tbuckley/cabot-search huggingface dataset:
Deimplementing arthroscopy, improving concussion reporting and celebrating research quality
Authors: Karim M Khan
Journal: British Journal of Sports Medicine (2020)

As we say on the British Journal of Sports Medicine (BJSM) podcast—thanks for choosing to engage with BJSM. Your worldwide author team brings you the full spectrum sport and exercise medicine, sports physiotherapy, as well as sports science in this 22nd of our 24 annual issues.

Three articles relate to arthroscopy: the Finnish Degenerative Meniscal Lesion Study (FIDELITY) knee surgery randomised controlled trial (RCT) (see page 1332) was a landmark because it: (i) included a sham surgery control group and, (ii) patients had an MRI-proven meniscal tear along with their symptoms and signs. These were classic patients for arthroscopy—classic in the sense that they very typically were slam-dunks for surgery. In the FIDELITY trial, sham surgery produced great results at 1 year (reported in the New England Journal of Medicine 1) and that sham group continues to do well at 5 years as you can read here. They are doing just as well as the patients who underwent arthroscopic partial meniscectomy. Read two leading orthopaedic surgeons’ take home messages—thank you Drs Lars Engebretsen (Norway) and …
FRI0026 Therapeutic strategy with sodium aurothio- malate as first choice dmard in early rheumatoid arthritis: preliminary results
Authors: R Sanmartí, A Gómez, J Gratacós, M Larrosa, JD Cañete, G Salvador, J Muñoz-Gómez
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The role of gold salts in the present therapy of rheumatoid arthritis (RA) remains controversial. <h3>Objectives</h3> To analyse the clinical efficacy (according to ACR response criteria) of a therapeutic protocol, that includes sodium aurothiomalate as first option DMARD in patients with recent onset RA. <h3>Methods</h3> All patients with RA (ACR diagnostic criteria) for less than two years disease duration and no previous DMARD therapy, attending our Rheumatology Units during 1998–99, have been included in a therapeutic protocol, in which the first administered DMARD was sodium aurothiomalate at a dose of 50 mg/week. According to the ACR response at 6 months (no improvement, ACR-20 or ACR-50) patients were treated with methotrexate (MTX) alone, aurothiomalate plus MTX or aurothiomalate alone, respectively. Low dose of steroids (&lt; 10 mg/d of prednisone) were allowed and intraarticular therapy with triamcionolone hexacetonide was performed in large joint with persistent synovitis. <h3>Results</h3> Forty seven (7M/40F) patients were included (age:54 ± 16 years; disease duration:10 ± 7 months; RF+:40(85%)). The percentages of ACR responders at 6 and 12 months were as shown at the Table 1. Twenty-four per cent of patients discontinued gold salts due to adverse events or inefficacy at 12 months. Aurothiomalate was continued in 61% of patients as monotherapy and in 15% of patients in combination with MTX. <h3>Conclusion</h3> Gold salts still have an important role in RA treatment. The use of aurothiomalate should be taken into account in the present therapeutic strategies of patients with early RA.
Abstract 509: Oxytocin Mediates Neuroendocrine Reprogramming of the Epicardium in Heart Regeneration
Authors: Aaron H Wasserman, Amanda R Huang, Aitor Aguirre
Journal: Circulation Research (2020)

Cardiovascular disease (CVD) is the leading cause of mortality both in the United States and worldwide. CVD often results in the massive loss of contractile cardiac cells and tissue. Critical work in the last two decades demonstrates that lost cells can be partially replenished by the epicardium, the outermost mesothelial layer of the heart. Upon cardiac injury, mature epicardial cells activate and undergo epithelial-mesenchymal transition (EMT) to form epicardium-derived progenitor cells (EPDCs), which are a type of multipotent stem cell that can differentiate into several important cardiac lineages, including cardiomyocytes and vascular cells. This process alone is insufficient for significant regeneration, but its efficiency can be improved by priming with specific factors (e.g., thymosin beta-4). Our group has recently discovered evidence that oxytocin (OT), a hypothalamic neuroendocrine peptide, induces a pro-regenerative phenotype in vitro in human induced pluripotent stem cell (iPSC) derived epicardial cells. We hypothesize that upon cardiac injury, oxytocin is released into the bloodstream, causing activation of the epicardium and mobilization of EPDCs to elicit regeneration of damaged tissue and restoration of function. Here, we show that we can differentiate mature, high-quality epicardial cells from iPSCs and that Ki67 levels and cell counts increase after three days of OT exposure. In addition, the peptide alters gene expression levels of several epithelial, mesenchymal, and EMT markers, indicating a transition to a dedifferentiated gene profile characteristic of EPDCs. Finally, when OT is administered intravenously to mice, it accelerates healing from cardiac injury by inducing epicardial activation. Future studies will aim to further reveal the physiological contribution of OT to heart regeneration in vivo and determine its molecular mechanism of action. Our findings have the potential to uncover a novel mechanism of neuroendocrine reprogramming of the injured heart and yield significant translational advances in the treatment of CVD.
