tbuckley/cabot-search huggingface dataset:
FRI0254 SERUM IL-17 AND IL-21 AFFECT THE HEMODYNAMICS IN CONNECTIVE TISSUE DISEASE ASSOCIATED-PULMONARY HYPERTENSION
Authors: S. Nakashima, T. Kameda, H. Shimada, R. Wakiya, M. Mahmoud Fahmy Mansour, M. Kato, T. Miyagi, K. Sugihara, Y. Ushio, H. Dobashi
Journal: Annals of the Rheumatic Diseases (2020)

Background: Pulmonary hypertension associated with connective tissue disease (CTD-PH) has complicated pathology including immune abnormalities, cardiac and pulmonary lesions. Therefore, it is difficult for rheumatologist to manage CTD-PH. We hesitate to use immunosuppressants in addition to pulmonary vasodilators to treat CTD-PH. Although there is a report that the cytokine such as Interleukin (IL)-6, IL-17 and IL-21 are involved in the development of PH 1) , changes in the hemodynamics of theses cytokines with treatment are not clear. Objectives: We investigate serum cytokine profile and clinical appearance in CTD-PH, and clarify the relationship between change in cytokines and hemodynamics before and after treatment. Methods: 14 cases of CTD-PH (8 cases in Scleroderma; SSc-PH group, 4 cases in Mixed connective tissue disease; MCTD-PH group, 2 cases in Systemic lupus erythematosus; SLE-PH group), 6 cases in Other-PH group, and 2 cases of SSc without PH as controls were included. The following clinical data were collected: age, gender, underlying disease, complication of interstitial lung disease, treatment (immunosuppressant and pulmonary vasodilator). Serum samples in pre- and post-capillary before and after treatment were collected during cardiac catheterization examination. Serum cytokines (MCP-1, IL-6, IL-17 and IL-21) of these samples were measured by ELISA (ABCAM, UK). Results: Serum MCP-1, IL-6, and IL-21 levels were higher in SSc-PH group than in the other groups. Conversely, serum IL-17 levels tended to be higher in non-SSc group compared to SSc-PH group. Additionally, serum MCP-1 levels in SSc-PH group decreased in post-capillary as compared to pre-capillary. Furthermore, patients with decreased serum IL-17 and IL-21 levels before and after treatment showed improved pulmonary hemodynamics. Conclusion: SSc-PH had a different cytokine profile compared with non-SSc-PH. We suggested that the serum IL-17 and IL-21 levels effect the hemodynamics in CTD-PH. References: [1]Hashimoto-Kataoka T. et al. Proc Natl Acad Sci U S A. 2015 May 19;112(20):E2677-86. Disclosure of Interests: None declared
Stochastic non-enzymatic modification of long-lived macromolecules - A missing hallmark of aging
Authors: Alexander Fedintsev, Alexey Moskalev
Journal: Ageing Research Reviews (2020)

Damage accumulation in long-living macromolecules (especially extracellular matrix (ECM) proteins, nuclear pore complex (NPC) proteins, and histones) is a missing hallmark of aging. Stochastic non-enzymatic modifications of ECM trigger cellular senescence as well as many other hallmarks of aging affect organ barriers integrity and drive tissue fibrosis. The importance of it for aging makes it a key target for interventions. The most promising of them can be AGE inhibitors (chelators, O-acetyl group or transglycating activity compounds, amadorins and amadoriases), glucosepane breakers, stimulators of elastogenesis, and RAGE antagonists.
