tbuckley/cabot-search huggingface dataset:
PD-1/PD-L1 inhibitor plus chemotherapy versus bevacizumab plus chemotherapy in first-line treatment for non-squamous non-small-cell lung cancer
Authors: Hui Yu, Ping Chen, Liangping Xia, Sha Fu, Chen Chen, Xuanye Zhang, Lina He, Bei Zhang, Yixin Zhou, Shaodong Hong
Journal: Journal for ImmunoTherapy of Cancer (2021)

Anti-PD-1)/programmed cell death-ligand 1 (PD-L1) antibody plus platinum-based chemotherapy (PBC) has replaced PBC as first-line treatment for patients with non-squamous (sq) non-small cell lung cancer (NSCLC) lacking targetable driver mutations. However, few studies have directly compared immune checkpoint inhibitor (ICI) plus chemotherapy with bevacizumab plus chemotherapy (beva +chemo) in this setting. Herein, we conducted an indirect comparison for anti-PD-1/PD-L1 antibody plus chemotherapy (ICI +chemo) versus beva +chemo in non-sq NSCLC using the frequentist methods. The main outcomes analyzed include progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Data were subtracted from randomized trials comparing ICI +chemo or beva +chemo against PBC. Fourteen trials involving 6165 patients were included. Direct meta-analyses showed that both ICI +chemo (PFS: HR 0.58, OS: HR 0.73, ORR: relative risk (RR) 1.66) and beva +chemo (PFS: HR 0.74, OS: HR 0.89, ORR: RR 1.62) improved clinical outcomes compared with PBC. Indirect comparison showed that ICI +chemo reduced the risk of disease progression (HR 0.78, 95% CI 0.60 to 1.00) and death (HR 0.82, 95% CI 0.71 to 0.94) compared with beva +chemo. The PFS benefits with ICI +chemo over beva +chemo were non-significant in those with negative PD-L1 expression and non-smokers. In conclusion, ICI +chemo is superior to beva +chemo in first-line treatment for non-sq NSCLC.
Clonal Compositions Involving Epigenetic Regulator Gene Mutations in Clonal Hematopoiesis, Clonal Cytopenias of Undetermined Significance and Chronic Myelomonocytic Leukemia
Authors: Zhuoer Xie, Gina Campestri, Terra Lasho, Christy Finke, Marissa Li, Moritz Binder, Keith Robertson, Jenna Fernandez, Meredith C. Hyun, Rami S. Komrokji, Amer M. Zeidan, Jan Philipp Bewersdorf, Joshua F. Zeidner, Catherine C. Coombs, Yazan F. Madanat, Elizabeth A. Griffiths, Catherine Lai, Michael R. Savona, Mithun V. Shah, Mark R. Litzow, Ayalew Tefferi, Abhishek A. Mangaonkar, Naseema Gangat, Aref Al-Kali, Mrinal M. Patnaik
Journal: Blood (2021)
Predictive Assay for Chemotherapy-Induced Peripheral Neuropathy Associated with Vinca Alkaloids in Lymphoid Malignancies
Authors: Kathleen C Degen, Vibha Ahuja, Nolan L Metz, Arezoo Ghaneie, Aarti L Shevade, Erik L. Zeger, Tracey L Evans, Zonera A. Ali, U. Margaretha Wallon
Journal: Blood (2021)
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Authors: Kasper B. Hansen, Lonnie P. Wollmuth, Derek Bowie, Hiro Furukawa, Frank S. Menniti, Alexander I. Sobolevsky, Geoffrey T. Swanson, Sharon A. Swanger, Ingo H. Greger, Terunaga Nakagawa, Chris J. McBain, Vasanthi Jayaraman, Chian-Ming Low, Mark L. Dell’Acqua, Jeffrey S. Diamond, Chad R. Camp, Riley E. Perszyk, Hongjie Yuan, Stephen F. Traynelis
Journal: Pharmacological Reviews (2021)