Functional Genomics Identifies Metabolic Vulnerabilities in Pancreatic Cancer
Authors: Douglas E. Biancur, Kevin S. Kapner, Keisuke Yamamoto, Robert S. Banh, Jasper E. Neggers, Albert S.W. Sohn, Warren Wu, Robert T. Manguso, Adam Brown, David E. Root, Andrew J. Aguirre, Alec C. Kimmelman
Journal: Cell Metabolism (2020)
Abstract MP143: Harnessing Glycomics to Understand Cardiac Biology and Disease
Authors: Christopher Ashwood, Linda Berg Luecke, Rebekah L Gundry
Journal: Circulation Research (2020)

Cell surface glycoproteins play critical roles in maintaining cardiac structure and function, and the glycan-moiety attached to a protein is critical for proper protein folding, stability, and signaling. Despite mounting evidence that glycan structures are key modulators of heart function and must be considered when developing cardiac biomarkers, we currently do not have a comprehensive view of the glycans present in the normal human heart. Here, we used an innovative mass spectrometry approach to generate the first glycan structure libraries for primary human heart tissue, cardiomyocytes (CM) enriched from human heart tissue, and human induced pluripotent stem cell derived CM (hiPSC-CM), containing &gt;260 N- and O- glycans. Comparing the glycome of CM enriched from primary heart tissue to that of heart tissue homogenate, 21 structures significantly differed, and the high mannose class is increased in enriched CM. Moreover, &gt;30% of the glycome significantly changed across 20-100 days of in vitro differentiation, and only 23% of the N -glycan structures were shared between hiPSC-CM and primary CM. Overall, these observations are an important complement to genomic, transcriptomic, and proteomic profiling and reveal new considerations for the use and interpretation of hiPSC-CM models for studies of human development, disease, and drug testing. These data are also expected to aid in the evaluation of the immunogenic potential of hiPSC-CM for transplantation. Finally, harnessing differences observed between immature, proliferative hiPSC-CM and adult primary CM may be exploited to drive in vitro differentiation towards a more mature phenotype. Building on these data, current efforts are underway to develop chamber- and cell-type specific views ( e.g. cardiomyocytes, fibroblasts) of the glycome in the healthy and failing human heart. Such analyses provide a key link to understand the role glycosylation plays in cell-type specific functions and cardiac disease. The structural differences observed here, either among cell types or stages of differentiation, require complex regulation of multiple enzymes in the biosynthetic pathway, and therefore would be challenging to measure with antibody arrays, RNAseq, or proteomics. Therefore, continued application of structure-based glycomics approaches, such as the method used here, will be essential for elucidating the roles that glycans and glycoproteins play during developmental and disease processes in the human heart.