Derivation and external validation of the SIMPLICITY score as a simple immune-based risk score to predict infection in kidney transplant recipients
Authors: Mario Fernández-Ruiz, Daniel Seron, Ángel Alonso, David Lora, Domingo Hernández, Esther González, María José Pérez-Sáez, Gonzalo Gómez, Luis Manuel Pallardó-Mateu, Luisa Jimeno-García, Frederic Cofán, Alex Gutierrez-Dalmau, Juan Carlos Ruiz, Ana Ramírez-Puga, Raquel Santana Estupiñán, Roberto Marcén, José María Portolés, Miguel Ángel Muñoz-Cepeda, Francisco López-Medrano, Rafael San Juan, Amado Andrés, José María Aguado
Journal: Kidney International (2020)
THU0589 ‘KU FEVER’: A CASE REPORT
Authors: N. Cernovschi-Feasey, D. Christidis, M. Lloyd, S. Melath, J. Wajed
Journal: Annals of the Rheumatic Diseases (2020)

Background: Anti-Ku antibodies have been associated with various connective tissue diseases, including myositis, arthritis, interstitial lung disease and glomerulonephritis 1 . Objectives: We present a case of a woman initially diagnosed with biopsy proven Kikuchi-Fujimoto disease who later developed a rapidly progressive myositis in association with anti-Ku antibodies. Methods: A 47 year-old woman, originally from Myanmar, presented with lymphadenopathy, myalgia, fatigue, livedo reticularis and low-grade fever for the previous 6 months. This was initially diagnosed as a viral infection. Her myalgia progressed with proximal muscle weakness in both legs and associated rise in creatine kinase levels to 349U/L (normal range 25-200). She also developed dyspnoea, an erythematous rash, mouth ulcers and unintentional weight loss. Blood tests show a lymphopenia and progressively rising CK, with a maximum level of 516 U/L. MRI whole body confirmed a widespread diffuse myositis in her upper and lower limbs, with an unusual ‘speckled’ pattern. High resolution CT Chest was normal. C3 0.40 g/l (normal range 0.75-1.65) and C4 0.12 g/l (0.14-0.54) were low, with a positive ANA (1:160) and Ro-60 antibody. dsDNA, antiphospholipid screen and virology screens were all negative. Extended myositis panel revealed positive anti-Ku antibodies. Axillary lymph node biopsy confirmed necrotising lymphadenitis, consistent with Kikuchi-Fujimoto disease. Results: She was initially treated with low dose Prednisolone and Hydroxychloroquine, with a limited response. Due to progressive myositis, pulsed IV Methylprednisolone 1g was provided over 3 days and mycophenolate mofetil (MMF) was started. An inpatient stay was needed after developing an axillary node abscess and a chest infection. This was treated with intravenous antibiotics and repeated aspirations. Due to progressive myositis on a background of sepsis, intravenous immunoglobulin (IVIG) was administered over 5 days. Our patient made a good recovery, with normalization of CK levels and resolution of the myositis noted on repeat MRI scan. She remains on MMF as maintenance therapy. Conclusion: Anti Ku antibodies appear to be associated with 2 spectrums of disease – elevated CK levels with interstitial lung disease and renal disease associated with anti-dsDNA antibodies 1 To our knowledge this is the first report in association with Kikuchi-Fujimoto disease. The combination of MMF and IVIG appears to have been effective treatment and her renal function remains stable, although we are monitoring the patient carefully for the possible development of interstitial lung disease. References: [1]Spielmann L, Nespola B, Séverac F, et al. Anti-Ku syndrome with elevated CK and anti-Ku syndrome with anti-dsDNA are two distinct entities with different outcomes. Annals of the Rheumatic Diseases 2019;78:1101-1106. Disclosure of Interests: None declared
Occupational Pesticide Use and Risk of Renal Cell Carcinoma in the Agricultural Health Study
Authors: Gabriella Andreotti, Laura E. Beane Freeman, Joseph J. Shearer, Catherine C. Lerro, Stella Koutros, Christine G. Parks, Aaron Blair, Charles F. Lynch, Jay H. Lubin, Dale P. Sandler, Jonathan N. Hofmann
