tbuckley/cabot-search huggingface dataset:
POS0883 DETECTION OF AUTOANTIBODIES AGAINST MUSCLE-SPECIFIC FOUR-AND-A-HALF-LIM DOMAIN 1 (FHL1) IN INFLAMMATORY MYOPATHIES: RESULTS FROM A SINGLE-CENTER COHORT
Authors: A. S. Galindo-Feria, B. Horuluoglu, J. Day, C. Cerqueira, S. Proudman, I. E. Lundberg, V. Limaye
Journal: Annals of the Rheumatic Diseases (2021)

Background: Autoantibodies targeting a muscle-specific autoantigen, four-and-a-half-LIM-domain 1 (FHL1), have been previously identified in patients with idiopathic inflammatory myopathies (IIM) (1). Objectives: The aim of this project was to determine the prevalence and associations of anti-FHL antibody in South Australian patients with histologically-confirmed IIM and in an autoimmune disease control (systemic sclerosis (SSc)). Methods: Sera from patients with IIM (n=267) from the South Australian Myositis Database (SAMD), and SSc (n=174) from the Australian Scleroderma Cohort Study (ASCS) followed at the Royal Adelaide Hospital, and healthy controls (HC, n=100) were analyzed for anti-FHL1 autoantibodies by Enzyme-Linked ImmunoSorbent Assay (ELISA). Clinical, serological and histological details were retrieved from the SAMD and the ASCS. Results: Autoantibodies to FHL1 were more frequent in patients with IIM (55/267, 20.5%) compared with SSc (18/174, 10%) (p&lt;0.001) and HC (4/100, 4%) (p&lt;0.001). Muscular vessel inflammation and atrophy were seen more frequently in IIM anti-FHL1 + patients compared with anti-FHL1 - (p&lt;0.01 and p&lt;0.05). Dysphagia, marked muscle atrophy, and high CK levels were frequent in anti-FHL1 + patients with inclusion body myositis (IBM) and immune-mediated necrotizing myopathy (IMNM). In 35/54 anti-FHL1 + patients, there were no other myositis-specific autoantibodies present. Anti-FHL1 autoantibodies in patients with SSc were associated with gastric antral vascular ectasia. Conclusion: Anti-FHL1 autoantibodies were detected in 20.5% of IIM patients. In IBM and IMNM, the presence of anti-FHL1-autoantibodies was associated with a severe myopathy as suggested by presence of dysphagia and muscle atrophy. References: [1]Albrecht I, Wick C, Hallgren A, Tjarnlund A, Nagaraju K, Andrade F, et al. Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies. J Clin Invest. 2015;125(12):4612-24. Disclosure of Interests: Angeles Shunashy Galindo-Feria: None declared, Begum Horuluoglu: None declared, Jessica Day: None declared, Catia Cerqueira: None declared, Susanna Proudman: None declared, Ingrid E. Lundberg Consultant of: Consulting fees from Corbus Pharmaceuticals, Inc, Grant/research support from: Research grants from Bristol Myers Squibb and Astra Zeneca, Vidya Limaye Consultant of: Scientific adviser for Actelion and Boehringer-Ingelheim, Grant/research support from: PI for clinical trials for Bayer, Boehringer-Ingelheim, Corbus, and CSL
Use of Probiotics to Prevent Necrotizing Enterocolitis
Authors: Abdul Razak, Ravi Mangal Patel, Kanekal Suresh Gautham
Journal: JAMA Pediatrics (2021)

This Viewpoint summarizes assessment of the benefits and harms of probiotics, describes current options for clinicians, and discusses the theoretical influence of future trials on treatment effect estimates for probiotic supplementation.
Место пункционной биопсии в диагностике хронических диффузных заболеваний печени
Authors: D.V. Orlovsky, N.Yu. Oshmyanskaya, N.V. Nedzvetskaya
Journal: GASTROENTEROLOGY (2013)

