tbuckley/cabot-search huggingface dataset:
Chimeric Antigen Receptor T Cell Targeting to CD19 and CD22 Combined with Anti-PD-1 Antibody Induce High Response in Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Authors: Ying Zhang, Jiaqi Li, Xiangping Zong, Jin Zhou, Sixun Jia, Hongzhi Geng, Xiaoyan Lou, Liqing Kang, Lei Yu, Depei Wu, Caixia Li
Journal: Blood (2021)
An Intergenic Noncoding Chromosome 18 Variant Suppresses Lethal Thrombosis in Mice By Normalizing Blood Coagulation and Reducing Platelet Reactivity
Authors: Marisa A Brake, Audrey C Cleuren, Dakota R Redshaw, Caitlin Schneider, Aaron Scholl, Adrianna Jurek, Martijn A van der Ent, Randy J Westrick
Journal: Blood (2021)
Eight-Day Point of Care CAR T-Cell Manufacturing on Clinimacs Prodigy from Healthy Donors As a Proof-of-Concept Study
Authors: Kim G. Hankey, Tim Luetkens, Stephanie Avila, John McLenithan, John Braxton, Karen Underwood, Clarissa Saba, Rena G. Lapidus, Forat Lufti, Philip Margiotta, Jean A. Yared, Nancy M. Hardy, Ulrike Abramowski-Mock, Joerg Mittelstaet, Ron Dudek, Xiaoxuan Fan, Djordje Atanackovic, Aaron P. Rapoport, Saurabh Dahiya
Journal: Blood (2021)
Unraveling the Cytoprotective Effects of Valproic Acid: A Transcriptomics Meta-Analysis of Transfusion Strategies for Hemorrhagic Shock and Traumatic Brain Injury
Authors: Simone E Dekker, Ted Bambakidis, Martin Sillesen, Baoling Liu, Yongqing Li, Hasan B Alam
Journal: Blood (2021)
Abstract 13753: Clinical Characteristics and Outcomes of Patients Presenting With Acute Myocardial Infarction and Cardiogenic Shock During Coronavirus Disease 2019: An Analysis From the National Cardiogenic Shock Initiative
Authors: Pratyaksh K Srivastava, Michael Ahlers, Mir B Basir, Michael Hacala, William W O'Neill, Ali Nsair
Journal: Circulation (2021)

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has created challenges in the delivery of acute cardiovascular care. Here, we evaluate the clinical characteristics and outcomes of patients presenting with acute myocardial infarction and cardiogenic shock (AMICS) during the COVID-19 pandemic. Hypothesis: COVID-19 time period will associate with longer door to intervention times, and increased all-cause mortality among patients presenting with AMICS. Methods: Using the National Cardiogenic Shock Initiative database, we identified 406 patients who presented with AMICS. This group was divided into those who presented prior to COVID-19 (N=346, 5/9/2016-2/29/20) and those who presented during the pandemic (N=60, 3/1/20-11/10/20). Clinical characteristics, treatment patterns, and outcomes were compared between the two groups. Results: The median age (25 th -75 th percentile) of the cohort was 64 (55-72) years, and 23.7% of the group was female. There were no significant differences in age, sex, and medical comorbidities between the two groups. Patients presenting during the pandemic were less likely to be of Black race, and more likely to be of Hispanic and White race than patients presenting prior to COVID-19. Median door to balloon (89.5 vs. 88 mins, p=0.38), door to support (88 vs. 78 mins, p=0.13), and onset of shock to support (73.5 vs. 62 mins, p=0.15) times were not significantly different when comparing those who presented prior to with those who presented during the pandemic. Rates of transfer from another hospital, and cardiac arrest prior to arrival in the cardiac catheterization lab were similar between the two groups. ST-Elevation Myocardial Infarction presentations were increased during the COVID-19 period (95% vs 80%, p=0.01). In adjusted logistic regression models, time period (during vs pre-COVID-19) did not significantly associate with survival to discharge (OR 1.17, 95% CI 0.59-2.35, p=0.65) or with one month survival (OR 0.82, 95% CI 0.42-1.61, p=0.56). Conclusions: Care of patients presenting with AMICS has remained robust among hospitals participating in the National Cardiogenic Shock Initiative during the COVID-19 pandemic.