Journal: Environmental Health Perspectives (2020)

BACKGROUND: Agricultural work and occupational pesticide use have been associated with increased risk of renal cell carcinoma (RCC), the most common form of kidney cancer.However, few prospective studies have investigated links to specific pesticides.OBJECTIVE: We evaluated the lifetime use of individual pesticides and the incidence of RCC.METHODS: We evaluated the associations between intensity-weighted lifetime days (IWDs) of 38 pesticides and incident RCC in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina.Among 55,873 applicators, 308 cases were diagnosed between enrollment (1993)(1994)(1995)(1996)(1997) and the end of follow-up (2014)(2015).We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) using Poisson regression, controlling for potential confounding factors, with lagged and unlagged pesticide exposures.RESULTS: There was a statistically significant increased risk of RCC among the highest users of 2,4,5-T compared with never users [unlagged RR IWD Tertile 3 = 2:92 (95% CI: 1.65, 5.17; p trend = 0:001)], with similar risk estimates for lagged exposure [20-y lag RR IWD Tertile 3 = 3:37 (95% CI: 1.83, 6.22; p trend = 0:001)].In 20-y lagged analyses, we also found exposure-response associations with chlorpyrifos [RR IWD Quartile 4 = 1:68 (95% CI: 1.05, 2.70; p trend = 0:01)], chlordane [RR IWD Tertile 3 = 2:06 (95% CI: 1.10, 3.87; p trend = 0:02)], atrazine [RR IWD Quartile 4 = 1:43 (95% CI: 1.00, 2.03; p trend = 0:02)], cyanazine [RR IWD Quartile 4 = 1:61 (95% CI: 1.03, 2.50; p trend = 0:02)], and paraquat [RR IWD >Median = 1:95 (95% CI: 1.03, 3.70; p trend = 0:04)].CONCLUSIONS: This is, to our knowledge, the first prospective study to evaluate RCC risk in relation to various pesticides.We found evidence of associations with RCC for four herbicides (2,4,5-T, atrazine, cyanazine, and paraquat) and two insecticides (chlorpyrifos and chlordane).Our findings provide insights into specific chemicals that may influence RCC risk among pesticide applicators.Confirmation of these findings and investigations of the biologic plausibility and potential mechanisms underlying the observed associations are warranted.
FRI0444 HPVB19 INFECTION IN ADULT 53 CASES
Authors: M. Minoda, M. Suda, K. Muranaka
Journal: Annals of the Rheumatic Diseases (2020)

Background: Human parvovirus B19(HPVB19) is a member of the large Parvoviridae family and, as a human pathogen, is responsible for various diseases. 1) In children, HPVB19 infections usually presents as red rash, which is often described as a“slapped cheek.” However, the presentation varies in adults. 2) HPVB19 outbreaks mostly occur in the winter and spring. 1) The serum IgM test is the preferred means for diagnosing acute HPVB19 infections. 2) Objectives: We investigated the epidemiology, clinical symptoms, and time course of HPVB19 infections in real-world practice by examining patients treated at a community hospital in Japan. Methods: We studied adult patients with HPVB19 infections at Suwa Central Hosptial from April 2010 to November2019. Patients who were age 18 years or older, anti HPV B19 IgM antibody-positive, and symptomatic were included. We retrospectively examined the patients’ medical records to determine onset days, clinical symptoms and antinuclear antibody(ANA)-postitive rates. We defiend day 1 as the day when clinical symptoms first appeared. Results: 53 patients were included in the study. Patient characteritistics were mean age 43 years, female 79.2%, mean period from onset to diagnosis 13days. Epidemic season were 4year cycle. (Figure 1) Clinical symptoms and time course from onset day were upper respiratory symptoms(17.0%, 1.7days), fever(54.7%, 1.9days), abdominal symptoms(15.1%, 4.4days), edema(47.2%, 5.6days), arthralgia(71.7%, 6.6days), itching(15.1%, 6.9days), rash(62.3%, 8.9days) and lymphoadenopathy(30.2%, 10.2days). (Figure 2) ANA positive rate was 50%(13/26) and average was 92.3. Conclusion: 53 adult patients infected HPVB19 in 10 years at community hospital in Japan. Epidemic season were 4year cycle and skin eruption and joint symptoms appeared 4-5 days after upper respiratory symptoms. Previous study show that a second-phase illness with rash and arthralgia appear 10-11 days after the appearance of upper respiratory sympotms. 