В статье рассматриваются вопросы диагностики хронических диффузных заболеваний печени. Представлен краткий обзор неинвазивных методов диагностики фиброза печени и чрескожной пункционной трепан-биопсии. Проведено сравнение между гистологическими изменениями (активность воспалительного процесса и стадия фиброза), уровнем трансаминаз крови, неинвазивными расчетными индексами (Forns, AAR, FIB-4, APRI, HALT-C, GUCI) и эхографическими характеристиками печени. По результатам проведенного исследования показано, что гистологическое исследование биоптата печени является единственным достоверным способом оценки активности и стадии фиброза при хронических диффузных заболеваний печени. Наиболее эффективным и безопасным методом получения ткани печени является пункционная биопсия под непрерывным УЗ-контролем с применением при необходимости допплерографических методов. При наличии опытного персонала, необходимого оборудования, соблюдении методики вмешательства и мер профилактики осложнений чрескожная пункционная трепан-биопсия должна выполняться каждому больному хроническими диффузными заболеваниями печени для постановки точного диагноза и контроля лечения.
STK11/LKB1 Loss of Function Is Associated with Global DNA Hypomethylation and <i>S</i>-Adenosyl-Methionine Depletion in Human Lung Adenocarcinoma
Authors: Michael J. Koenig, Bernice A. Agana, Jacob M. Kaufman, Michael F. Sharpnack, Walter Z. Wang, Christoph Weigel, Fabio C.P. Navarro, Joseph M. Amann, Nicole Cacciato, Rajeswara Rao Arasada, Mark B. Gerstein, Vicki H. Wysocki, Christopher Oakes, David P. Carbone
Journal: Cancer Research (2021)

Abstract STK11 (liver kinase B1, LKB1) is the fourth most frequently mutated gene in lung adenocarcinoma, with loss of function observed in up to 30% of all cases. Our previous work identified a 16-gene signature for LKB1 loss of function through mutational and nonmutational mechanisms. In this study, we applied this genetic signature to The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples and discovered a novel association between LKB1 loss and widespread DNA demethylation. LKB1-deficient tumors showed depletion of S-adenosyl-methionine (SAM-e), which is the primary substrate for DNMT1 activity. Lower methylation following LKB1 loss involved repetitive elements (RE) and altered RE transcription, as well as decreased sensitivity to azacytidine. Demethylated CpGs were enriched for FOXA family consensus binding sites, and nuclear expression, localization, and turnover of FOXA was dependent upon LKB1. Overall, these findings demonstrate that a large number of lung adenocarcinomas exhibit global hypomethylation driven by LKB1 loss, which has implications for both epigenetic therapy and immunotherapy in these cancers. Significance: Lung adenocarcinomas with LKB1 loss demonstrate global genomic hypomethylation associated with depletion of SAM-e, reduced expression of DNMT1, and increased transcription of repetitive elements.
Trends in Suicide Rates by Race and Ethnicity in the United States
Authors: Rajeev Ramchand, Joshua A. Gordon, Jane L. Pearson
Journal: JAMA Network Open (2021)

The US Centers for Disease Control and Prevention reported a decrease in the 2019 suicide rate, from 14.2 per 100 000 individuals in 2018 to 13.9 per 100 000 individuals in 2019, representing 833 fewer suicides.1 This is the first national year-over-year decrease since 1999, but efforts need to consider trends among subgroups. Growing concerns regarding increasing rates of suicides among Black youth2 led us to examine subgroup trends over the past 2 decades.
Creating health promoting schools will improve population health and help reduce inequalities
Authors: Michael Craig Watson, John Lloyd
Journal: BMJ (2021)

We agree with Oliver that simply renaming government agencies will not improve population health and tackle health inequalities.1 We need an industrial shift in the scale of our activity in this area. Moreover, instead of putting the responsibility for health solely on individuals, we need to create environments that help to maintain and improve health.

The idea of health promoting …
POS0421 COMBINED ANALYSIS OF METABOLIC AND TRANSCRIPTOMIC KIDNEY PROFILES OF NZW/B-F1 MURINE LUPUS UNCOVERS BIOLOGICAL MECHANISMS PRECEDING THE ONSET OF NEPHRITIS
Authors: T. Manolakou, I. Tsiara, D. Nikolopoulos, P. Garantziotis, D. Benaki, E. Gikas, E. Frangou, E. Mikroa, D. Boumpas
Journal: Annals of the Rheumatic Diseases (2021)