Abstract 11127: Clinical Heart Failure Events After Doxorubicin Treatment in High Grade Osteosarcoma Patients
Authors: Julius C Heemelaar, Elissa S Polomski, Ahmed A al Jaff, Richard E Evenhuis, Michiel A van de Sande, Hans J Gelderblom, Frank M Speetjens, Maria Louisa D Antoni
Journal: Circulation (2021)

Introduction: Osteosarcoma patients are at high risk of developing an anthracycline-induced cardiomyopathy (AC-CMP) due to their cancer treatment. The purpose of the study was to evaluate incidence of heart failure (HF) in this specific population and to identify predictors of HF. Methods: We conducted a retrospective cohort study at a tertiary sarcoma center (timeframe: 1982-2017) among 400 high grade osteosarcoma patients whom underwent surgery and received chemotherapy. Relevant data on demographics, cardiovascular risk profile, medications, osteosarcoma diagnosis and treatment was acquired from the electronic healthcare records and local oncology clinical registry. The primary endpoint was the composite of initiation of HF medication, hospitalization for HF and ICD implantation as primary prevention of sudden cardiac death in reduced left ventricular function. Results: The median age at sarcoma diagnosis in our cohort was 19 [p25-p75: 15-32] years with a median follow up time of 6 [2-14] years. At baseline, few patients used any medication or had cardiovascular risk factors: resp. 5 (1.3%) and 15 (3.8%). The endpoint occurred in 5.8% (23 patients). In 10 patients (2.5%) an admission for decompensated HF was the first presentation of AC-CMP, and ICD-implantation due to a reduced left ventricular ejection fraction occurred in 4 patients (1%). When sarcoma was diagnosed after 30 years of age, patients had near 5-fold increased risk of reaching the primary endpoint within 10 years after diagnosis (competing risk regression with competing risk of death due to malignancy: SHR 5.8 [2.0-16.9], p =0.001) and the time to a first HF event was shorter than younger patients: 3.4 [0.8-7.9] vs. 11.7 [5.2-16.0] years, p =0.027. Conclusions: The risk of developing HF in sarcoma patients is substantial, which warrants close monitoring during treatment and long term follow-up. Older age at diagnosis is associated with higher risk of developing HF and a shorter duration to events.
Interim Efficacy Analysis of a Phase II Study Demonstrates Promising Activity of the Combination of Pembrolizumab (PEM) and Entinostat (ENT) in Relapsed and Refractory (R/R) Hodgkin Lymphoma (HL)
Authors: David J. Sermer, Santosha Vardhana, Erin Biggar, Alison J. Moskowitz, Erel Joffe, Niloufer Khan, David J. Straus, Anita Kumar, Andrew D. Zelenetz, Steven M. Horwitz, Ariela Noy, Connie Lee Batlevi, Audrey Hamilton, Colette Owens, Matthew J. Matasar, M. Lia Palomba, Christina Y. Lee, Lorenzo Falchi, William T. Johnson, Heiko Schoder, Ahmet Dogan, Tira Bunyaviroch, Venkatraman Seshan, Gilles Salles, Anas Younes, Gottfried von Keudell
Journal: Blood (2021)
Predictive Factors and Outcomes after Allogeneic Stem-Cell Transplantation for Adults with Acute Lymphoblastic Leukemia in Brazil
Authors: Wellington F Silva, Dalila Cysne, Mariana Nassif Kerbauy, Iago Colturato, Ana Carolina Arrais Maia, Luciana Tucunduva, George Barros, Vergilio Rensi Colturato, Nelson Hamerschlak, Vanderson Rocha
Journal: Blood (2021)
Nanocatalyst‐Mediated Chemodynamic Tumor Therapy
Authors: Lu Zhang, Chu‐Xin Li, Shuang‐Shuang Wan, Xian‐Zheng Zhang
Journal: Advanced Healthcare Materials (2021)

Abstract Traditional tumor treatments, including chemotherapy, radiotherapy, photodynamic therapy, and photothermal therapy, are developed and used to treat different types of cancer. Recently, chemodynamic therapy (CDT) has been emerged as a novel cancer therapeutic strategy. CDT utilizes Fenton or Fenton‐like reaction to generate highly cytotoxic hydroxyl radicals (•OH) from endogenous hydrogen peroxide (H 2 O 2 ) to kill cancer cells, which displays promising therapeutic potentials for tumor treatment. However, the low catalytic efficiency and off‐target side effects of Fenton reaction limit the biomedical application of CDT. In this regard, various strategies are implemented to potentiate CDT against tumor, including retrofitting the tumor microenvironment (e.g., increasing H 2 O 2 level, decreasing reductive substances, and reducing pH), enhancing the catalytic efficiency of nanocatalysts, and other strategies. This review aims to summarize the development of CDT and summarize these recent progresses of nanocatalyst‐mediated CDT for antitumor application. The future development trend and challenges of CDT are also discussed.
