tbuckley/cabot-search huggingface dataset:
POS1131 THE INCIDENCE AND PREVALENCE OF CARDIOVASCULAR DISEASES IN GOUT: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: P. Cox, S. Gupta, S. S. Zhao, D. Hughes
Journal: Annals of the Rheumatic Diseases (2021)

Background: Gout is an inflammatory crystal arthropathy characterised by hyperuricaemia and sodium urate crystal deposition. Both gout and subclinical hyperuricaemia are associated with adverse cardiovascular outcomes. Several studies have found gout to cause an increased risk of cardiovascular disease, but the evidence is not unanimous. The conflicting evidence has made it difficult to establish the extent of the cardiovascular risk to patients with gout. Objectives: To describe the incidence and prevalence of cardiovascular disease in gout, compare these results with non-gout controls. Methods: PubMed, Scopus and Web of Science were systematically searched in January 2021 for studies reporting prevalence of any cardiovascular disease in a gout population. Studies with non-representative sampling, where a cohort had been used in another study, small sample size (&lt; 100) and where gout could not be distinguished from other rheumatic conditions were excluded. Sample size, prevalence of the investigated cardiovascular disease, definition of gout and cardiovascular disease, demographic data, data source and any comparisons with non-gout controls were extracted from each study. Where prevalence data was reported in ≥3 cohorts meta-analysis was performed using random-effect models. Results: Of the 6164 titles identified, 105 full texts were assessed for eligibility with 30 included in the review, producing a gout population of 1,125,988. Pooled prevalence estimates were calculated for six cardiovascular diseases: heart failure (8.73%; 95% confidence interval (CI), 2.85 – 23.76), cerebrovascular accident (4.27%; 95% CI, 1.83 – 9.67), myocardial infarction (2.82%; 95% CI, 1.58 – 5.01), venous thromboembolism (2.05%; 95% CI, 1.22 – 3.43), hypertension (63.94%; 95% CI, 24.51 – 90.64) and cardiovascular mortality (4.75%; 95% CI, 3.56 – 6.31). Twenty studies reported comparisons with non-gout controls, illustrating an increased risk in the gout group across all cardiovascular diseases, particularly for myocardial infarction. Conclusion: Cardiovascular diseases are more prevalent in patients with gout and should prompt vigilance from clinicians to the need to assess and stratify cardiovascular risk. These results are in line with other studies which have shown an increased cardiovascular risk for sufferers of hyperuricaemia, highlighting the need for future research to explain this finding. There are limited studies in the literature investigating less common cardiovascular conditions, illustrating the need for future work if a more thorough picture of prevalence is to be established. Figure 1. Forest plots of pooled prevalence of: ( A ) 8.73% for heart failure, ( B ) 4.27% for cerebrovascular accident, ( C ) 2.82% for myocardial infarction, ( D ) 2.05% for venous thromboembolism, ( E ) 63.94% for hypertension and ( F ) 4.75% for cardiovascular mortality. Disclosure of Interests: None declared.
Current challenges and unmet medical needs in myelodysplastic syndromes
Authors: Uwe Platzbecker, Anne Sophie Kubasch, Collin Homer-Bouthiette, Thomas Prebet
Journal: Leukemia (2021)

Abstract Myelodysplastic syndromes (MDS) represent a heterogeneous group of myeloid neoplasms that are characterized by ineffective hematopoiesis, variable cytopenias, and a risk of progression to acute myeloid leukemia. Most patients with MDS are affected by anemia and anemia-related symptoms, which negatively impact their quality of life. While many patients with MDS have lower-risk disease and are managed by existing treatments, there currently is no clear standard of care for many patients. For patients with higher-risk disease, the treatment priority is changing the natural history of the disease by delaying disease progression to acute myeloid leukemia and improving overall survival. However, existing treatments for MDS are generally not curative and many patients experience relapse or resistance to first-line treatment. Thus, there remains an unmet need for new, more effective but tolerable strategies to manage MDS. Recent advances in molecular diagnostics have improved our understanding of the pathogenesis of MDS, and it is becoming clear that the diverse nature of genetic abnormalities that drive MDS demands a complex and personalized treatment approach. This review will discuss some of the challenges related to the current MDS treatment landscape, as well as new approaches currently in development.
Covid-19: Pfizer-BioNTech vaccine is “likely” responsible for deaths of some elderly patients, Norwegian review finds
Authors: Ingrid Torjesen
Journal: BMJ (2021)