Background: Metabolic pathways are important regulators of immune differentiation and activation in kidneys. Kidneys directly impact systemic metabolism, circulating metabolite levels, and express intrinsic metabolic activity. The integration of renal metabolomic and transcriptomic profiles may unravel unique gene-metabolite pairs of biological significance in lupus nephritis (LN). Objectives: To decipher gene-metabolite signatures at both pre-nephritic and nephritic stages of lupus. Methods: Kidneys were isolated and snap-frozen after perfusion from female NZB/NZW-F1 lupus mice at the pre-nephritic (3-month-old) and nephritic (6-month-old exhibiting ≥100 ng/dL of urine protein) stage of lupus (n=6/group). Age-matched female C57BL/6 mice were used as healthy controls. Sample extracts were used for RNA sequencing and 1 H-NMR spectroscopy metabolic profiling. DESeq2 was used to identify differentially expressed genes. Univariate analysis was used to reveal metabolic differences characteristic for nephritis. Results: Comparative transcriptomic analyses uncovered multiple transcripts related to metabolic pathways: In pre-nephritic kidneys, lipid metabolism, cellular respiration, TCA cycle, amino acid metabolism processes were overrepresented in the upregulated genes while in nephritic kidneys, amino acid metabolism processes were overrepresented among the downregulated genes (Figure 1). 1 H-NMR analysis revealed a total of 49 metabolites. Comparison of the metabolic levels of nephritic and pre-nephritic animals revealed that ADP, ATP, NAD+, Taurine and Myo-inositol decreased, while Thr increased significantly. The comparison to corresponding control animals, demonstrated that only myo-inositol increased significantly. Integration of kidney metabolomics and transcriptomics indicated the involvement of processes related to glutathione metabolism, leukocyte trans-endothelial migration and antigen presentation during the established renal disease stage. Conclusion: The combined transcriptomics and metabolomics analysis revealed metabolic derangements in lupus-affected kidneys both during subclinical and overt LN. Deregulated tissue-levels of taurine and myo-inositol at the subclinical stage of the disease suggest aberrant renal biochemistry preceding the development of overt LN that may directly impact systemic metabolism and circulating metabolite levels. Figure 1. Pathways linked to cell metabolism were overrepresented among 3-month upregulated and 6-month lupus mice (F1) downregulated DEGS ( differentially expressed genes ) compared to controls (C57BL/6). Acknowledgements: This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 742390). Disclosure of Interests: None declared
AB0511 EFFECT OF SECUKINUMAB ON THE REDUCTION OF MYOCARDIAL DYSFUNCTION IN PATIENTS WITH ANKYLOSING SPONDYLITIS
Authors: S. Lapshina, L. Feiskhanova
Journal: Annals of the Rheumatic Diseases (2021)

Background: In ankylosing spondylitis (AS), early subclinical changes in the myocardium mostly remain undiagnosed. The impact of genetic engineering biological therapy on these changes is also unclear. Objectives: Aim: to establish the relationship between taking of secukinumab and changes in systolic and diastolic myocardial function in patients with AS. Methods: 69 patients with AS were examined, of which the first group included 33 people (average age 38.8±4.74, 63.6% of men) who received the interleukin 17 inhibitor (IL17) - secukinumab, the second group - 36 people who did not receive biological therapy, average age 42.5±11 years, 66.7% of men. The control group included 40 healthy individuals, comparable in gender and age. Patients underwent tissue dopplerography of the heart and transthoracic echocardiography. The research materials were subjected to statistical processing using the program STATISTICA 10.0. Results: The patients with AS had significantly higher left ventricular mass index and ejection fraction (p&lt;0.01) compared to the control group. Moreover, among patients who do not take biological therapy, the indicators were the highest (tabl.1). Table 1. Comparison of transthoracic echocardiography parameters in the study groups according to the Craskell-Wallis test. Показатель group 1 group 2 control group р LVMI 85 [81; 100] 93 [81,3; 114,2] 79,5 [72; 86,5] р=0,002 EF 63 [62; 64] 64,5 [63; 66] 60 [59,5; 64,5] р=0,003 LVMI – ventricular myocardial mass index, EF – ejection fraction. A comparison of tissue dopplerography of the heart between the groups established statistically higher values of peak velocity of the ring of the mitral valve in early diastole (e’L) in the 1st group (14 [9,5; 14]) and control (13 [11; 15,5]) compared with the indicator of the second group (10,5 [8,3; 13]), p&lt;0,01; the peak speed of movement of the septum in early diastole, (e’S) in patients with secukinumab is higher (11 [9; 11]) compared to 2th (8.1 [7; 12]) and control groups 10 [8.5; 11]), p&lt;0.05, and in the 2nd group lower than in the control (p=0.03). Significant differences in the parameters were supported by a comparison of the frequency of detection of diastolic dysfunction in the study groups. Diastolic dysfunction was diagnosed only in this group - in 38.9%. Against the background of the use of secukinumab, an increase in the systolic function of the myocardium was revealed. Conclusion: The patients with AS are characterized by a high frequency of subclinical heart dysfunction. Inhibition of IL17 can reduce diastolic dysfunction, which is confirmed by an improvement in myocardial contractility during secukinumab therapy. References: [1]ankylosing spondylitis, spondylarthritis, diastolic myocardial dysfunction, secukinumab Disclosure of Interests: None declared.
AB0273 HYPERSENSIVITY REACTIONS TO NON STEROID ANTI INFLAMMATORY DRUGS: A BOUT 87 CASES
Authors: K. Ksouda, R. Sahnoun, R. Atheymen, I. Bouaziz, A. Hanène, S. Hammami, L. Chtourou, Z. Khaled
Journal: Annals of the Rheumatic Diseases (2021)