Many physiologic effects of l-glutamate, the major excitatory neurotransmitter in the mammalian central nervous system, are mediated via signaling by ionotropic glutamate receptors (iGluRs). These ligand-gated ion channels are critical to brain function and are centrally implicated in numerous psychiatric and neurologic disorders. There are different classes of iGluRs with a variety of receptor subtypes in each class that play distinct roles in neuronal functions. The diversity in iGluR subtypes, with their unique functional properties and physiologic roles, has motivated a large number of studies. Our understanding of receptor subtypes has advanced considerably since the first iGluR subunit gene was cloned in 1989, and the research focus has expanded to encompass facets of biology that have been recently discovered and to exploit experimental paradigms made possible by technological advances. Here, we review insights from more than 3 decades of iGluR studies with an emphasis on the progress that has occurred in the past decade. We cover structure, function, pharmacology, roles in neurophysiology, and therapeutic implications for all classes of receptors assembled from the subunits encoded by the 18 ionotropic glutamate receptor genes. SIGNIFICANCE STATEMENT: Glutamate receptors play important roles in virtually all aspects of brain function and are either involved in mediating some clinical features of neurological disease or represent a therapeutic target for treatment. Therefore, understanding the structure, function, and pharmacology of this class of receptors will advance our understanding of many aspects of brain function at molecular, cellular, and system levels and provide new opportunities to treat patients.
Clinical Outcomes of Patients with Epstein-Barr Virus-Driven Post-Transplant Lymphoproliferative Disease Following Hematopoietic Stem Cell Transplantation Who Fail Rituximab: A Multinational, Retrospective Chart Review Study
Authors: Jaime Sanz, Jan Storek, Gérard Socié, Dhanalakshmi Thirumalai, Norma Guzman-Becerra, Pengcheng Xun, Deepali Kumar, Natalia Sadetsky, Daan Dierickx, John Reitan, Arie Barlev, Mohamad Mohty
Journal: Blood (2021)
Results of the 6-Year Follow-up of the Gimema AML1310 Trial: A Risk-Adapted, MRD-Directed Therapy for Young Adults with Newly Diagnosed Acute Myeloid Leukemia
Authors: Adriano Venditti, Alfonso Piciocchi, Raffaele Palmieri, Valentina Arena, Anna Candoni, Valeria Calafiore, Lorella MA Melillo, Roberto Cairoli, Paolo De Fabritiis, Gabriella Storti, Prassede Salutari, Francesco Lanza, Giovanni Martinelli, Mario Luppi, Saveria Capria, Luca Maurillo, Maria Ilaria Del Principe, Giovangiacinto Paterno, Elisa Buzzatti, Maria Teresa Voso, Tiziana Ottone, Maria irno Consalvo, Paola Fazi, Marco Vignetti, William Arcese, Sergio Amadori, Francesco Buccisano
Journal: Blood (2021)
Response Adaptive Salvage Treatment with Carfilzomib-Thalidomide-Dexamethasone for Newly Diagnosed Transplant Eligible Multiple Myeloma Patients Failing Front-Line Bortezomib-Based Induction Therapy - Final Analysis from the Australasian Leukemia and Lymphoma Group (ALLG) MM17 Trial
Authors: Rose Turner, Hang Quach, Noemi Horvath, Ian H Kerridge, Flora Yuen, Edwin Sze-Hung Lee, Edward S. Morris, Anna Kalff, Krystal Bergin, Shreerang Sridesai, Malgorzata Gorniak, Sridurga Mithraprabhu, Tiffany Khong, John Reynolds, Andrew Spencer
Journal: Blood (2021)
Correction: Analyses of oligodontia phenotypes and genetic etiologies
Authors: Mengqi Zhou, Hong Zhang, Heather Camhi, Figen Seymen, Mine Koruyucu, Yelda Kasimoglu, Jung-Wook Kim, Hera Kim-Berman, Ninna M. R. Yuson, Paul J. Benke, Yiqun Wu, Feng Wang, Yaqin Zhu, James P. Simmer, Jan C-C. Hu
Journal: International Journal of Oral Science (2021)
A Possible Sterilizing Cure of HIV-1 Infection Without Stem Cell Transplantation
