tbuckley/cabot-search huggingface dataset:
When steroids are not enough in immune-related hepatitis: current clinical challenges discussed on the basis of a case report
Authors: Dimitrios C Ziogas, Aikaterini Gkoufa, Evangelos Cholongitas, Panagiotis Diamantopoulos, Amalia Anastasopoulou, Paolo Antonio Ascierto, Helen Gogas
Journal: Journal for ImmunoTherapy of Cancer (2020)

Unleashing adaptive immunity via immune checkpoint inhibitors (ICPIs) in many cancer types led to durable antitumor responses and prolonged survivals and also added some new immune-related adverse events (irAEs) to the 'old-fashioned' safety profile of chemotherapy. Among bowel and endocrine irAEs, immune-mediated hepatotoxicity/hepatitis is a less common and far less well-studied toxicity, which, however, could develop into a serious complication, especially when it becomes persistent or refractory to steroids. Its incidence, onset and severity vary widely, depending on the type of underlying treated cancer, the class, the dosage and the duration of immunotherapy as well as the way of its administration (as a single agent or in combination with other ICPI or chemotherapy). In this study, we present a patient with metastatic melanoma who developed severe steroid-resistant ir-hepatitis after treatment with ipilimumab and required triple concurrent immunosuppression with prednisolone, mycofenolate mofetil and tacrolimus in order for his liver toxicity to be resolved. Intrigued by this case, we focused further on melanoma, as the disease-paradigm of immunotherapy in cancer, reviewed the reported incidence of hepatotoxicity among phase III ICPIs-containing trials on melanoma and discussed the main clinical considerations regarding the diagnosis and the management of persistent/steroid-refractory ir-hepatitis. As more clinical experience is gradually gained on this challenging topic, better answers are provided to questions about the appropriate diagnostic workup, the necessity of liver biopsy, the available immunosuppressive options beyond corticosteroids (their combinations and/or their sequence) as well as the correct decision on withdrawing or resuming immunotherapy. Nonetheless, a thorough multidisciplinary discussion is still required to individualize the overall approach in each case after failure of steroids.
T cell factor 1: A master regulator of the T cell response in disease
Authors: Giulia Escobar, Davide Mangani, Ana C. Anderson
Journal: Science Immunology (2020)

Recent advances have redefined a role for T cell factor 1 (TCF1) that goes beyond T cell development and T memory formation and encompasses new functions in the regulation of T cell biology. Here, we discuss the multifaceted and context-dependent role of TCF1 in peripheral T cells, particularly during disease-induced inflammatory states such as autoimmunity, cancer, and chronic infections. Understanding how TCF1 fine-tunes peripheral T cell biology holds the potential to tailor improved immune-targeted therapies.
COVID-19 Prognostic Score Utilizing Hematological and Inflammatory Markers to Determine Outcomes of Hospitalized Patients
Authors: Amardeep Kalsi, Sana Irfan Khan, Asad Rehman, Neil Nimkar, Angelica Singh, Nivetha Vishnuvardhan, Sonal Paul, Farah Ashraf, Anita Mazloom, Nisha Patel, Rich Kodama, Abeer Ashfaq, Chathula Kumarasinghe, Soeb Usta, Peter Gregos, Eshan Patel, Uqba Khan
Journal: Blood (2020)
