tbuckley/cabot-search huggingface dataset:
OP0124 The painful shoulder. sonographic study in 425 patients
Authors: A Iagnocco, G Palombi, G Valesini
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Shoulder pain is a common symptom and it may be related to many different diseases. Both articular structures and periarticular soft tissues may be involved and for the complex anatomy of the shoulder girdle it is often difficult to identify the site of anatomic alterations with clinical examination. In contrast, sonography of soft tissues successfully evaluates changes of both articular and periarticular structures. <h3>Objectives</h3> The aim of the present study was to identify sonographically the site and the entity of alterations in patients with shoulder pain. <h3>Methods</h3> Sonography of the shoulder was performed in 425 patients with shoulder pain. They were 282 female and 143 male; their mean age was 57.9 years (range 18–90). 228 patients had a clinically suspected diagnosis of periarticular disorders of soft tissues of the shoulder, 23 of polyarthritis, 14 of osteoarthritis, 15 of previous trauma, 14 of other rheumatic diseases. In 137 patients no clinical diagnosis had been made yet. In 103 cases bilateral involvement was present; for this reason 528 shoulders were studied totally. Moreover both the shoulders of 198 healthy control subjects were examined. They were 109 female and 89 male and their mean age was 56.3 years (range 19–69). Using a combination of already reported techniques, sonography of the shoulder was performed using a 7.5 MHz linear transducer. Investigations included the long head of biceps tendon (peritendinous effusion, thickening, thinning, tears, echotexture changes); the supraspinatus tendon, the infraspinatus tendon and the subscapularis tendon (thickening, thinning, tears, echotexture changes); the subacromial and the subscapularis bursae (effusion); the acromioclavicular joint (irregularity, effusion); the glenohumeral joint (effusion). Moreover calcifications were searched for. The chi square was used for statistical analysis of the results. <h3>Results</h3> Generals Results are reported on Table 1. In 25 patients (5.9%) sonography did not show any changes of articular and periarticular soft tissues of the shoulder girdle. Calcifications were found in 38 cases (72%, p &lt; 0.00001). <h3>Conclusion</h3> The present study showed the high diagnostic capacities of sonography in the detection of changes of the soft tissues of the shoulder in patients with shoulder pain. The sensitiveness of the technique is confirmed by the finding of alterations in 94.1% of cases. The girdle?s complex anatomy makes it difficult to identify alterations by clinical examination, and the application of other diagnostic techniques is often limited by the high costs and the low availability of equipment. In contrast, sonography is a noninvasive and low cost imaging method that can be applied successfully to the study of shoulder?s disorders. As well, it is also valuable for monitoring the therapeutic response and for the possibility of ultrasound guided interventions.
Caplacizumab As New Paradigm-Changing Therapy for Patients with Autoimmune Thrombotic Thrombocytopenic Purpura (aTTP): Real-World Data from TTP Spanish Registry
