tbuckley/cabot-search huggingface dataset:
Response to: ‘Correspondence on ‘Effectiveness of secukinumab versus an alternative TNF inhibitor in patients with axial spondyloarthritis previously exposed to TNF inhibitors in the Swiss Clinical Quality Management cohort’ by Micheroli<i>et al’</i>by Huang<i>et al</i>
Authors: Adrian Ciurea, Raphael Micheroli
Journal: Annals of the Rheumatic Diseases (2020)

We would like to thank Huang et al 1 for their interest in our study2 and the opportunity to discuss some aspects in more detail.

The limited sample size precluded subgroup analyses with regard to either the type of tumour necrosis factor inhibitor (TNFi) agent or the reason for discontinuation of the previous biologic disease-modifying antirheumatic drug (bDMARD). Moreover, drug discontinuation might be due to a combination of reasons (eg, only partial effectiveness combined with otherwise acceptable adverse events (AE)) further impeding this type of analysis in a real-world setting and requiring the definition of a hierarchy of reasons for discontinuation as introduced in a previous study.3

We have used two different statistical methods to account for potential …
The Longitudinal Immune Response to Coronavirus Disease 2019: Chasing the Cytokine Storm
Authors: Alice S. Chau, Andrew G. Weber, Naomi I. Maria, Sonali Narain, Audrey Liu, Negin Hajizadeh, Prashant Malhotra, Ona Bloom, Galina Marder, Blanka Kaplan
Journal: Arthritis & Rheumatology (2020)

The clinical progression of the severe acute respiratory syndrome coronavirus 2 infection, coronavirus 2019 (COVID‐19), to critical illness is associated with an exaggerated immune response, leading to magnified inflammation termed the “cytokine storm.” This response is thought to contribute to the pathogenicity of severe COVID‐19. There is an initial weak interferon response and macrophage activation that results in delayed neutrophil recruitment leading to impeded viral clearance. This causes prolonged immune stimulation and the release of proinflammatory cytokines. Elevated inflammatory markers in COVID‐19 (e.g., d ‐dimer, C‐reactive protein, lactate dehydrogenase, ferritin, and interleukin‐6) are reminiscent of the cytokine storm seen in severe hyperinflammatory macrophage disorders. The dysfunctional immune response in COVID‐19 also includes lymphopenia, reduced T cells, reduced natural killer cell maturation, and unmitigated plasmablast proliferation causing aberrant IgG levels. The progression to severe disease is accompanied by endotheliopathy, immunothrombosis, and hypercoagulability. Thus, both parts of the immune system—innate and adaptive—play a significant role in the cytokine storm, multiorgan dysfunction, and coagulopathy. This review highlights the importance of understanding the immunologic mechanisms of COVID‐19 as they inform the clinical presentation and advise potential therapeutic targets.
Cell Fate Decisions: The Role of Transcription Factors in Early B-cell Development and Leukemia
Authors: Ute Fischer, Jun J. Yang, Tomokatsu Ikawa, Daniel Hein, Carolina Vicente-Dueñas, Arndt Borkhardt, Isidro Sánchez-García
Journal: Blood Cancer Discovery (2020)

Abstract B cells are an integral part of the adaptive immune system and regulate innate immunity. Derived from hematopoietic stem cells, B cells mature through a series of cell fate decisions. Complex transcriptional circuits form and dissipate dynamically during these lineage restrictions. Genomic aberrations of involved transcription factors underlie various B-cell disorders. Acquired somatic aberrations are associated with cancer, whereas germline variations predispose to both malignant and nonmalignant diseases. We review the opposing role of transcription factors during B-cell development in health and disease. We focus on early B-cell leukemia and discuss novel causative gene–environment cooperation and their implications for precision medicine. Childhood leukemia is frequently initiated during fetal hematopoiesis. Clinical silent preleukemic clones are detectable in cord blood of a large number of healthy newborns. These predisposing alterations cooperate with environmental factors to trigger leukemia onset. Understanding of the underlying principles is a prerequisite for the development of measures to prevent leukemia in children.
Rectal Neuroendocrine Tumor With Inferior Vena Cava Tumor Thrombosis Diagnosed With 68Ga-DOTANOC PET/CT
Authors: Sarai Morón, Carlos Cortés, Monica Naranjo, Carlos Granados, Julián Rojas
Journal: Clinical Nuclear Medicine (2020)