Prognosis of Acute Myeloid Leukemia with Myelodysplasia-Related Changes According to the Different Subgroups of the WHO 2016 Classification in Patients Candidates to Intensive Chemotherapy
Authors: Claudia Nunez-Torron, Juan Marquet Palomanes, Valentín Garcia-Gutiérrez, Adolfo Saez, Alejandro Luna, Jesus Villarrubia, Gemma Moreno Jiménez, Javier Lopez Jimenez, Pilar Herrera Puente
Journal: Blood (2020)
Somatic Mutations in a Single Residue of <i>UBA1</i> Cause Vexas, a Severe Adult-Onset Rheumatic Disease Associated with Myeloid Dysplasia
Authors: David B. Beck, Zhijie Wu, Bhavisha A Patel, Marcela A Ferrada, Keith A Sikora, Amanda Ombrello, Alina E. Dulau Florea, Weixin Wang, Emma M. Groarke, Shawn M. Burgess, Ivona A Aksentijevich, Achim A Werner, Neal S. Young, Katherine R. Calvo, Daniel L Kastner, Peter C Grayson
Journal: Blood (2020)
Nivolumab and Ipilimumab in Metastatic Uveal Melanoma: Results From a Single-Arm Phase II Study
Authors: Meredith S. Pelster, Stephen K. Gruschkus, Roland Bassett, Dan S. Gombos, Michael Shephard, Liberty Posada, Maura S. Glover, Rinata Simien, Adi Diab, Patrick Hwu, Brett W. Carter, Sapna P. Patel
Journal: Journal of Clinical Oncology (2020)

Metastatic uveal melanoma has poor overall survival (OS) and no approved systemic therapy options. Studies of single-agent immunotherapy regimens have shown minimal benefit. There is the potential for improved responses with the use of combination immunotherapy.We conducted a phase II study of nivolumab with ipilimumab in patients with metastatic uveal melanoma. Any number of prior treatments was permitted. Patients received nivolumab 1 mg/kg and ipilimumab 3 mg/kg for four cycles, followed by nivolumab maintenance therapy for up to 2 years. The primary outcome of the study was overall response rate (ORR) as determined by RECIST 1.1 criteria. Progression-free survival (PFS), OS, and adverse events were also assessed.Thirty-five patients were enrolled, and 33 patients were evaluable for efficacy. The ORR was 18%, including one confirmed complete response and five confirmed partial responses. The median PFS was 5.5 months (95% CI, 3.4 to 9.5 months), and the median OS was 19.1 months (95% CI, 9.6 months to NR). Forty percent of patients experienced a grade 3-4 treatment-related adverse event.The combination regimen of nivolumab plus ipilimumab demonstrates activity in metastatic uveal melanoma, with deep and sustained confirmed responses.
Population Distribution of GvL and GvH Minor Histocompatibility Antigens
Authors: Kelly Shea Olsen, Hancong Tang, Junke Wang, Sarah Entwistle, Dante S. Bortone, Steven Vensko, Loreall Pooler, Xin Sheng, Christopher Haiman, David Van Den Berg, Stephen R. Spellman, Theresa E. Hahn, Paul M. Armistead, Lara E. Sucheston-Campbell, Benjamin G. Vincent
Journal: Blood (2020)
Distinct Prognostic Effects of <i>TP53</i> Mutations in Newly Diagnosed Versus Relapsed/Refractory (R-R) Patients (pts) with B-Acute Lymphoblastic Leukemia (ALL) Treated with Mini-Hcvd-Inotuzumab Ozogamicin with or without Blinatumomab Regimens
Authors: Rashmi Kanagal-Shamanna, Hagop M. Kantarjian, Joseph D. Khoury, Koichi Takahashi, Guillermo Montalban-Bravo, Nicholas J. Short, C. Cameron Yin, Keyur Patel, Sanam Loghavi, Farhad Ravandi, Marina Konopleva, Nitin Jain, Guillermo Garcia-Manero, Naval Daver, Tapan M. Kadia, Courtney D. DiNardo, Susan M. O'Brien, Rajyalakshmi Luthra, Elias Jabbour
Journal: Blood (2020)