3) In our study, a second-phase symptoms appeared about one week earlier than in previous study. Half of the patients were weakly ANA positive. References: [1]Human Parvoviruses. Jianming Qie, Maria Soderlund-Venermo, Neal S. Young. Clinical Microbiology Reviews 2017; 30: 43-113 [2]Clinical Presentations of Parvovirus B19 Infection. Jessica T. LT COL, etc. American Family Physician 2007; 75: 373-6 [3]Experimental Parvoviral Infection in Humans. M J Anderson, etc. J Infect Dis 1985; 152: 257-65 Disclosure of Interests: None declared
Clinically Actionable Strategies for Studying Neural Influences in Cancer
Authors: Ihsan Ekin Demir, Carmen Mota Reyes, Wasfi Alrawashdeh, Güralp O. Ceyhan, Sylvie Deborde, Helmut Friess, Kivanc Görgülü, Rouzanna Istvanffy, David Jungwirth, Rohini Kuner, Maria Maryanovich, Shorook Na’ara, Simon Renders, Jami L. Saloman, Nicole N. Scheff, Hendrik Steenfadt, Pavel Stupakov, Vera Thiel, Divij Verma, Bengi Su Yilmaz, Ruth A. White, Timothy C. Wang, Richard J. Wong, Paul S. Frenette, Ziv Gil, Brian M. Davis
Journal: Cancer Cell (2020)
AB0134 SERUM LL-37, GALECTIN-3, AND TOLL-LIKE RECEPTORS-3 LEVELS DECREASE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: A. Karatas, R. F. Akkoc, S. S. Koca
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic lupus erythematosus (SLE) is a systemic inflammatory disease characterized by heterogeneous clinical manifestations (1). Although there are significant developments with its pathogenesis, it is still not fully known. In recent years, pathways such as NETosis and plasmacytoid dendritic cell (pDC) activation have been emphasized in the pathogenesis of SLE (2, 3). Objectives: In our study, we aimed to investigate serum LL-37, Galectin-3, and Toll-like receptors-3 (TLR)-3 levels, which are thought to be related to pathogenetic pathways in SLE patients. Methods: 17 SLE patients and 33 healthy controls were included in the study. The clinical and laboratory features of the patients were determined. Serum LL-37, Galectin-3, and TLR-3 levels were determined by ELISA (enzyme-linked immunosorbent assay) method using the appropriate commercial kit, and the results were evaluated according to the manufacturer’s instructions. Results: The clinical and laboratory features of the groups are described in Table 1. In our study, serum LL-37, Galectin-3, and TLR-3 levels were decreased statistically significantly in SLE patients compared to healthy control (p = 0.007, p = 0.002, and p = 0.008, respectively). Table 1. Clinical and laboratory features of the groups in the study Healthy control (n=33 ) SLE (n=17 ) p Age (years ) 34.1 ± 3.7 40 ± 11.4 0.05 Sex (n; female/male ) 33/0 17/0 LL-37(ng/ml ) 78.6 ± 92.6 14.2 ± 19.3 0.007 Galectin-3 (ng/ml ) 25.5 ± 23.2 6.7 ± 7.6 0.002 Toll-like receptors-3 (pg/ml ) 7893.4 ± 1041.3 916.2 ± 469.7 0.008 Conclusion: It is suggested that LL-37, galectin-3, and TLR-3 levels have various effects on NEtosis and pDc activation pathways in SLE pathogenesis. In our study, low levels of serum LL-37, galectin-3, and TLR-3 in SLE patients suggest that they are associated with SLE pathogenesis. References: [1]Aringer M, Schneider M. [Systemic lupus erythematosus]. Dtsch Med Wochenschr. 2016;141:537-43. [2]Panda SK, Kolbeck R, Sanjuan MA. Plasmacytoid dendritic cells in autoimmunity. Curr Opin Immunol. 2017;44:20-25. [3]van der Linden M, van den Hoogen LL, Westerlaken GHA, Fritsch-Stork RDE, van Roon JAG, Radstake TRDJ, Meyaard L. Neutrophil extracellular trap release is associated with antinuclear antibodies in systemic lupus erythematosus and anti-phospholipid syndrome. Rheumatology (Oxford). 2018;57:1228-1234. Disclosure of Interests: None declared
