tbuckley/cabot-search huggingface dataset:
SAT0056 INITIAL PRESENTATION OF RHEUMATOID ARTHRITIS (RA) – IS IT STILL “SYMMETRIC POLYARTHRITIS”?
Authors: T. Sokka-Isler, K. Paalanen, M. Kauppi, E. Nikiphorou
Journal: Annals of the Rheumatic Diseases (2020)

Background: RA is traditionally described as a symmetric polyarthritis. The ACR/EULAR 2010 criteria are met if patient has high positive ACPA, symptoms &gt;=6 wks and one small joint swollen. The public and all steps of health care have been informed for many years that RA should be found early. Objectives: To study variations in pattern on first presentation of RA. Methods: All patients with the new diagnosis of RA were extracted from the GoTreatIT clinical database between 2008 to 2019 at a single RA clinic that covers a population of 250.000. Demographic data, clinical variables, labs, x-rays, joint status and PROs at baseline were included in the analysis. Appropriate parametric/non-parametric tests were used to study differences between groups. Results: A total of 1044 (73.5% CCP+) patients with no prior diagnosis of RA were included; 683 (65%) female, mean age 56; 361 (35%) male, mean age 61. At initial presentation in 2008, 60% had &gt;=6 swollen joints (Figure) and a mean DAS28 of 4.4 compared to 22% and 3.8 respectively, in 2019 (p&lt;0.007). Duration of symptoms prior to diagnosis decreased from 6 to 4 months (p=0.033), and the proportion of patients with erosions from 20% in 2008 to 14% in 2019 (ns). Symptoms (PROs) such as pain, fatigue and global health were similar/slightly worse in 2019 compared to 2008. Conclusion: RA cannot be marketed as “symmetric polyarthritis”, as more than half of the patients have a maximum of 2 swollen joints at the time of the diagnosis at the most recent years. Patients with RA can be identified earlier, with less disease activity and damage, compared to previous years. Figure: Disclosure of Interests: None declared
AB0465 ANALYSIS OF VASCULITIS PATTERNS IN PATIENTS WITH GIANT CELL ARTERITIS COMPARED TO PATIENTS WITH GIANT CELL ARTERITIS AND POLYMYALGIA RHEUMATICA
Authors: L. C. Burg, P. Brossart, C. Behning, V. S. Schäfer
Journal: Annals of the Rheumatic Diseases (2020)

Background: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) often coexist. 1 The role of modern ultrasound in diagnosis of GCA as well as PMR is well known. 2 To date it is unknown, whether patients with GCA and PMR have a different vasculitis pattern in ultrasound (US) examination than patients with GCA only. Objectives: To prospectively identify differences in vasculitis patterns in consecutive patients with newly diagnosed GCA and PMR compared to newly diagnosed GCA patients without PMR. Methods: US examination of the arteries typically affected in GCA, such as axillary arteries, vertebral arteries, superficial temporal arteries with both frontal and parietal branches and facial arteries was performed in patients with GCA and PMR (GCA-PMR-group) as well as in patients with GCA only (GCA-group) at time of first diagnosis. Arteries were defined as pathological, if measured intima-media-thickness by US was above respective cut-off values. 3 Results: The GCA-PMR-group consisted of 27 patients, the GCA-group of 18 patients. In the GCA-PMR-group, a total of 206 arteries were affected, while in the GCA-group 131 arteries were affected. Mean age and gender distribution was 74 years (SD± 9) with 10 (37%) females in the GCA-PMR-group and 76 years (SD± 9) with 10 (55%) females in the GCA-group. Median values of C-reactive protein (CRP) were 57.2 (IQR 31.7-75.7) in the GCA-group and 48.3 (IQR 17.5- 79.9) in the GCA-PMR-group, no significance was observed (p= 0.3577). Mean number of affected arteries per patient was 7.63 and 7.28 in the GCA-PMR-group and GCA-group, respectively. Altogether, no significant difference in vascular pattern between the two groups was observed. Exact numbers, distribution and IMT-values for all measured arteries are depicted in table 1. Conclusion: In our cohort, we did not observe a significant difference in vascular patterns between patients with GCA and PMR and GCA only patients. References: [1] Salvarani C, Cantini F, Hunder GG. Polymyalgia rheumatica and giant-cell arteritis. The Lancet 2008;372:234–45. [2] Dejaco C, Ramiro S, Duftner C, et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann Rheum Dis 2018;77:636–43. [3] Schäfer VS, Juche A, Ramiro S, Krause A, Schmidt WA. Ultrasound cut-off values for intima-media thickness of temporal, facial and axillary arteries in giant cell arteritis. Rheumatology (Oxford) 2017;56:1479–83. Disclosure of Interests: None declared
Homeostatic and early-recruited CD101<sup>−</sup> eosinophils suppress endotoxin-induced acute lung injury
Authors: Chen Zhu, Qing-Yu Weng, Ling-Ren Zhou, Chao Cao, Fei Li, Yin-Fang Wu, Yan-Ping Wu, Miao Li, Yue Hu, Jia-Xin Shen, Xue-Fang Xiong, Fen Lan, Li-Xia Xia, Bin Zhang, Hao Zhang, Man Huang, Song-Min Ying, Hua-Hao Shen, Zhi-Hua Chen, Wen Li
Journal: European Respiratory Journal (2020)

