tbuckley/cabot-search huggingface dataset:
Cardiac Phenotypes and Markers of Adverse Outcome in Elite Athletes With Ventricular Arrhythmias
Authors: Øyvind H. Lie, Lars Gunnar Klaboe, Lars A. Dejgaard, Eystein T. Skjølsvik, Jostein Grimsmo, Gerhard Bosse, Einar Hopp, Thor Edvardsen, Kristina H. Haugaa
Journal: JACC. Cardiovascular imaging (2020)

This study describes the cardiac phenotypes and markers of adverse outcome in athletes with ventricular arrhythmias with no other discernable etiology than high exercise doses. Little is known about phenotypes and risk markers of life-threatening arrhythmic events in athletes with ventricular arrhythmia. We compared high-performance athletes who have ventricular arrhythmia with healthy controls using clinical data and cardiac imaging. None of the patients had family history of arrhythmogenic cardiomyopathy or any other discernable etiology of ventricular arrhythmia. Right (RV) and left ventricular (LV) function was assessed by echocardiographic longitudinal strain (right ventricular free wall strain longitudinal [RVFWSL] and left ventricular global longitudinal strain [LVGLS]). Mechanical dispersion was defined as the standard deviation of time to peak strain in 16 LV segments. RV ejection fraction and presence of late gadolinium enhancement was assessed by cardiac magnetic resonance. We included 43 athletes (45 ± 14 years of age, 16% female) with ventricular arrhythmias and 30 healthy athletes (41 ± 9 years of age, 7% female). Athletes with ventricular arrhythmias had worse RV function than healthy athletes by echocardiography (RVFWSL: −22.9 ± 4.8% vs. −26.6 ± 3.3%; p < 0.001) and by cardiac magnetic resonance (RV ejection fraction 48 ± 7% vs. 52 ± 6%; p = 0.04), and had more late gadolinium enhancement (24% vs. 3%; p = 0.03). Life-threatening arrhythmic events (aborted cardiac arrest, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator therapy) had occurred in 23 (53%) athletes with ventricular arrhythmias. These had impaired LV function compared to those with less severe ventricular arrhythmias (LVGLS: -17.1 ± 3.0% vs. -18.8 ± 2.0%; p = 0.04). LV mechanical dispersion was an independent marker of life-threatening events (adjusted odds ratio: 2.2 [1.1 to 4.8] by 10 ms increments; p = 0.03). Athletes with ventricular arrhythmias had impaired RV function and more myocardial fibrosis compared to healthy athletes. Athletes with life-threatening arrhythmic events had additional LV contraction abnormalities. These phenotypes mimic arrhythmogenic cardiomyopathy and may potentially be induced by high doses of exercise in susceptible individuals.
Interrelation of 5q-Deletions and Mutations of <i>TP53</i> in Patients with Myelodysplastic Syndromes and Complex Aberrations
Authors: Christina Ganster, Lea Naomi Eder, Katayoon Shirneshan, Katharina Rittscher, Paolo Mazzeo, Roxana Schaab, Ahmet H. Elmaagacli, Uwe Platzbecker, Bertram Glass, Ulrich Germing, Maria Kamper, Elzbieta Barbara Brzuszkiewicz, Detlef Haase
Journal: Blood (2020)
Abstract 530: Mechanisms Underlying Phospholamban L39 Stop (PLN L39X) Cardiomyopathy
Authors: Rasheed A Bailey, Francesca Stillitano, Irene Turnbull, Kobra Haghigi, Kenneth Fish, Fadi Akar, Nicole Dubois, Nadeera Wickramasinghe, Roger J Hajjar, Bruce D GELB, Kevin D Costa, Evangelia Kranias, MariaGiovanna Triveri
Journal: Circulation Research (2020)

Background: Defective calcium (Ca++) handling is a hallmark of HF across species. Together with the Sarco/Endoplasmic Reticulum Ca-ATPase (SERCA2a), Phospholamban (PLN) has emerged as a critical regulator of Ca++homeostasis. Worldwide, PLN mutations are identified with increasing frequency in patients with dilated, hypertrophic and arrhythmogenic cardiomyopathy (CMPs) but the causative defects leading to the CMP remain incompletely understood. While preclinical studies have unequivocally shown that absence of PLN (PLNKO) is therapeutic in rodent HF models, the discovery of a human pathogenic mutation (L39X) presumed to be the human equivalent of the PLNKO lead to the conclusion that PLN ablation was lethal in human, mitigating any enthusiasm in targeting PLN inhibition in PLN-associated disease or HF treatment. The objective of this proposal is to levarge the use