Targeted Therapy and Diagnostic Test for Non–Small Cell Lung Cancer
Authors: Rebecca Voelker
Journal: JAMA (2020)

Fourth-Line Treatment Approved For Gastrointestinal TumorThe kinase inhibitor ripretinib has approval as a fourth-line treatment for adults with advanced gastrointestinal stromal tumor (GIST) who already have been treated with 3 or more kinase inhibitors.An estimated 4000 to 6000 adults are diagnosed with a GIST each year, according to the FDA."Despite the progress that has been made over the past 20 years in developing treatments for GIST, including four FDA-approved targeted therapies…some patients don't respond to treatment and their tumors continue to progress," Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence, said in a statement.According to the agency, the drug's approval was based on a clinical trial involving 129 patients who previously were treated with imatinib, sunitinib, and regorafenib.The participants were randomized to receive ripretinib or placebo once daily in 28-day cycles to determine progressionfree survival (PFS).On average, PFS was 6.3 months in the treatment group compared with 1 month in the placebo group.Median overall survival was 15.1 months among treated patients compared with 6.6 months among patients in the placebo group, according to the drug's manufacturer, Deciphera Pharmaceuticals Inc.Common adverse events included alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, and palmar-plantar erythrodysesthesia syndrome.Serious adverse events included skin cancer, hypertension, and cardiac dysfunction manifested as ejection fraction decrease.Marketed as Qinlock, a 1-month supply reportedly will cost $32 000.
AB0637 EFFICACY OF COMEDICATION OF CONVENTIONAL SYNTHETIC DMARDS WITH TNF BLOCKERS IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS
Authors: K. Ben Abdelghani, Y. Gzam, A. Fazaa, S. Miladi, K. Ouenniche, S. Kassab, L. Souabni, S. Chekili, A. Laatar
Journal: Annals of the Rheumatic Diseases (2020)

Background: Tumour necrosis factor blockers (anti-TNFs) are typically used in axial spondyloarthritis (ax-SpA) when the disease has not responded adequately to conventional therapy. However, the effects of the comedication conventional synthetic disease modifying antirheumatic drugs (csDMARDs) with anti-TNFs are inconclusive. Objectives: The aim of this study was to evaluate the efficacy of comedication csDMARD and anti-TNF compared with anti-TNFs on monotherapy. Methods: A descriptive retrospective study including 85 patients with ax-SpA according to the criteria of the group ASAS on 2009 and having received anti-TNFs between January 2000 and October 2019. The patients were divided on two groups, those who had received combined therapy with cs-DMARDs and those who had received anti-TNFs on monotherapy. The response to treatment was assessed with the ASAS 40 response and partial remission at 3 and 6 months of treatment and was compared between the two groups. Results: Our populations consists of 67 men and 18 women with a mean age of 44,4 ± 10,9 years. The mean period of evolution was 12,3 ± 9,1 years and 52,2% of patients were HLA-B27 positive. The ax-SpA was associated with peripheral arthritis, enthesitis and dactylitis in 17,6%, 17,6% and 1,2% respectively. Fifty-nine patients (69,4%) were treated with anti-TNF alpha on monotherapy and 26 patients (30,6%) had combined therapy. The ASAS 40 response was achieved in 45,6% of patients at 3 months and 64,1 % of them at 6 months of anti-TNFs treatment. Among them, 7,4% had obtained partial remission at 3 months and 20,3% at 6 months of treatment. There was statically significant difference between the two groups on the ASAS 40 response or the partial remission at 3 and 6 months of treatments. Conclusion: The comedication therapy with csDMARDs does not influence the efficacy of anti-TNFs in ax-SpA patients suggesting no benefit in the concomitant use of these drugs in clinical practice. References: [1]Simone Det al. J Rheumatol Suppl. 2015;93:65–9. Disclosure of Interests: None declared
