tbuckley/cabot-search huggingface dataset:
SAT0396 INFLUENCE OF SMOKING AND OBESITY ON THERAPEUTIC RESPONSE IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS: A SYSTEMATIC LITERATURE REVIEW
Authors: P. Zurita-Prada, C. Urrego-Laurín, C. Guillén-Astete, V. Navarro-Compán
Journal: Annals of the Rheumatic Diseases (2020)

Background: Biological therapies have substantially improved the prognosis of patients with Spondyloarthritis (SpA). However, a satisfactory clinical response is not achieved in all patients and it is essential for the clinician to identify all those factors that predict treatment response. Although they are supposed as unfavorable and potentially avoidable factors, the influence of smoking and obesity as predictors of treatment response in SpA is unknown. Objectives: To determine if smoking and obesity are factors of worse therapeutic response in patients with axial spondyloarthritis (axSpA). Methods: Systematic review of the literature in MEDLINE and EMBASE until June 30, 2019 based on the PICO design method. Population (P): patients with axSpA. Intervention (I): smoking or obesity. Comparator (C): non-smokers and normal weight. Outcome (O): any of the response criteria currently validated for axSpA. A specific excel form was used for data collection, EndNote software for the management and organization of papers and the Oxford 2009 level for evidence evaluation. Results: 1873 citations were recovered, 46 studies were selected for full-text review and 12 for data extraction: 6 for smoking and 6 for obesity. The design of all studies was observational and longitudinal with data from national registries except one cross-sectional. In total, these studies included 5291 patients (3917 patients for smoking and 1333 patients for obesity), all treated with a TNF inhibitor (iTNF). The Oxford level of evidence for all studies was 2b except the cross-sectional study, which was 4. Regarding smoking, the evidence found is not consistent. Two of the studies concluded an unfavorable effect on the response to the iTNF (Glintborg and Ciurea) but the remaining 4 studies found no differences in the clinical response to iTNF (Zhao), the cause of discontinuity of the iTNF (Zhao, Hernandez) or quality of life indexes (Kydd). For obesity, the evidence is more consistent, so that 5 of the 6 studies observed a negative influence on the therapeutic response to iTNF (Ottaviani, Gremese, Micheroli, Hernández-Breijo and Rosas). Conclusion: According to scientific evidence in patients with axSpA, obesity is associated with a worse therapeutic response to iTNF. However, this negative effect is not clearly evidenced for smoking. Disclosure of Interests: Pablo Zurita-Prada: None declared, Claudia Urrego-Laurín: None declared, Carlos Guillén-Astete: None declared, Victoria Navarro-Compán Consultant of: Abbvie, Lilly, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Lilly, Novartis, Pfizer, UCB
Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients
Authors: Y. Nakamura, K. Namikawa, K. Yoshino, S. Yoshikawa, H. Uchi, K. Goto, Y. Nakamura, S. Fukushima, Y. Kiniwa, T. Takenouchi, H. Uhara, T. Kawai, N. Hatta, T. Funakoshi, Y. Teramoto, A. Otsuka, H. Doi, D. Ogata, S. Matsushita, T. Isei, T. Hayashi, Y. Shibayama, N. Yamazaki
Journal: Annals of Oncology (2020)
Effective interventions for homeless populations: the evidence remains unclear
Authors: Sophie Wickham
Journal: The Lancet Public Health (2020)

A wealth of evidence demonstrates the damaging long-term effects of homelessness on health. Homeless individuals are at higher risk of infections, traumatic injuries, and violence, and are more likely to have multimorbidities, disabilities, and to die young.1 The Organisation for Economic Co-operation and Development (OECD) estimate that at present, 1·9 million people across OECD countries are homeless.2 In the USA, on a single night in January, 2019, an estimated 567 715 people were experiencing homelessness, representing an increase of 3% from 2018.
AB1267 ONLINE CASE-BASED EDUCATION SIGNIFICANTLY IMPROVED RHEUMATOLOGISTS’ KNOWLEDGE AND CONFIDENCE IN MANAGING PATIENTS WITH RA
Authors: E. Bell, A. Sendaydiego, P. C. Taylor
Journal: Annals of the Rheumatic Diseases (2020)