KarMMa-3: A Phase 3 Study of Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Directed CAR T Cell Therapy Vs Standard Regimens in Relapsed and Refractory Multiple Myeloma
Authors: Michel Delforge, Rachid C. Baz, Michele Cavo, Natalie S. Callander, Armin Ghobadi, Paula Rodriguez-Otero, María-Victoria Mateos, Monica Massaro, Li Ding, Payal Patel, Gianfranco Pittari, Steven Novick, Sergio A. Giralt, Jesus G. Berdeja
Journal: Blood (2020)
Novel Method for Clonal Selection of Multiplexed Engineered CAR-T Cells Which Uniquely Demonstrate Anti-Tumor Functionality in the Tumor Microenvironment
Authors: Eigen Peralta, David Robbins, Emily Carron, Matthew Denholtz, Natalie Navarrete, Dan Lu, Joyee Yao, Sandeep Kothapally Hanok, Yinghui Sui, Angela Gentile, Eric Sung, Jason ORourke, Tom Lee, Daniel Shoemaker, Cokey Nguyen, Bahram Valamehr
Journal: Blood (2020)
Plasma Methylglyoxal Levels Are Associated With Amputations and Mortality in Severe Limb Ischemia Patients With and Without Diabetes
Authors: Nordin M.J. Hanssen, Martin Teraa, Jean L.J.M. Scheijen, Marjo Van de Waarenburg, Hendrik Gremmels, Coen D.A. Stehouwer, Marianne C. Verhaar, Casper G. Schalkwijk
Journal: Diabetes Care (2020)

OBJECTIVE Diabetes is a risk factor for severe limb ischemia (SLI), a condition associated with high mortality, morbidity, and limb loss. The reactive glucose-derived dicarbonyl methylglyoxal (MGO) is a major precursor for advanced glycation end products (AGEs) and a potential driver of cardiovascular disease. We investigated whether plasma MGO levels are associated with poor outcomes in SLI. RESEARCH DESIGN AND METHODS We measured plasma levels of MGO, free AGEs, and d-lactate, the detoxification end product of MGO, with ultraperformance liquid chromatography–tandem mass spectrometry at baseline in 160 patients (64.8 ± 13.3 years, 67.5% male, 37.5% with diabetes) with no-option SLI and recorded major adverse outcomes (n = 86, comprising n = 53 deaths and n = 49 amputations [first event counted]) over the 5-year follow-up. Data were analyzed with linear or Cox regression, after Ln-transformation of the independent variables, adjusted for sex, age, trial arm, diabetes, estimated glomerular filtration rate, systolic blood pressure, cholesterol levels, and BMI. Associations are reported per 1 SD plasma marker. RESULTS Higher plasma MGO levels were associated with more adverse outcomes (relative risk 1.44; 95% CI 1.11–1.86) and amputations separately (1.55; 1.13–2.21). We observed a similar but weaker trend for mortality (1.28; 0.93–1.77). The MGO-derived AGE Nε-(carboxyethyl)lysine was also associated with more adverse outcomes (1.46; 1.00–2.15) and amputations (1.71; 1.04–2.79). d-Lactate was not associated with adverse incident outcomes. Higher plasma MGO levels were also associated with more inflammation and white blood cells and fewer progenitor cells. CONCLUSIONS Plasma MGO levels are associated with adverse outcomes in SLI. Future studies should investigate whether MGO-targeting therapies improve outcomes in SLI.
Return-to-Play Guidelines for Athletes After COVID-19 Infection—Reply
Authors: Dermot Phelan, Jonathan H. Kim, Eugene H. Chung
Journal: JAMA Cardiology (2020)

Diana Santos-Ferreira, MD, MMed, IOC Dip Sp Phy; Rita Tomás, MD, MS, IOC Dip Sp Phy; Hélder Dores, PhD