Poor quality Vβ recombination signal sequences stochastically enforce TCRβ allelic exclusion
Authors: Glendon S. Wu, Katherine S. Yang-Iott, Morgann A. Klink, Katharina E. Hayer, Kyutae D. Lee, Craig H. Bassing
Journal: The Journal of Experimental Medicine (2020)

The monoallelic expression of antigen receptor (AgR) genes, called allelic exclusion, is fundamental for highly specific immune responses to pathogens. This cardinal feature of adaptive immunity is achieved by the assembly of a functional AgR gene on one allele, with subsequent feedback inhibition of V(D)J recombination on the other allele. A range of epigenetic mechanisms have been implicated in sequential recombination of AgR alleles; however, we now demonstrate that a genetic mechanism controls this process for Tcrb. Replacement of V(D)J recombinase targets at two different mouse Vβ gene segments with a higher quality target elevates Vβ rearrangement frequency before feedback inhibition, dramatically increasing the frequency of T cells with TCRβ chains derived from both Tcrb alleles. Thus, TCRβ allelic exclusion is enforced genetically by the low quality of Vβ recombinase targets that stochastically restrict the production of two functional rearrangements before feedback inhibition silences one allele.
From NAFLD to MAFLD: Implications of a Premature Change in Terminology
Authors: Zobair M. Younossi, Mary E. Rinella, Arun J. Sanyal, Stephen A. Harrison, Elizabeth M. Brunt, Zachary Goodman, David E. Cohen, Rohit Loomba
Journal: Hepatology (2020)

Despite the substantial gains in our understanding of NAFLD/NASH over the past 2 decades, there has been some dissatisfaction with the terminology "non-alcoholic" which overemphasizes "alcohol" and underemphasizes the root cause of this liver disease, namely, the predisposing metabolic risk factors. As a potential remedy, a name change from NAFLD to metabolic associated fatty liver disease (MAFLD) has been proposed. Although MAFLD reflects the relevant risk factors for this liver disease, this term is still suboptimal, leaving a great deal of ambiguity. Here, we caution that changing the name without understanding its broad implications can have a negative impact on the field. In this context, changing the terminology without new understanding of the molecular basis of the disease entity, new insights in risk stratification or other important aspect of this liver disease, can create unnecessary confusion which could negatively impact the field. At a time when the field is facing substantial challenges around disease awareness as well as clarity of acceptable endpoints for drug development and biomarker discovery, changing the terminology from one suboptimal name to another suboptimal name without full assessment is expected to deepen these challenges. In the context of this debate about terminology, we recommend the creation of a true international consensus group to include all the relevant scientific liver societies (AASLD, EASL, ALEH, APASL), patient advocacy organizations, bio-pharmaceutical industry, regulatory agencies and policy makers. A consensus meeting must assess the impact and consequences of changing the terminology based on the available evidence and make recommendations that will move the field forward. By this approach, a true collaborative international and inclusive consensus can be adopted by all stakeholders dealing with this important global liver disease.
Abstract 12554: Diastolic Dysfunction is a Stronger Predictor of Cardiovascular Morbidity and Mortality in Individuals With Diabetes as Compared to Individuals Without Diabetes in the General Population
Authors: Burcu Tas Özbek
Journal: Circulation (2018)

Background: Poor glucose metabolism and hyperinsulinemia have been linked with diastolic dysfunction in diabetic patients with normal ejection fraction, and diabetes is a major risk factor for hear...