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the leading causes of hypersensitivity reactions to drugs. The pathogenesis may be immunological mechanisms (allergic reactions) or non specific immunological reactions often incriminated in cross reactivity independently of chemical structure of these molecules. Understanding of the underlying mechanism is necessary for prevention and choice of safe alternatives [1, 2]. Objectives: Analyze all cases of non-steroidal anti-inflammatory drugs cutaneous eruption reported to sfax pharmacovigilance service since January 2015 to December 2020 and evaluate the possibility of cross-reactions between different molecules in this class. Methods: We conducted a retrospective study of all cases reported to sfax pharmacovigilance department. An enquiry of pharmacovigilance was performed in patients who presented side effects to AINS. The imputability study was carried out by the French method of Imputability. Medical history specifies if there is a re-administration to assess tolerance and cross-reactivity. Results: Our study included 87 patients whose average age was 45, 8 years. The sex ratio (F/M) was 1.18. lysine salicylate acetyl is the most incriminated (31%), then mefenamic acid (19.5%), diclofenac (19.5 %), ketoprofen in (9.2%), piroxicam in (6.9 %), ibuprofen in (5.4%), celocoxib in (3.4%), tiaprofenic acid in (1.1%) and naproxen in 1.1% of cases. The most common skin injury was urticaria in 29 cases (33.3%). Fixed drug eruption was observed in 17 cases. Maculopapular rash was observed in 19 cases, anaphylaxis in 5 cases and 4 cases of photosensitivity were observed. In our study we found cross-reactivity between (NSAIDs) in 8 patients. Conclusion: The diagnostic approach is often based on the controlled administration of the drug to assess tolerance and to identify safe alternatives. In cases of intolerance to COX 1 inhibitors, cross-reactions to selective cox 2 inhibitors are very rare [3]. References: [1]Inmaculada Dona, Maria Salas, James R Perkins and al. Hypersensitivity Reactions to Non-Steroidal Anti-Inflammatory Drugs. Curr Pharm Des 2016; 22(45):6784-6802. [2]Flavia Angeletti, Franziska Meier, Nadja Zöller, Markus Meissner, Roland Kaufmann, Eva Maria Valesky. Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) - a retrospective study. J Dtsch Dermatol Ges 2020 Dec; 18(12):1405-1414. [3]N Blanca-López, J A Cornejo-García, M C Plaza-Serón, and al. Hypersensitivity to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Cross-Intolerance Reactions. J Investig Allergol Clin Immunol 2015; 25(4):259-69. Disclosure of Interests: None declared
Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration
Authors: Ulf Lindström, Daniela Di Giuseppe, Bénédicte Delcoigne, Bente Glintborg, Burkhard Möller, Adrian Ciurea, Manuel Pombo-Suarez, Carlos Sanchez-Piedra, Kari Eklund, Heikki Relas, Bjorn Gudbjornsson, Thorvardur Jon Love, Gareth T Jones, Catalin Codreanu, Ruxandra Ionescu, Lucie Nekvindova, Jakub Závada, Nuh Atas, Servet Yolbas, Karen Minde Fagerli, Brigitte Michelsen, Žiga Rotar, Matija Tomšič, Florenzo Iannone, Maria Jose Santos, Pedro Avila-Ribeiro, Lykke Midtbøll Ørnbjerg, Mikkel Østergaard, Lennart TH Jacobsson, Johan Askling, Michael J Nissen
Journal: Annals of the Rheumatic Diseases (2021)

Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy.Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed.In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept.This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab.
Intravital Imaging Identifies the VEGF–TXA2 Axis as a Critical Promoter of PGE2 Secretion from Tumor Cells and Immune Evasion
Authors: Yoshinobu Konishi, Hiroshi Ichise, Tetsuya Watabe, Choji Oki, Shinya Tsukiji, Yoko Hamazaki, Yasuhiro Murakawa, Akifumi Takaori-Kondo, Kenta Terai, Michiyuki Matsuda
Journal: Cancer Research (2021)

