tbuckley/cabot-search huggingface dataset:
AB0631 THE PREVALENCE AND FACTORS ASSOCIATED WITH CORONARY HEART DISEASE IN PATIENTS WITH GOUT
Authors: E. Markelova, M. Elisеev, E. Ilinykh, S. Glukhova, T. Popkova
Journal: Annals of the Rheumatic Diseases (2021)

Background: Gout is associated with increased risk of cardiovascular disease (CVD) morbidity and mortality. Therefore, an association between coronary heart disease (CHD) and gout deserves careful examination. Objectives: The aim of this study was to determine the prevalence of CHD and factors associated with CHD in patients (pts) with gout. Methods: 286 male patients fulfilling Wallace proposed criteria for gout were included: age 51.2 [42.8;59.4] years (ys), disease duration – 6.2 [3.8;12.1] ys. All patients underwent standard clinical examination, screening traditional risk factors (TRF) of CVD, blood chemistry test with estimation of serum uric acid, serum creatinine, C-reactive protein (CRP), as well as lipid profile. Carotid intima-media thickness (cIMT) was measured using a high-resolution B-mode ultrasound machine. CHD included history of angina pectoris and/or myocardial infarction. We estimated the adjusted odds ratio (OR) and 95% confidence interval (95% CI). Results: CHD was found in 111 out of the 286 pts (38.8 %). Compared to individuals with CHD, participants without CHD were older (56.7[52.1; 61.1] vs 46.2[40.6; 53.4] ys), had longer duration of gout (9.3[4.7; 15.1] vs 5.6[3.3; 9.7] ys), higher number of joints involved during disease course (8[6; 15] vs 6[4; 10]), duration of smoking (24[10; 40] vs 20[10; 28]), higher serum creatinine level accordingly, (for all p&lt;0.05). The frequency of family history of CHD (63% vs 46.8%), intraosseous tophi (61.3% vs 33.1%), was higher in pts with CHD compared pts without CHD accordingly, (for all p&lt;0.01). Prevalence of arterial hypertension, diabetes mellitus, nephrolithiasis, heart failure and renal failure was greater in pts with CHD than pts without CHD (p&lt;0.001). Gout pts with CHD had a significantly higher cIMT compare to those without CHD - 0.95[0.8;1.08]/0.8[0.7;0.9] accordingly, p&lt;0.001. We didn’t find differences of lipid profile, serum uric acid, and CRP level in gout pts with/without CHD. Abdominal obesity (OR, 5.5; 95% CI, 2.2-13.6), body mass index &gt;30 kg/m 2 (OR, 5.8; 95% CI, 1.8-18.5), family history of CHD (OR, 2.7; 95% CI, 1.3-5.4), disease duration of gout more 10 ys (OR, 2.6; 95% CI, 1.3-5.1), age of gout onset &lt; 35 ys (OR, 3.0; 95% CI, 1.5-6.1), intraosseous tophi (OR, 3.1; 95% CI, 1.4-7.0), C-RP (OR, 2.2; 95% CI, 1.1-4.7), renal failure (OR, 18,8; 95% CI, 1.1-312.9), increased the risk for CHD in patients with a gout. Conclusion: The prevalence of CHD was 38.8% among individuals with gout. Our study showed that both TRFs of CVD and the severity of gout and a history of renal failure contribute to the development of CHD in patients with gout. Disclosure of Interests: None declared.
