tbuckley/cabot-search huggingface dataset:
POS0153-HPR IDENTIFYING TARGETS FOR BEHAVIOURAL INTERVENTIONS IN FIBROMYALGIA: PHYSICAL ACTIVITY BEHAVIOUR
Authors: K. Mayana, Y. Prior
Journal: Annals of the Rheumatic Diseases (2021)

Background: There has been much interest in the efficacy of exercise and physical activity interventions in people with Fibromyalgia. This has resulted in guidelines recommending exercise as the first line of management (Macfarlane et al., 2017). Notwithstanding the efficacy of exercises, adherence to structured exercise and interventions aiming to increase physical activities remains a considerable challenge in this population. Exploring behavioural factors that may hinder exercise and physical activity participation in people with Fibromyalgia may help to identify targets for interventions to improve adherence and engagement with physical activities and support self-management. Objectives: To explore people with Fibromyalgia’s perspectives on the personal, social and contextual factors impacting their physical activity behaviour and pain perception. Methods: Twelve participants with Fibromyalgia were recruited from Social Media, Fibromyalgia charities, organisations and associations across the UK. Semi-structured, one-to-one in-depth telephone interviews were conducted with each participant. Interviews were audio-recorded and transcribed verbatim. Qualitative data analysis was conducted by two researchers independently, using Thematic Analysis. Critical Realism framework was employed to inform the interpretation of the findings. Results: Four main themes emerged from the data: (i) Lack of guidance on physical activity: most participants expressed increased pain intensity following a vigorous physical activity which, have led to spending more time on sedentary behaviour to recover from pain. (ii) Participants expressed fear of fatigue as a barrier to physical activity participation: This also led to increased sedentary and protective behaviours. (iii) Impact of treatments on physical activity: Participants who received multimodal therapies and patient education reported better coping strategies e.g., pacing physical activities and less pain. (iv): Impact of social support on physical activity participation: Participants felt that a lack of understanding from employers, their family and friends and the wider society has negatively impacted their physical activity behaviours, access to workplace support and psychological wellbeing. Conclusion: A multimodal approach, incorporating patient education with behavioural components is essential to increase adherence to and engagement with exercise and physical activity interventions to support self-management of Fibromyalgia. There is a need to improve the public perception of this syndrome to increase social and workplace support. Disclosure of Interests: None declared
Genetic, Clinical, and Sociodemographic Factors Associated With Stimulant Treatment Outcomes in ADHD
Authors: Isabell Brikell, Theresa Wimberley, Clara Albiñana, Emil Michael Pedersen, Bjarni Jóhann Vilhjálmsson, Esben Agerbo, Ditte Demontis, Anders D. Børglum, Andrew J. Schork, Sonja LaBianca, Thomas Werge, Ole Mors, David M. Hougaard, Anita Thapar, Preben Bo Mortensen, Søren Dalsgaard
Journal: American Journal of Psychiatry (2021)

Stimulant medications are effective for treating attention deficit hyperactivity disorder (ADHD), yet discontinuation and switch to nonstimulant ADHD medications are common. This study aimed to identify genetic, clinical, and sociodemographic factors influencing stimulant treatment initiation, discontinuation, and switch to nonstimulants in individuals with ADHD.
Abstract 16779: Mitochondrial Related Intragraft Gene Expression During Acute Rejection After Heart Transplantation
Authors: Erick S Romero, Eleanor Chang, Laurel Villarente, Gregory A Fishbein, Martin Cadeiras
Journal: Circulation (2018)