Acute lung injury (ALI) is a fatal but undertreated condition with severe neutrophilic inflammation, although little is known about the functions of eosinophils in the pathogenesis of ALI. Our objectives were to investigate the roles and molecular mechanisms of eosinophils in ALI.Pulmonary eosinophils were identified by flow cytometry. Mice with abundant or deficient eosinophils were used. Cellularity of eosinophils and neutrophils in bronchoalveolar lavage fluid, inflammatory assessment, and survival rate were determined. Human samples were also used for validating experimental results.Blood eosinophils were increased in surviving patients with acute respiratory distress syndrome (ARDS) independent of corticosteroid usage. There existed homeostatic eosinophils in lung parenchyma in mice and these homeostatic eosinophils, originating from the bone marrow, were predominantly CD101-. More CD101- eosinophils could be recruited earlier than lipopolysaccharide (LPS)-initiated neutrophilic inflammation. Loss of eosinophils augmented LPS-induced pulmonary injury. Homeostatic CD101- eosinophils ameliorated, while allergic CD101+ eosinophils exacerbated, the neutrophilic inflammation induced by LPS. Likewise, CD101 expression in eosinophils from ARDS patients did not differ from healthy subjects. Mechanistically, CD101- eosinophils exhibited higher levels of Alox15 and Protectin D1. Administration of Protectin D1 isomer attenuated the neutrophilic inflammation.Collectively, our findings identify an uncovered function of native CD101- eosinophils in suppressing neutrophilic lung inflammation and suggest a potential therapeutic target for ALI.
Clinical outcome and hemodynamic changes following HCV eradication with oral antiviral therapy in patients with clinically significant portal hypertension
Authors: Sabela Lens, Anna Baiges, Edilmar Alvarado-Tapias, Elba LLop, Javier Martinez, Jose Ignacio Fortea, Luís Ibáñez-Samaniego, Zoe Mariño, Sergio Rodríguez-Tajes, Adolfo Gallego, Rafael Bañares, Ángela Puente, Agustín Albillos, Jose Luis Calleja, Xavier Torras, Virginia Hernández-Gea, Jaume Bosch, Cándid Villanueva, Juan Carlos García-Pagán, Xavier Forns
Journal: Journal of Hepatology (2020)
AB0956 VERTICAL NAIL RIDGING IN PATIENTS WITH FIBROMYALGIA: FREQUENCY, PROPOSED GRADING AND CORRELATION WITH OTHER DISEASE FEATURES
Authors: A. Moshrif, M. Abdelkareem, M. Moneer, A. Mosallam, A. Ismail, M. Elwan, A. Saad, T. Abdelaziz
Journal: Annals of the Rheumatic Diseases (2020)