Partial recovery of visual function in a blind patient after optogenetic therapy
Authors: José-Alain Sahel, Elise Boulanger-Scemama, Chloé Pagot, Angelo Arleo, Francesco Galluppi, Joseph N. Martel, Simona Degli Esposti, Alexandre Delaux, Jean-Baptiste de Saint Aubert, Caroline de Montleau, Emmanuel Gutman, Isabelle Audo, Jens Duebel, Serge Picaud, Deniz Dalkara, Laure Blouin, Magali Taiel, Botond Roska
Journal: Nature Medicine (2021)
Cap-assisted large cold snare removal of a giant phytobezoar
Authors: Zhang Tao, Wenfeng Pu, Liang Sun, Xiaoqing Zhou, Yan Zhang, Zhonghan Du, Ji Wu
Journal: Endoscopy (2021)

A 56-year-old woman presented to our department with a 1-day history of hematemesis and a 2-year history of eating persimmons. After the patient had received an injection of proton pump inhibitor, we found a giant phytobezoar (about 6 × 4 cm) in her stomach on gastroscopy ([Fig. 1 a]). The phytobezoar was turned into an upright position with the endoscope in the inverted position ([Video 1]). A large snare (4 cm in diameter) was used to trap the phytobezoar ([Fig. 1 b]); however, it was hard to crush the phytobezoar when tightening the snare. Therefore, the tightened snare was pulled into the cap to cold-cut the phytobezoar using cap assistance. After repeated snare-trapping and cap-assisted cold-cutting, the phytobezoar was finally cut into several pieces. The larger pieces were pulled out using the snare ([Fig. 2]); the leftover small pieces were washed out of the body using oral polyethylene glycol. A subsequent gastroscopy, 2 days after the cap-assisted cold-cutting snare removal procedure, revealed a clear stomach ([Fig. 3]).
POS1103 SLEEP DISTURBANCE AND BONE MINERAL DENSITY, RISK OF FALLS AND FRACTURE: RESULTS FROM A 10.7-YEAR PROSPECTIVE COHORT STUDY
Authors: F. Pan, J. Tian, F. Cicuttini, G. Jones
Journal: Annals of the Rheumatic Diseases (2021)

Background: Sleep problems are common in the general population and have been reported to adversely affect bone health and increase risk of falls and fracture. However, no study has investigated whether an increased risk of fracture is attributable to sleep-related low bone mineral density (BMD) and/or an increased risk of falls. Objectives: This study, therefore, sought to describe the associations of sleep disturbance with BMD, risk of falls and fractures. Methods: The analyses were performed in a population-based prospective cohort study with 1,099 participants (aged 50–80 years) enrolled at baseline, and 875, 768 and 563 participants traced at a mean follow-up of 2.6, 5.1 and 10.7 years, respectively. At each visit, self-reported sleep disturbance was recorded. BMD (by DXA), falls risk and fracture were measured at each visit. The short-form Physiological Profile Assessment was used to measure falls risk expressed as Z-score. Fractures were self-reported. Mixed-effects model and generalised estimating equations were used for the analyses. Results: In multivariable analysis, there was a dose-response relationship between extent of sleep disturbance and falls risk score with the strongest association in those reporting the worst sleep disturbance (β=0.15/unit; 95%CI 0.02-0.28). The worst sleep disturbance was associated with an increased risk of any (relative risk [RR] 1.30/unit; 95%CI 1.01-1.67) and vertebral fracture (RR 2.41/unit; 95%CI 1.00-5.80) compared with those reporting no interrupted sleep. This was independent of covariates, hip BMD and falls risk. There was no statistically significant association between sleep disturbance and BMD at hip, spine or total body. Conclusion: Sleep disturbance was independently associated with a greater falls risk score and an increased risk of fractures, suggesting that correcting sleep disturbance has the potential to reduce both falls risk and fractures. Disclosure of Interests: None declared.