Introduction: Endomyocardial biopsies (EMB) for the surveillance of acute cellular rejection (ACR) after heart transplant (HT) is inconsistent and provides limited information. Mitochondrial dysfunction is associated with poor allograft prognosis and can overstimulate the inflammatory response. Mitochondrial related gene expression (GE) in EMB may be useful as a functional surrogate for EMB. Hypothesis: We hypothesize that down-regulated mitochondrial associated GE in EMB correlates with ACR. Methods: We collected 64 EMB from 47 post HT patients (mean age 50 ± 14.7 years). Purified mRNA was subjected to whole-genome next-generation sequencing. Weighted gene co-expression network analysis was applied to construct functional gene modules. Module derived eigengenes were correlated with ISHLT EMB criteria or using an unsupervised classification method we previously developed and B-type natriuretic peptide (BNP) levels. Biological significance and function of each module were assessed by gene ontology (GO) and pathway analyses. Highly relevant genes were identified by Hub gene analysis. Results: The reconstructed network resulted in 16 modules including two mitochondria-related modules (MRM) and one immune response module (IRM). Compared to 0R (n= 30/46.9%) samples, 2R (n= 11/17.2%) EMB showed enrichment of IRM and decreased expression of MRM. ISHLT 1R (n= 23/35.9%) samples did not show a significant correlation with IRM or MRM. Following the unsupervised classification method, findings were concordant, with higher phenotype-module eigengene correlation and significance level. MRM Hub genes included ATP5B, ATP5O, ACO2, COX14, COX4I1 , FH, NDUFV1, PDK2, SDHA and UQCR11 among others. GO categories enriched by these genes included oxidative phosphorylation, beta-oxidation, tricarboxylic acid cycle, glycolysis and gluconeogenesis. There was an inverse correlation between MRM and BNP level and positive correlation between IRM and BNP (Figure). Conclusions: EMB of patients with ISHLT 2R ACR show decrease activity of MRM, increased activity of IRM and elevated BNP suggesting an inverse functional relationship between immune activation, mitochondrial activity and cardiac allograft function.
POS1385 AUTOIMMUNE DISEASES ASSOCIATED WITH CHRONIC LIVER DISEASES
Authors: N. Trad, G. Mohamed, B. Ben Slimen, K. Boughoula, S. Bizid, H. Ben Abdallah, R. Bouali, M. N. Abdelli
Journal: Annals of the Rheumatic Diseases (2021)

Background: Chronic liver diseases whatever their etiologies could be associated with immunological disturbances. Objectives: Our aim was to evaluate the prevalence and the characteristics of autoimmune diseases associated with chronic liver diseases. Methods: We performed a retrospective analysis of data from consecutive patients followed in our department for chronic liver diseases recruited from January 2010 to December 2019. Demographic, clinical, and paraclinical data were collected. Results: A total of 224 patients were included. The mean age was 61.02 ±13.2 years and the sex-ratio was 1.6. The main etiology of chronic liver diseases was viral infection C (32.1%) followed by viral infection B (22.8%) and non-alcoholic steatohepatitis (21.4%). The prevalence of autoimmune chronic liver diseases was 7.58%: autoimmune hepatitis (AIH) in four cases, primary biliary cholangitis (PBC) in huit cases, primary sclerosing cholangitis (PSC) in three cases and overlap syndrome (AIH-PBC) in two cases. Autoimmune diseases were noted in 31 cases (13.9%): autoimmune hemolytic anemia in 15 cases, autoimmune thyroiditis in 12 cases, one case of psoriasis, one case of CREST syndrome, one case of Sjögren’s syndrome and one case of autoimmune thrombocytopenia. Autoimmune pathologies were more associated with autoimmune chronic liver disease than other causes of chronic liver disease (47% vs 11.1%, p &lt;0.001). Autoimmune pathologies were not statistically associated with female gender (p = 0.085) or young age (p = 0.483). Conclusion: In our study, the prevalence of autoimmune diseases during chronic liver diseases was 13.9%. This prevalence was higher in the case of autoimmune chronic liver diseases (47%), which would underline the importance of systematic screening for clinical and biological immune manifestations in those patients. Disclosure of Interests: None declared
POS0556 USEFULNESS OF FDG-PET/CT FOR PREDICTING SPONTANEOUS REGRESSION IN MTX ASSOCIATED LYMPHOPROLIFERATIVE DISORDER WITH RHEUMATOID ARTHRITIS
Authors: T. Kameda, S. Nakashima, H. Shimada, R. Wakiya, M. Mahmoud Fahmy Mansour, M. Kato, K. Sugihara, Y. Ushio, H. Dobashi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Recently, there are many reports from Japan about methotrexate associated lymphoproliferative disorder (MTX-LPD). We are investigating the predictive factor of spontaneous regression (SR) in MTX-LPD. On the other hand, FDG-PET/CT is used for diagnosis of LPD including malignant lymphoma. In addition, it was reported that imaging biomarkers such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) could predict the prognosis of malignant tumor (1, 2). However, there is no report that these imaging biomarkers could predict the SR of MTX-LPD. Objectives: We investigate the usefulness of FDG-PET/CT for predictive factor of SR in MTX-LPD. Methods: We enrolled 24 RA patients who diagnosed MTX-LPD and performed FDG-PET/CT from 2005 to 2019. We divided these cases into spontaneous regression cases (SR group; 15 cases) and cases that treated with chemotherapy after MTX discontinuation (CTx group; 9 cases), and compared the difference as follow subjects between two groups; clinical data including histopathological findings, SUVmax to evaluate malignant tumor activity by FDG-PET/CT, MTV and TLG which refer to metabolically active volume of the tumor segmented FDG-PET/CT. In addition, we analyzed cut off levels, sensitivity and specificity using statistical software JMP. Results: Diffuse large B cell lymphoma (DLBCL) and Hodgkin lymphoma (HL) were 5 and 1 cases in SR group, and 1 and 5 cases in CTx group. In addition, MTV and TLG by FDG-PET/CT was significantly lower in SR group, although SUVmax is no difference between two groups (figure 1). Cut off levels of MTV and TLG were 103.12 ml (sensitivity; 88.9%, specificity; 86.7%) and 361.75 ml (sensitivity; 88.9%, specificity; 86.7%), respectively. Conclusion: We suggested that MTV and TLG were useful for predict of SR in MTX-LPD. References: [1]Chen HH, Chiu NT, Su WC. et al. Prognostic value of whole-body total lesion glycolysis at pretreatment FDG PET/CT in non-small cell lung cancer. Radiology. 2012 Aug;264(2):559-66. [2]Chu KP, Murphy JD, La TH. et al. Prognostic value of metabolic tumor volume and velocity in predicting head-and-neck cancer outcomes. Int J Radiat Oncol Biol Phys. 2012 Aug 1;83(5):1521-7. Figure 1. Comparison of the level of MTV(a) and TLG (b). Disclosure of Interests: None declared
Correspondence re: R. J. Spiegel, I. T. Magrath, and J. A. Shutta. Role of Cytoplasmic Lipids in Altering Diphenylhexatriene Fluorescence Polarization in Malignant Cells. Cancer Res., 41: 452–458, 1981
Authors: W. J. Van Blitterswijk, R. P. Van Hoeven, P. Emmelot
Journal: Cancer Research (1981)
Financial interests: Government supports local solution despite doctors’ calls for central register
Authors: Abi Rimmer
Journal: BMJ (2021)

