutaneous sarcoidosis. 1 To our knowledge, its responsiveness to changes in disease activity over time has not been established.The objective of this study was to measure the responsiveness of the CSAMI to changes in disease activity over time and establish a minimal clinically important difference (MCID).Methods | Patients 18 years and older were recruited from the cutaneous sarcoidosis clinic at the University of Pennsylvania between March 1, 2014, and December 31, 2016.Their demographic characteristics can be found in the eTable in the Supplement.This study was reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline.A diagnosis of cutaneous sarcoidosis was based on clinical presentation and skin biopsy results consistent with the diagnosis.Treatments and follow-up visits were recommended as appropriate for routine clinical care.Written informed consent was obtained from all participants prior to participation, and this study was approved by the institutional review board at the University of Pennsylvania.Standard physician-and patient-reported instruments were used to measure disease activity and health-related quality of life at each appointment.Physician-reported CSAMI was used to measure cutaneous sarcoidosis activity. 1 Patients completed a visual analog scale as a self-assessment of disease, the Dermatology Life Quality Index 2 to measure health-related quality of life, and the Sarcoidosis Assessment Tool-skin concerns module. 3Additionally, at follow-up appointments the physician change rating (PCR) was documented as improved, no change, or worsened (Table 1).Descriptive statistics were used to characterize the demographic information, disease severity, and health-related quality of life at baseline.The median change in CSAMI score between baseline and follow-up was calculated for each PCR group (improved, no change, or worsened) and in those who met the MCID for the other standard instruments.An anchorbased approach was used to establish the MCID for the CSAMI, using PCR as the criterion standard for determining correct classification. 6A receiver operating characteristic curve analysis was performed to determine the sensitivity, specificity, and percentage of patients correctly classified as showing improvements in the CSAMI score.The final determination of MCID
GENE-30. PRELIMINARY STUDY ON WHOLE-EXOME SEQUENCING TECHNOLOGY IN THE GENETIC ANALYSIS OF PEDIATRIC PATIENTS WITH GLIOMAS
Authors: Mingyao Lai, Juan Li, Junjie Zhen, jiangfen zhou, Qingjun Hu, Minting ye, Shaoqun Li, Lichao Wang, Cheng Zhou, Zhaoming Zhou, Linbo Cai
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVE To analyze the genes related to the signaling pathways in pediatric gliomas and drug-related genes with whole-exome sequencing technology. METHODS The tumor tissues and matched blood samples of 17 enrolled patients were detected with whole-exome sequencing technology. There were 3 cases of diffuse midline gliomas, 2 cases of childhood glioblastomas, 3 cases of disffuse astrocytoma, 1 case of pleomorphic xanthoastrocytoma, 1 case of ganglioglioma, 6 cases of anaplastic ependymoma and 1 case of ependymoma in this study. All the enrolled patients who were no more than 14 years old received surgery in the Department of Neurosurgery, Guangdong Sanjiu Brain Hospital. The diagnosis was confirmed by pathological examination and the sample acquisition was approved by hospital ethics committee. RESULTS With the use of whole-exome sequencing technology, a total of 31 related genetic mutations were detected in 15 cases, while no genetic mutation was detected in the other 2 cases. The genes related to the signaling pathways in pediatric gliomas included ATRX, ASL1, BCOR, EP300, FGFR1, H3F3A, IGF1R, MED12, PIK3R1, PRKDC, RB1, SETD2, SMARCA4, SOX2, TGFBR2, and the drug-related genes included AKT1, BCL2, BRAF, BRCA2, CCND1, CCND2, CDK6, EGFR, FGF3, KRAS, MET, PDGFRA, PIK3CA, PTEN, TP53, TSC1. One patient only had genes related to the signaling pathways, and 14 patients had drug-related genes. CONCLUSION Applying whole-exome sequencing technology in the genetic analysis of pediatric patients with gliomas has remarkable guiding significance for revealing the mechanism of disease, searching for therapeutic targets and adopting individualized treatment, which can bring potential benefits to pediatric patients. However, more samples and further data analysis and verification are needed in future study.