Authors: Irene Garcia-Garcia, Moraima Jiménez, David Valcárcel, Maria Eva Mingot-Castellano, Maria Cristina Pascual Izquierdo, Aurora Viejo, Miquel Lozano, Rosa Goterris, Jorge Martínez Nieto, Ana Oliva, Inés Gómez-Seguí, Luis Hernandez, Saioa Zalba, Verónica Campuzano, Yolanda Martínez, Helena González, Inmaculada Tallon, Miguel Fernández Zarzoso, Gemma Moreno Jiménez, Sunil Lakhwani Lakhwani, Sandra Ortega, María Solé, Jon Ander Atucha Fernández, Julio Del Rio-Garma, Joan Cid
Journal: Blood (2020)
A Novel in-Vivo Model to Examine Homing of Multiple Myeloma Cells in Postnatal, Inducible, and Reversible Loss of Mature Osteoblasts
Authors: Cristina Panaroni, Keertik Fulzele, Tomoaki Mori, Chukwuamaka Onyewadume, Noopur S. Raje
Journal: Blood (2020)
Clonal Dynamics after Venetoclax-Obinutuzumab Therapy: Novel Insights from the Randomized, Phase 3 CLL14 Trial
Authors: Othman Al-Sawaf, Can Zhang, Sandra Robrecht, Cameron Wilson, Maneesh Tandon, Travers Ching, Anna-Maria Fink, Matthias Ritgen, Eugen Tausch, Karl-Anton Kreuzer, William Schary, Clemens-Martin Wendtner, Barbara Eichhorst, Stephan Stilgenbauer, Yanwen Jiang, Michael Hallek, Kirsten Fischer
Journal: Blood (2020)
Antimetabolic Cooperativity with l-Asparaginase and Tyrosine Kinase Inhibitor Quizartinib to Eradicate Persistant FLT3-ITD Leukemic Cells
Authors: Quentin Fovez, Raeeka Khamari, Anne Trinh, William Laine, Bruno Quesnel, Philippe Marchetti, Jérôme Kluza
Journal: Blood (2020)
Identification of Chemo-Resistant Residual Cell Population in Pediatric AML of Complete Remission By Single Cell RNA Sequencing
Authors: Shuting Jiang, Fuhong He, Li Gao, Aili Chen, Yixin Hu, Liyan Fan, Lin Zhang, Yongping Zhang, Haiyang Hu, Dan Liu, Zihan Zhou, Yanxun Su, Lei Qin, Jun Lu, Peifang Xiao, Raul Ribeiro, Shaoyan Hu, Qian-fei Wang
Journal: Blood (2020)
Non-Infectious Pulmonary Toxicity after Allogeneic Hematopoietic Cell Transplantation (HCT): A Center for International Blood and Marrow Transplant Research (CIBMTR) Study
Authors: Sagar S. Patel, Kwang Woo Ahn, Manoj Khanal, Caitrin Fretham, Celalettin Ustun, Betty K. Hamilton, Navneet S. Majhail, Shin Mineishi, Bipin N. Savani, Mohamed Sorror, Edward A. Stadtmauer, Brent Logan, Marcelo C. Pasquini, Saurabh Chhabra
Journal: Blood (2020)
Engineering IL-2 to Give New Life to T Cell Immunotherapy
Authors: Willem W. Overwijk, Mary A. Tagliaferri, Jonathan Zalevsky
Journal: Annual Review of Medicine (2020)

Interleukin-2 (IL-2) is integral to immune system regulation. Its opposing immunostimulatory and immunosuppressive actions make it an attractive therapeutic target for cancer and autoimmune diseases. A challenge in developing IL-2-directed anticancer therapies has been how to stimulate effector T cells (Teffs) without inducing regulatory T cells (Tregs) in the tumor microenvironment; conversely, IL-2 therapy for autoimmune diseases requires Treg induction without further stimulation of Teffs. High-dose IL-2 is approved for melanoma and renal cell carcinoma, but its therapeutic value is limited by a need for frequent dosing at specialist centers, its short half-life, severe toxicity, and a lack of efficacy in most patients. Re-engineered IL-2 therapeutics are designed to have longer in vivo half-lives, target specific IL-2 receptor conformations to stimulate specific T cell subsets, or localize to target tissues to optimize efficacy and reduce toxicity. We discuss recent studies that elucidate the potential of newly engineered IL-2-based therapeutics for cancer and autoimmune diseases.