The government believes that employers, rather than the General Medical Council (GMC), should hold registers of doctors’ financial interests, The BMJ has discovered.

A confidential document from the Department of Health and Social Care, seen by The BMJ , sets out government proposals for a register of financial and non-pecuniary interests for all doctors.

Last year the Independent Medicines and Medical Devices Safety Review, chaired by Julia Cumberlege, called for the GMC to expand …
Calcium phosphate-based materials regulate osteoclast-mediated osseointegration
Authors: Xiaogang Wang, Yuanman Yu, Luli Ji, Zhen Geng, Jing Wang, Changsheng Liu
Journal: Bioactive Materials (2021)

Calcium phosphate-based materials (CaP) have been widely used as bone graft substitutes with a decent osseointegration. However, the mechanism whereby cells function and repair the bone defect in CaP micro-environment is still elusive. The aim of this study is to find the mechanism how osteoclast behaviors mediate bone healing with CaP scaffolds. Recent reports show that behaviors of osteoclast are closely related with osteogenesis, thus we make a hypothesis that active osteoclast behaviors induced by CaP facilitate bone healing. Here, we found a new mechanism that CaP can regulate osteoclast-mediated osseointegration. Calcium phosphate cement (CPC) is selected as a representative CaP. We demonstrate that the osteoclast-mediated osseointegration can be strongly modulated by the stimulation with CaP. An appropriate Ca/P ratio in CaP can effectively promote the RANKL-RANK binding and evoke more activated NF-κB signaling transduction, which results in vigorous osteoclast differentiation. We observe significant improvement of bone healing in vivo, owing to the active coupling effect of osteoclasts. What is more noteworthy is that the phosphate ions released from CaP can be a pivotal role regulating osteoclast activity by changing Ca/P ratio readily in materials. These studies suggest the potential of harnessing osteoclast-mediated osteogenesis in order to develop a materials-manipulated approach for improving osseointegration.
Multi-strategy intervention increases school implementation and maintenance of a mandatory physical activity policy: outcomes of a cluster randomised controlled trial
Authors: Nicole Nathan, Alix Hall, Nicole McCarthy, Rachel Sutherland, John Wiggers, Adrian E Bauman, Chris Rissel, Patt-Jean Naylor, Angie Cradock, Cassandra Lane, Kirsty Hope, Benjamin Elton, Adam Shoesmith, Christopher Oldmeadow, Penny Reeves, Karen Gillham, Bernadette Duggan, James Boyer, Christophe Lecathelinais, Luke Wolfenden
Journal: British Journal of Sports Medicine (2021)