Anomalous Right Coronary Originating from the Left main Coronary or the mid of Left Anterior Descending Coronary Artery
Authors: Xuju Qin, Lin Yang, Weiguo Xiong, Chunpeng Lu, Xuguang Qin
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Coronary artery anomalies (CAAs) are very rare a relatively uncommon, diverse group of congenital disorders of coronary arterial anatomy with a clinical presentations. Though most commonly detected incidentally finding during routine catheter, CT angiograms or at autopsy, these anomalies have generated considerable interest as they constitute the second most common cause of sudden cardiac death in young competitive athletes after hypertrophic cardiomyopathy1. Their prevalence ranges from 0.2% to 1.3% based published series 2-4. The most common coronary artery anomaly is origination of the left circumflex coronary (LCX) artery from the proximal of right coronary artery (RCA) or right sinus of Valsalva. The second is separate origination of the left anterior descending coronary artery (LAD) and LCX artery from the left sinus of Valsalva. Herein, we present five cases that the anomalous RCA arises from the left main coronary artery or the mid of left left anterior descending coronary artery (LAD). These cases are extremely rare. we bring forth them in an attempt to highlight their significance, and make cardiologist to understand what important the anomalies are, and how to diagnosis and treatment these bifurcation lesions of coronary anomalies.
Prodrug Polymeric Nanoconjugates Encapsulating Gold Nanoparticles for Enhanced X‐Ray Radiation Therapy in Breast Cancer
Authors: Hamed Nosrati, Farzad Seidi, Ali Hosseinmirzaei, Navid Mousazadeh, Ali Mohammadi, Mohammadreza Ghaffarlou, Hossein Danafar, João Conde, Ali Sharafi
Journal: Advanced Healthcare Materials (2021)

An optimal radiosensitizer with improved tumor retention has an important effect on tumor radiation therapy. Herein, gold nanoparticles (Au NPs) and drug-containing, mPEG-conjugated CUR (mPEG-CUR), self-assembled NPs (mPEG-CUR@Au) are developed and evaluated as a drug carrier and radiosensitizer in a breast cancer mice model. As a result, cancer therapy efficacy is improved significantly by applying all-in-one NPs to achieve synchronous chemoradiotherapy, as evidenced by studies evaluating cell viability, proliferation, and ROS production. In vivo anticancer experiments show that the mPEG-CUR@Au system improves the radiation sensitivity of 4T1 mammary carcinoma and completely abrogates breast cancer.