Validation of the High-Risk Prognostic Score Defined By the Presence of Mutations in NRAS or TP53 in a Cohort of 497 Patients with Acute Myeloid Leukemia
Authors: Rosa Ayala, Pau Montesinos, Eva Barragán, Joaquin Martinez-Lopez, Miguel A. Sanz, Yanira Ruiz-Heredia, Santiago Barrio, Juan Manuel de la Rosa, Inmaculada Rapado, Pilar Martinez, Rafael Colmenares, Maria Pozas, Xabier Gutierrez, María Luz Morales, Noemí Álvarez Sánchez-Redondo
Journal: Blood (2020)
Optical Mapping, a Promising Alternative to Gold Standard Cytogenetic Approaches in Acute Lymphoblastic Leukemias: A Blind Comparison on 10 Patients
Authors: Valentin Lestringant, Nicolas Duployez, Dominique Penther, Nathalie Grardel, Anne Lutun, Claude Preudhomme, Michaela West, Joyce Lee, Jean-Pierre Marolleau, Loïc Garçon, Yann Ferret
Journal: Blood (2020)
FRI0176 Antibodies to cardiolipin and b2gpi in the group of women?s population with the history of recurrent spontaneous abortions
Authors: YV Ershova, AA Baranov, NY Karpov, SE Aleksandrov, SY Nestuley, NE Abaytova, DL Guriev, VL Krylov
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To determine the significance of IgG anticardiolipin antibodies (aCL) and IgG antibodies to b2GPI (anti-b2GPI) in the group of women?s population with the history of recurrent spontaneous abortions. <h3>Methods</h3> 58 women with one, two, three and more spontaneous abortions (mean age ? 29,9 ± 5,7 years) were examined. Three of them were observed out of pregnancy. In control groups 12 healthy female donors (mean age ? 29,7 ± 4,2 years) and 10 normal pregnant women (mean age? 23,2 ± 4,6 years) without history of any spontaneous abortions were included. IgG aCL and IgG anti-b2GPI were measured by ELISA. <h3>Results</h3> The elevated levels of both autoantibodies were not noted in both control groups. In the main group in 17 (29,3%) of 58 patients (pts) IgG aCL or IgG anti-b2GPI were found. Elevated levels of IgG aCL only in 11 (64,7%) of 17 pts with antiphospholipid antibodies were noted respectively. Elevated level of IgG anti-b2GPI only wasn't noted in any pts. Elevated level of IgG anti-b2GPI and IgG aCL together had 6 (35,3%) pts. In the group with IgG aCL without IgG anti-b2GPI (n = 11): 1) the history of one or two spont.ab. had 6 (54,5%) pts, three and more spont.ab.? 5 (45,5%) pts (mean number? 2,2 ± 1,8); 2) the clinical manifestations of the antiphospholipid syndrome (APS) were noted in 8 (72,7%), among them: 1(12,5%) pts had definite APS, 4 (50%) pts ?probable APS and 3 (37,5%) pts ? dubious APS; 3) the clinical manifestations of APS, such as deep venous thrombosis had 2 (18,2%) pts, migraine ? 7 (63,6%) pts, thrombocytopenia ? 1 (9,1%) pts. The evidences of stroke, livedo reticularis and ulcers of extremities had no one; 4) titers of antibodies were low in 3 (27,3%), medium ? in 7 (63,6%) and high ? in 1 (9,1%) pts. In the group with IgG aCL and IgG anti-b2GPI (n = 6): 1) the history of one or two spont.ab. had 2 (33,4%) pts, three and more spont.ab.? 4 (66,7%) pts (mean number ? 5,3 ± 4,2); 2) the clinical manifestations of APS were noted in 6 (100%) pts, among them: 4 (66,7%) had definite APS, 2 (33,3%)? probable APS and no one had dubious APS; 3) the clinical manifestations of APS, such as thrombosis (arterial and venous, deep and superior) had 2 (33,3%) pts, migraine?5 (83,3%), thrombocytopenia? 5 (83,3%), stroke ? 2 (33,3%), livedo reticularis? 4 (66,7%) and ulcers of extremities? 1 (16,7%) pts; 4) titers of both antibodies were medium and high. <h3>Conclusion</h3> We found that IgG aCL and IgG anti-b2GPI, especially their combination is one of the most important tests for APS in the pregnant women?s population with the history of spontaneous abortions, especially among the women with habitual abortion; simultaneous production of both antibodies correlated with severity of clinical manifestations of APS. The discovery of IgG anti-b2GPI make the clinical manifestations of APS more severe.