Authors: Gabriela Turk, Kyra Seiger, Xiaodong Lian, Weiwei Sun, Elizabeth M. Parsons, Ce Gao, Yelizaveta Rassadkina, Maria Laura Polo, Alejandro Czernikier, Yanina Ghiglione, Alejandra Vellicce, Joseph Varriale, Jun Lai, Yuko Yuki, Maureen Martin, Ajantha Rhodes, Sharon R. Lewin, Bruce D. Walker, Mary Carrington, Robert Siliciano, Janet Siliciano, Mathias Lichterfeld, Natalia Laufer, Xu G. Yu
Journal: Annals of Internal Medicine (2021)

Background: A sterilizing cure of HIV-1 infection has been reported in 2 persons living with HIV-1 who underwent allogeneic hematopoietic stem cell transplantations from donors who were homozygous for the CCR5Δ32 gene polymorphism. However, this has been considered elusive during natural infection. Objective: To evaluate persistent HIV-1 reservoir cells in an elite controller with undetectable HIV-1 viremia for more than 8 years in the absence of antiretroviral therapy. Design: Detailed investigation of virologic and immunologic characteristics. Setting: Tertiary care centers in Buenos Aires, Argentina, and Boston, Massachusetts. Patient: A patient with HIV-1 infection and durable drug-free suppression of HIV-1 replication. Measurements: Analysis of genome-intact and replication-competent HIV-1 using near-full-length individual proviral sequencing and viral outgrowth assays, respectively; analysis of HIV-1 plasma RNA by ultrasensitive HIV-1 viral load testing. Results: No genome-intact HIV-1 proviruses were detected in analysis of a total of 1.188 billion peripheral blood mononuclear cells and 503 million mononuclear cells from placental tissues. Seven defective proviruses, some of them derived from clonally expanded cells, were detected. A viral outgrowth assay failed to retrieve replication-competent HIV-1 from 150 million resting CD4+ T cells. No HIV-1 RNA was detected in 4.5 mL of plasma. Limitations: Absence of evidence for intact HIV-1 proviruses in large numbers of cells is not evidence of absence of intact HIV-1 proviruses. A sterilizing cure of HIV-1 can never be empirically proved. Conclusion: Genome-intact and replication-competent HIV-1 were not detected in an elite controller despite analysis of massive numbers of cells from blood and tissues, suggesting that this patient may have naturally achieved a sterilizing cure of HIV-1 infection. These observations raise the possibility that a sterilizing cure may be an extremely rare but possible outcome of HIV-1 infection. Primary Funding Source: National Institutes of Health and Bill & Melinda Gates Foundation.
Safety and Efficacy of CD19 CAR-T Cells Co-Expressing IL-7 and CCL19 in Combination with Anti-PD-1 Antibody for Refractory/Relapsed DLBCL: Preliminary Data from the Phase Ⅰb Trial (NCT04381741)
Authors: Wenbin Qian, Aiqi Zhao, Hui Liu, Wen Lei, Yun Liang, Xianggui Yuan
Journal: Blood (2021)
Circulating Plasma Cells Are the Most Powerful Prognostic Marker in Transplant Ineligible Multiple Myeloma with 2% As a New Cut-Off for Primary Plasma Cell Leukemia
Authors: Tomas Jelinek, Renata Bezděková, David Zihala, Tereza Sevcikova, Lenka Capkova, Petra Polackova, Martin Stork, Zdenka Knechtova, Ondrej Venglar, Artur Jurczyszyn, Jorge J. Castillo, Miroslav Penka, Jakub Radocha, Sabina Sevcikova, Ludek Pour, Lucie Rihova, Roman Hajek
Journal: Blood (2021)
Prevention of Fetal/Neonatal Alloimmune Thrombocytopenia in a Preclinical Model By Monoclonal Anti-HPA-1a Antibody Prophylaxis: Structural and Functional Properties of Antibody Variant Isoforms
Authors: Trude Victoria Mørtberg, Huiying Zhi, Gestur Vidarsson, Stian Foss, Terje E Michaelsen, Bjørn Skogen, Tor Brynjar Stuge, Jan Terje Andersen, Peter J. Newman, Maria Therese Ahlen
Journal: Blood (2021)