Novel Salvage Regimens Lead to Better Response and Survival in Relapsed Refractory Classic Hodgkin Lymphoma after Autologous Stem Cell Transplant
Authors: Sanjal H Desai, Michael A Spinner, Kevin A. David, Veronika Bachanova, Gaurav Goyal, Jacques Azzi, Kathleen Dorritie, Vaishalee P. Kenkre, Cheryl Chang, Sally Arai, Brendon Fusco, Nuttavut Sumransub, Haris Hactic, Uroosa Ibrahim, Elyse Harris, Matthew J. Maurer, KC Rappazzo, Victor M. Orellana-Noia, Catherine S. Diefenbach, Saba Raya, Grzegorz S. Nowakowski, Ranjana Advani, Ivana N. Micallef
Journal: Blood (2021)
Donor-Derived CAR T Cells Engineered with Sleeping Beauty in Pediatric and Adult Patients with Acute Lymphoblastic Leukemia Relapsed Post-HSCT
Authors: Chiara F Magnani, Giuseppe Gaipa, Federico Lussana, Giuseppe Gritti, Daniela Belotti, Sara Napolitano, Chiara Buracchi, Gian Maria Borleri, Benedetta Rambaldi, Silvia Zaninelli, Giuliana Rizzuto, Gianluca Cavallaro, Sarah Tettamanti, Giovanni Cazzaniga, Stefania Galimberti, Silvia Ferrari, Martino Introna, Adriana Balduzzi, Maria Grazia Valsecchi, Giuseppe Dastoli, Alessandro Rambaldi, Andrea Biondi
Journal: Blood (2021)
Updated Phase I/II Safety and Efficacy Results for Oral Bruton Tyrosine Kinase Inhibitor Rilzabrutinib in Patients with Relapsed/Refractory Immune Thrombocytopenia
Authors: David J. Kuter, Nikolay Tzvetkov, Merlin Efraim, Zane Kaplan, Jiří Mayer, Philip Choi, A.J. Gerard Jansen, Vickie McDonald, Ross Baker, Robert J. Bird, Mamta Garg, Jaromir Gumulec, Milan Kostal, Terry Gernsheimer, Waleed Ghanima, Olga Bandman, Puneet Arora, Regan Burns, Mengjie Yao, Ahmed Daak, Timothee Sourdille, Fareha Iqbal, Dolca Thomas, Ann Neale, Nichola Cooper
Journal: Blood (2021)
TP53 Mutations and RNA Binding Protein Musashi 2 Drive Resistance to PRMT5-Targeted Therapy in B-Cell Lymphoma
Authors: Ingrid Tatiana Erazo, Chiara M Evans, Daniel Zakheim, Karen L Chu, Olena Barbash, Alice Yunsi Refermat, Connie Lee Batlevi, Anas Younes, Michael G Kharas
Journal: Blood (2021)
CD200 Expression on Multiple Myeloma Cells Induces Attenuation of T Cell-Mediated Cytotoxicity Via DOK2
Authors: Pooja Shah, Thorsten Stuehmer, Daniela Bruennert, Umair Munawar, Ellen Leich, Sabrina Kraus, Michael Hudecek, Manik Chatterjee, Andreas Schlosser, Ralf C Bargou, Hermann Einsele, Friederike Berberich-Siebelt, Torsten Steinbrunn
Journal: Blood (2021)
CD45RA-Depleted Haploidentical Transplantation Combined with NK Cell Addback Results in Promising Long-Term Outcomes in Pediatric Patients with High-Risk Hematologic Malignancies
Authors: Swati Naik, Aimee C Talleur, Ying Li, Renee M. Madden, Ewelina Mamcarz, Amr Qudeimat, Akshay Sharma, Ashok Srinivasan, Ali Y Suliman, Rebecca Epperly, Esther A. Obeng, Mireya Paulina Velasquez, Diego Hijano, Gabriela Maron, Stephen Gottschalk, Brandon M Triplett
Journal: Blood (2021)
Abstract 9561: Loss of Full Length Pumilio 1 Abrogates Gene P27 Silencing-Mediated Cell Proliferation and Secures Mirna-221 Mimics Therapeutics in the Heart
Authors: Peipei Wang, Yue Zhou, Yu En Ng, A Mark Richards
Journal: Circulation (2021)