Objectives To assess if a multi-strategy intervention effectively increased weekly minutes of structured physical activity (PA) implemented by classroom teachers at 12 months and 18 months. Methods A cluster randomised controlled trial with 61 primary schools in New South Wales Australia. The 12-month multi-strategy intervention included; centralised technical assistance, ongoing consultation, principal’s mandated change, identifying and preparing school champions, development of implementation plans, educational outreach visits and provision of educational materials. Control schools received usual support (guidelines for policy development via education department website and telephone support). Weekly minutes of structured PA implemented by classroom teachers (primary outcome) was measured via teacher completion of a daily log-book at baseline (October–December 2017), 12-month (October–December 2018) and 18-month (April–June 2019). Data were analysed using linear mixed effects regression models. Results Overall, 400 class teachers at baseline, 403 at 12 months follow-up and 391 at 18 months follow-up provided valid primary outcome data. From baseline to 12-month follow-up, teachers at intervention schools recorded a greater increase in weekly minutes of PA implemented than teachers assigned to the control schools by approximately 44.2 min (95% CI 32.8 to 55.7; p&lt;0.001) which remained at 18 months, however, the effect size was smaller at 27.1 min (95% CI 15.5 to 38.6; p≤0.001). Conclusion A multi-strategy intervention increased mandatory PA policy implementation. Some, but not all of this improvement was maintained after implementation support concluded. Further research should assess the impact of scale-up strategies on the sustainability of PA policy implementation over longer time periods. Trial registration number Australian New Zealand Clinical Trials Registry (ACTRN12617001265369).
Iron deficiency contributes to resistance to endogenous erythropoietin in anaemic heart failure patients
Authors: Michał Tkaczyszyn, Josep Comín‐Colet, Adriaan A. Voors, Dirk J. van Veldhuisen, Cristina Enjuanes, Pedro Moliner, Marcin Drozd, Radosław Sierpiński, Piotr Rozentryt, Jolanta Nowak, Tomasz Suchocki, Waldemar Banasiak, Piotr Ponikowski, Peter van der Meer, Ewa A. Jankowska
Journal: European Journal of Heart Failure (2021)
Inorganic Agents for Enhanced Angiogenesis of Orthopedic Biomaterials
Authors: Monika Šalandová, Ingmar A. J. van Hengel, Iulian Apachitei, Amir A. Zadpoor, Bram C. J. van der Eerden, Lidy E. Fratila‐Apachitei
Journal: Advanced Healthcare Materials (2021)

Abstract Aseptic loosening of a permanent prosthesis remains one of the most common reasons for bone implant failure. To improve the fixation between implant and bone tissue as well as enhance blood vessel formation, bioactive agents are incorporated into the surface of the biomaterial. This study reviews and compares five bioactive elements (copper, magnesium, silicon, strontium, and zinc) with respect to their effect on the angiogenic behavior of endothelial cells (ECs) when incorporated on the surface of biomaterials. Moreover, it provides an overview of the state‐of‐the‐art methodologies used for the in vitro assessment of the angiogenic properties of these elements. Two databases are searched using keywords containing ECs and copper, magnesium, silicon, strontium, and zinc. After applying the defined inclusion and exclusion criteria, 59 articles are retained for the final assessment. An overview of the angiogenic properties of five bioactive elements and the methods used for assessment of their in vitro angiogenic potential is presented. The findings show that silicon and strontium can effectively enhance osseointegration through the simultaneous promotion of both angiogenesis and osteogenesis. Therefore, their integration onto the surface of biomaterials can ultimately decrease the incidence of implant failure due to aseptic loosening.
Dapagliflozin in heart failure with preserved and mildly reduced ejection fraction: rationale and design of the <scp>DELIVER</scp> trial
Authors: Scott D. Solomon, Rudolf A. de Boer, David DeMets, Adrian F. Hernandez, Silvio E. Inzucchi, Mikhail N. Kosiborod, Carolyn S.P. Lam, Felipe Martinez, Sanjiv J. Shah, Daniel Lindholm, Ulrica Wilderäng, Fredrik Öhrn, Brian Claggett, Anna Maria Langkilde, Magnus Petersson, John J.V. McMurray
Journal: European Journal of Heart Failure (2021)