Chest pain with a cold
Authors: Andrew J Morrow, Thomas J Ford, Margaret McEntegart
Journal: BMJ (2020)

A man in his 60s presented to the emergency department with two hours of gradually worsening right-sided chest pain that occurred at rest.

During the week before presentation he had also experienced a coryzal illness, including rhinorrhoea, non-productive cough, fever, and lethargy.

He described shorter episodes of chest pain, lasting less than 15 minutes, for four weeks before this attendance, but he had not sought medical advice. 

His vital signs were stable, he was apyrexial, and had normal heart sounds and no pericardial rub. His right chest wall was tender to palpation, particularly at the costochondral margins.

The patient was a smoker, had a history of hypertension and dyslipidaemia, and a family history of angina. …
Bleeding in Patients with Clinically Severe Von Willebrand Disease: Preliminary Results of Athn 9, a Natural History Study of the Safety, Effectiveness, and Practice of Treatment for People with Severe Von Willebrand Disease (VWD)
Authors: Angela C. Weyand, Kenneth D Friedman, Sweta Gupta, Kristina M. Haley, Chunla He, Salley Pels, Jonathan C. Roberts, Crystal Watson, Robert F. Sidonio
Journal: Blood (2020)
Effects of Canagliflozin on Amino-Terminal Pro–B-Type Natriuretic Peptide
Authors: James L. Januzzi, Jialin Xu, JingWei Li, Wayne Shaw, Richard Oh, Michael Pfeifer, Javed Butler, Naveed Sattar, Kenneth W. Mahaffey, Bruce Neal, Michael K. Hansen
Journal: Journal of the American College of Cardiology (2020)
Management of Patients with Aggressive B Cell Non-Hodgkin Lymphoma after Relapse from Axicabtagene Ciloleucel: Single Center Real-World Experience
Authors: Jose V. Forero, Paula A. Lengerke Diaz, Eider F. Moreno Cortes, Megan Melody, Allison C. Rosenthal, Mohamed A. Kharfan-Dabaja, Januario E. Castro
Journal: Blood (2020)
Prophylactic Donor Lymphocyte Infusion Based on Two Different Time for Preventing Relapse in Advanced Acute Leukemia Undergoing Allo-HSCT: Comparison of Two Independent Prospective Cohorts
Authors: Qiongqiong Su, Zhiping Fan, Fen Huang, Na Xu, Danian Nie, Dongjun Lin, Ziwen Guo, Shi Pengcheng, Zhixiang Wang, Ling Jiang, Jing Sun, Zujun Jiang, Qifa Liu, Li Xuan
Journal: Blood (2020)
Setting the Pick: Can PI3K Inhibitors Circumvent CDK4/6 Inhibitor Resistance?
Authors: Amy S. Clark, Igor Makhlin, Angela DeMichele
Journal: Clinical Cancer Research (2020)

PI3K and CDK4/6 inhibitors (CDK4/6i) are targeted therapies approved to treat advanced breast cancer; CDK4/6is are more widely used. Here, we discuss trials that examine PI3K inhibitors with novel drug combinations, including a CDK4/6i, given data implicating the pathway in CDK 4/6 resistance.