Background: The vertical nail ridging (VNR) has long been reported to be related to stressful conditions 1 Objectives: to evaluate the frequency of VNS in FM patients and its relation to other disease parameters depending on a proposed grading. Methods: VNR has been searched for in 212 FM patients (2016 criteria). The number of fingers, the degree of VNR according to this proposed grading (0: no ridging, 1: ridging only detected by a magnifying lens, 2: ridging seen by naked eye and 3: ridging that can be seen and felt) and other FM features according to the new and old ACR criteria have been recorded. 80 subjects of those consulting for knee osteoarthritis have been examined for VNR and those found positive were asked about the FM features and examined for tender points. Patients aged &gt;50 years and those with psoriasis and fungal infections were excluded. Results: the mean age of patients was 32.4±9.9 (73.6% were female). The mean disease duration was 5.8±3.7, while the means of WPI, SSS and tender points were 9.4±2.9, 7.3±1.2 and 14.7±2.3 respectively. VNR was found in 209 patients (98.6%). Of 80 controls, VNR has been found in 61 subjects, of whom FM has been diagnosed in 32 patients (52.4%) by 2016 FM criteria and in 46 (75.4%) by 1990 criteria. The number of fingers with VNR has been found only correlated with the disease duration (r= 0.276, P = 0.000). The severity of VNR was significantly correlating with fatigue (P= 0.002), sleep disturbance (P= 0.001), awaking unrefreshed (P = 0.000), WPI (p = 0.01) and mean tender points (P =0.02). Considering the 2016 criteria as a gold standard, the sensitivity of VNR was 98.37%, the specificity was 9.68% and the diagnostic accuracy was 82.8%. Conclusion: vertical nail ridging is a frequent finding and can be considered helpful for diagnosis of patients with FM. Further studies are needed to validate this sign for diagnosis and follow up of FM patients. References: [1]American Academy of Dermatology. (2007, November 12). Feeling Stressed? How Your Skin, Hair And Nails Can Show It. Science Daily . Retrieved December 30, 2019 from www.sciencedaily.com/releases/2007/11/071109194053.htm Disclosure of Interests: None declared
Clinical outcome of endoscopic treatment for symptomatic sterile walled-off necrosis
Authors: Lotte Boxhoorn, Jeska A. Fritzsche, Paul Fockens, Jeanin E. van Hooft, Pieter J. F. de Jonge, Jan-Werner Poley, Marco J. Bruno, Rogier P. Voermans
Journal: Endoscopy (2020)

Background The majority of patients with symptomatic sterile walled-off necrosis (WON) can be treated conservatively. Although endoscopic transluminal drainage (ETD) is often performed in cases of persistent symptoms, post-procedural iatrogenic infection may occur. This study aimed to evaluate clinical outcomes after ETD of symptomatic sterile WON. Methods This was a retrospective, multicenter, open-label case series of 56 patients with necrotizing pancreatitis who underwent ETD for symptomatic sterile WON between July 2001 and August 2018 at two tertiary referral hospitals. Primary end point was clinically relevant post-procedural iatrogenic infection, defined as need for endoscopic transluminal necrosectomy. Secondary end points included mortality, total number of interventions, hospital stay, and resolution of symptoms at 1-year follow-up. Results ETD of sterile WON was performed in 56 patients (median age 55 years, 57 % male), who presented with abdominal pain (71 %), gastric outlet obstruction (45 %), jaundice (20 %), and failure to thrive (27 %). A total of 41 patients (73 %) developed clinically relevant post-procedural iatrogenic infection, resulting in a median of 3 (interquartile range [IQR] 2 – 4) endoscopic, radiological, and/or surgical interventions. Mortality rate was 2 %. Median total hospital stay was 12 days (IQR 6 – 17). Resolution of symptoms was reported in 40 of 46 patients (87 %) for whom long-term follow-up data were available (median follow-up 13 months, IQR 6 – 29). Conclusions ETD of symptomatic sterile WON resulted in high clinical success. Nonetheless, the majority of patients required additional reinterventions for clinically relevant post-procedural iatrogenic infection.
Abstract 44: Monitoring of ctDNA burden from noncoding DNA
Authors: Guo Yu, Zhong Wee Poh, Guanhua Zhu, Iain Tan, Sarah Ng, Patrick Tan, Anders Skanderup
Journal: Clinical Cancer Research (2020)