Introduction: MiR-221 mimics have been demonstrated to be cardioprotective and anti-fibrotic in the treatment of myocardium infarction and heart failure. However, miR-221 is a known oncomiR as the upregulation of miR-221 and the downregulation of its target p27 are associated with tumor progression and poor prognosis. Therefore the treatment of miR-221 mimics raise safety concerns. Hypothesis: miR-221 fails to trigger P27 mediated neoplastic cellular proliferation due to loss of full length pumilio-1 (FL PUM-1) expression in vivo . Methods: H9c2, Hela and primary cardiac fibroblasts were used to study the regulations of miR-221 mimics on P27 by RT-qPCR and Western blot, cell proliferation by cell number, CCk-8 and Ki67 staining. The interaction with PUM1 was assessed by siRNA transfection, p27 3’UTR cloning and luciferase reporter assay. In vivo 2 days after miR-221 mimic (1mg/kg and 4mg/kg) i.v. injection in the rats, the liver, heart, kidney and muscle were collected to measure p27 and PUM1 by RT-qPCR and WB. Pum1 cDNA was cloned using primers flanking its start and stop codons, and inserted into pcDNA3.1 vector. 10 colonies from each tissue were sequenced to verify mRNA splicing variants. PUM1 cleavage were verified by the incubations of cathepsin K (CatK) inhibitor odanacatib (ODN). Results: in vitro miR-221 mimics significantly downregulated the expression of P27 and increased cell proliferation. FL PUM1 (140kDa) and isoforms of 105 and 90 kDa were detected. The transfections of siRNAs to knockdown PUM1 but not PMU2 abolished miR-221-mediated effects and direct binding of miR-221 on p27 3’UTR. In vivo following two dosages miR-221 mimic treatments, the expressions of miR-221 increased in the heart, liver, kidney and muscle for 6.8 and 17.3 fold, 33.4 and 506.5 fold, 2.2 and 3.5 fold, and no significant increases respectively. P27 was not affected. FL-PUM1 was not detected in all tissues, but only isoforms. 105 kDa was generated through alternative RNA slicing and 90 kDa by CatK cleavage. Conclusions: This is the first study to address the safety concerns with respect to the possible pro-proliferative effects of miR-221 mimic therapeutics in cardiovascular applications. It provides essential insights of the context-dependent nature of miRNA functionality.
Meta-analysis of the clinical performance of commercial SARS-CoV-2 nucleic acid and antibody tests up to 22 August 2020
Authors: Ivo Van Walle, Katrin Leitmeyer, Eeva K Broberg
Journal: Eurosurveillance (2021)

Background Reliable testing for SARS-CoV-2 is key for the management of the COVID-19 pandemic. Aim We estimate diagnostic accuracy for nucleic acid and antibody tests 5 months into the COVID-19 pandemic, and compare with manufacturer-reported accuracy. Methods We reviewed the clinical performance of SARS-CoV-2 nucleic acid and antibody tests based on 93,757 test results from 151 published studies and 20,205 new test results from 12 countries in the European Union and European Economic Area (EU/EEA). Results Pooling the results and considering only results with 95% confidence interval width ≤ 5%, we found four nucleic acid tests, including one point-of-care test and three antibody tests, with a clinical sensitivity ≥ 95% for at least one target population (hospitalised, mild or asymptomatic, or unknown). Nine nucleic acid tests and 25 antibody tests, 12 of them point-of-care tests, had a clinical specificity of ≥ 98%. Three antibody tests achieved both thresholds. Evidence for nucleic acid point-of-care tests remains scarce at present, and sensitivity varied substantially. Study heterogeneity was low for eight of 14 sensitivity and 68 of 84 specificity results with confidence interval width ≤ 5%, and lower for nucleic acid tests than antibody tests. Manufacturer-reported clinical performance was significantly higher than independently assessed in 11 of 32 and four of 34 cases, respectively, for sensitivity and specificity, indicating a need for improvement in this area. Conclusion Continuous monitoring of clinical performance within more clearly defined target populations is needed.