Comparative Effectiveness of Rasburicase Versus Allopurinol for Cancer Patients with Renal Dysfunction and Hyperuricemia
Authors: Kylee L Martens, Parisa R Khalighi, Shan Li, Andrew A White, Emily Silgard, Deborah Frieze, Elihu H. Estey, David A. Garcia, Sangeeta R Hingorani, Ang Li
Journal: Blood (2019)
ATIM-20. A RETROSPECTIVE STUDY EVALUATING THE SAFETY AND SURVIVAL OF THE COMBINATION OF PD-1 IMMUNE CHECKPOINT BLOCKADE AND BEVACIZUMAB IN RECURRENT GLIOBLASTOMA
Authors: Joshua Friedman, Adilia Hormigo
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Immune checkpoint inhibitors (ICI) have demonstrated clinical efficacy in a variety of cancers. It is known that cancer including glioblastoma (GBM) induces an immunosuppression. Bevacizumab by normalizing blood vessels in the tumor can facilitate immune surveillance and potentially improve the efficacy of ICI in GBM patients. We analyze GBM patients with recurrent disease treated with ICI and bevacizumab. METHODS We retrospectively review records of patients diagnosed with recurrent GBM treated at our institution with Pembrolizumab or Nivolumab and bevacizumab and evaluate for tolerance and outcomes. RESULTS Twenty-one patients, 12 men and 9 women with median age 62 (range 36–78) and KPS 70 (range 60–90) were treated with a median of 10 ICI cycles (range 4–29) and 5 of bevacizumab (range 0–21). A total of 8 patients (38%) had immune-related adverse events (IRAE): 3 grade 1, 3 grade 2 and 2 grade 3. A patient with pneumonitis required cessation of ICI. Median OS for the 21 patients was 22 months (range 6–41). The 7 patients that had MGMT detected in their tumors had a median OS of 27 months (range 23–41) compared to a survival of 21 months (range 6–24) for the 13 patients that had MGMT undetected. One had undetermined MGMT and her OS was 21 months. The median survival for all the patients from onset of ICI was 10 months (range 1–25) and 10 of them (47.6%) survived &gt; 12 months. DISCUSSION The development of IRAE was common but self-limiting, allowing continuation of the treatment in all but one patient. The combination of ICI and bevacizumab increased survival. Our data needs to be interpreted with caution, as it is a retrospective analysis of a small group of patients. However, these results warrant prospective studies using the combination of ICI and bevacizumab to treat recurrent GBM.
Use of Machine Learning in 2074 Cases of Acute Myeloid Leukemia for Genetic Risk Profiling
Authors: Shaun Fleming, Cheng-Hong Tsai, Hartmut Döhner, Konstanze Döhner, Elli Papaemmanuil, Hwei-Fang Tien, John Reynolds, Andrew H. Wei, Hsin-An Hou
Journal: Blood (2019)
Single-Cell RNA Sequencing Reveals Stromal Evolution into LRRC15+ Myofibroblasts as a Determinant of Patient Response to Cancer Immunotherapy
Authors: Claudia X. Dominguez, Sören Müller, Shilpa Keerthivasan, Hartmut Koeppen, Jeffrey Hung, Sarah Gierke, Beatrice Breart, Oded Foreman, Travis W. Bainbridge, Alessandra Castiglioni, Yasin Senbabaoglu, Zora Modrusan, Yuxin Liang, Melissa R. Junttila, Christiaan Klijn, Richard Bourgon, Shannon J. Turley
Journal: Cancer Discovery (2019)

Abstract With only a fraction of patients responding to cancer immunotherapy, a better understanding of the entire tumor microenvironment is needed. Using single-cell transcriptomics, we chart the fibroblastic landscape during pancreatic ductal adenocarcinoma (PDAC) progression in animal models. We identify a population of carcinoma-associated fibroblasts (CAF) that are programmed by TGFβ and express the leucine-rich repeat containing 15 (LRRC15) protein. These LRRC15+ CAFs surround tumor islets and are absent from normal pancreatic tissue. The presence of LRRC15+ CAFs in human patients was confirmed in &amp;gt;80,000 single cells from 22 patients with PDAC as well as by using IHC on samples from 70 patients. Furthermore, immunotherapy clinical trials comprising more than 600 patients across six cancer types revealed elevated levels of the LRRC15+ CAF signature correlated with poor response to anti–PD-L1 therapy. This work has important implications for targeting nonimmune elements of the tumor microenvironment to boost responses of patients with cancer to immune checkpoint blockade therapy. Significance: This study describes the single-cell landscape of CAFs in pancreatic cancer during in vivo tumor evolution. A TGFβ-driven, LRRC15+ CAF lineage is associated with poor outcome in immunotherapy trial data comprising multiple solid-tumor entities and represents a target for combinatorial therapy. This article is highlighted in the In This Issue feature, p. 161
How to Collect the Minimum-Targeted CD3+ Cells for CAR-T Therapy- the Bern Approach
Authors: Katarzyna Aleksandra Jalowiec, Thomas Pabst, Christoph Bocksrucker, Claudio Brunold, Barbara Jeker, Gabriela M Baerlocher, Urban Novak, Ulrike Bacher, Michael Daskalakis, Behrouz Mansouri, Sacha S Zeerleder
Journal: Blood (2019)
High-Throughput RNA Sequencing Analysis Reveals Distinct Molecular Signature in NRAS and PTPN11 JMML Patients
Authors: Pier Paolo Leoncini, Alessandro Domenico Silvestris, Patrizia Vitullo, Marco Zecca, Christian Flotho, Charlotte M. Niemeyer, Angela Gallo, Alice Bertaina, Franco Locatelli, Pietro Merli
Journal: Blood (2019)