The Pfizer-BioNTech covid-19 vaccine is “likely” to have been responsible for at least 10 deaths of frail elderly people in nursing homes in Norway, an expert review commissioned by the Norwegian Medicines Agency has concluded.

The expert group was established at the end of February 2021 to look into the cause of the first 100 reported deaths of nursing home residents who had received the Pfizer-BioNTech vaccine. At the time, around 30 000 elderly nursing home residents had been vaccinated.

Although the mortality rate in nursing homes is generally very high and the deaths of some nursing home residents after vaccination was anticipated, the Norwegian Medicines Agency wanted to determine whether the vaccine had possibly hastened any deaths and to gain a clearer understanding of the risks and benefits of its use in frail elderly people.

The review reported on 19 May and concluded that a causal link between the Pfizer-BioNTech vaccine and death was considered “likely” in 10 of the 100 …
AB0095 EXPRESSION AND PATHOGENIC ROLES OF INTEGRIN FAMILY GENE IN SYSTEMIC SCLEROSIS
Authors: D. Xu, T. Li, R. Mu
Journal: Annals of the Rheumatic Diseases (2021)

Background: Emerging evidence have shown that some integrin members are associated with inflammation and fibrosis in systemic sclerosis (SSc) patients [1-2] . However, the expression patterns and pathogenic significance of the whole integrin family in SSc are still unclear. Objectives: This study aimed at evaluating the integrin family gene expression in skin lesion from SSc patients and exploring its potential pathogenic mechanism. Methods: We utilized the public datasets of SSc skin tissue from Gene Expression Omnibus (GEO) database to analyze the expression and clinical significance of integrin family genes in SSc. In addition, functional enrichment and pathway analysis were also conducted. Results: Compared with healthy controls, ITGA5, ITGA7, ITGA8, ITGB2, ITGB5, ITGAE and ITGB3BP were abnormally overexpressed in the skin of SSc. Further analysis indicated that ITGA5, ITGA7, ITGA8, ITGB2 and ITGB5 were positively correlated with modified Rodnan skin thickness score (mRSS), while ITGAE and ITGB3BP were negatively correlated with mRSS in SSc. Increased ITGB5 expression was associated with positive of anti-centromere antibody (ACA). Functional enrichment and pathway analysis showed that integrin members had multiple functions in SSc. Among them, ITGA5, ITGB2 and ITGB5 might synergistically promote SSc through affecting extracellular matrix (ECM) turn over, ECM-receptor interaction, focal adhesion and leukocyte trans-endothelial migration. ITGA5 and ITGB5 also affected angiogenesis and endothelial cell function. In addition, ITGA5 was uniquely enriched for actin organization, ITGB5 was uniquely enriched for TGF-β signaling, and ITGB2 was uniquely associated with immune cells activation. Conclusion: Our results implied that integrins, especially ITGA5, ITGB5, ITGB2 participated in the process of inflammation, vasculopathy and fibrosis in SSc. Together, they might render important therapeutic targets for SSc. References: [1]Brown M, O’Reilly S. The immunopathogenesis of fibrosis in systemic sclerosis. Clin Exp Immunol. 2019;195(3):310-321. [2]Gerber, E.E., et al., Integrin-modulating therapy prevents fibrosis and autoimmunity in mouse models of scleroderma. Nature, 2013. 503(7474): p. 126-30. Disclosure of Interests: None declared
Corrigendum to ’Endometrial membrane organoids from human embryonic stem cell combined with the 3D Matrigel for endometrium regeneration in asherman syndrome’ [Bioactive Mater. 6 (2021) 3935–3946]
Authors: Xiuxiu Jiang, Xingmiao Li, Xiangwei Fei, Jiajie Shen, Jianhua Chen, Meijun Guo, Yangyang Li
Journal: Bioactive Materials (2021)
68Ga-FAPI PET/CT Versus 18F-FDG PET/CT for Detecting Metastatic Lesions in a Case of Radioiodine-Refractory Differentiated Thyroid Cancer
Authors: Hao Fu, Jie Fu, Jingxiong Huang, Yizhen Pang, Haojun Chen
Journal: Clinical Nuclear Medicine (2021)

