tbuckley/cabot-search huggingface dataset:
AB0852 BREAKING THE GLASS CEILING IN MEXICAN RHEUMATOLOGY
Authors: I. J. Colunga-Pedraza, G. Serna-Peña, D. Alpizar-Rodriguez, N. Guajardo-Jauregui, R. Galarza-Molina, D. Á. Galarza-Delgado, C. F. Pacheco Tena, M. A. Reyes Soto
Journal: Annals of the Rheumatic Diseases (2021)

Background: The term “glass ceiling” has been used since the late eighties, to designate an invisible barrier that prevents highly qualified women from reaching positions of responsibility in the organizations they work. (1) At first, this concept was used to analyze the career of women who, having a professional career and a high level of competition in their workplaces, encountered an interference when trying to advance in their careers. (2). The so-called “glass ceiling” refers to a last barrier based on prejudice towards women that prevents them from advancing to high-level positions. Currently, there is almost the same number of men and women affiliated to the Mexican College of Rheumatology (CMR). The position of president is the highest directorial position, we undertook the task of evaluating the percentage of women who have historically held that leadership position. Objectives: To assess the percentage of woman who have occupied the position of president of the Mexican College of Rheumatology. Methods: Observational, cross-sectional study. We evaluated the number of man and women who have historically held the position of president of the CMR. Results: Currently, the CMR has 630 active members, 308 women (48.9%) and 322 men (51.1%). Among rheumatologists younger than 40 years of age, women represent 58% (n=128). We found that historically the CMR has had 48 presidents, of which only 4 (8.3%) are women. Conclusion: There is a big gender gap between presidents of the CMR. It is important to talk about the gender perspective and recognize the causes that have originated this gap. Incorporating the gender perspective in senior management is a pending issue for our CMR. References: [1]Barberá E, Ramos A, Sarrió M, et al. Laberinto de cristal en el liderazgo de las mujeres. Psicothema 2011;23(2):173-179. [2]Bustos O. Mujeres rompiendo el techo de cristal: el caso de las universidades. OMNIA - Revista de la Coordinación de Estudios de Posgrado 2002(41);1-7. Acknowledgements: We have no acknowledgements to declare. Disclosure of Interests: None declared
Calcineurin inhibitors target Lck activation in graft-versus-host disease
Authors: Nicole M. Carter, Joel L. Pomerantz
Journal: Journal of Clinical Investigation (2021)

Calcineurin inhibitors (CNIs) such as cyclosporin A and FK506 are widely administered immunosuppressive drugs. Calcineurin relieves inhibitory phosphorylation from nuclear factor of activated T cells (NFAT) transcription factors downstream of T cell receptor engagement, resulting in their nuclear translocation and the production of cytokines, including IL-2, IFN-γ, and TNF-α. It was previously believed that CNIs downregulate immunity by reducing NFAT activation. However, work from Otsuka et al. in this issue of the JCI revealed a second mechanism by which CNIs suppress T cell function. The authors previously reported that calcineurin removes an inhibitory phosphate from the tyrosine kinase Lck at Ser59 (Lck-S59) and that this dephosphorylation positively regulates T cell activation. In the present work, the authors showed that inhibition of Lck-S59 dephosphorylation was essential for the CNI-mediated suppression of acute graft-versus-host disease (aGVHD). These findings have important implications for future approaches to the management of aGVHD, organ transplant rejection, and autoimmune disease.
T cell engaging bispecific antibodies targeting CD33 IgV and IgC domains for the treatment of acute myeloid leukemia
Authors: Sayed Shahabuddin Hoseini, Mallika Vadlamudi, Madelyn Espinosa-Cotton, Hoa Tran, Yi Feng, Hong-fen Guo, Hong Xu, Irene Cheung, Nai-Kong V Cheung
Journal: Journal for ImmunoTherapy of Cancer (2021)