Abstract A 69-year-old man with a history of back pain, urinary obstruction, and deep vein thrombosis of both lower extremities 4 years earlier was diagnosed with rectal neuroendocrine tumor, grade 2, Ki-67 index 3%. 68 Ga-DOTANOC PET/CT images showed a left pelvic mass extended to the lumen of the inferior vena cava with a high affinity for somatostatin receptor. A tubular focus of radiotracer accumulation after the course of inferior vena cava with filling defect was suggestive of tumor thrombus.
B cell acute lymphoblastic leukemia cells mediate RANK-RANKL–dependent bone destruction
Authors: Sujeetha A. Rajakumar, Eniko Papp, Kathy K. Lee, Ildiko Grandal, Daniele Merico, Careesa C. Liu, Bedilu Allo, Lucia Zhang, Marc D. Grynpas, Mark D. Minden, Johann K. Hitzler, Cynthia J. Guidos, Jayne S. Danska
Journal: Science Translational Medicine (2020)

Primary B-ALL cells cause RANKL-mediated trabecular bone and growth plate destruction in patient-derived xenograft models.
Integrating the ABC-Bleeding Risk Score Into Practice
Authors: Celina M. Yong, John A. Bittl
Journal: JAMA Network Open (2020)

Ziad Hijazi, MD, PhD; Jonas Oldgren, MD, PhD; Johan Lindbäck, MSc; John H. Alexander, MD, MHS; Marco Alings, MD, PhD; Raffaele De Caterina, MD, PhD; John W. Eikelboom, MD; Michael D. Ezekowitz, MBChB, DPhil; Claes Held, MD, PhD; Kurt Huber, MD; Elaine M. Hylek, MD, MPH; Christopher B. Granger, MD; Renato D. Lopes, MD, PhD; Dragos Vinereanu, MD, PhD; Agneta Siegbahn, MD, PhD; Lars Wallentin, MD, PhD
Rapid introduction of National Health Service Attend Anywhere video consultation during the COVID-19 pandemic
Authors: R. Jones, G. Gupta, C. Stothart, C. Bertram, D. McKay
Journal: British Journal of Dermatology (2020)

Early in the COVID-19 pandemic, it was apparent that capacity for face-to-face (F2F) dermatology appointments would plummet  Within 2 weeks we introduced the National Health Service (NHS) Attend Anywhere video consultation platform  In the absence of a pilot project we undertook an analysis of our initial experience with the platform  Data were collected prospectively through a paper-based survey of clinical users within outpatients over 4 weeks in May 2020  We collected data on 103 virtual appointments  Twenty-six (25 2%) patients failed to attend  Of 77 consultations there were 33 general dermatology, 28 tumour, 12 allergy and four paediatric patients  Good video quality was reported in 34 of 77 consultations (44%)  Good audio quality was reported in 47 of 77 consultations (61%)  For general patients, 58% of consultations resulted in a subsequent F2F consultation, 21% further virtual consultation, 18% were discharged or received advice only and 3% attended for investigations  Forty-eight per cent of consultations were felt to be better than or as good as F2F  For tumour patients, 57% of consultations resulted in a subsequent F2F consultation, 29% went directly to surgery, 11% were discharged or received advice only, and 3% were referred to another specialty  All consultations were felt to be inferior to a F2F appointment  For allergy patients, 50% attended for further investigations  Thirty-three per cent of consultations resulted in a subsequent F2F consultation, 8 3% of patients had a further virtual consultation and 8 3% received advice only or were discharged  Sixty-six per cent of allergy consultations were felt to be better than F2F, often owing to the requirement for patient shielding  The remaining 34% of consultations were felt to be as good as F2F  Positive themes from users included a reduced need for F2F consultations, especially for patients who were shielding  In some cases, patients were referred directly for investigations or treatment, reducing the overall visits to the department  The main negative theme was that clinical examination was very limited  In particular, clinicians were concerned about the inability to palpate the skin, use dermoscopy and perform a full skin survey  NHS Attend Anywhere was introduced out of necessity  In our experience, it is not suitable for the assessment of patients with skin tumours  With F2F clinic capacity likely to be constrained for some time, the platform has some utility in the assessment of new general patients, allergy patients and in monitoring of existing patients, particularly those on immunosuppression
Assessing self-medication for obstructive airway disease during COVID-19 using <i>Google Trends</i>
Authors: Sabina Sahanic, Anna Boehm, Alex Pizzini, Thomas Sonnweber, Magdalena Aichner, Guenter Weiss, Judith Loeffler-Ragg, Ivan Tancevski
Journal: European Respiratory Journal (2020)