Risk-Adapted Therapy with ABVD for Low- and Intermediate-Risk Patients and Oepa-Copdac for High Risk Patients Plus Involved-Field Radiation Therapy (IFRT) Based on Prognosis at Diagnosis and Early Response: Results from Pediatric Argentinian Collaborative Group Gatla Study for Children and Adolescents with Hodgkin Lymphoma
Authors: David Alejandro Veron, Patricia Streitenberger, Cecilia Riccheri, Monica Matus, Pedro Negri Aranguren, Maria Alejandra Costa, Nestor Alfredo Rossi, Elizabeth Hiramatsu, Maria Alejandra Cedola, María Constanza Drozdowski, Sandra Borchichi, Marcelo Coirini, María Cecilia Murray, Karina D'Aloi, Carlos Holmann, Matilde Gomel, Gisela Drago, Horacio Daniel Caferri, Maria Angelica Fernandez Barbieri, Mara Villamil, Claudia Mabel Ruiz, Sandra Ethel Zirone, Monica Makiya
Journal: Blood (2020)
Real-World Effectiveness and Safety of Blinatumomab in Adults with Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukaemia in Europe: 3-Year Results in Philadelphia Chromosome-Negative Patients and a Subset of Patients with Late First Relapse
Authors: Xavier Thomas, Anita W Rijneveld, Nicola Fracchiolla, Cyril Šálek, Alexandros Spyridonidis, Sabina Chiaretti, Naufil Alam, Isabella Pezzani Grueter, Abeera Mohammad, William Kormany, Georg Kreuzbauer, Alessandro Rambaldi
Journal: Blood (2020)
Venetoclax Effectiveness, Safety, and Treatment Patterns in Chronic Lymphocytic Leukemia Patients: Results from the CLL Collaborative Study of Real-World Evidence (CORE)
Authors: Dandan Zheng, Kavita Sail, Lindsey E Roeker, Beenish S Manzoor, Hande H. Tuncer, John N. Allan, Chaitra S. Ujjani, Paul M. Barr, Jennifer R. Brown, Toby A. Eyre, Alan Skarbnik, Rajat Bannerji, Barbara Eichhorst, Danielle M. Brander, Simon Sharmokh, Daniel Dingfeng Jiang, German Pena, Rajesh Kamalakar, Nnadozie Emechebe, Irina Pivneva, Rebecca Burne, Annie Guerin, Matthew S. Davids, Anthony Mato
Journal: Blood (2020)
Treatment Outcome and Prognostic Factors for Adult Langerhans Cell Histiocytosis
Authors: Xinxin Cao, Ming-hui Duan, Ai-lin Zhao, Hao Cai, Jia Chen, Xue-min Gao, Ting Liu, Hua-cong Cai, Lu Zhang, Jian Sun, Zhi-yong Liang, Dao-Bin Zhou, Jian Li
Journal: Blood (2020)
Molecular Imaging of Chimeric Antigen Receptor T Cells By ICOS-Immunopet
Authors: Federico Simonetta, Israt S. Alam, Juliane K. Lohmeyer, Bita Sahaf, Zinaida Good, Weiyu Chen, Zunyu Xiao, Toshihito Hirai, Lukas Scheller, Pujan Engels, Ophir Vermesh, Elise Robinson, Tom Haywood, Ataya Sathirachindra, Jeanette Baker, Meena B. Malipatlolla, Liora M. Schultz, Jay Y. Spiegel, Jason T. Lee, David B. Miklos, Crystal L. Mackall, Sanjiv S. Gambhir, Robert S. Negrin
Journal: Blood (2020)
Predictive Model of Response to Blinatumomab Therapy in Children and Adults with Relapsed/Refractory B-ALL
Authors: Inna Markova, Sergey N. Bondarenko, Olesia V Paina, Anna A. Osipova, Bella I Ayubova, Eugene A. Bakin, Anna G. Smirnova, Elena Babenko, Elena Vladimirovna Semenova, Ivan S. Moiseev, Axel R. Zander, Ludmila S Zubarovskaya
Journal: Blood (2020)
Overexpression of PD-L1 Correlates with <i>JAK2</i>-V617F Mutational Burden and Is Associated with Chromosome 9p Uniparental Disomy in MPN
Authors: Jelena D. Milosevic Feenstra, Fiorella Schischlik, Roland Jäger, Daniel Ivanov, Gregor Eisenwort, Alexandra Keller, Michael Schuster, Emir Hadzijusufovic, Maria-Theresa Krauth, Robert Spörk, Bettina Gisslinger, Elisabeth Koller, Michael Fillitz, Michael Pfeilstocker, Thamer Sliwa, Felix Keil, Christoph Bock, Heinz Gisslinger, Robert Kralovics, Peter Valent