Acute myeloid leukemia (AML) remains one of the most challenging hematological malignancies. Despite progress in therapeutics, majority of patients succumb to this neoplasm. CD33 is a proven therapeutic target, given its expression on most AML cells. Almost all anti-CD33 antibodies target the membrane distal immunoglobulin V (IgV) domain of the CD33 extracellular domain. In this manuscript, we present data on three bispecific antibodies (BsAbs) against the CD33 IgV and membrane proximal immunoglobulin C (IgC) domains. We use in vitro binding and cytotoxicity assays to show the effect of these BsAbs on AML cell lines. We also use immunodeficient mice-bearing leukemias from cell lines and patient-derived xenografts to show the effect of these BsAbs in vivo. In vitro, the IgV-targeting BsAb had higher binding to AML cell lines using flow cytometry and delivered more potent cytotoxicity in T-cell-dependent cytotoxicity assays; importantly, the IgC domain-targeting outperformed the IgV domain-targeting BsAb in medullary and extramedullary leukemia animal models. These data support further clinical development of this BsAb for first-in-human phase I clinical trial.
POS1479-HPR PATIENTS’ PERCEPTIONS OF PERSON-CENTRED CARE IN EARLY RA: A QUALITATIVE STUDY
Authors: E. Landgren, A. Bremander, E. Lindqvist, M. Nylander, I. Larsson
Journal: Annals of the Rheumatic Diseases (2021)

Background: Data on patients’ experience can identify strengths and weaknesses with given care, why a person-centred care will improve health care quality. In rheumatology care, most research on patient preferences for and experiences of RA care is performed in patients with established RA and less often in patients with early RA. In the early course of RA patients often struggle to manage their new life situation with a chronic disease and its treatment. Expectations and experiences of health care may change over time why it is important to understand how newly diagnosed patients perceive person-centred care. Objectives: To explore patients’ perceptions of person-centred care early in the RA disease course within the framework of person-centred care. Methods: In this qualitative study 31 patients with early RA from four rheumatology specialist outpatient clinics were interviewed. An abductive qualitative content analysis was conducted based on the framework of McCormack and McCance (2006, 2016). The four constructs; prerequisites, care environment, person-centred processes, and person-centred outcomes constituted the four categories in the deductive part of the study. An inductive analysis revealed eleven sub-categories exploring the content of person-centred care for patients with early RA. Results: For patients with early RA person-centred care was described as; 1. Prerequisites were to be treated with respect, to meet dedicated healthcare professionals, and to meet professional competence. 2. The care environment was to have access to a multidisciplinary team, to have access to health care, and a supportive organization. 3. Person-centred processes were to be listened to, to be supported, and to be involved in decision-making. 4. The person-centred outcomes were to be satisfied with received health care and to achieve optimal health. Conclusion: A true person-centred care is important to patients early in the RA disease course, supporting the relevance to implement person-centred approach at all stages in the health care system. This study contributes to information about how to further develop person-centredness in rheumatology care also early in the disease course. References: [1]McCormack, B., &amp; McCance, T. V. (2006). Development of a framework for person-centred nursing. J Adv Nurs, 56 (5), 472-479. doi:10.1111/j.1365-2648.2006.04042.x [2]McCormack, B., &amp; McCance, T. V. (2016). Person-centred practice in nursing and health care: theory and practice (2nd edition ed.): John Wiley &amp; Sons. Disclosure of Interests: None declared
HIV Viral Load Monitoring Among Patients Receiving Antiretroviral Therapy — Eight Sub-Saharan Africa Countries, 2013–2018
Authors: Shirley Lee Lecher, Peter Fonjungo, Dennis Ellenberger, Christiane Adje Toure, George Alemnji, Nancy Bowen, Frank Basiye, Anita Beukes, Sergio Carmona, Michael de Klerk, Karidia Diallo, Eric Dziuban, Charles Kiyaga, Henry Mbah, Johannes Mengistu, Tsietso Mots’oane, Christina Mwangi, Jane W. Mwangi, Michael Mwasekaga, Jonathan N’tale, Mary Naluguza, Isaac Ssewanyana, Wendy Stevens, Innocent Zungu, Ravikiran Bhairavabhotla, Helen Chun, Nicholas Gaffga, Stephen Jadczak, Spencer Lloyd, Shon Nguyen, Ritu Pati, Katrina Sleeman, Clement Zeh, Guoqing Zhang, Heather Alexander
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

One component of the Joint United Nations Programme on HIV/AIDS (UNAIDS) goal to end the HIV/AIDS epidemic by 2030, is that 95% of all persons receiving antiretroviral therapy (ART) achieve viral suppression.
POS1278 THE PREVALENCE AND CLINICAL SIGNIFICANCE OF ULTRASONOGRAPHIC FINDINGS OF DISTAL MEDIAL HAMSTRING TENDONS IN PATIENTS WITH POSTEROMEDIAL KNEE PAIN
Authors: H. Saad, Y. Gazar, S. Ghanem, A. Maaty
Journal: Annals of the Rheumatic Diseases (2021)