Prostaglandin E2 (PGE2) promotes tumor progression through evasion of antitumor immunity. In stark contrast to cyclooxygenase-dependent production of PGE2, little is known whether PGE2 secretion is regulated within tumor tissues. Here, we show that VEGF-dependent release of thromboxane A2 (TXA2) triggers Ca2+ transients in tumor cells, culminating in PGE2 secretion and subsequent immune evasion in the early stages of tumorigenesis. Ca2+ transients caused cPLA2 activation and triggered the arachidonic acid cascade. Ca2+ transients were monitored as the surrogate marker of PGE2 secretion. Intravital imaging of BrafV600E mouse melanoma cells revealed that the proportion of cells exhibiting Ca2+ transients is markedly higher in vivo than in vitro. The TXA2 receptor was indispensable for the Ca2+ transients in vivo, high intratumoral PGE2 concentration, and evasion of antitumor immunity. Notably, treatment with a VEGF receptor antagonist and an anti-VEGF antibody rapidly suppressed Ca2+ transients and reduced TXA2 and PGE2 concentrations in tumor tissues. These results identify the VEGF-TXA2 axis as a critical promoter of PGE2-dependent tumor immune evasion, providing a molecular basis underlying the immunomodulatory effect of anti-VEGF therapies. SIGNIFICANCE: This study identifies the VEGF-TXA2 axis as a potentially targetable regulator of PGE2 secretion, which provides novel strategies for prevention and treatment of multiple types of malignancies.
The contact activation inhibitor AB023 in heparin-free hemodialysis: results of a randomized phase 2 clinical trial
Authors: Christina U. Lorentz, Erik I. Tucker, Norah G. Verbout, Joseph J. Shatzel, Sven R. Olson, Brandon D. Markway, Michael Wallisch, Martina Ralle, Monica T. Hinds, Owen J. T. McCarty, David Gailani, Jeffrey I. Weitz, András Gruber
Journal: Blood (2021)
POS1071 DETERMINATION OF THE RELIABILITY AND VALIDITY OF THE BETY-BIOPSYCHOSOCIAL QUESTIONNAIRE IN PATIENTS WITH A DIAGNOSIS OF PSORIATIC ARTHRITIS
Authors: S. Bulut, E. Ünal, J. Karakaya, U. Kalyoncu
Journal: Annals of the Rheumatic Diseases (2021)

Background: In the literature, there is a lack of questionnaires, which is evaluate patients with psoriatic arthritis (PsA) from a biopsychosocial perspective. Objectives: This study was planned to examine the reliability and validity of the BETY- Biopsychosocial Questionnaire (BQ) in individuals diagnosed with PsA. Methods: Test-retest method was used to examine the reliability of the BETY-BQ. In comparing the reliability of test-retest results, intraclass coefficient (ICC) was checked. For the internal consistency analysis of the BETY-BQ, the total score of the responses given to the first filled scale was calculated and the Cronbach’s Alpha coefficient was found. Psoriatic Arthritis Quality of Life Questionnaire (PsAQoL), Health Assessment Questionnaire (HAQ), Hospital Anxiety and Depression Scale (HADS) and Short Form-36 (SF-36) were used in the validity study of 150 individuals with PsA included in the study. Results: Test-retest method and intraclass coefficient were examined for reliability analysis (for 30 patients). The correlation (r = 0.844, p &lt;0.001) of the answers given to the BETY-BQ by individuals with 30 PsA after one week interval was very high. While the ICC coefficient (0.915, p &lt;0.001) showed excellent reliability. The Cronbach’s Alpha coefficient (0.940) was examined for internal consistency and the internal consistency of the scale was also found to be excellent. As a result of statistical analysis, the correlation between the scales used and the BETY-BQ was found between r = -0.432 and 0.807 (p &lt;0.001). Conclusion: With this study, it was concluded that the BETY-BQ is a reliable and valid assessment tool in individuals diagnosed with PsA, and is also a biopsychosocial tool that can be used to evaluate individuals with PsA. References: [1]Unal E, Arin G, Karaca Nb, Kiraz S, Akdoğan A, Kalyoncu U, et al. Romatizmali hastalar için bir yaşam kalitesi ölceginin gelistirilmesi: madde havuzunun olussturulmasi. Journal of Exercise Theraphy and Rehabilitation. 2017;4(2):67-75. [2]Husni ME, Merola JF, Davin S. The psychosocial burden of psoriatic arthritis. Semin Arthritis Rheum. 2017;47(3):351-60 Disclosure of Interests: None declared.