Abstract 18 F-FDG PET/CT is a useful imaging modality for detecting disease recurrence and metastases in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). However, the sensitivity of 18 F-FDG PET/CT in RAIR-DTC is not very satisfactory. 68 Ga-FAPI is a promising PET tracer that allowed imaging of various types of cancer. In this case, 68 Ga-FAPI showed a far better signal-to-background ratio than 18 F-FDG for detecting the RAIR-DTC metastatic lesions, especially for detecting the small pulmonary metastases. Therefore, 68 Ga-FAPI may be a promising alternative to 18 F-FDG for detecting tumor recurrence and metastases in RAIR-DTC. It could also be used for guiding FAP-targeted radionuclide therapy.
Response by Birks et al to Letters Regarding Article, “Prospective Multicenter Study of Myocardial Recovery Using Left Ventricular Assist Devices (RESTAGE-HF [Remission from Stage D Heart Failure]): Medium-Term and Primary End Point Results”
Authors: Emma J. Birks, Jesus E. Rame, Christopher Cunningham, Stavros G. Drakos
Journal: Circulation (2021)
Identification and validation of viral antigens sharing sequence and structural homology with tumor-associated antigens (TAAs).
Authors: Concetta Ragone, Carmen Manolio, Beatrice Cavalluzzo, Angela Mauriello, Maria Lina Tornesello, Franco M Buonaguro, Filippo Castiglione, Luigi Vitagliano, Emanuela Iaccarino, Menotti Ruvo, Maria Tagliamonte, Luigi Buonaguro
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background The host’s immune system develops in equilibrium with both cellular self-antigens and non-self-antigens derived from microorganisms which enter the body during lifetime. In addition, during the years, a tumor may arise presenting to the immune system an additional pool of non-self-antigens, namely tumor antigens (tumor-associated antigens, TAAs; tumor-specific antigens, TSAs). Methods In the present study, we looked for homology between published TAAs and non-self-viral-derived epitopes. Bioinformatics analyses and ex vivo immunological validations have been performed. Results Surprisingly, several of such homologies have been found. Moreover, structural similarities between paired TAAs and viral peptides as well as comparable patterns of contact with HLA and T cell receptor (TCR) α and β chains have been observed. Therefore, the two classes of non-self-antigens (viral antigens and tumor antigens) may converge, eliciting cross-reacting CD8 + T cell responses which possibly drive the fate of cancer development and progression. Conclusions An established antiviral T cell memory may turn out to be an anticancer T cell memory, able to control the growth of a cancer developed during the lifetime if the expressed TAA is similar to the viral epitope. This may ultimately represent a relevant selective advantage for patients with cancer and may lead to a novel preventive anticancer vaccine strategy.
Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial
Authors: David J Straus, Monika Długosz-Danecka, Joseph M Connors, Sergey Alekseev, Árpád Illés, Marco Picardi, Ewa Lech-Maranda, Tatyana Feldman, Piotr Smolewski, Kerry J Savage, Nancy L Bartlett, Jan Walewski, Radhakrishnan Ramchandren, Pier Luigi Zinzani, Martin Hutchings, Javier Munoz, Hun Ju Lee, Won Seog Kim, Ranjana Advani, Stephen M Ansell, Anas Younes, Andrea Gallamini, Rachael Liu, Meredith Little, Keenan Fenton, Michelle Fanale, John Radford
Journal: The Lancet Haematology (2021)
Covid-19: Delta variant is now UK’s most dominant strain and spreading through schools
Authors: Ingrid Torjesen
Journal: BMJ (2021)