Background: Periarticular abnormalities are common ultrasonographic (U/S) findings in individuals with knee pain. Incidental U/S observations, including thickening of the distal hamstring tendons, require explanations for their clinical importance. Tendon thickness may be a good indicator of tendinopathy and tendon dysfunction. Also, it is uncertain whether these tendon changes are correlated with knee pain or not? Objectives: The aim of this study was to determine U/S findings of distal medial hamstring tendons in patients with posteromedial (PM) knee pain and assess the diagnostic values of tendon thickness in predicting tendinopathy. Methods: We studied distal medial hamstring tendons (semimembranosus [SM] and semitendinosus [ST]) of 104 patients (104 knees) with non-traumatic unilateral PM knee pain and 118 healthy controls (236 knees). U/S evaluations included tendon thickness, echogenicity, the presence of intrasubstance tears, calcification, and vascularity. Results: The mean age (standard deviation) of the patients and control groups were 51.7 (10.4) years and 49.8 (9.9) years, respectively. The mean visual analogue scale (VAS) for pain among patients was 5.1 and 58.6% of them located the pain at medial joint line. The studied patients had significantly higher mean SM thickness (7.17 mm vs. 5.46 mm, respectively) and ST thickness (3.93 mm vs. 3.45 mm, respectively) than the controls. U/S abnormalities among patients were hypoechogenicity (62.5%), intrasubstance tears (31.7%), loss of fibrillar pattern (23.1%), Baker cyst (20.2%), calcification (18.3%), Anserine bursitis (11.5%), and neovascularization (6.7%). We found significant correlations between tendon thickness and VAS (r=0.752, p=0.004), and pain location (r=0.680, p=0.008). SM thickness had higher accuracy to predict tendinopathy than ST thickness (80.6% vs. 68.9%, respectively). Table 1. Diagnostic values of tendon thickness in predicting tendinopathy. Tendons Cutoff Sensitivity Specificity +PV -PV Accuracy AUC SM &gt;6.6 70.2 89.8 85.7 76.8 80.6 0.835 ST &gt;3.7 56.7 79.6 71.1 67.6 68.9 0.696 SM: semimembranosus, ST: semitendinosus, +PV: positive predictive value, -PV: negative predictive value, AUC: area under curve. Conclusion: U/S changes are frequently present in patients with PM knee pain. Tendon thickness is an accurate predictor of tendinopathy. These findings suggest that U/S screening of all individuals with PM knee pain is a useful tool for improving patients’ outcomes and decreasing tendon-related disability. Disclosure of Interests: None declared
POS0324 SMOKING HISTORY AND SCLERODERMA CLINICAL TRIALS CONSORTIUM DAMAGE INDEX (SCTC-DI) AS INDEPENDENT PREDICTORS OF MORTALITY IN SYSTEMIC SCLEROSIS IN A SINGLE-CENTRE ITALIAN COHORT
Authors: M. Breda, M. G. Lazzaroni, F. Franceschini, P. Airò
Journal: Annals of the Rheumatic Diseases (2021)