TET2 Inhibitory Effects of Eltrombopag Contribute Its Hematopoietic Activity
Authors: Yihong Guan, Metis Hasipek, Bhumika J. Patel, Dale Grabowski, Anand D. Tiwari, Sunisa Kongkiatkamon, Cassandra M Kerr, Aziz Nazha, Yogenthiran Saunthararajah, Mikkael A. Sekeres, Jaroslaw P. Maciejewski, Babal K. Jha
Journal: Blood (2020)
Proposed Scheme for Dosing Venetoclax in Pediatric Patients with Relapsed/Refractory Acute Myeloid Leukemia: Analysis of Developmental Pharmacokinetics and Exposure-Response Relationships
Authors: Mohamed A Badawi, Sathej Gopalakrishnan, Benjamin Engelhardt, Tammy L. Palenski, Su Young Kim, Seth E. Karol, Jeffrey E. Rubnitz, Rajeev Menon, Ahmed Hamed Salem
Journal: Blood (2020)
Abstract 235: Hypertrophic Cardiomyopathy, a Disease of Altered Cardiac Energetics
Authors: Sara Ranjbarvaziri, Mathew Ellenberger, Kristi Kooiker, Giovanni Fajardo, Mingming Zhao, Alison Schroer, Y Joseph Y Woo, Kathleen M Ruppel, James A Spudich, Michael Snyder, Kevin Contrepois, Daniel Bernstein
Journal: Circulation Research (2020)

Hypertrophic cardiomyopathy (HCM) is a complex disease, the phenotypes of which are only partly explained by the biomechanical effects of individual genetic variants. At the cellular level, HCM sarcomeric mutations generally enhance maximal force production ultimately leading to higher energy demands. Despite significant advances in elucidating sarcomeric structure-function relationships, there is limited knowledge on the link between altered cardiac energetics and HCM phenotypes. In this work, we test the hypothesis that changes in cardiac energetics are a common pathway leading to the clinical pathophysiological phenotypes of HCM. We performed a comprehensive multi-omic study of the molecular, ultrastructural, and functional features of HCM energetics using septal myectomy samples from 27 HCM patients and 13 normal controls (donor hearts). Combined mass spectrometry and RNA-Seq revealed dramatic alterations in multiple metabolic pathways,with major dysregulation in fatty acid metabolism leading to reduced acylcarnitines and accumulation of free fatty acids. Additionally, HCM hearts showed clear signs of global energetic decompensation manifested by a decrease in high energy phosphate metabolites (ATP, ADP, and PCr) and reduction in several mitochondrial genes involved in creatine kinase and ATP synthesis machinery. Quantitative electron microscopy showed a marked increase in severely damaged mitochondria with reduced cristae density, affecting 10-12% of total mitochondria, coinciding with reduced citrate synthase (CS) activity and mitochondrial respiration. These mitochondrial abnormalities were associated with elevated ROS and reduced antioxidant defenses along with insufficient mitophagic clearance. Overall, our findings suggest that perturbed metabolic signaling and mitochondrial dysfunction are common pathogenic mechanisms in HCM. A central role for compromised energetics in HCM could also help explain the delayed age of onset of the clinical phenotype and present novel drug targets for attenuation of the clinical disease through reducing mitochondrial injury and improving function.
Sabatolimab (MBG453) Dose Selection and Dose-Response Analysis in Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML): Population Pharmacokinetics (PK) Modeling and Evaluation of Clinical Efficacy/Safety By Dose