Background: With the rapid evolution in treatment strategies and the increasing range of available therapeutics for rheumatoid arthritis (RA), keeping pace with advances can be a challenge for busy physicians. Objectives: We assessed whether online CME can improve rheumatologists’ knowledge of RA management focusing on the assessment and monitoring of RA, the selection of appropriate treatments and the clinical efficacy and safety data for JAK inhibitors. Methods: Rheumatologists participated in a text-based activity featuring two patient cases with questions that “tested” knowledge and discussion of the main “teaching” points. Educational effect was assessed using a repeated-pair design, pre-/post-assessment. A Chi-square test of independence determined if a statistically significant improvement (5% significance level, P &lt;.05) existed in the number of correct responses between the pretest and posttest scores. Cramer’s V estimated the effect size of the education. The activity launched on 15 December 2018 with data collection through 27 February 2019. Results: •Significant improvement in average percentage of correct responses, rising from 47% at baseline to 92% post-activity ( P &lt;.001) and extensive educational impact (Cramer’s V=0.496) •Significant increase in percentage of rheumatologists (n=111) answering all 3 questions correctly (9% at baseline rising to 78% post assessment) •Significant improvements in knowledge of EULAR/ACR assessment criteria (86% improvement, P &lt;.001), EULAR treatment recommendations for a patient failing on MTX and a TNF inhibitor (100% improvement, P &lt;.001), and the VTE risk associated with having RA or receiving RA treatments (108% improvement, P &lt;.001) •46% of rheumatologists reported greater confidence in their ability to appropriately incorporate JAK inhibitors into the treatment of patients with RA (average confidence shift 20%) Conclusion: Overall, this learning activity was highly successful in improving rheumatologists’ knowledge and confidence in managing patients with RA, particularly with regard to the appropriate use of JAK inhibitors in patients for whom such treatment is suitable. The extensive impact of this interactive ‘test then teach’ activity is likely to directly translate into patient benefit. Further education on this topic would be useful to enhance and reinforce this knowledge and to support physician confidence in the use of JAK inhibitors in clinical practice. References: [1]https://www.medscape.org/viewarticle/906202 Disclosure of Interests: Elaine Bell: None declared, Anne Sendaydiego: None declared, Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB
MRI of sacroiliac joints for the diagnosis of axial SpA: prevalence of inflammatory and structural lesions in nulliparous, early postpartum and late postpartum women
Authors: Adel Hoballah, Cédric Lukas, Christophe Leplat, Patrice Taourel, Jean-Baptiste Pialat, Nicolas Sans, Sonia Ramos-Pascual, Catherine Cyteval
Journal: Annals of the Rheumatic Diseases (2020)

To determine the prevalence of bone marrow oedema (BME) at the sacroiliac joint (SIJ) in early postpartum (EPP), nulliparous (NP) and late postpartum (LPP) women, and to identify factors associated with BME presence at the SIJ.Three groups were obtained: NP (never given birth), EPP (given birth within 12 months) and LPP (given birth more than 24 months). The primary outcome was the presence of BME and/or structural lesions (erosions, osteophytes, ankylosis and sclerosis) at the SIJ MRI.BME prevalence was greater among EPP (33%) than NP (14%, p=0.001), but was not different to LPP (21%, p=0.071). The Assessment of SpondyloArthritis international Society (ASAS) MRI criteria for sacroiliitis were positive in 75%, 71% and 80%, respectively, of EPP, NP and LPP women with BME. EPP (38%) had similar prevalence of sclerosis than LPP (28%, p=0.135), but greater than NP (18%, p=0.001). Lastly, EPP (28%) had similar prevalence of osteophytes than LPP (42%) and NP (27%), although there was a difference between LPP and NP (p=0.006).EPP have higher BME prevalence at the SIJ than NP, EPP tend to have higher BME prevalence compared with LPP and BME presence decreases with time from delivery. Three-quarters of women with BME at the SIJ had a positive ASAS MRI criteria for sacroiliitis, indicating that BME presence as the main criterion for a positive diagnosis can lead to false-positive results. SIJ MRIs should not be interpreted in isolation, since age, time from delivery and other factors may outweigh the pertinence of MRI findings. Trial registration number NCT02956824.
Underwater endoscopic resection of an ileal neuroendocrine tumor
Authors: Daniel T. Rezende, Fábio S. Kawaguti, Adriana V. Safatle-Ribeiro, Luciano H. L. Tolentino, Ulysses Ribeiro Junior, Fauze Maluf-Filho
Journal: Endoscopy (2020)

The small bowel is the third most common site of neuroendocrine tumors (NETs) after the lung and rectum, and NETs represent the most frequent malignancy of the small bowel [1]. Small bowel NETs are usually managed with surgical resection [2]. However, in some situations surgery may be too difficult or not feasible.
Cardiac events after atypical transient ischemic attack
Authors: P. J. Koudstaal, A. Algra, G. A. Pop, G. Hankey
Journal: Annals of Internal Medicine (1992)