Lymphoma and multiple myeloma in cohorts of persons exposed to ionising radiation at a young age
Authors: Mark P. Little, Richard Wakeford, Lydia B. Zablotska, David Borrego, Keith T. Griffin, Rodrigue S. Allodji, Florent de Vathaire, Choonsik Lee, Alina V. Brenner, Jeremy S. Miller, David Campbell, Siegal Sadetzki, Michele M. Doody, Erik Holmberg, Marie Lundell, Michael Jacob Adams, Benjamin French, Martha S. Linet, Amy Berrington de Gonzalez
Journal: Leukemia (2021)
Structural and functional characterization of multiple myeloma associated cytoplasmic poly(A) polymerase FAM46C
Authors: Hong Zhang, Shi‐Hui Zhang, Jia‐Li Hu, Yu‐Tong Wu, Xiao‐Yan Ma, Yang Chen, Bing Yu, Shuang Liao, Huilin Huang, Song Gao
Journal: Cancer Communications (2021)

Abstract Background Multiple myeloma (MM) is a hematologic malignancy characterized by the accumulation of aberrant plasma cells within the bone marrow. The high frequent mutation of family with sequence similarity 46, member C (FAM46C) is closely related with the occurrence and progression of MM. Recently, FAM46C has been identified as a non‐canonical poly(A) polymerase (PAP) that functions as a tumor suppressor in MM. This study aimed to elucidate the structural features of this novel non‐canonical PAP and how MM‐related mutations affect the structural and biochemical properties of FAM46C, eventually advancing our understandings towards FAM46C mutation‐related MM occurrence. Methods We purified and crystallized a mammalian FAM46C construct, and solved its structure. Next, we characterized the property of FAM46C as a PAP through a combination of structural analysis, site‐directed mutagenesis and biochemical assays, and by comparison with its homolog FAM46B. Finally, we structurally analyzed MM‐related FAM46C mutations and tested the enzymatic activity of corresponding mutants. Results We determined the crystal structure of a mammalian FAM46C protein at 2.35 Å, and confirmed that FAM46C preferentially consumed adenosine triphosphate (ATP) and extended A‐rich RNA substrates. FAM46C showed a weaker PAP activity than its homolog FAM46B, and this difference was largely dependent on the residue variance at particular sites. Of them, residues at positions 77, 290, and 298 of mouse FAM46C were most important for the divergence in enzymatic activity. Among the MM‐associated FAM46C mutants, those residing at the catalytic site (D90G and D90H) or putative RNA‐binding site (I155L, S156F, D182Y, F184L, Y247V, and M270V) showed abolished or compromised PAP activity of FAM46C, while N72A and S248A did not severely affect the PAP activity. FAM46C mutants D90G, D90H, I155L, S156F, F184L, Y247V, and M270V had significantly lower inhibitory effect on apoptosis of RPMI‐8226 cells as compared to wild‐type FAM46C. Conclusions FAM46C is a prokaryotic‐like PAP with preference for A‐rich RNA substrates, and showed distinct enzymatic efficiency with its homolog FAM46B. The MM‐related missense mutations of FAM46C lead to various structural and biochemical outcomes to the protein.
Abstract 11576: Impact of Baseline Low-Density Lipoprotein Cholesterol Level and Aggressive Lipid-Lowering Therapy by Ezetimibe on Prognosis of Statin Naïve Acute Coronary Syndrome Patients: A Sub-Analysis of the HIJ-PROPER Trial
Authors: Erisa Kawada-Watanabe, Junichi Yamaguchi, Haruki Sekiguchi, Jihaeng Im, Keisuke Suzuki, Masataka Ogiso, Hiroyuki Arashi, Hiroshi Ogawa, Nobuhisa Hagiwara
Journal: Circulation (2018)

Introduction: There were few reports examining the difference of treatment effect of lipid lowering therapy by ezetimibe in accordance with baseline low-density lipoprotein cholesterol (LDL-C) leve...