Background: Systemic Sclerosis (SSc) is characterized by increased mortality and organ damage accrual. A composite SSc Damage Index was recently developed by the Scleroderma Clinical Trials Consortium (SCTC-DI) and was demonstrated as a predictor of mortality both in the Australian derivation cohort and in the Canadian validation cohort (1). Several independent predictors of mortality in SSc have been reported, but only limited data are available on the role of smoking. Objectives: To evaluate smoking history and SCTC-DI as independent predictors of mortality in SSc in a single centre Italian cohort. Methods: A retrospective analysis was performed on patients prospectively followed in our centre from 1989 to 2019, with at least 2 evaluations and/or cause of death available. Organ damage was evaluated through the SCTC-DI (0-55 scale; severe damage&gt;12), while comorbidities through the Charlson Comorbidity Index (CCI). Survival analysis was performed with Kaplan-Meier curves and with Log-rank test to compare different subsets. Cox-regression analysis was performed to identify baseline independent predictors of mortality. Results: 648 SSc patients were 99% Caucasian, 90% female and had a median age at diagnosis of 55.5 years (IQR: 45.0-65.6); 19% had diffuse cutaneous involvement. ACA was positive in 52%; anti-TopoI in 22% and anti-RNA Polymerase III in 5%. Median SCTC-DI at diagnosis was 2 (0-4) (n=560); ever smokers were 27%. During the follow-up 240 patients died after a median period of 10.2 years (4.9-16.8). The cause of death was related to SSc in 41% (n=65; most frequent causes pulmonary arterial hypertension (n=35) and interstitial lung disease (n=30)) and to other diseases in 40% (n=95; most frequent cause cancer (n=40)), while was indeterminate in 19%. Overall survival at 5, 10, 15, 20 years was 87.8% (SE 1.3%), 75.6% (1.9), 63.8% (2.3), 47.7% (2.8), respectively and was higher in females vs. males (p&lt;0.0001) and in ACA+ vs ACA- (p=0.005), but did not differ between cutaneous subsets. 111 patients were lost at follow-up (17%). In the Cox-regression analysis smoking history and severe organ damage at diagnosis (score&gt;12) were identified as independent predictors of death, while age at diagnosis, female gender, diffuse cutaneous subsets, ACA positivity and CCI were not (Table 1). Conclusion: Smoking history and severe organ damage were independent predictors of death in a large Italian single centre SSc cohort. SCTC-DI was confirmed as a useful tool to predict mortality at every timepoint References: [1]Ferdowsi N, et al. Ann Rheum Dis. 2019;78:807-16. Disclosure of Interests: None declared
Considering Trial Registries as a Platform for Timely Access to Study Results
Authors: Vanessa Piechotta, Nina Kreuzberger
Journal: JAMA Network Open (2021)

Xu Liu, MD, PhD; Yuan Zhang, MD, PhD; Wen-Fei Li, MD, PhD; Everett Vokes, MD; Ying Sun, PhD; Quynh-Thu Le, MD; Jun Ma, MD
How elite controllers and posttreatment controllers inform our search for an HIV-1 cure
Authors: Jonathan Z. Li, Joel N. Blankson
Journal: Journal of Clinical Investigation (2021)

A small percentage of people living with HIV-1 can control viral replication without antiretroviral therapy (ART). These patients are called elite controllers (ECs) if they are able to maintain viral suppression without initiating ART and posttreatment controllers (PTCs) if they control HIV replication after ART has been discontinued. Both types of controllers may serve as a model of a functional cure for HIV-1 but the mechanisms responsible for viral control have not been fully elucidated. In this review, we highlight key lessons that have been learned so far in the study of ECs and PTCs and their implications for HIV cure research.
Safety and efficacy of rituximab in systemic sclerosis (DESIRES): a double-blind, investigator-initiated, randomised, placebo-controlled trial
Authors: Satoshi Ebata, Ayumi Yoshizaki, Koji Oba, Kosuke Kashiwabara, Keiko Ueda, Yukari Uemura, Takeyuki Watadani, Takemichi Fukasawa, Shunsuke Miura, Asako Yoshizaki-Ogawa, Yoshihide Asano, Naoko Okiyama, Masanari Kodera, Minoru Hasegawa, Shinichi Sato
Journal: The Lancet Rheumatology (2021)
Abstract 19324: The Effect of Outpatient Systolic Blood Pressure and Mean Arterial Pressure on the Occurrence of Stroke and Pump Thrombosis in Patients on Axial Continuous-Flow Left Ventricular Assist Device Support
Authors: Alberto Pinsino, Amelia M Zuver, Francesco Castagna, Melana Yuzefpolskaya, Eric J Stöhr, Eugene A Royzman, Danielle L Brunjes, Arthur R Garan, Veli K Topkara, Koji Takeda, Hiroo Takayama, Yoshifumi Naka, P C Schulze, Ryan T Demmer, Joshua Z Willey, Paolo C Colombo
Journal: Circulation (2017)

Introduction: Elevated blood pressure (BP) represents a risk factor for stroke and pump thrombosis (PT) in continuous-flow left ventricular assist devices (CF-LVADs). Current guidelines recommendin...
Prayer Whistle in the SARS-CoV-2 Ward
Authors: Nuria M. Pastor-Soler
Journal: JAMA (2021)

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AB0031 METABOLIC ADAPTATION OF HUMAN NEUTROPHILS TO GLUCOSE DEPRIVATION IS IMPAIRED WITH INCREASING AGE
Authors: M. Pfeiffenberger, P. L. Krauß, T. Buttgereit, Y. Chen, A. Damerau, T. Gaber, F. Buttgereit
Journal: Annals of the Rheumatic Diseases (2021)