Journal: Blood (2020)
Phase 3 Study of Pomalidomide with Cyclophosphamide and Dexamethasone Versus Pomalidomide and Dexamethasone in Asian Patients with Relapsed/Refractory Myeloma (RRMM) - Interim Analysis of a Trial By the Asian Myeloma Network (AMN)
Authors: Wee-Joo Chng, Xinhua Li, Cindy Lin, Jin Seok Kim, Hiroshi Handa, Brian G.M. Durie
Journal: Blood (2020)
Abstract PO-014: Harnessing the heterogeneity of circulating hybrid cells in pancreatic adenocarcinoma
Authors: Brett Scott Walker, Sidharth Sengupta, Michael Parappilly, Aysegul Ors, Jared Fischer, Thomas Sutton, Brett Sheppard, Skye Mayo, Melissa Wong
Journal: Cancer Research (2020)

Abstract Pancreatic adenocarcinoma (PDAC) remains one of the most lethal malignancies in the United States and tumor heterogeneity has major implications on the effectiveness of systemic therapies. Comprehensive tumor analysis at the single cell level offers an in-depth examination of neoplastic cells with metastatic potential and supports development of individualized treatment strategies to ultimately improve survival. Hybrid cells are a novel cell population derived from immune-cancer cell fusion within solid tumors and disseminate into peripheral blood, where they can be detected as circulating hybrid cells (CHCs) based on their dual expression of tumor and immune cell epitopes. Compared to conventionally-defined circulating tumor cells (CTCs), CHCs are found in patients at higher levels which allows for more robust phenotypic analyses of tumor cell features and collection for downstream multi-omic profiling. To investigate heterogeneity among disseminated CHCs in patients with PDAC, we assessed for tumor cell features using immunohistochemical analyses of single cells from peripheral blood mononuclear cell smears and by single cell RNA sequencing (scRNA-seq) from FACS-isolated cells. Downstream image analyses was performed Zeiss Zen blue software and scRNA-seq was analyzed using the Seurat analysis package. We determined that PDAC patients harbored heterogeneous populations of CHCs with differential protein expression that mirrored expression in corresponding primary tumors. Further, scRNA-seq analyses identified CHC populations with varying degrees of retained tumor identity, as well as subsets derived from different immune cell lineages. Unsupervised clustering of CHCs with tumor-dominate phenotypes demonstrated high differential expression of cancer related genes with known implications in PDAC tumors and treatment resistant pathways. Inference copy number variation analysis revealed chromosomal amplifications of 1q and 19q along with deletions of 6p, 12q, and 22q, characteristic of PDAC tumors. Additionally, a myriad of KRAS mutations were identified in patient CHCs but absent in normal leukocytes. As the product of tumor and immune cell fusion, CHCs provide a rich source for assessing PDAC heterogeneity through genetic and protein expression analyses. Ultimately, CHCs have great potential as a liquid biopsy in pancreatic cancer which could be harnessed to guide therapy. Citation Format: Brett Scott Walker, Sidharth Sengupta, Michael Parappilly, Aysegul Ors, Jared Fischer, Thomas Sutton, Brett Sheppard, Skye Mayo, Melissa Wong. Harnessing the heterogeneity of circulating hybrid cells in pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-014.