<b><i>Google Trends</i> reveals public information-seeking for self-medication in patients with obstructive respiratory disease during the COVID-19 outbreak, illustrating the urgent need to implement digital health support in patients with respiratory disease</b>https://bit.ly/2GRccSU
New indicators will track doctors’ careers to expose racism
Authors: Elisabeth Mahase
Journal: BMJ (2020)

NHS England has launched a new set of indicators to expose ethnic disparities in the medical workforce, with data set to be presented to trusts later this year.1

The Medical Workforce Race Equality Standard (MWRES) has been created to capture “several issues” particular to doctors that are not picked up by the general NHS staff WRES introduced in 2015.

Around two fifths (41%) of the NHS’s doctors are from ethnic minority groups, but evidence shows that they are less likely to be treated favourably than their white colleagues and have poorer experience and progression opportunities.

The document outlining the new indicators says that there are several areas in which more granular data …
Convalescent plasma treatment of severe COVID-19: a propensity score–matched control study
Authors: Sean T. H. Liu, Hung-Mo Lin, Ian Baine, Ania Wajnberg, Jeffrey P. Gumprecht, Farah Rahman, Denise Rodriguez, Pranai Tandon, Adel Bassily-Marcus, Jeffrey Bander, Charles Sanky, Amy Dupper, Allen Zheng, Freddy T. Nguyen, Fatima Amanat, Daniel Stadlbauer, Deena R. Altman, Benjamin K. Chen, Florian Krammer, Damodara Rao Mendu, Adolfo Firpo-Betancourt, Matthew A. Levin, Emilia Bagiella, Arturo Casadevall, Carlos Cordon-Cardo, Jeffrey S. Jhang, Suzanne A. Arinsburg, David L. Reich, Judith A. Aberg, Nicole M. Bouvier
Journal: Nature Medicine (2020)