of “induced-pluripotent” stem cells (iPSCs) derived cardiomyocytes (CM) from homozygote L39X carriers to elucidate the role of PLN (L39) in human pathophysiology. Methodology and Results: We obtained mononuclear cells from Homozygotes (Hom) L39 carriers and generated 11 iPSC clones. To derive CMs, we used the direct differentiation method temporally modulating the Wnt/β-catenin signaling. Immunocytostaining revealed positive expression of cardiac troponin T as well as PLN. In Hom L39 derived CMs, PLN showed an abnormal cytoplasmic distribution, formed intracellular aggregates and there was loss of perinuclear localization when compared to matched WT iPSC-CMs. Using fura-2AM, we observed decreased calcium transient amplitude in iPSC-CMs from L39 compared to WT with prolongation of the time constant of relaxation and early after depolarization (EAD). Lastly, we saw a 70% and 50% reduction in the protein and mRNA expression of PLN and SERCA2a respectively. Conclusions: Our data suggest that the L39 PLN mutant is expressed but mis-located within the cardiomyocytes. The mis-location of PLN was associated to decreased SERCA2a expression impaired Ca++ handling and increased arrhythmogenicity. Further studies will be required to fully elucidate the impact of the mutation in HF pathophysiology
Identifying Myeloid Mutations By NGS in Patients with Unexplained Erythrocytosis
Authors: Eri Kawata, Anargyros Xenocostas, Cyrus C. Hsia, Alejandro Lazo-Langner, Michael Levy, Stephanie Santos, Hanxin Lin, Chris Howlett, Bekim Sadikovic, Ian Chin-Yee
Journal: Blood (2020)
Dynamics of Leukocyte Subpopulations Reconstitution Predict Infection Propensity in a Multiethnic Real World Cohort Treated with Anti-CD19 CAR-T Cell Therapy (Axicabtagene-Ciloleucel)
Authors: Astha Thakkar, Zhu Cui, Stephen Zachary Peeke, Nishi Shah, Amanda Lombardo, Fariha Khatun, Jennat Mustafa, Alyssa De Castro, Kailyn Gillick, Felisha Joseph, Anjali Naik, Shafia Rahman, Angelica D'Aiello, Richard Elkind, Susan Sakalian, Karen Fehn, Karen Wright, Michelly Abreu, Latoya Townsend Nugent, Nicole Chambers, Rosmi Mathew, Donika Binakaj, Randin Nelson, Carlo Palesi, Monika Paroder, Joan Uehlinger, Yanhua Wang, Yang Shi, Xingxing Zang, Hao Wang, Christopher Nishimura, Xiaoxin Ren, Ulrich G. Steidl, Kira Gritsman, Murali Janakiram, Noah Kornblum, Olga Derman, Ioannis Mantzaris, Aditi Shastri, Rachel Bartash, Yoram Puius, Margaret McCort, Mendel Goldfinger, Lizamarie Bachier-Rodriguez, Amit Verma, Ira Braunschweig, R. Alejandro Sica
Journal: Blood (2020)
Correspondence to ‘Risk factors for hospital admissions related to COVID-19 in patients with autoimmune inflammatory rheumatic diseases’
Authors: Hendrik Schulze-Koops, Alla Skapenko, Andreas Krause, Klaus Krueger, Hanns-Martin Lorenz, Philipp Sewerin, Christof Specker, Ulf G Wagner, Anna Voormann, Ulf Mueller-Ladner, Reinhard E Voll
Journal: Annals of the Rheumatic Diseases (2020)

against SARS-CoV-2, and these reports show that the absence of antibodies against SARS-CoV-2 is not evidence of absence of infection and that patients may perform poorly if infected during anti-cytokine therapies.In light of these considerations, any proposals that might affect the consistent and strict adherence of patients to the hygiene and prevention rules could pose an increased risk to the health of patients with IMIDs.This is underscored by the recent publication of Nuñez et al, 1 which points to a risk of more severe COVID-19 in patients with IRDs.Although it is possible that certain cytokine inhibitors may have a positive effect in the prevention of severe COVID-19 in SARS-CoV-2 infected patients, depending on the time of application, type of therapy and various other factors, 21 we suggest that statements regarding the protective effect of cytokine inhibitors against infection with SARS-CoV-2 should be made with extreme caution.Until more definite data are available, patients with IMIDs are well advised to follow the guidelines of the professional societies, that is, to continue to take their anti-inflammatory drugs unless exposure to SARS-CoV-2 has occurred and/or clinical signs suggesting COVID-19, but also to strictly follow hygiene and distance measures to avoid infection with SARS-CoV-2.