5-Azacytidine Depletes Hematopoietic Stem Cells and Synergizes with an Anti-CD117 Antibody to Augment Engraftment of Donor Stem Cells in Immunocompetent Mice
Authors: Andriyana K Bankova, Wendy W Pang, Brenda J Velasco, Janel R Long-Boyle, Judith A Shizuru
Journal: Blood (2020)
Regulatory eosinophils induce the resolution of experimental arthritis and appear in remission state of human rheumatoid arthritis
Authors: Darja Andreev, Mengdan Liu, Katerina Kachler, Mireia Llerins Perez, Philipp Kirchner, Julia Kölle, Andreas Gießl, Simon Rauber, Rui Song, Oliver Aust, Anika Grüneboom, Arnd Kleyer, Juan D Cañete, Arif Ekici, Andreas Ramming, Susetta Finotto, Georg Schett, Aline Bozec
Journal: Annals of the Rheumatic Diseases (2020)

Objectives Eosinophils possess pro-inflammatory functions in asthma. However, our recent studies have suggested that innate lymphoid cells type 2 (ILC2s) and eosinophils have proresolving properties in rheumatoid arthritis (RA). Nothing is known yet about the mechanisms determining the double-edged role of eosinophils. Therefore, we investigated whether asthma, a paradigm eosinophilic disease, can elicit resolution of chronic arthritis. Methods Ovalbumin-triggered eosinophilic asthma was combined with K/BxN serum-induced arthritis, where lung and synovial eosinophil subsets were compared by single-cell RNA sequencing (scRNA-seq). To investigate the involvement of the ILC2–interleukin-5 (IL-5) axis, hydrodynamic injection (HDI) of IL-25 and IL-33 plasmids, IL-5 reporter mice and anti-IL-5 antibody treatment were used. In patients with RA, the presence of distinct eosinophil subsets was examined in peripheral blood and synovial tissue. Disease activity of patients with RA with concomitant asthma was monitored before and after mepolizumab (anti-IL-5 antibody) therapy. Results The induction of eosinophilic asthma caused resolution of murine arthritis and joint tissue protection. ScRNA-seq revealed a specific subset of regulatory eosinophils (rEos) in the joints, distinct from inflammatory eosinophils in the lungs. Mechanistically, synovial rEos expanded on systemic upregulation of IL-5 released by lung ILC2s. Eosinophil depletion abolished the beneficial effect of asthma on arthritis. rEos were consistently present in the synovium of patients with RA in remission, but not in active stage. Remarkably, in patients with RA with concomitant asthma, mepolizumab treatment induced relapse of arthritis. Conclusion These findings point to a hitherto undiscovered proresolving signature in an eosinophil subset that stimulates arthritis resolution.
グリオーマ治療と光感受性物質 ～5-アミノレブリン酸を中心に～
Authors: 淳考 山本, 雄大 北川, 亮 宮岡, 恒平 鈴木, 健 齋藤, 良昭 中野
Journal: Neuro-Oncology (2019)
Acquired Mutations in BAX Confer Resistance to BH3 Mimetics in Acute Myeloid Leukemia
Authors: Donia M Moujalled, Fiona C Brown, Giovanna Pomilio, Natasha S Anstee, Veronique Litalien, Ella R Thompson, Thomas Morley, Sarah MacRaild, Chong C Chua, SéBastien Banquet, Maia Chanrion, Ana-Leticia Maragno, Marie Schoumacher, Marco J Herold, Guillaume Lessene, Olivier Geneste, David C.S. Huang, Andrew W Roberts, Piers Blombery, Andrew Wei
Journal: Blood (2020)
Correspondence on ‘Tapering towards DMARD-free remission in rheumatoid arthritis’
Authors: Iveth Eunice García, Carlos Abud-Mendoza
Journal: Annals of the Rheumatic Diseases (2020)

Correspondence on 'Tapering towards DMARDfree remission in rheumatoid arthritis'We believe that the article 'Tapering towards DMARD-free remission in established rheumatoid arthritis: 2-year results of the TARA trial' by Mulligen et al, 1 is of great interest since it addresses important information on the gradual reduction of treatment in patients with rheumatoid arthritis (RA), to achieve disease-modifying antirheumatic drug (DMARD)-free remission (DFR).However, we would like to highlight and complement the importance of some potentially relevant points, and broaden the horizon and the approach to a topic of such complexity: 1.Although the 'European League Against Rheumatism (EULAR) 2019 recommendations on the management of RA suggest a gradual decrease in glucocorticoids prior to the reduction of DMARD in patients with sustained complete remission, it also refers the possible therapeutic benefits of their concomitant use at very low doses (1-3 mg of prednisone (PDN)), if there are no unacceptable adverse events. 2 This is also suggested in a study by Buttgereit et al 3 that evaluated 350 randomised patients with RA assigned to 5 mg of PDN plus DMARD versus placebo plus DMARD; they detected greater responses in ACR20, ACR50 and improvement in pain, fatigue, stiffness and function with the use of low doses of glucocorticoids.Hence, this could be a therapeutic strategy fostering a decrease in the rate of exacerbations during DMARD withdrawal.2.