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new human disease with few effective treatments1. Convalescent plasma, donated by persons who have recovered from COVID-19, is the acellular component of blood that contains antibodies, including those that specifically recognize SARS-CoV-2. These antibodies, when transfused into patients infected with SARS-CoV-2, are thought to exert an antiviral effect, suppressing virus replication before patients have mounted their own humoral immune responses2,3. Virus-specific antibodies from recovered persons are often the first available therapy for an emerging infectious disease, a stopgap treatment while new antivirals and vaccines are being developed1,2. This retrospective, propensity score–matched case–control study assessed the effectiveness of convalescent plasma therapy in 39 patients with severe or life-threatening COVID-19 at The Mount Sinai Hospital in New York City. Oxygen requirements on day 14 after transfusion worsened in 17.9% of plasma recipients versus 28.2% of propensity score–matched controls who were hospitalized with COVID-19 (adjusted odds ratio (OR), 0.86; 95% confidence interval (CI), 0.75–0.98; chi-square test P value = 0.025). Survival also improved in plasma recipients (adjusted hazard ratio (HR), 0.34; 95% CI, 0.13–0.89; chi-square test P = 0.027). Convalescent plasma is potentially effective against COVID-19, but adequately powered, randomized controlled trials are needed. Convalescent plasma for treatment of hospitalized patients with COVID-19 is associated with improved survival in a retrospective comparison with matched controls, supporting further study in randomized controlled trials.
SARS-CoV-2–triggered neutrophil extracellular traps mediate COVID-19 pathology
Authors: Flavio Protasio Veras, Marjorie Cornejo Pontelli, Camila Meirelles Silva, Juliana E. Toller-Kawahisa, Mikhael de Lima, Daniele Carvalho Nascimento, Ayda Henriques Schneider, Diego Caetité, Lucas Alves Tavares, Isadora M. Paiva, Roberta Rosales, David Colón, Ronaldo Martins, Italo Araujo Castro, Glaucia M. Almeida, Maria Isabel Fernandes Lopes, Maíra Nilson Benatti, Letícia Pastorelli Bonjorno, Marcela Cavichioli Giannini, Rodrigo Luppino-Assad, Sérgio Luna Almeida, Fernando Vilar, Rodrigo Santana, Valdes R. Bollela, Maria Auxiliadora-Martins, Marcos Borges, Carlos Henrique Miranda, Antônio Pazin-Filho, Luis Lamberti P. da Silva, Larissa Dias Cunha, Dario S. Zamboni, Felipe Dal-Pizzol, Luiz O. Leiria, Li Siyuan, Sabrina Batah, Alexandre Fabro, Thais Mauad, Marisa Dolhnikoff, Amaro Duarte-Neto, Paulo Saldiva, Thiago Mattar Cunha, José Carlos Alves-Filho, Eurico Arruda, Paulo Louzada-Junior, Renê Donizeti Oliveira, Fernando Queiroz Cunha
Journal: The Journal of Experimental Medicine (2020)

Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that neutrophil extracellular traps (NETs) have been described as important mediators of tissue damage in inflammatory diseases, we investigated whether NETs would be involved in COVID-19 pathophysiology. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and healthy controls were enrolled. The concentration of NETs was augmented in plasma, tracheal aspirate, and lung autopsies tissues from COVID-19 patients, and their neutrophils released higher levels of NETs. Notably, we found that viable SARS-CoV-2 can directly induce the release of NETs by healthy neutrophils. Mechanistically, NETs triggered by SARS-CoV-2 depend on angiotensin-converting enzyme 2, serine protease, virus replication, and PAD-4. Finally, NETs released by SARS-CoV-2-activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represents a potential therapeutic target for COVID-19.
Immunomodulation in Pomalidomide, Dexamethasone, and Daratumumab-Treated Patients with Relapsed/Refractory Multiple Myeloma
Authors: William E. Pierceall, Michael D. Amatangelo, Nizar J. Bahlis, David S. Siegel, Adeeb Rahman, Oliver Van Oekelen, Paola Neri, Mary Young, Weiyuan Chung, Natalya Serbina, Samir Parekh, Amit Agarwal, Anjan Thakurta
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Addition of daratumumab to pomalidomide and low-dose dexamethasone (LoDEX) is a safe and effective combination for relapsed/refractory multiple myeloma treatment. We sought to better understand immune combinational benefit of pomalidomide and daratumumab with LoDEX. Patients and Methods: Immunophenotypic changes were analyzed in peripheral blood from longitudinal sampling of patients treated with this triplet regimen from cohort B of the CC4047-MM-014 phase II trial (NCT01946477). Results: Consistent with the daratumumab mechanism, treatment led to decreased natural killer (NK) and B cells. In contrast, pronounced increases occurred in activated and proliferating NK and T cells, appreciably in CD8+ T cells, along with reduction in naïve and expansion of effector memory compartments. Timing of T-cell changes correlated with pomalidomide dosing schedule. Enhanced activation/differentiation did not result in increased exhausted T-cell phenotypes or increases in regulatory T cells. Similar immune enhancements were also observed in patients previously refractory to lenalidomide. Conclusions: These data support a potential mechanism for enhanced immune-mediated cytotoxicity in which daratumumab-mediated NK-cell diminution is partially offset by pomalidomide effects on the remaining NK-cell pool. Furthermore, daratumumab antimyeloma activity and elimination of CD38+ T cells (regulatory/activated) provide a rationale for therapeutic combination with direct tumoricidal activity and immunomodulation of pomalidomide-directed T-cell enhancements. These data highlight enhancements in immune subpopulations for the combination of daratumumab with pomalidomide and potentially with next-generation cereblon-targeting agents.
Abstract 12816: National Variation in Congenital Heart Surgery Outcomes and Impact on Strategies For Improvement
Authors: Sara K Pasquali, Dylan Thibault, Jeffrey P Jacobs, J. W Gaynor, Jennifer C Romano, Michael G Gaies, Sean M O’Brien, Kevin D Hill, Marshall L Jacobs, David M Shahian, John E Mayer
Journal: Circulation (2019)