Abstract Aims Sodium–glucose co‐transporter 2 (SGLT2) inhibitors, originally developed as glucose‐lowering agents, have been shown to reduce heart failure hospitalizations in patients with type 2 diabetes without established heart failure, and in patients with heart failure with and without diabetes. Their role in patients with heart failure with preserved and mildly reduced ejection fraction remains unknown. Methods Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure (DELIVER) is an international, multicentre, parallel group, event‐driven, randomized, double‐blind trial in patients with chronic heart failure and left ventricular ejection fraction (LVEF) &gt;40%, comparing the effect of dapagliflozin 10 mg once daily, vs. placebo, in addition to standard of care. Patients with or without diabetes, with signs and symptoms of heart failure, a LVEF &gt;40%, elevation in natriuretic peptides and evidence of structural heart disease are eligible. The primary endpoint is time‐to‐first cardiovascular death or worsening heart failure event (heart failure hospitalization or urgent heart failure visit), and will be assessed in dual primary analyses – the full population and in those with LVEF &lt;60%. The study is event‐driven and will target 1117 primary events. A total of 6263 patients have been randomized. Conclusions DELIVER will determine the efficacy and safety of the SGLT2 inhibitor dapagliflozin, added to conventional therapy, in patients with heart failure and preserved and mildly reduced ejection fraction.
Acute myeloid leukemia with IDH1 and IDH2 mutations: 2021 treatment algorithm
Authors: Ghayas C. Issa, Courtney D. DiNardo
Journal: Blood Cancer Journal (2021)

Abstract Acute myeloid leukemia is a genetically heterogeneous hematologic malignancy; approximately 20% of AML harbors a mutation in the isocitrate dehydrogenase ( IDH ) genes, IDH1 or IDH2 . These recurrent mutations in key metabolic enzymes lead to the production of the oncometabolite 2-hydroxyglutarate, which promotes leukemogenesis through a block in normal myeloid differentiation. Since this discovery, selective oral inhibitors of mutant IDH1 and IDH2 have subsequently been developed and are now approved as single agent therapy, based on clinical efficacy observed within the original first-in-human trials. The investigation of IDH inhibitors in combination with standard therapies such as azacytidine, with intensive chemotherapy, and with other small molecule targeted therapies in rational combinations are currently under evaluation to further improve upon clinical efficacy.
AB0747 MATERNAL AND FETAL OUTCOMES IN PREGNANT WOMEN WITH JUVENILE IDIOPATHIC ARTHRITIS: A SYSTEMATIC LITERATURE REVIEW
Authors: R. Pinheiro Torres, M. H. Fernandes Lourenco, A. Neto, F. Pimentel Dos Santos, I. Silva, A. F. Mourão, H. Donato, M. Costa, J. Branco
Journal: Annals of the Rheumatic Diseases (2021)

Background: Juvenile idiopathic arthritis (JIA), one of the most common chronic diseases in children, can be classified in seven different categories according to its onset presentation. Concerns about pregnancy outcomes play a secondary role in disease approach. However, recent data showed an increased risk of pre-term birth in women with JIA instead the small patient samples analysed. Objectives: In this review, our aim is to describe the current available knowledge on JIA adverse, maternal and fetal, outcomes. Methods: A systematic literature review was conducted since January of 2000 until December 2020, by searching the PubMed and Embase bibliographic databases. The search was limited to articles in English language, presenting a comparator group (healthy individuals or patients without known auto-immune rheumatic diseases) and at least one clinical outcome of interest. Two independent reviewers screened the titles and abstracts followed by a full-text review to assess papers regarding their eligibility. Results: Ten observational studies out of 1560 references, fulfilled the inclusion criteria, of which, 9 were retrospective and 1 prospective. A total of 6.214 women with JIA (with 6.811 pregnancies) and 18.659.513 healthy controls (with 21.339.194 pregnancies) were included in this review. Concerning maternal outcomes, delivery by caesarian section (CS) was more frequent among JIA women (in 4 out of 6 studies). Pre-eclampsia was referred in 3 out of 6 studies and a higher risk of vaginal bleeding and placenta previa in one additional study. No study found an increased risk for gestational diabetes or hypertension in pregnant women with JIA. Regarding fetal outcomes, 8 studies revealed significantly increased of pre-term birth (only in first births in one study) but one study didn’t show any increased risk. Two studies showed a higher risk of small gestational age (SGA) and in another 2, increased risk for low birth weight (LBW). No evidence of increased risk of major congenital malformations. Conclusion: This systematic review suggests an increased risk for pre-eclampsia, preterm birth, delivery by CS, SGA and LBW, among pregnant women with JIA. Conclusions should be carefully interpreted, giving the heterogeneity of studied populations regarding demography, disease type, disease activity, and prescribed medication. Disclosure of Interests: None declared