Severe/Life-Threatening/Fatal Chronic Health Conditions (CHCs) after Allogeneic Blood or Marrow Transplantation (BMT) in Childhood - a Report from the BMT Survivor Study (BMTSS)
Authors: Anna Sallfors Holmqvist, Yanjun Chen, Jessica Wu, Lindsey Hageman, Kevin D. Battles, Liton F. Francisco, Michelle Kung, Frederick Goldman, Joseph Rosenthal, Stephen J. Forman, Daniel J. Weisdorf, Mukta Arora, Saro H. Armenian, Smita Bhatia
Journal: Blood (2020)
An Encouraging Successful Result of Allogeneic Hematopoietic Stem Cell Transplantation in a Boy Both with Juvenile Myelomonocytic Leukemia and Osteogenesis Imperfecta : A Case Report
Authors: Fang Liu, Xiaofan Zhu, Wenyu Yang, Ye Guo, Xia Chen, Xiaoyan Zhang
Journal: Blood (2020)
Exposure-Response (E-R) Analysis of Olverembatinib (HQP1351) in Chinese Patients with Chronic Myeloid Leukemia (CML)
Authors: Ming Lu, Chenhui Deng, Yifeng Xiong, Hengbang Wang, Ping Xu, Lichuang Men, Tanhong Xie, Qian Jiang, Zi Chen, Qian Niu, Ping Liu, Dajun Yang, Yifan Zhai
Journal: Blood (2020)
AB0980 CASE-REVIEW ON FAMILIAL MEDITERRANEAN FEVER IN A SPECIALIZED CENTRE
Authors: R. Dos Santos Sobrín, M. Martí Masanet, B. Lopez-Montesinos, L. Lacruz Pérez, I. Calvo
Journal: Annals of the Rheumatic Diseases (2020)

Background: Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disorder caused mostly by mutations in MEFV gene. Its inheritance is autosomal recessive and is the most frequent periodic fever syndrome. First-line treatment is based in colchicine use, so biologics (anti-IL-1) are reserved for refractory cases 1, 2 . Objectives: To account for clinic and treatment features of patients with FMF in a specialized center as opposed to non-referent centers. Methods: This study was developed in the Pediatric Rheumatology Service in Hospital Universitario y Politécnico La Fe de Valencia. Demographic, clinic and treatment data were collected from patients diagnosed of FMF since January 2004 to September 2019. Results: 106 patients met last FMF criteria 3 . 55% had a pathogenic mutation in genetic analysis. 52% were female. Before 10 years old, 71% of patients had the diagnosis (51% before 4 years old). Arthralgia/myalgia (73%), periodic fever (62%) and abdominal pain (54%) were the most common symptoms. Systemic Juvenile Idiopathic Arthritis (JIA, 6), other forms of JIA (9) and vasculitis (10) were the most prevalent comorbidities. When talking about treatment, 76,4% received Colchicine (60,5% with good response), 22,6% needed a classical disease modifying antirheumatic drug (mostly Methotrexate) and 22 patients got biologic treatment (73% anti-IL-1). Conclusion: When analyzing this case-review, JIA has a strong association with our patients, so it could explain severe disease activity and more articular involvement. This could be an illustration to the higher use of Methotrexate. Also, the most relevant symptom was arthralgia while fever is the most frequent in literature. Likewise, age of diagnosis has been earlier than other case-series (this would be more frequent in other autoinflammatory syndromes, as literature relates) 1, 2, 4 . References: [1]Ozdogan H, Ugurlu S. Familial Mediterranean Fever. Presse Med. (2019). [2]Ozen S, Demirkaya E, Erer B, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis 2016;75:644-651. [3]Sag E, Demirel D, Demir S, et al. Performance of the new “Eurofever/PRINTO classification criteria” in FMF patients. Semin Arthritis Rheum. 2019;19:30369-5. [4]Rozenbaum M, Rosner I. Severe outcome of juvenile idiopathic arthritis (JIA) associated with familial Mediterranean fever (FMF). Clin Exp Rheumatol. 2004;22:S75-8. Disclosure of Interests: Raquel Dos Santos Sobrín: None declared, Miguel Martí Masanet: None declared, B Lopez-Montesinos: None declared, Lucía Lacruz Pérez: None declared, Inmaculada Calvo Grant/research support from: Bristol-Myers Squibb, Clementia, GlaxoSmithKline, Hoffman-La Roche, Merck Sharpe &amp; Dohme, Novartis, Pfizer, Sanofi, Speakers bureau: AbbVie, GlaxoSmithKline, Hoffman-La Roche, Novartis