Introduction: Optimal strategies to improve national congenital heart surgery (CHS) outcomes and reduce variability across centers remain unclear. Many policy and quality improvement efforts have f...
Factors associated with hospitalization due to COVID-19 in patients with psoriasis: Insights from a global registry
Authors: S. Mahil, N. Dand, K. Mason, Z. Yiu, T. Tsakok, F. Meynell, B. Coker, H. McAteer, L. Moorhead, T. Mackenzie, P. Calzavara Pinton, R. Rivera, E. Mahe, A. Carugno, M. Magnano, G. Rech, E. Balogh, S. Feldman, D. McMahon, E. Freeman, P. Gisondi, L. Puig, R. Warren, P. Di Meglio, S. Langan, F. Capon, C. Griffiths, J. Barker, C. Smith
Journal: British Journal of Dermatology (2020)

Psoriasis is a common immune-mediated inflammatory skin disease with frequent multimorbidity, and immunosuppressants are the mainstay of treatment in moderate-to-severe disease  An understanding of the impact of COVID-19 on individuals with psoriasis and the effect of psoriasis therapies on the course of COVID-19 is urgently required to inform clinical decision-making  This study sought to characterize the clinical course of COVID-19 in patients with psoriasis and to identify factors associated with hospitalization  Clinicianreported cases of confirmed or suspected COVID-19 in psoriasis were collected via an international online registry  Multivariable-adjusted logistic regression identified factors associated with hospitalization  Patient risk-mitigating behaviours were characterized using an independent global selfreport registry  In total, 334 clinician-reported cases (median age 50 years, 62% male, median body mass index 28 kg m-2, 85% white) from 22 countries [most frequently, the U K  (35%), Italy (22%) and Spain (16%)] were available between 27 March and 20 June 2020  Altogether, 245 (73 3%) patients were receiving a biologic, 54 (16 2%) a nonbiologic and 31 (9 3%) no systemic treatment  Overall, 311 (93 1%) achieved a full recovery, 71 (21 2%) were hospitalized and nine (2 7%) died  Risk factors associated with hospitalization were older age [adjusted odds ratio (aOR) 1 71, 95% confidence interval (CI) 1 26-2 32], male sex (aOR 2 37, 95% CI 1 11-5 04) and nonwhite ethnicity (aOR 3 40, 95% CI 1 27-9 11), in addition to chronic lung disease (aOR 4 37, 95% CI 1 62-11 74) and hypertension (aOR 2 23, 95% CI 1 05-4 74)  Reduced risk of hospitalization was associated with use of a biologic (aOR 0 42, 95% CI 0 18-0 98) vs  nonbiological systemic therapy  There was no difference in risk of hospitalization between classes of biologics  An independent selfreport psoriasis registry (1167 patients from 39 countries) suggested increased social isolation (76% vs  66%;P < 0 05) but similar nonadherence to medication (18% vs 22%) in patients receiving biologics vs  nonbiological systemic treatments  In this international moderate-to-severe psoriasis case series, most patients fully recovered from COVID-19;older age, being male and being of nonwhite ethnicity increased risk of hospitalization  Use of biologics, when compared with nonbiological systemic therapies, was associated with reduced risk of hospitalization;however, this requires further study owing to potential selection bias and unmeasured confounding such as a difference in risk-mitigating behaviours
An Mb1-Cre-driven oncogenic Kras mutation results in a mouse model of T-acute lymphoblastic leukemia/lymphoma with short latency and high penetrance
Authors: Jacob J. Junco, Taylor Chen, Raushan Rashid, Maci Terrell, Vincent U. Gant, Matthew Miller, Rachel Rau, H. Daniel Lacorazza, Karen R. Rabin
Journal: Leukemia (2020)
A Comparison of Clinical Characteristics and Treatment Outcome in Myeloid Sarcoma Versus Acute Myeloid Leukemia Patients without Extramedullary Involvement — Case Control Study of the Polish Adult Leukemia Group (PALG)
Authors: Elżbieta Patkowska, Andrzej Szczepaniak, Marta Baranska, Maciej Kazmierczak, Monika Paluszewska, Wieslaw Jedrzejczak, Renata Guzicka Kazmierczak, Wanda Knopinska Posluszny, Olga Grzybowska-Izydorczyk, Agnieszka Pluta, Jaroslaw Piszcz, Izabela Deren-Wagemann, Ewa Lech Maranda, Krzysztof Warzocha, Joanna Gora Tybor
Journal: Blood (2017)
AB1251 VALIDITY OF RHEUMATOID ARTHRITIS DIAGNOSES IN FINNISH BIOBANK PATIENTS
Authors: A. Palomäki, J. Paltta, L. Pirilä, H. K. Heikkilä, P. Isomäki, J. Huhtakangas, T. Sokka-Isler, O. Kaipiainen-Seppänen, K. Eklund
Journal: Annals of the Rheumatic Diseases (2020)