Background: Age-related impairment of classical neutrophil functions is well described (Fortin, McDonald et al. 2008). However, experimental evidence for age-related alterations of neutrophil metabolic adaptation towards nutrient deprivation -a feature of neutrophil battlefields- remains elusive. Moreover, age-related differences in neutrophil metabolic adaptation may contribute to age-related pathologies such as atherosclerosis, cancer, and autoimmune diseases including rheumatoid arthritis. Objectives: Therefore, we hypothesized that metabolic adaptation of human neutrophils to glucose deprivation is impaired with increasing age. Methods: We isolated human peripheral CD15+ neutrophils from four healthy young donors (mean age: 23.4 ± 2.7) and four healthy donors with a mean age of 58.7 ± 2.4. First, we analyzed the survival of neutrophils either stimulated with PMA or left untreated and subsequently incubated for 0 h and 6 h under varying glucose concentrations (0, 0.5, 1, 5, and 10 mM). To address this, we used 7-AAD staining and flow cytometry. Using Seahorse™ technology, we determined basal respiration, ATP-bound respiration, and maximal and spare capacity. Results: We show that neutrophils (purity &gt; 95%) survived for 6 hours in vitro , independent of treatment with PMA or concentrations of glucose in the culture medium. With negligible differences between the various concentrations of glucose used, the percentage of living cells after 6 h was 95% ± 2.5 without PMA and 75% ± 4.7 with PMA stimulation. No differences were uncovered in this respect between the two age groups. However, Seahorse™ technology revealed significant differences in basal, maximal, and spare respiratory capacity. Briefly, OCR (pmol/min/cell count) with respect to basal, maximal and reserve respiratory capacity was lower in the elderly donors compared to the young donors. For instance, with a concentration of 5 mM glucose, the basal respiration (OCR) was 17 ± 0.7 in elderly donors compared to 22.5 ± 1 in young donors, while the maximal respiration was 25 ± 0.8 in elderly and 41 ± 0.6 in the young donor group. Interestingly, these differences were independent of glucose concentration in the medium. Conclusion: Our data show that basal metabolic parameters differ between neutrophils from young and older donors. Further experiments are needed to understand in detail the mechanisms and effects of age-related differences in metabolism on neutrophil functions. References: [1]Fortin, C. F., P. P. McDonald, O. Lesur and T. Fülöp, Jr. (2008). “Aging and neutrophils: there is still much to do.” Rejuvenation Res 11 (5): 873-882. Disclosure of Interests: None declared
Analysing cord blood levels of TNF inhibitors to validate the EULAR points to consider for TNF inhibitor use during pregnancy
Authors: Nafise Ghalandari, Erik Kemper, Ineke (Hubertina) Crijns, Gertjan Wolbink, Theo Rispens, Hieronymus TW Smeele, Radboud JEM Dolhain
Journal: Annals of the Rheumatic Diseases (2021)

To minimise placental transfer of tumour necrosis factor inhibitors (TNFi), the European League Against Rheumatism (EULAR) created points to consider (PtC) for the use of TNFi during pregnancy. We are the first to validate the EULAR-PtC by analysing TNFi concentrations in cord blood.Patients were derived from the Preconceptional Counselling in Active Rheumatoid Arthritis Study. TNFi was stopped at the time points recommended by the EULAR. Maternal blood and cord blood were collected and analysed for the concentration of TNFi.111 patients were eligible for the analysis. Median stop time points were gestational age (GA) 37.0 weeks for certolizumab pegol, GA 25.0 weeks for etanercept, GA 19.0 weeks for adalimumab and GA 18.4 weeks for infliximab. Certolizumab pegol (n=68) was detectable in 5.9% of cord blood samples, with a median concentration of 0.3 µg/mL (IQR: 0.2-1.3) and a median cord/maternal concentration ratio of 0.010. Etanercept (n=30) was not detected in any cord blood samples. Adalimumab (n=25) was detectable in 48.0% of cord blood samples, with a median concentration of 0.5 µg/mL (IQR: 0.2-0.7) and a median concentration ratio of 0.062 (IQR: 0.018-0.15). Infliximab (n=14) was detectable in 57.1% of cord blood samples, with a median concentration of 0.4 µg/mL (IQR: 0.1-1.2) and a median concentration ratio of 0.012 (IQR: 0.006-0.081).Compliance with the EULAR-PtC results in absence or low levels of TNFi in cord blood.