Abstract 9303: Delay in Coronary Artery Bypass Grafting for ST Elevated Acute Myocardial Infarction Patients is Associated With Beneficial Outcomes: Further Evidence and Opportunities
Authors: Jessica W Guite, Jing Tang, Jyotsna Rao, Sailee Bhambere, Shaikh D Mahmood, Richard W Singerman, Christine Hsieh
Journal: Circulation (2021)

Introduction: Coronary artery bypass grafting (CABG) surgery for patients with acute ST Elevated Acute Myocardial Infarction (STEMI) in the first 24 hrs of admission is associated with greater hospital morbidity and mortality. Delaying CABG &gt;24 hrs may provide opportunities to improve patient outcomes. This study replicates and extends recent research and considers practice implications. Hypothesis: Patients with STEMI undergoing non-elective CABG surgery &lt;24 hrs after admission will have worse outcomes than patients receiving later non-elective or elective CABG surgery. Methods: Patients age &gt;= 30 yrs undergoing CABG &lt;7 days of admission from the National Inpatient Sample 2016-2017 were examined. Non-elective and elective CABG was compared with 4 subgroups examined: Non-elective admission, STEMI diagnosis, CABG &lt;24 hrs (Group A); CABG in 2-3 days (Group B); CABG in 4-7 days (Group C) and elective admission, CABG &lt;7 days (Group D). Outcomes included postoperative complications (bleeding, cardiac, renal, respiratory), in-hospital mortality, post-operative and total hospital length of stay (LOS), and total hospital cost. Results: Patients with STEMI (n=2793, age=65.9±9.7 yrs) non-electively hospitalized (group A=47.2%, B=25.7% and C=27.0%) and elective admissions without STEMI (n=28096, mean=63.8 ±10.8 yrs, group D) were analyzed. Complication rates did not consistently differ for groups A, B, and C, however group A rates were significantly higher than group D. Group A had the highest mortality (6.06%) — significantly greater than groups B (3.62%) and C (3.32%) — with all non-elective groups greater than the elective group D (1.01%). Group A had significantly longer postoperative and total LOS. Total median hospitalization cost was lowest for elective group D ($135,446) but not significantly different between groups A ($191,344) and B ($203,944). Conclusions: STEMI cases typically need urgent intervention and CABG surgery can be critical for management. Delaying non-elective CABG &gt;24 hours after admission is associated with better outcomes. Elective CABG has the best outcomes. More pre-surgical time provides opportunities to better prepare patients and caregivers with tailored coaching and content which can further improve outcomes.
Abstract 13727: Prediction of Pacemaker Implantation in Patients With Postoperative Heart Block: A Data Analytics Approach
Authors: Son Q Duong, Yuan Shi, Heather Giacone, Brittany Navarre, Dana Gal, Brian Han, Danielle Sganga, Michael Ma, Charitha Reddy, Andrew Shin, Anne M Dubin, David Scheinker, Claudia Algaze
Journal: Circulation (2021)

Introduction: Current guidelines recommend observation for AV node recovery until postoperative days (POD) 7 to 10 for patients with complete heart block (CHB) after congenital cardiac surgery prior to permanent pacemaker (PPM) placement. We created a predictive tool to identify patients at high risk of requiring PPM before POD 7 to aid in surgical decision making. Methods: Postoperative CHB cases from August 2009 to January 2019 were identified. We collected demographic, anatomic, and surgical details. Random forest, logistic regression, and decision tree models were trained and evaluated using 5-fold cross validation, then prospectively validated on data from January 2019 to April 2021. Separate models were developed for all patients on POD 0 and those without recovery on POD 4. Results: Of 101 cases of CHB (22 in validation cohort), 60 (59%) required PPM. Median days [IQR] to AVN recovery was 3 [1-7] and PPM was 10 [7-13]. A decision tree model was used for its performance and interpretability, and included: (1) aortic valve replacement, subaortic stenosis repair, or Konno incision; (2) ventricular L-loop; (3) atrioventricular valve replacement; (4) use of preoperative antiarrhythmic agent (in POD 0 model only; figure 1). The POD 4 model (table 1) had a positive predictive value (PPV) of 0.94 [95% CI 0.81-0.98], which was stable in prospective validation (PPV 1.0). Conclusions: Our decision tool identified patients requiring PPM with high specificity and PPV. On POD 4, patients with left ventricular outflow tract repair, AV valve replacement, or ventricular L-Looping could be considered for PPM placement before POD 7 to reduce risks of temporary pacing and improve care efficiency.