Ruxolitinib Rechallenge in Resistant/Intolerant MF Patients: Frequency, Therapeutic Effects, and Impact on Outcome
Authors: Francesca Palandri, Mario Tiribelli, Massimo Breccia, Daniela Bartoletti, Elena M Elli, Giulia Benevolo, Bruno Martino, Francesco Cavazzini, Alessia Tieghi, Alessandra Iurlo, Novella Pugliese, Monica Crugnola, Gianni Binotto, Giovanni Caocci, Giuseppe Auteri, Daniele Cattaneo, Lucia Catani, Rossella Stella, Luigi Scaffidi, Nicola Polverelli, Giorgia Micucci, Elena Masselli, Costanza Bosi, Florian H. Heidel, Roberto Latagliata, Fabrizio Pane, Antonio Cuneo, Mauro Krampera, Gianpietro Semenzato, Roberto M. Lemoli, Nicola Vianelli, Michele Cavo, Giuseppe A. Palumbo, Massimiliano Bonifacio
Journal: Blood (2020)
The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia
Authors: Nianyi Li, Guangjie Zhao, Wanling Wu, Mengxue Zhang, Weiyang Liu, Qinfen Chen, Xiaoqin Wang
Journal: JAMA Network Open (2020)

It remains uncertain whether vitamin C routinely used with oral iron supplements is essential for patients with iron deficiency anemia (IDA).To compare the equivalence and assess the safety of oral iron supplements plus vitamin C or oral iron supplements alone in patients with IDA.This single-center, open-label, equivalence randomized clinical trial was conducted from January 1, 2016, to December 30, 2017, in Huashan Hospital, Fudan University. Adult patients with newly diagnosed IDA were enrolled. Participants were randomly assigned (1:1) to the oral iron supplements plus vitamin C group or the oral iron supplements-only group. Data analysis was performed from March to December 2018.Patients were randomized to receive a 100-mg oral iron tablet plus 200 mg of vitamin C or a 100-mg iron tablet alone every 8 hours daily for 3 months.The primary outcome was the change in hemoglobin level from baseline to 2 weeks of treatment, and an equivalence margin of 1 g/dL in hemoglobin was chosen for the demonstration of comparable efficacy. Secondary outcomes included the change in the reticulocyte percentage after 2 weeks of treatment, the increase in hemoglobin level after 4 weeks of treatment, the increase in serum ferritin level after 8 weeks of treatment, and adverse events.Among the 440 randomized patients (220 each in the oral iron supplements plus vitamin C group and iron-only group; 426 women [96.8%]; mean [SD] age, 38.3 [11.7] years), all were assessed for the primary outcome, and 432 (98.2%) completed the trial. From baseline to the 2-week follow-up, the mean (SD) change in hemoglobin level was 2.00 (1.08) g/dL in the oral iron supplements plus vitamin C group and 1.84 (0.97) g/dL in the oral iron supplements-only group (between-group difference, 0.16 g/dL; 95% CI, -0.03 to 0.35 g/dL), thus meeting the criteria for equivalence. The mean (SD) change in serum ferritin level from baseline to 8-week follow-up was 35.75 (11.52) ng/mL in the vitamin C plus iron group and 34.48 (9.50) ng/mL in the iron-only group (between-group difference, 1.27 ng/mL; 95% CI, -0.70 to 3.24 ng/mL; P = .21). There were no significant differences between the 2 groups regarding the rates of adverse events (46 [20.9%] vs 45 [20.5%]; difference, 0.4%; 95% CI, -6.7% to 8.5%; P = .82). No patient withdrew because of adverse events.Among patients with IDA, oral iron supplements alone were equivalent to oral iron supplements plus vitamin C in improving hemoglobin recovery and iron absorption. These findings suggest that on-demand vitamin C supplements are not essential to take along with oral iron supplements for patients with IDA.ClinicalTrials.gov Identifier: NCT02631668.