Source Citation Koudstaal PJ, Algra A, Pop GA, et al, for the Dutch TIA Study Group. Risk of cardiac events in atypical transient ischaemic attack or minor stroke. Lancet. Sep
AB0057 THE ROLE OF NON-INFLAMMATORY MACROPHAGES INITIATING AND RESOLVING THE INFLAMMATORY RESPONSE OF MONOSODIUM URATE IN MICE
Authors: Y. J. Huang, L. C. Wang, C. F. Kuo
Journal: Annals of the Rheumatic Diseases (2020)

Background: Gout is the most common chronic inflammatory arthritis around the world which is associated with many conditions that affect longevity and well-being, such as metabolic syndrome, cardiovascular diseases, and renal diseases. [1] Objectives: Gout is the most common inflammatory arthritis around the world. Innate immunity has been implicated in gout inflammation in recent years. However, the phenomena of maintenance of ‘asymptomatic’ hyperuricemia, the spontaneous resolution of acute gouty arthritis and non-inflammatory tophus and its association with immune regulation are still elusive. We propose that resident macrophages may be a key player in the suppression of gouty inflammation. To address this hypothesis, we used non-inflammatory macrophages to explore the role played in initiating or resolving the inflammatory response. Methods: Bone marrow-derived macrophages (BMDM) were stimulated with monosodium rate (MSU), then analyzed the expression of RNA and protein of inflammatory cytokines, including IL-1β, IL-18 and TNF-α. In addition, we also observe the ability of macrophage to phagocyte and hydrolyze MSU crystal. Results: Our results indicate that MSU alone could not induce IL-1β, IL-18, and TNF-α mRNA expression and protein production. However, when macrophages were pre-stimulated with lipopolysaccharide (LPS) or MSU, as well as in combination the production of IL-1β and IL-18 were significantly increased. Furthermore, MSU maybe amplifies LPS-induced protein production of IL-1β and IL-18 but not in TNF-α. A temporal delay in the correlation between mRNA expression and protein production was shown. The results also indicated that macrophages could not only phagocytize MSU crystals but may also hydrolyze MSU crystals. Conclusion: These data indicate that MSU crystal alone is insufficient to induce pro-inflammatory cytokines production, however, when exposed to an infectious source of infection, it will amplify the inflammatory response and there is a synergistic effect between MSU and LPS. This may explain the diverse clinic phenomena of ‘asymptomatic’ hyperuricemia, non-inflammatory tophus and acute gouty arthritis. The high efficiency of phagocytosis and hydrolyzed MSU crystals of macrophages may explain the spontaneous regression of acute gouty arthritis. These findings may provide a new therapy for the prevention and treatment of acute gout attacks. References: [1]Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Comorbidities in patients with gout prior to and following diagnosis: case-control study. Annals of the rheumatic diseases. 2014 Nov 14. Disclosure of Interests: None declared
AB0513 GLOMERULONEPHRITIS IN LEVAMISOLE-ADULTERATED COCAINE VASCULOPATHY (LACIV): A 51-CASE SERIES
Authors: C. Muñoz, D. Jaramillo Arroyave, L. Hernandez, L. A. González, G. Vásquez, M. Restrepo Escobar, T. Urrego Callejas, A. Vanegas
Journal: Annals of the Rheumatic Diseases (2020)