Covid-19: Delta variant is now UK's most dominant strain and spreading through schools Ingrid TorjesenThe delta covid-19 variant (B.1.617.2), which was first detected in India, has overtaken the alpha variant, better known as the UK or Kent variant (B.1.1.7),to make it the most dominant strain circulating in the UK, Public Health England has said.
Use of an antiviral mouthwash as a barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: a multicentre, randomized, double-blind controlled trial
Authors: Florence Carrouel, Martine Valette, Emilie Gadea, Aurélie Esparcieux, Gabriela Illes, Marie Elodie Langlois, Hervé Perrier, Claude Dussart, Paul Tramini, Mélina Ribaud, Maude Bouscambert-Duchamp, Denis Bourgeois
Journal: Clinical Microbiology and Infection (2021)

ObjectivesTo determine if commercially available mouthwash with β-cyclodextrin and citrox (bioflavonoids) (CDCM) could decrease the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) salivary viral load.MethodsIn this randomized controlled trial, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive patients aged 18–85 years with asymptomatic to mild coronavirus disease 2019 (COVID-19) symptoms for <8 days were recruited. A total of 176 eligible patients were randomly assigned (1:1) to CDCM or placebo. Three rinses daily were performed for 7 days. Saliva sampling was performed on day 1 at 09.00 (T1), 13.00 (T2) and 18.00 (T3). On the following 6 days, one sample was taken at 15.00. Quantitative RT-PCR was used to detect SARS-CoV-2.ResultsThe intention-to-treat analysis demonstrated that, over the course of 1 day, CDCM was significantly more effective than placebo 4 hours after the first dose (p 0.036), with a median percentage (log10 copies/mL) decrease T1–T2 of –12.58% (IQR –29.55% to –0.16%). The second dose maintained the low median value for the CDCM (3.08 log10 copies/mL; IQR 0–4.19), compared with placebo (3.31 log10 copies/mL; IQR 1.18–4.75). At day 7, there was still a greater median percentage (log10 copies/mL) decrease in salivary viral load over time in the CDCM group (–58.62%; IQR –100% to –34.36%) compared with the placebo group (–50.62%; IQR –100% to –27.66%). These results were confirmed by the per-protocol analysis.ConclusionsThis trial supports the relevance of using CDCM on day 1 (4 hours after the initial dose) to reduce the SARS-CoV-2 viral load in saliva. For long-term effect (7 days), CDMC appears to provide a modest benefit compared with placebo in reducing viral load in saliva.
Evaluation of tumor immune contexture among intrinsic molecular subtypes helps to predict outcome in early breast cancer
Authors: Quentin Klopfenstein, Valentin Derangère, Laurent Arnould, Marion Thibaudin, Emeric Limagne, Francois Ghiringhelli, Caroline Truntzer, Sylvain Ladoire
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background The prognosis of early breast cancer is linked to clinic-pathological stage and the molecular characteristics of intrinsic tumor cells. In some patients, the amount and quality of tumor-infiltrating immune cells appear to affect long term outcome. We aimed to propose a new tool to estimate immune infiltrate, and link these factors to patient prognosis according to breast cancer molecular subtypes. Methods We performed in silico analyses in more than 2800 early breast cancer transcriptomes with corresponding clinical annotations. We first developed a new gene expression deconvolution algorithm that accurately estimates the quantity of immune cell populations (tumor immune contexture, TIC) in tumors. Then, we studied associations between these immune profiles and relapse-free and overall survival among the different intrinsic molecular subtypes of breast cancer defined by PAM50 classification. Results TIC estimates the abundance of 15 immune cell subsets. Both myeloid and lymphoid subpopulations show different spread among intrinsic molecular breast cancer subtypes. A high abundance of myeloid cells was associated with poor outcome, while lymphoid cells were associated with favorable prognosis. Unsupervised clustering describing the 15 immune cell subsets revealed four subgroups of breast tumors associated with distinct patient survival, but independent from PAM50. Adding this information to clinical stage and PAM50 strongly improves the prediction of relapse or death. Conclusions Our findings make it possible to refine the survival stratification of early patients with breast cancer by incorporating TIC in addition to PAM50 and clinical tumor burden in a prognostic model validated in training and validation cohorts.
POS0397 AGGREGATED SURVIVIN BINDING AROUND HISTONE H3 EPIGENETIC MODIFICATIONS IN RISK LOCI ASSOCIATED WITH RHEUMATOID ARTHRITIS
Authors: V. Chandrasekaran, G. Katona, M. I. Bokarewa, K. M. Andersson, M. C. Erlandsson, M. Jensen, N. Oparina, A. Damdimopoulos
Journal: Annals of the Rheumatic Diseases (2021)