Interferon-Alpha (IFN) Therapy Discontinuation Is Feasible in Myeloproliferative Neoplasm (MPN) Patients with Complete Hematological Remission
Authors: Rafael Daltro De Oliveira, Juliette Soret-Dulphy, Lin-Pierre Zhao, Clemence Marcault, Nicolas Gauthier, Emmanuelle Verger, Nabih Maslah, Nathalie Parquet, Emmanuel Raffoux, William Vainchenker, Christine Chomienne, Bruno Cassinat, Lina Benajiba, Jean-Jacques Kiladjian
Journal: Blood (2020)
Prognostic Role of Multiparameter Flow Cytometry-Based Measurable Residual Disease Assessment in Patients with Acute Myeloid Leukemia Harboring DNMT3A/TET2/ASXL1 Mutation
Authors: Muhned Alhumaid, Georgina S. Daher-Reyes, Aaron D Schimmer, Andre C. Schuh, Anne Tierens, Caroline J McNamara, Dawn Maze, Igor Nicolas Novitzky-Basso, Karen W.L. Yee, Mark D. Minden, Steven M Chan, Tracy Murphy, Vikas Gupta, Dennis Dong Hwan Kim, Hassan Sibai
Journal: Blood (2020)
Results from the Phase I Clinical Studies Evaluating Cyad-01, a First-Generation NKG2D CAR T-Cell Product in Relapsed or Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients
Authors: David A. Sallman, A. Samer Al-Homsi, Marco L. Davila, Tessa Kerre, Ine Moors, Xavier Poire, Violaine Havelange, Philippe Lewalle, Daniel A. Pollyea, Eunice S. Wang, William Blum, Benjamin Demoulin, Panagiota A. Sotiropoulou, Erik Alcantar-Orozco, Eytan Breman, Marie-Sophie Dheur, Nathalie Braun, Caroline Lonez, David E Gilham, Anne Flament, Frédéric F. Lehmann
Journal: Blood (2020)
Tumor and microenvironment response but no cytotoxic T-cell activation in classic Hodgkin lymphoma treated with anti-PD1
Authors: Sarah Reinke, Paul J. Bröckelmann, Ingram Iaccarino, Maria Garcia-Marquez, Sven Borchmann, Franziska Jochims, Michaela Kotrova, Karol Pal, Monika Brüggemann, Elena Hartmann, Stephanie Sasse, Carsten Kobe, Stephan Mathas, Martin Soekler, Ulrich Keller, Matthias Bormann, Andreas Zimmermann, Julia Richter, Michael Fuchs, Bastian von Tresckow, Peter Borchmann, Hans Schlößer, Michael von Bergwelt-Baildon, Andreas Rosenwald, Andreas Engert, Wolfram Klapper
Journal: Blood (2020)
Short-Term Risk for Progression in Patients with Smoldering Multiple Myeloma: The Impact of CD56 Expression
Authors: Laura Notarfranchi, Rosanna Vescovini, Roberta Segreto, Sabrina Bonomini, Paola Storti, Valentina Marchica, Federica Costa, Gabriella Sammarelli, Giannalisa Todaro, Maria Teresa Catarozzo, Dario De Giovanni, Vincenza Fabiano, Anna Benedetta Dalla Palma, Nicola Giuliani
Journal: Blood (2020)
A Bank of CD30.CAR-Modified, Epstein-Barr Virus-Specific T Cells That Lacks Host Reactivity and Resists Graft Rejection for Patients with CD30-Positive Lymphoma
Authors: David H. Quach, Haran R. Ganesh, Sachin Thakkar, Luis Becerra-Dominguez, Birju Mehta, Silvana Perconti, Eric Anderson, Emily M. Hsieh, Olga Dakhova, Huimin Zhang, Bambi J. Grilley, Malcolm K. Brenner, Helen E. Heslop, Carlos A. Ramos, Rayne H. Rouce, Natalia Lapteva, Cliona M. Rooney
Journal: Blood (2020)
Impact of Donor Search Strategy for Allogeneic Hematopoietic Stem Cell Transplantation from Haploidentical or Matched Unrelated Donor for Patients Older Than 55 Years with Hematological Malignancies: Randomized Prospective Phase III Study
Authors: Samia Harbi, jean Marie Boher, Edouard Forcade, Patrice Chevallier, Peffault De Latour Régis, Florent Malard, Sylvie Francois, Amandine Charbonnier, Eric Hermet, Claude-Eric Bulabois, Anne Huynh, Ana Berceanu, Thomas Cluzeau, Marie Thérèse Rubio, Sabine Furst, Mohamad Mohty, Raynier Devillier, Didier Blaise