Authors: Andrew H. Wei, Jordi Esteve, Kimmo Porkka, Steve Knapper, Norbert Vey, Sebastian Scholl, Guillermo Garcia-Manero, Martin Wermke, Jeroen Janssen, Elie Traer, Sun Loo, Rupa Narayan, Natalia Tovar, Mika Kontro, Oliver Ottmann, Siyan Xu, Serena Liao, Andrew Stein, Fariba Khanshan, Purushotham Naidu, Na Zhang, Anisa Mohammed, Mikael L. Rinne, Haiying Sun, Andrew M. Brunner, Uma Borate
Journal: Blood (2020)
Interleukin-7 Receptor Gene Heterozygous Mutations in Recipients Significantly Increase Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Fan Yang, Yang LEI, Qinlong Zheng, Caiyan Zhang, Yueqian Feng, Changwei Dong, Zhihui Li, Yongqiang Zhao, Yanzhi Song, Tong Wu
Journal: Blood (2020)
Survival Trends over 18 Years of Patients with Multiple Myeloma Harboring Del(17p) and/or t(4;14): A Retrospective Real-World Study
Authors: Thomas Chalopin, Nicolas Vallet, Marlene Ochmann, Mourad Tiab, Pascal Godmer, Carole Barin, Olivier Theisen, Olivier Herault, Emmanuel Gyan, Lotfi Benboubker, Philippe Moreau, Herve Avet-Loiseau, Cyrille Touzeau
Journal: Blood (2020)
DREAMM-6: Safety, Tolerability and Clinical Activity of Belantamab Mafodotin (Belamaf) in Combination with Bortezomib/Dexamethasone (BorDex) in Relapsed/Refractory Multiple Myeloma (RRMM)
Authors: Rakesh Popat, Ajay Nooka, Keith Stockerl-Goldstein, Rafat Abonour, Ryan Ramaekers, Amit Khot, Adam Forbes, Cindy Lee, Bradley Augustson, Andrew Spencer, Maria-Victoria Mateos, Bikramjit Chopra, Rachel Rogers, Deborah A Smith, Jacqueline Davidge, Rocio Montes de Oca, Geraldine Ferron-Brady, Anne Yeakey, Mala Talekar, Brandon E. Kremer, Ira Gupta, Hang Quach
Journal: Blood (2020)
Chronic Lymphocytic Leukemia Treatment in México: Up to Half Patients May Not Requiere Treatment
Authors: Luisa Fernanda Sánchez-Valledor, Carmina Alejandra Córdova-Ramírez, Gilberto David Elias-de-la-Cruz, Montserrat Rivera-Álvarez, Antonio Cruz-Mora, Yahveth Cantero-Fortiz, Dina Khalaf, Juan Carlos Olivares-Gazca, Andrés A. León-Peña, Iván Murrieta-Álvarez, Guillermo J. Ruiz-Delgado, Guillermo J. Ruiz-Argüelles
Journal: Blood (2020)
Correlation Analyses of Imetelstat Exposure with Pharmacodynamic Effect, Efficacy and Safety in a Phase 2 Study in Patients with Higher-Risk Myelofibrosis Refractory to Janus Kinase Inhibitor Identified an Optimal Dosing Regimen for Phase 3 Study
Authors: John Mascarenhas, Rami S. Komrokji, Michele Cavo, Bruno Martino, Dietger Niederwieser, Andreas Reiter, Bart L. Scott, Maria R. Baer, Ronald Hoffman, Olatoyosi Odenike, Laurie Sherman, Souria Dougherty, Tymara Berry, Faye Feller, Libo Sun, Ying Wan, Aleksandra Rizo, Fei Huang, Jean-Jacques Kiladjian
Journal: Blood (2020)
Outcome of Patients with Immunoglobulin Light-Chain Amyloidosis with t(11;14) Undergoing Autologous Hematopoietic Stem Cell Transplantation
Authors: Aimaz Afrough, Leonard C Alsfeld, Samer A. Srour, Qaiser Bashir, Neeraj Saini, Chitra Hosing, Uday R. Popat, Partow Kebriaei, Elizabeth J. Shpall, Ruby Delgado, Regan Murphy, Elisabet E. Manasanch, Hans C. Lee, Gregory P. Kaufman, Krina K. Patel, Sheeba K. Thomas, Donna M. Weber, Robert Z. Orlowski, Richard E. Champlin, Muzaffar H. Qazilbash
Journal: Blood (2020)
Clofarabine Significantly Increases Eradication of Minimal Residual Disease of B-Precursor ALL Compared to High-Dose Cytarabine in Randomized Trial Coall 08-09
Authors: Gabriele Escherich, Udo Zur Stadt, Dagmar Dilloo, Joerg Faber, Tobias Feuchtinger, Thomas Imscheiler, Norbert Jorch, Arnulf Pekrun, Irene Schmid, Martin Zimmermann, Martin A. Horstmann
Journal: Blood (2020)
Native T1 Values and Cardiac Involvement in Patients with Thalassemia Major