Abstract 8925: Current Clinical AF Treatment Targets Do Not Reflect Patient Priorities
Authors: Brian Zenger, Yue Zhang, Morgan Millar, T. J Bunch, Jonathan P Piccini, Rachel Hess, Benjamin A Steinberg
Journal: Circulation (2021)

Background: AF clinical trials define success as freedom from any AF episode &gt;30 seconds. Clinically AF treatment is geared towards managing patient symptoms, yet little is known about patients’ expectations for successful AF treatment. Objective: Determine patient expectations for successful AF treatment. Methods: Patients with an AF diagnosis from a tertiary electrophysiology clinic were asked to complete the Toronto Atrial Fibrillation Severity Scale (AFSS) from the perspective of current symptoms, worst ever symptoms, and expected symptoms after successful treatment. Survey and patient clinical data were linked through the EMR. Results: Of the survey respondents (n=27), 41% were female, mean age was 69 (SD 9.7 years), and 30% had prior ablation. Overall, 59% of these patients considered AF treatment successful even with AF occurring one per year or more, and 70% would still consider treatment successful with episodes lasting minutes or more. When selecting the most important factor of success, 80% of patients selected decrease in AF frequency, 20% selected decrease in severity of symptoms, and 0 selected decrease in episode duration. A minority of patients (19%) considered treatment successful only if they never had AF again. Conclusion: A small minority of patients with AF would consider their treatment successful if they never experienced an AF episode again, which contradicts our current assessment of AF treatments. If confirmed in larger cohorts, these data support redesigning AF clinical studies to match outcomes prioritized by patients.
Re-examining remission definitions in rheumatoid arthritis: considering the 28-Joint Disease Activity Score, C-reactive protein level and patient global assessment
Authors: David Felson, Diane Lacaille, Michael P LaValley, Daniel Aletaha
Journal: Annals of the Rheumatic Diseases (2021)

### Editors’ note

The Editors of the 5 journals of the American College of Rheumatology and European Alliance of Associations for Rheumatology have been reminded by this editorial that ACR and EULAR have jointly agreed on various classification criteria, definitions, recommendations, or points to consider, which do not always find reflection in manuscripts submitted to the journals. Consequently, in the future, the Editors will enforce the use of the products obtained in the course of joint ACR/EULAR or EULAR/ACR activities in all respective papers. For rheumatoid arthritis this would mean use of the ACR/EULAR or EULAR/ACR classification criteria, remission definitions, recommendations on what to report in clinical trials, and others, as pertinent. The same applies to other diseases. There are valid and important reasons that these activities have been undertaken by ACR and EULAR, and therefore, the conclusions of the various task forces, which have been endorsed by ACR and EULAR, should be respected by investigators and study administrators. This does not mean other methods could not be used in a study, but at the least, the reports should address the methods agreed on by the two organisations. Maintaining uniformity across major publications regarding rheumatoid arthritis remission or other definitions not only allows for more appropriate comparison across analyses, but also enhances readers' ability to interpret results. Author instructions across the five journals will more strongly reflect this requirement.