Microvascular Dysfunction in Diabetes Mellitus and Cardiometabolic Disease
Authors: William B Horton, Eugene J Barrett
Journal: Endocrine Reviews (2020)

Abstract This review takes an inclusive approach to microvascular dysfunction in diabetes mellitus and cardiometabolic disease. In virtually every organ, dynamic interactions between the microvasculature and resident tissue elements normally modulate vascular and tissue function in a homeostatic fashion. This regulation is disordered by diabetes mellitus, by hypertension, by obesity, and by dyslipidemia individually (or combined in cardiometabolic disease), with dysfunction serving as an early marker of change. In particular, we suggest that the familiar retinal, renal, and neural complications of diabetes mellitus are late-stage manifestations of microvascular injury that begins years earlier and is often abetted by other cardiometabolic disease elements (eg, hypertension, obesity, dyslipidemia). We focus on evidence that microvascular dysfunction precedes anatomic microvascular disease in these organs as well as in heart, muscle, and brain. We suggest that early on, diabetes mellitus and/or cardiometabolic disease can each cause reversible microvascular injury with accompanying dysfunction, which in time may or may not become irreversible and anatomically identifiable disease (eg, vascular basement membrane thickening, capillary rarefaction, pericyte loss, etc.). Consequences can include the familiar vision loss, renal insufficiency, and neuropathy, but also heart failure, sarcopenia, cognitive impairment, and escalating metabolic dysfunction. Our understanding of normal microvascular function and early dysfunction is rapidly evolving, aided by innovative genetic and imaging tools. This is leading, in tissues like the retina, to testing novel preventive interventions at early, reversible stages of microvascular injury. Great hope lies in the possibility that some of these interventions may develop into effective therapies.
Descriptive Analysis of Isatuximab Use Following Prior Daratumumab in Patients with Relapsed/Refractory Multiple Myeloma
Authors: Melody R Becnel, Sandra B. Horowitz, Sheeba K. Thomas, Swami P. Iyer, Krina K. Patel, Elisabet E. Manasanch, Donna M. Weber, Gregory P. Kaufman, Hans C. Lee, Robert Z. Orlowski
Journal: Blood (2020)
Extramedullary Relapse after Chemotherapy-Only Conditioning in Latin-Americans with Acute Leukemia: A Common Problem
Authors: Christianne Bourlon De Los Rios, Aldo A. Acosta-Medina, Luis Arias-Espinosa, Perla R Colunga Pedraza, Jose Angel Hawing-Zarate, José Miguel Alvarez Blanco, Guillermo Pacheco-Gutierrez, Georgina Barrera-Lumbreras, Andres Gomez-De Leon
Journal: Blood (2020)
Mesothelin Expression Is Associated with Extramedullary Disease and Promotes <i>In Vivo</i> Leukemic Growth in Acute Myeloid Leukemia
Authors: Katherine Tarlock, Todd A. Alonzo, Robert B. Gerbing, Quy Le, Thao T. Tang, Darcy Hamill, Anilkumar Gopalakrishnapillai, Sonali Barwe, Rhonda E. Ries, Richard Aplenc, Andrew C. Wood, E. Anders Kolb, Soheil Meshinchi
Journal: Blood (2020)
Severity of Sars-Cov-2 Infection in Patients with Hematologic Malignancies: A COVID-19 and Cancer Consortium (CCC19) Registry Analysis
Authors: Samuel Rubinstein, Ryan C. Lynch, Aakash Desai, Catherine Stratton, Alokkumar Jha, Ziad Bakouny, Andrew Schmidt, R. Alejandro Sica, Divaya Bhutani, Dimpy P. Shah, Sarah A Wall, Gary H. Lyman, Nicole M. Kuderer, Matthias Weiss, Jeremy L. Warner, Keith E. Stockerl-Goldstein, Ruben Mesa, Michael A. Thompson