Journal: Blood (2020)
FRI0063 Anakinra reduces the rate of joint destruction after 1 year of treatment in a randomised controlled cohort of patients with rheumatoid arthritis
Authors: B Bresnihan, RD Newmark, S Robbins, D McCabe, HK Genant
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To assess the effect of ankinra on progressive joint damage in patients with rheumatoid arthritis after 12 months of treatment. <h3>Methods</h3> 472 patients were randomised to a 24 week study. On completing the 24 week, placebo-controlled, randomised clinical trial, patients receiving anakinra 30, 75 or 150 mg daily continued blinded treatment for a further 24 weeks. Patients originally randomised to placebo were re-randomised to blinded treatment with one of the 3 anakinra doses for an additional 24 weeks resulting in a blinded cohort of patients (N = 309) followed for up to 1 year by radiographic assessments, using a modified Sharp method (Genant A&amp;R, 41:1583, 98). <h3>Results</h3> Treatment with 75 or 150 mg anakinra was significantly superior in terms of reducing joint destruction after 1 year, when compared to the group of patients originally randomised to placebo. This analysis demonstrated a dose proportional relationship with increasing doses of anakinra providing superior reduction of joint destruction when measured by a modified Sharp score. <h3>Conclusion</h3> Anakinra provides a statistically significant reduction in joint destruction, compared with patients originally randomised to placebo after 1 year of treatment. The reduction in joint destruction was dose proportional.
Genome-wide association study of non-tuberculous mycobacterial pulmonary disease
Authors: Jaeyoung Cho, Kyungtaek Park, Sun Mi Choi, Jinwoo Lee, Chang-Hoon Lee, Jung-Kyu Lee, Eun Young Heo, Deog Kyeom Kim, Yeon Joo Lee, Jong Sun Park, Young-Jae Cho, Ho Il Yoon, Jae Ho Lee, Choon-Taek Lee, Nayoung Kim, Kyu Yeong Choi, Kun Ho Lee, Joohon Sung, Sungho Won, Jae-Joon Yim
Journal: Thorax (2020)

Background The prevalence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing in South Korea and many parts of the world. However, the genetic factors underlying susceptibility to this disease remain elusive. Methods To identify genetic variants in patients with NTM-PD, we performed a genome-wide association study with 403 Korean patients with NTM-PD and 306 healthy controls from the Healthy Twin Study, Korea cohort. Candidate variants from the discovery cohort were subsequently validated in an independent cohort. The Genotype-Tissue Expression (GTEx) database was used to identify expression quantitative trait loci (eQTL) and to conduct Mendelian randomisation (MR). Results We identified a putatively significant locus on chromosome 7p13, rs849177 (OR, 2.34; 95% CI, 1.71 to 3.21; p=1.36×10 −7 ), as the candidate genetic variant associated with NTM-PD susceptibility. Its association was subsequently replicated and the combined p value was 4.92×10 −8 . The eQTL analysis showed that a risk allele at rs849177 was associated with lower expression levels of STK17A , a proapoptotic gene. In the MR analysis, a causal effect of STK17A on NTM-PD development was identified (β, −4.627; 95% CI, −8.768 to −0.486; p=0.029). Conclusions The 7p13 genetic variant might be associated with susceptibility to NTM-PD in the Korean population by altering the expression level of STK17A .