Over the last 30 years, treatment for rheumatoid arthritis (RA) has improved dramatically. By the early 2000s, disease remission had become a realistic goal, although definitions of remission varied widely, making it difficult to compare treatment strategies and gauge how often remission occurred. In 2009, the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) created a joint committee whose charge was to recommend a definition of remission. Members …
Is Symptom Burden Associated with Health Care Utilization: A Longitudinal Population-Based Cohort Study of Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma
Authors: Hira S Mian, Rinku Sutradhar, Gregory R Pond, Branavan Sivapathasundaram, Anita D'Souza, Tanya M. Wildes, Hsien Seow
Journal: Blood (2021)
Better outcomes of COVID-19 in vaccinated compared to unvaccinated patients with systemic rheumatic diseases
Authors: Charalampos Papagoras, George E Fragoulis, Nikoleta Zioga, Theodora Simopoulou, Kleopatra Deftereou, Eleni Kalavri, Evangelia Zampeli, Nafsika Gerolymatou, Evangelia Kataxaki, Konstantinos Melissaropoulos, Stylianos Panopoulos, Kalliopi Fragiadaki, Gerasimos Evangelatos, Vasiliki-Kalliopi Bournia, Aikaterini Arida, Anastasios Karamanakos, Maria Pappa, Alexandros Panagiotopoulos, Christos Koutsianas, Georgia Mparouta, Theodoros Dimitroulas, Stamatis-Nick Liossis, Maria G Tektonidou, Evrydiki Kravvariti, Nikolaos Kougkas, Panagiotis Georgiou, Paraskevi Voulgari, Antonia Elezoglou, Dimitrios P Bogdanos, Dimitrios Vassilopoulos, Petros P Sfikakis
Journal: Annals of the Rheumatic Diseases (2021)

Τo report outcomes of breakthrough COVID-19 in comparison with COVID-19 in unvaccinated patients with systemic rheumatic diseases (SRDs).Patients with SRD with COVID-19 (vaccinated and unvaccinated) were included by their rheumatologists in a registry operated by the Greek Rheumatology Society in a voluntarily basis. Type, date and doses of SARS-CoV-2 vaccines were recorded, and demographics, type of SRD, concurrent treatment, comorbidities and COVID-19 outcomes (hospitalisation, need for oxygen supplementation and death) were compared between vaccinated and unvaccinated patients.Between 1 March 2020 and 31 August 2021, 195 patients with SRD with COVID-19 were included; 147 unvaccinated and 48 vaccinated with at least one dose of a SARS-CoV-2 vaccine (Pfizer n=38 or AstraZeneca n=10). Among vaccinated patients, 29 developed breakthrough COVID-19 >14 days after the second vaccine dose (fully vaccinated), while 19 between the first and <14 days after the second vaccine dose (partially vaccinated). Despite no differences in demographics, SRD type, treatment or comorbidities between unvaccinated and vaccinated patients, hospitalisation and mortality rates were higher in unvaccinated (29.3% and 4.1%, respectively) compared with partially vaccinated (21% and 0%) or fully vaccinated (10.3% and 0%) patients.Vaccinated patients with SRD with breakthrough COVID-19 have better outcomes compared with unvaccinated counterparts with similar disease/treatment characteristics.
Trial in Progress: A Multicenter, Open Label, Randomized, Phase III Study of Asciminib (80 mg Once Daily) Vs Investigator-Selected TKI in Newly Diagnosed Adult Patients with Chronic Myeloid Leukemia in Chronic Phase
Authors: Jorge E. Cortes, Andreas Hochhaus, Naoto Takahashi, Richard A. Larson, Ghayas C. Issa, Felice Bombaci, Nicholas Ramscar, Shruti Kapoor, Sophie Ifrah, Timothy P. Hughes
Journal: Blood (2021)
Abstract 9349: The Relationship Between Combat-related Traumatic Injury and Cardiometabolic Risk
Authors: Christopher J Boos, Susie Schofield, Paul Cullinan, Daniel Dyball, Fear T Nicola, Anthony M Bull, David Pernet, Bennett N Alexander
Journal: Circulation (2021)