Journal: Blood (2020)
Evaluation of the Incidence and Risk Factors Associated with Major Cardiovascular Events in Patients Receiving Acalabrutinib Therapy
Authors: Leylah Azali, Lindsay Hazelden, Tracy Wiczer, Marilly Palettas, Rebekah Thomas, Connor Aossey, James S. Blachly, Michael R. Grever, Adam S. Kittai, Kerry A. Rogers, John C. Byrd, Jennifer A. Woyach, Daniel Addison, Seema A Bhat
Journal: Blood (2020)
Can Dual‐Energy Computed Tomography Be Used to Identify Early Calcium Crystal Deposition in the Knees of Patients With Calcium Pyrophosphate Deposition?
Authors: Jean‐François Budzik, Claire Marzin, Julie Legrand, Laurène Norberciak, Fabio Becce, Tristan Pascart
Journal: Arthritis & Rheumatology (2020)

Objective To assess the ability of dual‐energy computed tomography (DECT) in identifying early calcium crystal deposition in menisci and articular cartilage of the knee, depending on the presence/absence of chondrocalcinosis seen on conventional CT. Methods One hundred thirty‐two knee DECT scans from patients with suspected crystal‐associated arthropathy were reviewed and assigned to a calcium pyrophosphate deposition (CPPD) group (n = 50) or a control group (n = 82). Five DECT attenuation parameters were measured in preset regions of interest (ROIs) in menisci and articular cartilage and compared between groups using linear mixed models with adjustment for confounders. Subgroup analysis, excluding ROIs with chondrocalcinosis seen on conventional CT, was performed. Results In both menisci and articular cartilage, and for all 5 DECT attenuation parameters, calcified ROIs in CPPD patients showed significantly higher values than ROIs in controls ( P ≤ 0.036). Conversely, noncalcified ROIs in CPPD patients were comparable with those in controls ( P ≥ 0.09). While specific DECT parameters yielded good accuracy (area under the curve [AUC] 0.87–0.88) in differentiating calcified ROIs in CPPD patients from ROIs in controls, DECT failed to distinguish between noncalcified ROIs in CPPD patients and controls (AUC 0.58–0.59). Conclusion While DECT has the potential to characterize knee intraarticular mineralization, this technique cannot yet accurately identify early calcium crystal deposition that is not visible as chondrocalcinosis on conventional CT.
Watch Your Language!—Misusage and Neologisms in Clinical Communication
Authors: Andrew M. Luks, Zachary D. Goldberger
Journal: JAMA Internal Medicine (2020)

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Molecular Characterisation of Participants in the Phazar Trial Reveals Prognostic Impact of Mutations in Advanced-Phase-MPN
Authors: Charlotte K Brierley, Alba Rodriguez-Meira, Matthew Bashton, Angela Hamblin, Rachel S Fletcher, Sonia Fox, Charlotte Gaskell, Aimee Jackson, Jennifer O'Sullivan, Lauren C Murphy, Nikolaos Sousos, Amir Enshaei, Claire Harrison, Mark W. Drummond, Steve Knapper, Bethan Psaila, Adam J. Mead
Journal: Blood (2020)
Clinical Characteristics and Outcomes of COVID-19 in HSCT Recipients
Authors: Clarisse MARTINS Machado, Mariana Nassif Kerbauy, Iago Colturato, Leonardo Javier Arcuri, Ana Cláudia Ferrari dos Santos, Fernanda Rodrigues Silva, Anderson João Simioni, Juliana Folloni Fernandes, Mair Pedro de Souza, Vergilio Rensi Colturato, Nelson Hamerschlak
Journal: Blood (2020)