Background: Up to 88% of cocaine is tainted with levamisole, anthelmintic withdrawn from the market due to toxicity. Since 2010 LACIV patients, characterized by retiform purpura, ear necrosis, multisystemic compromise and positivity for multiple autoantibodies, have been reported. Renal involvement is the most serious and heterogeneous clinical manifestation. Objectives: To describe the renal involvement of patients with LACIV. Methods: We describe the renal manifestations of a 51 case series with LACIV admitted in four high complexity institutions in Colombia from December 2010 to December 2019. Results: All patients were mestizos, with median age of 32.5 years (SD 7.8), the male:female ratio was 4.7:1, and the time from symptoms to diagnosis 12 months (IR 32). Nephritis was found in 60.8%, with creatinine elevation in 61%, median 2.0 mg/dl (IR 3), 87% had proteinuria, median 3184 mg/day (IR 5735), 43% in nephrotic-range; 93% had hematuria and 48% pyuria and cilindruria. Biopsy was performed in 21 patients (64%), with immune complex mediated extracapillary glomerulonephritis (35%), immune complex mediated membranoproliferative glomerulonephritis (20%) pauci-immune proliferative glomerulonephritis (20%), membranous glomerulonephritis (15%), focal and segmental glomerulosclerosis (5%) and C3 mediated extracapillary glomerulonephritis (5%). Six patients (19%) developed end-stage kidney disease. Patients with nephritis had more ear necrosis, retiform purpura, leukopenia, lymphopenia, anemia, hypocomplementemia, anti-PR3 and anti-MPO antibodies, compared to patients without nephritis. Conclusion: Due to the higher abuse of cocaine and its contamination with levamisole, LACIV is an increasingly reported disease. Although skin manifestations are the most characteristic and prevalent, renal involvement is frequent, clinically and histologically heterogeneous, and potentially serious. Cytopenias, hypocomplementemia and antineutrophil cytoplasmic antibodies could identify patients at risk of nephritis References: [1]Collister D, Sathianathan C, Ryz K, Karpinski M, Bernstein K, Gibson IW. ANCA Associated Vasculitis Secondary to Levamisole-Adultered Cocaine with Associated Membranous Nephropathy: A Case Series. Am J Nephrol. 2017;45(3):209–16. [2]Carlson AQ, Tuot DS, Jen K-Y, Butcher B, Graf J, Sam R, et al. Pauci-immune glomerulonephritis in individuals with disease associated with levamisole-adulterated cocaine: a series of 4 cases. Medicine (Baltimore). 2014 Oct;93(17):290–7. Disclosure of Interests: None declared
Abstract B51: Performance assessment of total RNA sequencing of human biofluids and extracellular vesicles
Authors: Celine Everaert, Hetty Helsmoortel, Anneleen Decock, Eva Hulstaert, Ruben Van Paemel, Kimberly Verniers, Justine Nuytens, Jasper Anckaert, Nele Nijs, Joeri Tulkens, Bert Dhondt, An Hendrix, Pieter Mestdagh, Jo Vandesompele
Journal: Clinical Cancer Research (2020)

Abstract RNA profiling has emerged as a powerful tool to investigate the biomarker potential of human biofluids. Despite the interest in extracellular nucleic acids, RNA sequencing methods to quantify the total RNA content outside cells are rare. Therefore, we evaluated the performance of the SMARTer Stranded Total RNA-Seq method in human platelet-rich plasma, platelet-free plasma, urine, conditioned medium, and extracellular vesicles (EVs) from these biofluids. We found the method to be accurate, precise, compatible with low-input volumes, and able to quantify a few thousand genes. We picked up distinct classes of RNA molecules, including mRNA, lncRNA, circRNA, miscRNA, and pseudogenes. Notably, the read distribution and gene content drastically differed among biofluids. We also observed differences between EDTA and citrate platelet-free plasma, which are identical biofluids collected in different blood tubes and prepared with a slightly different centrifugation protocol. In conclusion, we are the first to show that the SMARTer method can be used for unbiased charting of the complete transcriptome of a wide range of biofluids and their extracellular vesicles. The advantage of the SMARTer Stranded Total RNA-Seq method is its potential to process low amounts of input material. Indeed, collecting samples is often the bottleneck in fundamental, (pre)clinical, or translational research projects, and being able to disseminate large amounts of information from only 200 μL (or less) can substantially impact research progress. Citation Format: Celine Everaert, Hetty Helsmoortel, Anneleen Decock, Eva Hulstaert, Ruben Van Paemel, Kimberly Verniers, Justine Nuytens, Jasper Anckaert, Nele Nijs, Joeri Tulkens, Bert Dhondt, An Hendrix, Pieter Mestdagh, Jo Vandesompele. Performance assessment of total RNA sequencing of human biofluids and extracellular vesicles [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B51.
Covid-19: Bolsonaro under fire as Brazil hides figures
Authors: Owen Dyer
Journal: BMJ (2020)