Resolving the Disproportionate Left Ventricular Enlargement in Mitral Valve Prolapse Due to Barlow Disease
Authors: K. Carlos El-Tallawi, Danai Kitkungvan, Jiaqiong Xu, Vittorio Cristini, Eric Y. Yang, Miguel A. Quinones, Gerald M. Lawrie, William A. Zoghbi, Dipan J. Shah
Journal: JACC. Cardiovascular imaging (2020)
LSD1 Inhibitor CPI-482 Shows Efficacy and Prolongs Survival in Mouse Models of AML and Post-MPN AML in the Context of Constitutive JAK-STAT Pathway Activation
Authors: Raajit K. Rampal, John P. McGrath, Aishwarya Krishnan, Bing Li, Wenbin Xiao, David Nikom, Jing Wang, Ross L. Levine, Patrick Trojer
Journal: Blood (2020)
Best Practices for Validation of Measurable Residual Disease Assessments By Multiparameter Flow Cytometry in Emerging Clinical Trials of Acute Myeloid Leukemia
Authors: Pavinder Kaur, Anil Pahuja, Kevin Nguyen, Pedro Marques Ramos, Ling Du, Jacqueline J Cloos, Maaike E Heidinga, Yvonne J.M Oussoren-Brockhoff, Angele Kelder, Xun Li, Sarah Larson, Shabnam Tangri, Ghanashyam Sarikonda, Naveen Dakappagari
Journal: Blood (2020)
Long-Term Follow-up of Ibrutinib Treatment for Rituximab-Refractory Waldenström's Macroglobulinemia: Final Analysis of the Open-Label Substudy of the Phase 3 iNNOVATETM Trial
Authors: Judith Trotman, Christian Buske, Alessandra Tedeschi, Jeffrey V. Matous, David MacDonald, Constantine Tam, Olivier Tournilhac, Shuo Ma, Steven P. Treon, Albert Oriol, Jerry Ping, Eva M. Briso, Israel Arango-Hisijara, Meletios A. Dimopoulos
Journal: Blood (2020)
OP0029 Association of plasma mmp-3 levels and the presence of the shared epitope in patients with rheumatoid arthritis
Authors: S Drynda, C Kühne, J Kekow
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatoid arthritis (RA) is characterised by an overexpression of proinflammatory cytokines such as IL-1 and TNFa. These cytokines are known to stimulate the production of matrix degrading enzymes. The family of matrix metalloproteinases (MMP) are considered as key enzymes in the destruction of cartilage and bone. One of the most abundant MMP found in RA is MMP-3. It is well established that levels of MMP-3 in peripheral blood are highly correlated with disease activity in RA. Furthermore high plasma levels of MMP-3 account for an early erosive form of RA. It was the aim of our study to determine whether there exist an association between plasma MMP-3 levels and the presence of the shared epitope (SE) and an association of MMP-3 levels in plasma samples and bone extracts. 45 RA patients were included in this study. HLA-DRB genotyping with DNA from peripheral blood was performed using sequence-specific primers and reverse hybridisation provided by AID GmbH Strassberg. Plasma MMP-3 concentrations were determined applying the biotrak MMP-3 ELISA system by Amersham Pharmacia Biotech. Our results show significant differences in plasma MMP-3 levels in RA patients depending on the presence of the shared epitope. The mean MMP-3 levels were significantly elevated in the SE positive compared to the SE negative group (99.50+13.74 ng/ml vs. 43.02+9.23 ng/ml, mean+SEM, p = 0.012 Mann Whitney U-test). The highest MMP-3 levels were found in patients with those allels encoding the amino acid sequence QRRAA at the position 70–74 in the third hypervariable region of the HLA-DRB1 molecule, i.e. *0101, *0102, *0404 and *0405. The MMP-3 levels in this group (139.99+27.25 ng/ml) were significantly higher compared not only to the SE negative group (p = 0.011) but also compared to the group with the SE QKRAA (68.17+6.53 ng/ml, p = 0.032). Concentrations of MMP-3 in the extract of non-collagenous proteins from defatted bone powder were shown to be strongly correlated to levels in corresponding plasma samples (r = 0.57, p &lt; 0.001), suggesting that plasma MMP-3 levels reflect at least in part the local situation in bone. Our data indicate that plasma MMP-3 levels in RA may reflect the situation in the bone and vary according to the presence of the shared epitope. This results may explain the association of early erosive RA with the presence of SE. <h3>Objectives</h3> <h3>Methods</h3> <h3>Results</h3> <h3>Conclusion</h3>