Background: Finnish healthcare registers are used in medical research, but there is little data about the validity of these registers in rheumatology. Objectives: The aim of our study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in the Finnish Biobanks. Methods: We reviewed the electronic patient charts of 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA and 250 age-and-sex matched controls. Patients were randomly selected from Finnish biobank participants. We evaluated whether the patients’ diagnosis of RA recorded in the hospital discharge registry at the participating hospital was correct according to chart review and expert opinion. In the control group it was investigated whether the diagnosis of RA was written in the patients’ chart, but the diagnosis code was not recorded. Results: The positive predictive value (PPV) of a single hospital registry diagnosis of seropositive RA was 0.74 but rose to 0.98 in patients with a special reimbursement for seropositive RA and 0.98 in anti-citrullinated protein antibody positive patients. For seronegative RA, the PPV of a diagnosis was 0.72 and in patients with a special reimbursement for seronegative RA 0.89. The PPV was higher in patients with more than one visit with the diagnosis: 0.92 if the patients had at least 5 visits with seropositive RA and 0.88 with at least 5 visits with seronegative RA. Negative predictive value for RA diagnosis was 0.99. Conclusion: These results demonstrate that the validity of RA diagnoses in healthcare registers can be markedly improved with data about special reimbursement for medication, number of visits and serological data. Disclosure of Interests: Antti Palomäki Consultant of: Pfizer, Speakers bureau: Pfizer, Sanofi, MSD, Johanna Paltta Consultant of: Lilly, Abbvie, Laura Pirilä Consultant of: Novartis, MSD Finland, Roche, Bristol-Myers-Squibb, Pfizer, Sanofi, Abbvie, Oy Eli LIlly Finland Ab, UCB Pharma Oy Finland, Jansen-Cilag, Mylan, Sandoz, Boehringer-Ingelheim, Paid instructor for: Boehringer -Ingelheim, MSD Finland, Speakers bureau: Boehringer-Ingelheim, Pfizer Finland, Hanna-Kaisa Heikkilä: None declared, Pia Isomäki Consultant of: Abbvie, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, Johanna Huhtakangas Consultant of: Boehringer Ingelheim, Tuulikki Sokka-Isler: None declared, Oili Kaipiainen-Seppänen Speakers bureau: Boehringer Ingelheim, Kari Eklund Consultant of: Celgene, Lilly, Speakers bureau: Pfizer, Roche