<h3>Background</h3> COVID-19 continues to pose a significant healthcare challenge throughout the world. Comorbidities including diabetes and hypertension are associated with a significantly higher mortality risk. However, the effect of cirrhosis on COVID-19 outcomes has yet to be systematically assessed. <h3>Objectives</h3> To assess the reported clinical outcomes of patients with cirrhosis who develop COVID-19 infection. <h3>Design/Method</h3> PubMed and EMBASE databases were searched for studies included up to 3 February 2021. All English language primary research articles that reported clinical outcomes in patients with cirrhosis and COVID-19 were included. The study was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The risk of bias was assessed using the Quality In Prognostic Score (QUIPS) risk-of-bias assessment instrument for prognostic factor studies template. Meta-analysis was performed using Cochrane RevMan V.5.4 software using a random effects model. <h3>Results</h3> 63 studies were identified reporting clinical outcomes in patients with cirrhosis and concomitant COVID-19. Meta-analysis of cohort studies which report a non-cirrhotic comparator yielded a pooled mortality OR of 2.48 (95% CI: 2.02 to 3.04). Analysis of a subgroup of studies reporting OR for mortality in hospitalised patients adjusted for significant confounders found a pooled adjusted OR 1.81 (CI: 1.36 to 2.42). <h3>Conclusion</h3> Cirrhosis is associated with an increased risk of all-cause mortality in COVID-19 infection compared to non-cirrhotic patients. Patients with cirrhosis should be considered for targeted public health interventions to prevent COVID-19 infection, such as shielding and prioritisation of vaccination.
Parkin, an E3 ubiquitin ligase, enhances airway mitochondrial DNA release and inflammation
Authors: Kris Genelyn Dimasuay, Niccolette Schaunaman, Richard J Martin, Nicole Pavelka, Christena Kolakowski, Roberta A Gottlieb, Fernando Holguin, Hong Wei Chu
Journal: Thorax (2020)

Introduction Parkin (Park2), an E3 ubiquitin ligase, is critical to maintain mitochondrial function by regulating mitochondrial biogenesis and degradation (mitophagy), but recent evidence suggests the involvement of Parkin in promoting inflammation. In the present study, we determined if Parkin regulates airway mitochondrial DNA (mtDNA) release and inflammatory responses to type 2 cytokine interleukin (IL)-13 and allergens. Methods We measured Parkin mRNA expression in brushed bronchial epithelial cells and mtDNA release in the paired bronchoalveolar lavage fluid (BALF) from normal subjects and asthmatics. Parkin-deficient primary human tracheobronchial epithelial (HTBE) cells generated using the CRISPR-Cas9 system were stimulated with IL-13. To determine the in vivo function of Parkin, Parkin knockout (PKO) and wild-type (WT) mice were treated with IL-13 or allergen (house dust mite, HDM) in the presence or absence of mtDNA isolated from normal mouse lungs. Results Parkin mRNA expression in asthmatic airway epithelium was upregulated, which positively correlated with the levels of released mtDNA in BALF. IL-13-stimulated HTBE cells increased Parkin expression. Moreover, IL-13 induced mtDNA release in Parkin-sufficient, but not in Parkin-deficient HTBE cells. PKO (vs WT) mice attenuated airway mtDNA release and inflammation following IL-13 or HDM treatments. mtDNA amplified airway inflammation in mice treated with IL-13 or HDM. Notably, Parkin also mediated mtDNA-induced exacerbation of airway inflammation. Conclusion Our research findings suggest that Parkin promotes mtDNA release and inflammation in airways, thus improving our understanding of the complex role of Parkin and mitochondrial dysfunction in asthma pathogenesis.
Collagen Sequence Analysis Reveals Evolutionary History of Extinct West Indies Nesophontes (Island-Shrews)
Authors: Michael Buckley, Virginia L Harvey, Johanset Orihuela, Alexis M Mychajliw, Joseph N Keating, Juan N Almonte Milan, Craig Lawless, Andrew T Chamberlain, Victoria M Egerton, Phillip L Manning
Journal: Molecular Biology and Evolution (2020)

Abstract Ancient biomolecule analyses are proving increasingly useful in the study of evolutionary patterns, including extinct organisms. Proteomic sequencing techniques complement genomic approaches, having the potential to examine lineages further back in time than achievable using ancient DNA, given the less stringent preservation requirements. In this study, we demonstrate the ability to use collagen sequence analyses via proteomics to assist species delimitation as a foundation for informing evolutionary patterns. We uncover biogeographic information of an enigmatic and recently extinct lineage of Nesophontes across their range on the Caribbean islands. First, evolutionary relationships reconstructed from collagen sequences reaffirm the affinity of Nesophontes and Solenodon as sister taxa within Solenodonota. This relationship helps lay the foundation for testing geographical isolation hypotheses across islands within the Greater Antilles, including movement from Cuba toward Hispaniola. Second, our results are consistent with Cuba having just two species of Nesophontes (N. micrus and N. major) that exhibit intrapopulation morphological variation. Finally, analysis of the recently described species from the Cayman Islands (N. hemicingulus) indicates that it is a closer relative to N. major rather than N. micrus as previously speculated. This proteomic sequencing improves our understanding of the origin, evolution, and distribution of this extinct mammal lineage, particularly with respect to the approximate timing of speciation. Such knowledge is vital for this biodiversity hotspot, where the magnitude of recent extinctions may obscure true estimates of species richness in the past.