Molecular determinants of clinical outcomes with pembrolizumab versus paclitaxel in a randomized, open-label, phase III trial in patients with gastroesophageal adenocarcinoma
Authors: K. Shitara, M. Özgüroğlu, Y.-J. Bang, M. Di Bartolomeo, M. Mandalà, M.-H. Ryu, C. Caglevic, H.C. Chung, K. Muro, E. Van Cutsem, J. Kobie, R. Cristescu, D. Aurora-Garg, J. Lu, C.-S. Shih, D. Adelberg, Z.A. Cao, C.S. Fuchs
Journal: Annals of Oncology (2021)

In the phase III KEYNOTE-061 trial (NCT02370498), pembrolizumab did not significantly improve overall survival versus paclitaxel as second-line therapy for gastric/gastroesophageal junction (GEJ) adenocarcinoma with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 tumors. The association of tissue tumor mutational burden (tTMB) status and clinical outcomes was determined, including the relationship with CPS and microsatellite instability-high (MSI-H) status.In patients with whole exome sequencing (WES) data [420/592 (71%); pembrolizumab, 218; paclitaxel, 202], the association of tTMB with objective response rate (ORR; logistic regression), progression-free survival (PFS; Cox proportional hazards regression), and overall survival (OS; Cox proportional hazards regression) were measured using one-sided (pembrolizumab) and two-sided [paclitaxel] P values. tTMB was also evaluated using FoundationOne®CDx [205/592 (35%)]. Prespecified equivalent cut-offs of 175 mut/exome for WES and 10 mut/Mb for FoundationOne®CDx were used.WES-tTMB was significantly associated with ORR, PFS, and OS in pembrolizumab-treated (all P < 0.001) but not paclitaxel-treated patients (all P > 0.6) in univariate analysis. The area under the receiver operating characteristics curve for WES-tTMB and response was 0.68 [95% confidence interval (CI) 0.56-0.81] for pembrolizumab and 0.51 (95% CI 0.39-0.63) for paclitaxel in univariate analysis. There was low correlation between WES-tTMB and CPS in both treatment groups (r ≤ 0.16). WES-tTMB remained significantly associated with all clinical endpoints with pembrolizumab after adjusting for CPS and with PFS and OS after excluding known MSI-H tumors (n = 26). FoundationOne®CDx-tTMB demonstrated a positive association with ORR, PFS, and OS in pembrolizumab-treated patients (all P ≤ 0.003) but not PFS or OS in paclitaxel-treated patients (P > 0.1).This exploratory analysis from KEYNOTE-061 is the first to demonstrate a strong association between tTMB and efficacy with pembrolizumab but not paclitaxel in patients with gastric/GEJ adenocarcinoma in a randomized setting. Data further suggest tTMB is a significant and independent predictor beyond PD-L1 status.
Annotation of snoRNA abundance across human tissues reveals complex snoRNA-host gene relationships
Authors: Étienne Fafard-Couture, Danny Bergeron, Sonia Couture, Sherif Abou-Elela, Michelle S. Scott
Journal: Genome biology (2021)

Small nucleolar RNAs (snoRNAs) are mid-size non-coding RNAs required for ribosomal RNA modification, implying a ubiquitous tissue distribution linked to ribosome synthesis. However, increasing numbers of studies identify extra-ribosomal roles of snoRNAs in modulating gene expression, suggesting more complex snoRNA abundance patterns. Therefore, there is a great need for mapping the snoRNome in different human tissues as the blueprint for snoRNA functions.We used a low structure bias RNA-Seq approach to accurately quantify snoRNAs and compare them to the entire transcriptome in seven healthy human tissues (breast, ovary, prostate, testis, skeletal muscle, liver, and brain). We identify 475 expressed snoRNAs categorized in two abundance classes that differ significantly in their function, conservation level, and correlation with their host gene: 390 snoRNAs are uniformly expressed and 85 are enriched in the brain or reproductive tissues. Most tissue-enriched snoRNAs are embedded in lncRNAs and display strong correlation of abundance with them, whereas uniformly expressed snoRNAs are mostly embedded in protein-coding host genes and are mainly non- or anticorrelated with them. Fifty-nine percent of the non-correlated or anticorrelated protein-coding host gene/snoRNA pairs feature dual-initiation promoters, compared to only 16% of the correlated non-coding host gene/snoRNA pairs.Our results demonstrate that snoRNAs are not a single homogeneous group of housekeeping genes but include highly regulated tissue-enriched RNAs. Indeed, our work indicates that the architecture of snoRNA host genes varies to uncouple the host and snoRNA expressions in order to meet the different snoRNA abundance levels and functional needs of human tissues.