Background: Survivin is an integral part of the Chromosomal Passenger Complex (CPC) which plays a vital role in mitosis. Experiments have demonstrated that survivin can physically bind to DNA. Crystallographic studies show that survivin binds to Threonine-3 of histone H3. In patients with autoimmune diseases, increased survivin expression contributes to an aggravated disease phenotype. Thus, functional, and mechanistic data point to a potential chromatin regulatory role for survivin, possibly in combination with the established gene regulatory function carried out by histone epigenetic modifications (EM). Objectives: The objective of the study was to analyse the co-localization of chromatin bound survivin with three histone H3 epigenetic modifications – acetylated lysine 27 (K27ac) and trimethylated lysine 4 (K4me3) and lysine-27 (K27me3). The second objective was to analyse if survivin-bound DNA sequences overlapped with sequences in the vicinity of 106 GWAS SNPs that are associated with a risk of developing rheumatoid arthritis (RA). Methods: Chromatin from CD4 T cells of 14 female subjects was immunoprecipitated with survivin antibodies and each of the histone H3 antibodies, and coupled with sequencing (ChIPseq, Hiseq2000, Illumina). After mapping the annotations of sequenced regions to the human reference genome hg38, enriched peaks were identified through Homer software. The identified survivin ChIP peaks were analysed for colocalization with peaks of the three histone H3 EMs and with RA risk loci, using the Bioconductor package ‘ChIPPeakAnno’ through RStudio. Results: Among the total of ~13,000 individual survivin ChIP-peaks, 33% colocalized with histone H3 EM peaks. The overlapping peaks show a linear increase in average peak size compared with the peaks showing no colocalization with any H3 EM peak. A maximum of 5.5-fold increase in average peak size was observed when survivin bound peaks overlap with peaks of all three H3 EMs. A major proportion (86%) of top RA risk SNPs was associated with either binding of survivin or H3 EMs. In this subset, 63% of RA risk SNPs were found within an area of 100 kilobases from survivin ChIP-peaks, with preferential enrichment of high-scoring peaks when survivin colocalizes with all 3 H3 EMs. Survivin was bound to risk SNPs annotated to, among others, the major immunological genes CD83, IRF4, CD28, ICOS and IL2RA Conclusion: This study presents experimental evidence that survivin binding to DNA preferentially occurred in regions with high density of histone EMs. The increased aggregation of survivin around histone H3 EMs point to its potential regulatory function in gene transcription. Since regions around RA risk SNPs overlap with survivin peaks, survivin’s nuclear function could have immunologically important effects in mechanisms of autoimmune diseases. Disclosure of Interests: None declared
AB0300 LUPUS DISEASE ACTIVITY CORRELATES WITH QUALITY OF LIFE BUT NOT WITH HEALTH LITERACY STATUS
Authors: E. Eraslan, R. Bilici Salman, H. Satiş, A. Avanoglu Guler, H. Karadeniz, H. Küçük, S. Haznedaroglu, M. A. Ozturk, A. Tufan, B. Goker
Journal: Annals of the Rheumatic Diseases (2021)