Authors: Alessia Pepe, Nicola Martini, Antonio De Luca, Vincenzo Positano, Laura Pistoia, Zelia Borsellino, Valentina Carrai, Maria Grazia Sanna, Pier Paolo Bitti, Sara Gentili, Aurelio Maggio, Gianfranco Sinagra, Antonella Meloni
Journal: Blood (2020)
Long Term Analysis of a Monocentric Cohort of Therapy-Related Acute Lymphoblastic Leukemia
Authors: Sylvain Garciaz, Amel Soua, Ilhem Rahal, Marie Anne Hospital, Colombe Saillard, Yosr Hicheri, Bilal Mohty, Evelyne D'Incan, Jerome Rey, Norbert Vey
Journal: Blood (2020)
Abstract 471: Combination of Allogeneic Mesenchymal and Kidney Stem Cells Ameliorates Chronic Kidney Disease Induced Heart Failure With Preserved Ejection Fraction
Authors: Angela C Castellanos, Bryon A Tompkins, Makoto Natsumeda, Victoria Florea, Monisha Banerjee, Jose Rodriguez, Marcos Rosado, Kristalenia Valasaki, Lauro Takeuchi, Sohil Desai, Michell Bellio, Aisha Khan, Darrell Hardin, Daniel Rodriguez, Wayne Balkan, Joshua M Hare, Ivonne H Schulman
Journal: Circulation Research (2020)

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous condition involving multiple comorbidities. Phenotypic classification of HFpEF associated with chronic kidney disease (CKD) manifests worse outcomes, compared to other HFpEF phenotypes. Few treatments improve morbidity and mortality in HFpEF. Stem cell therapy promotes cardiac repair in ischemic and non-ischemic cardiomyopathies. We hypothesized that allogeneic stem cell treatment ameliorates HFpEF in a large animal model of CKD. Methods: Yorkshire pigs (n=26) underwent 5/6 embolization-mediated nephrectomy and 4-weeks later received either: allogeneic mesenchymal stem cells (MSCs) (10х10 6 ), Kidney stem cells (KSC; 10х10 6 ), combination (ACCT; MSC+KSC; 1:1 ratio [5х10 6 each]), or placebo (n=6-7/ group). Cell therapy was delivered via the patent renal artery of the remnant kidney. RNAsec analysis compared placebo and ACCT groups. Results: Mean arterial pressure increased significantly in the placebo- (21.89±6.05 mmHg, p&lt;0.0001) compared to the ACCT-group (p=0.04) at 12 weeks. Glomerular filtration rate improved significantly in the ACCT group (p=0.002). RNAseq analysis revealed a significant decrease in genes normally increased during kidney transplant rejection (q&lt;10 -6 , NES = -2.32) in ACCT. Consistent with these results, there was a downregulation of canonical drivers of tubular damage and regeneration, including SOX9 (-2.39 fold, p=0.0004) and apoptosis of kidney cell types (-24.89 fold, p=0.004), including podocytes (-2.065 fold, p=0.04) with ACCT. ACCT administration also downregulated genes related to oxidative stress (-4.6 fold, p&lt;0.0001), fibrosis, inflammatory response (-4.760 fold, p=&lt;0.05), and renin-angiotensin signaling (-3.162 fold, p=0.024), which are related to cardiac hypertrophy pathways (-7.23, fold, p&lt;0.0001). EDPVR improved in with ACCT (p=0.003), indicating decreased ventricular stiffness. Ejection fraction, relative wall thickness, and left ventricular mass did not differ between groups at 12 weeks. Conclusion: Intra-renal artery allogeneic cell therapy was safe. Beneficial effects were observed in the ACCT and MSC groups in the kidney and heart. These findings have important implications on the use of cell therapy for HFpEF and cardiorenal syndrome.
Plasma Cell-Free DNA Chromosomal Instability As Surrogate Biomarker of Treatment Response and Minimal Residual Diseases for Multiple Myeloma
Authors: Juan Du, Baoan Chen, Wanting Qiang, Yanchun Jia, Jing Lu, Lu Li, Jing Liu, Hua Jiang, Ziliang Qian, Weijun Fu
Journal: Blood (2020)