Technical standards in allergen exposure chambers worldwide – an EAACI Task Force Report
Authors: Oliver Pfaar, Karl‐Christian Bergmann, Sergio Bonini, Enrico Compalati, Nathalie Domis, Frédéric de Blay, Pieter‐Jan de Kam, Philippe Devillier, Stephen R. Durham, Anne K. Ellis, Alina Gherasim, Laura Haya, Jens M. Hohlfeld, Friedrich Horak, Tomohisa Iinuma, Robert L. Jacobs, Henrik Hugo Jacobi, Marek Jutel, Susanne Kaul, Suzanne Kelly, Ludger Klimek, Mark Larché, Patrick Lemell, Vera Mahler, Hendrik Nolte, Yoshitaka Okamoto, Piyush Patel, Ronald L. Rabin, Cynthia Rather, Angelika Sager, Anne Marie Salapatek, Torben Sigsgaard, Alkis Togias, Christoph Willers, William H. Yang, René Zieglmayer, Torsten Zuberbier, Petra Zieglmayer
Journal: Allergy (2021)

Allergen exposure chambers (AECs) can be used for controlled exposure to allergenic and non-allergenic airborne particles in an enclosed environment, in order to (i) characterize the pathological features of respiratory diseases and (ii) contribute to and accelerate the clinical development of pharmacological treatments and allergen immunotherapy for allergic disease of the respiratory tract (such as allergic rhinitis, allergic rhinoconjunctivitis, and allergic asthma). In the guidelines of the European Medicines Agency for the clinical development of products for allergen immunotherapy (AIT), the role of AECs in determining primary endpoints in dose-finding Phase II trials is emphasized. Although methodologically insulated from the variability of natural pollen exposure, chamber models remain confined to supporting secondary, rather than primary, endpoints in Phase III registration trials. The need for further validation in comparison with field exposure is clearly mandated. On this basis, the European Academy of Allergy and Clinical Immunology (EAACI) initiated a Task Force in 2015 charged to gain a better understanding of how AECs can generate knowledge about respiratory allergies and can contribute to the clinical development of treatments. Researchers working with AECs worldwide were asked to provide technical information in eight sections: (i) dimensions and structure of the AEC, (ii) AEC staff, (iii) airflow, air processing, and operating conditions, (iv) particle dispersal, (v) pollen/particle counting, (vi) safety and non-contamination measures, (vii) procedures for symptom assessments, (viii) tested allergens/substances and validation procedures. On this basis, a minimal set of technical requirements for AECs applied to the field of allergology is proposed.
POS0577 EVALUATION OF COPING STRATEGIES IN RHEUMATOID ARTHRITIS PATIENTS
Authors: B. A. Hiba, S. Meriem, S. Miladi, F. Alia, S. Leila, O. Kmar, S. Kassab, S. Chikili, K. Ben Abdelghani, A. Laatar
Journal: Annals of the Rheumatic Diseases (2021)

Background: Studies have shown that the association of pain, stiffness, disability, and social restrictions in rheumatoid arthritis (RA) patients induce a significantly increased level of depressed mood and stress. The use of favorable coping strategies could lead to improve physical and psychological well-being. Objectives: To evaluate coping strategies of RA patients and their associations with health-related quality of life (HRQoL) outcomes. Methods: A cross-sectional sample of patients with established RA was evaluated using measures of coping: the Brief-COPE (scores presented for the two overarching coping styles: Approach coping including active coping, emotional support, use of informational support, positive reframing, planning and acceptance, and Avoidant coping including self-distraction, denial, substance use, behavioral disengagement, venting and self-blame), the HRQoL (Mental and Physical Components [MCS/PCS] of the Short Form 12), and the Rheumatoid Arthritis Impact of Disease score (RAID]. Multiple linear regression analyses were performed to evaluate the associations between