THU0116 Autoantibodies to vasoactive peptides and angiotensin-converting enzyme in patients with rheumatoid arthritis
Authors: ML Stanislav, RM Balabanova, MA Myagkova, TV Abramenko, OA Kost, None Nikolskaya, EV Garats
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Low levels of autoantibodies (AAb) are in fact a normal feature of a healthy immune response. The distinction between pathological and natural AAb is not well understand. <h3>Objectives</h3> To study the levels AAb specifically reacting with angiotensin-converting enzyme (ACE) and endogenous vasoactive mediators in sera patients with rheumatoid arthritis (RA) and healthy control group. <h3>Methods</h3> We tested sera from 19 patients with RA, 12 pts had extra-articular manifestations, 7 pts had only joint damage. The patients were compared with 10 healthy donors. Solid- phase enzyme immunoassay was used to examine the levels of IgM AAb to ACE prepared from human kidney tissue and AAb to low-molecular peptides – bradykinin (BK), angiotensin II (AII) and vasopressin (VP). <h3>Results</h3> Analysis of IgM AAb to vasoactive peptides showed a significant increase account AAb to bradykinin (BK) in sera from RA patients compared to donors (p = 0,0074). The highest value of AAb to BK were observed in RA patients without extra- articular features. Level of AAb to BK correlated with CIC, joint score (p &lt; 0,05). Significant discrepancies between levels AAb to AII and VP in RA pts and donors have not been revealed. Level of AAb to AII correlated negative with ERS (r = -0,464, p &lt; 0,05). Amount AAb to ACE was increasing in RA patients, but the differences were not significant. <h3>Conclusion</h3> The biological effects of AAb to vasoactive peptides and ACE are unknown. The possible role of AAb to BK in the pathophysiology of joint inflammation requires careful consideration.
Lactate As Metabolic Link between Cancer Cells and Tumor Microenvironment in Myelofibrosis Patients
Authors: Cesarina Giallongo, Mariarita Spampinato, Enrico La Spina, Nunziatina Laura Parrinello, Lucia Longhitano, Rosario Caltabiano, Lucia Salvatorelli, Alessandra Romano, Alessandro Barbato, Michelino Di Rosa, Giacomo Lazzarino, Giovanni Li Volti, Francesco Di Raimondo, Daniele Tibullo, Giuseppe A. Palumbo
Journal: Blood (2020)
Pattern of Sickle Cell Disorders: A Study from a Tertiary Care Center in Eastern Part of India
Authors: Ankita Sen, Tuphan Kanti Dolai, Tuhin Suvra Gayen, Riya Roy, Aditi Sen, Sumit Mitra, Indrani Mandal, Shipla Roy, Subham Bhattacharya, Shuvra Neel Baul, Prakas Kumar Mandal, Rajib De, Shyamali Dutta
Journal: Blood (2020)
Clinicopathological Features of Hematological Malignancies Presenting As Breast Lesions on Mammography: The Mount Sinai Medical Center Experience
Authors: Gliceida Galarza Fortuna, Kathrin Dvir, Christopher Febres-Aldana, Ruben Delgado, Maria Gonzalez Ferrua, Robert Poppiti, Vathany Sriganeshan
Journal: Blood (2020)
Endothelial Microparticles Delivering Lncrna NEAT1 Are Involved in the Pathophysiology of aGVHD Following Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Ran Zhang, Weijie Cao, Li Li, Dingming Wan, Zhongxing Jiang, Kai Sun, Linghui Xia
Journal: Blood (2020)