Introduction: The relationship between combat-related traumatic injury (CRTI) and cardiovascular risk is uncertain. Available data are largely derived from small retrospective or cross sectional studies. Hypothesis: This study was designed to investigate, prospectively, the link between CRTI and both metabolic syndrome (MetS) and arterial stiffness Methods: From March 2016 to August 2020, 1144 male combat veterans (UK-Afghanistan War 2003-14) were recruited into the ADVANCE cohort; they comprised 579 men with CRTI and 565 uninjured participants frequency-matched for age, service, rank, regiment, deployment period and role-in-theatre. Investigations included quantification of injury severity (New Injury Severity Scale [NISS]), whole body composition (dual-energy X-ray absorptiometry), arterial stiffness (heart rate-adjusted central augmentation index [cAIx] and pulse wave velocity [PWV]), fasting venous blood glucose, lipids and high sensitivity C-reactive protein (hs-CRP). Insulin resistance was quantified using the estimated glucose disposal rate. The relationships of CRTI to MetS and cAIx were examined using modified Poisson and multiple linear regression analyses respectively. Results: The participants were aged 34·1±5·4 years, which was similar in the CRTI and uninjured groups; the mean time from injury or relevant deployment was 8·3±2·1 years. MetS prevalence (18·0% vs 11·8%; adjusted IRR 1·46; 1·10, 1·94) and cAIx (17·61±8·79 vs 15·23±8·19: p&lt;0·0001) were higher among the CRTI than uninjured group. Abdominal waist circumference, visceral fat area, triglycerides, insulin resistance and hs-CRP were higher and HDL-cholesterol lower with CRTI. There were no significant between-group differences in blood glucose, blood pressure or PWV. CRTI, its severity (↑NISS), lower age and socioeconomic status (SEC) were independently associated with both MetS and cAIx. Conclusions: CTRI is associated with an increased prevalence of MetS and arterial stiffness which are also influenced by age, injury severity and SEC. The longitudinal impact of CRTI on clinical cardiovascular events needs further examination
Abstract 10011: Oral Rivaroxaban versus Subcutaneous Enoxaparin in the Prophylaxis of Covid-19 Induced Coagulopathy in Mild to Moderate Sars Cov-2 Infection
Authors: Vaishnavi Km, Sheeba Chandralekha -, Janvi Lalchandani, Dhiraj Kumar
Journal: Circulation (2021)

Introduction: Preliminary data highlights the importance of anticoagulation therapy in the prevention and treatment of thromboembolism in SARS CoV-2 infection. There is insufficient data comparing the safety and efficacy of direct oral anticoagulants (DOACs) and subcutaneous enoxaparin in the prophylactic management of COVID-19 associated thromboembolic disease, particularly in mild to moderate cases of COVID-19 infection. Hypothesis: Oral rivaroxaban is superior to subcutaneous enoxaparin in the prophylaxis of COVID-19 induced coagulopathy in mild to moderate SARS CoV-2 infection. Methods: In this randomized, open-label, prospective, superiority trial involving hospitalized patients with confirmed mild or moderate COVID-19 disease, we began enrolment of 230 patients from 1 st August 2020 to receive either once-daily oral rivaroxaban (10mg or 15mg) or once-daily subcutaneous enoxaparin (40mg or 60mg) for duration of in-hospital stay (median: 8 days). Patients were randomised in a 1:1 ratio into groups by computer-generated allocation software. The primary outcome was a composite of all major, clinically relevant haemorrhagic and thrombotic events. An intention-to-treat analysis was carried out on the dataset. The trial was registered with Clinical Trials Registry of India (CTRI/2021/05/033871). Results: The primary efficacy outcome occurred in 4 of 115 patients in the rivaroxaban group (3.5%) versus 16 of 113 patients in the enoxaparin group (14.2%) (hazard ratio 0.207, 95% confidence interval [CI], 0.069 to 0.621, P=0.005). Adverse events developed in 4.3% of patients in the study group and 12.4% in the enoxaparin group (hazard ratio 0.328; 95% CI, 0.118 to 0.910; P=0.032). Major bleeding was seen in 1 patient (0.9%) in the rivaroxaban group and 3 patients (2.7%) in the enoxaparin group. Conclusions: Rivaroxaban alone was superior to enoxaparin for the prophylactic management of coagulopathy associated with mild to moderate SARS CoV-2 infection.
Redefining Hyperviscosity in Acute Leukemia: Implications for Red Cell Transfusions
Authors: Jamie Oakley, Evelyn Kendall Williams, Dan Y. Zhang, Christina Caruso, Yumiko Sakurai, Reginald Tran, Melissa L. Kemp, Glen Lew, Ross M. Fasano, Wilbur A. Lam
Journal: Blood (2021)