coping strategies and HRQoL outcomes. Results: The study sample comprised 45 patients with a female predominance (91.9 %), and a mean age of 55.7± 9.9 years [38-77]. The median disease duration was 10 years [38-77]. The majority of patients (82.8 %) were positive for either rheumatoid factor or anti-CCP. Half of the patients were on biological disease-modifying antirheumatic drugs. Two active coping strategies were identified: Approach coping (E = 4.29) and Avoidant Coping (E=3.86), which explained 40% of the total variance. Mean RAID was 4.8± 1.6, while the mean PCS and MCS were 31.9 ± 9.4 and 39.7 ± 9.4, respectively. Approach coping and avoidant coping were associated with PCS (r= 0.4, p = 0.03), (r=0.3, p=0.008) respectively. However, no association was found between coping strategies and MCS or RAID (p&gt;0.05). In the multivariate model, approach coping and avoidant coping were significant to explain lower disease-specific HRQoL (PCS) (Beta= 0.4, p= 0.008), (Beta=0.3, p=0.02) respectively. Conclusion: Approach and avoidance are associated with lower disease-specific HRQoL (PCS) but not with lower disease-specific HRQoL (MCS). Doctors should not forget to help their patients developing adaptive coping strategies. Disclosure of Interests: None declared
AB0237 INFECTIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH RITUXIMAB AND ANTI-TNF INHIBITOR
Authors: N. Zehraoui, R. Benaziez.Boutaleb, H. Hafirassou, F. Mechid, N. Bahaz, C. Makhloufi-Dahou
Journal: Annals of the Rheumatic Diseases (2021)

Background: Biological therapies have significantly improved the management of rheumatoid arthritis (RA). These molecules are very effective, but are known for their specific risks, especially infectious. It depends on several factors including the type of molecule used. Objectives: The objective of our study is to compare the rate of infection in RA patients treated with rituximab and anti-TNFα. Methods: Prospective, observational, monocentric study. Were included RA patients (ACR / EULAR 2010 criteria) treated with rituximab and anti-TNFα (adalimumab, infliximab and Etanercept) after inadequate response to DMARDs. Demographic characteristics, comorbidities, association with methotrexate and corticosteroids were collected and compared for each group. The number, type and severity of the infections in both cases were noted. SPSS (Statistical Package for Social Science) was used for data analysis. Results: 40 RA patients treated with rituximab and 31 patients who received anti-TNFα were included. Patient characteristics and Comparison of rate of infection in RA patients between the two groups are summarized in Table 1 Table 1. Parameters Rituximab Anti-TNFα p Number of patients 40 31 Average age (years) 56,28 46,06 0,01 Sexratio 0,14 0,11 0,7 Average duration of evolution (years) 15,83 13,74 0,3 Patients under corticosteroid (%) 97,5 87,1 0,08 Average corticosteroid dose 6,41 5,48 0,3 patients under methotrexate (%) 37,5 45,2 0,5 Diabetes (%) 20 16,1 0,7 Patients with infection (%) 32,5 51,6 0,1 Number of infections 18 24 0,4 Number of serious infections 5 0 0,04 Conclusion: The rate of infections in patients with RA treated with rituximab or anti-TNF was similar. However, the infections observed were more serious in patients with RA treated with rituximab References: [1]Fabiola Atzeni MD PhD and al. Infections and Biological Therapy in Patients with Rheumatic Diseases. IMAJ . VOL 18. march-APRIL 2016. [2]Huifeng Yun and al. Comparative Risk of Hospitalized Infection Associated with Biologic Agents in Rheumatoid Arthritis Patients Enrolled in Medicare. ARTHRITIS &amp; RHEUMATOLOGY. Vol. 68, No. 1, January 2016, pp 56–66. [3]Manjari Lahiri and al. Risk of infection with biologic antirheumatic therapies in patients with rheumatoid arthritis. Best Practice &amp; Research Clinical Rheumatology (2015) 1-16. Disclosure of Interests: None declared