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology that can affect any organ of the body. SLE is associated with adverse effects on both health and non-health-related quality of life (HRQOL and non-HRQOL). Lupus PRO is a patient reported outcome measure that has been validated in many languages. It has 44 items that cover both HRQOL and non-HRQOL (1). Health literacy is defined as the degree to which individuals have the capacity to obtain, process and understand basic health information and services needed to make appropriate health decisions. Multiple studies indicate that people with limited health literacy have worse health status and higher rates of hospitalization (2). Objectives: We aimed to evaluate the relationship between the LLDAS (Lupus Low Disease Activity State) criteria and the Lupus PRO test, as well as the health literacy status of lupus patients. Methods: 83 SLE patients (94% women) were included in the study. We performed Lupus PRO and the European Health Literacy Survey tests during the routine follow-up visits of lupus patients to our rheumatology outpatient clinic and admissions to rheumatology inpatient clinic. Available clinical data on medical records were obtained, physician global assessments (PGA) were recorded by the attending physician. Results: LLDAS criteria strongly and inversely correlated with the total score, as well as the mood subunit of the Lupus PRO. Similarly, it also significantly inversely correlated with the body appearence and goals subunits. Health literacy status of the patients did not correlate with their LLDAS scores, ie their disease activities. Conclusion: Our results suggest that lupus disease activity, assessed by LLDAS criteria, significantly correlates with measures of quality of life, spesicifically Lupus PRO test, but not with health literacy status. Further studies are needed to evaluate if health literacy is related with damage, hospitalization or mortality associated with lupus. References: [1]Jolly M, Pickard AS, Block JA, Kumar RB, Mikolaitis RA, Wilke CT, et al., editors. Disease-specific patient reported outcome tools for systemic lupus erythematosus. Seminars in arthritis and rheumatism; 2012: Elsevier. [2]Paasche-Orlow MK, Parker RM, Gazmararian JA, Nielsen-Bohlman LT, Rudd RR. The prevalence of limited health literacy. Journal of general internal medicine. 2005;20(2):175-84. Disclosure of Interests: None declared
Adjuvant Olaparib for Patients with <i>BRCA1</i>- or <i>BRCA2</i>-Mutated Breast Cancer
Authors: Andrew N.J. Tutt, Judy E. Garber, Bella Kaufman, Giuseppe Viale, Debora Fumagalli, Priya Rastogi, Richard D. Gelber, Evandro de Azambuja, Anitra Fielding, Judith Balmaña, Susan M. Domchek, Karen A. Gelmon, Simon J. Hollingsworth, Larissa A. Korde, Barbro Linderholm, Hanna Bandos, Elżbieta Senkus, Jennifer M. Suga, Zhimin Shao, Andrew W. Pippas, Zbigniew Nowecki, Tomasz Huzarski, Patricia A. Ganz, Peter C. Lucas, Nigel Baker, Sibylle Loibl, Robin McConnell, Martine Piccart, Rita Schmutzler, Guenther G. Steger, Joseph P. Costantino, Amal Arahmani, Norman Wolmark, Eleanor McFadden, Vassiliki Karantza, Sunil R. Lakhani, Greg Yothers, Christine Campbell, Charles E. Geyer
Journal: New England Journal of Medicine (2021)

Poly(adenosine diphosphate–ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation–associated early breast cancer.