Abstract Our understanding of mutations in noncoding DNA is still nascent across most cancer types. Similarly, the potential clinical utility of noncoding DNA in cancer liquid biopsy assays remains mostly unexplored. Here, we identify high-frequency noncoding mutation hotspots in whole genomes from hundreds of gastrointestinal tumors and show that these mutations can be detected in liquid biopsy samples from cancer patients. We demonstrate how profiling of noncoding mutation hotspots can significantly increase the accuracy of ctDNA burden estimation, with minimal impact on sequencing cost, when paired with existing targeted cfDNA assays. Our results suggest that targeted NGS liquid biopsy assays should target both protein-coding and noncoding mutations when estimation and monitoring of ctDNA burden is a key clinical endpoint. Citation Format: Guo Yu, Zhong Wee Poh, Guanhua Zhu, Iain Tan, Sarah Ng, Patrick Tan, Anders Skanderup. Monitoring of ctDNA burden from noncoding DNA [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 44.
A Moderate Increase in the WT1 mRNA Copy Number in Peripheral Blood of Patients with Long-Standing Acquired Aplastic Anemia without Apparent Signs of Myelodysplastic Syndrome
Authors: Ken Ishiyama, Takeshi Yoroidaka, Noriharu Nakagawa, Hiroki Mizumaki, Tatsuya Imi, Kohei Hosokawa, Hirohito Yamazaki, Seishi Ogawa, Shinji Nakao
Journal: Blood (2017)
British Society of Gastroenterology endorsed guidance for the management of immune checkpoint inhibitor-induced enterocolitis
Authors: Nick Powell, Hajir Ibraheim, Tim Raine, Richard A Speight, Sophie Papa, Oliver Brain, Michael Green, Mark A Samaan, Lavinia Spain, Nadia Yousaf, Nikki Hunter, Lucy Eldridge, Polychronis Pavlidis, Peter Irving, Bu'Hussain Hayee, Samra Turajlic, James Larkin, James O Lindsay, Martin Gore
Journal: The Lancet. Gastroenterology & hepatology (2020)
Resource and Infrastructure-Appropriate Management of ST-Segment Elevation Myocardial Infarction in Low- and Middle-Income Countries
Authors: Y. Chandrashekhar, Thomas Alexander, Ajit Mullasari, Dharam J. Kumbhani, Samir Alam, Erick Alexanderson, Damodar Bachani, Jacobus Cornelius Wilhelmus Badenhorst, Ragavendra Baliga, Jeroen J. Bax, Deepak L. Bhatt, Eduardo Bossone, Roberto Botelho, Rabindra Nath Chakraborthy, Richard A. Chazal, Rupinder Singh Dhaliwal, Habib Gamra, Sivadasan Pillai Harikrishnan, Mohamed Jeilan, David Ian Kettles, Sameer Mehta, Padhinhare P. Mohanan, Christoph Kurt Naber, Nitish Naik, Mpiko Ntsekhe, Harun Argwings Otieno, Prem Pais, Daniel José Piñeiro, Dorairaj Prabhakaran, K. Srinath Reddy, Mustafa Redha, Ambuj Roy, Meenakshi Sharma, Robert Shor, Frederik Adriaan Snyders, Jack Weii Chieh Tan, C. Michael Valentine, B. Hadley Wilson, Salim Yusuf, Jagat Narula
Journal: Circulation (2020)

The 143 low- and middle-income countries (LMICs) of the world constitute 80% of the world’s population or roughly 5.86 billion people with much variation in geography, culture, literacy, financial resources, access to health care, insurance penetration, and healthcare regulation. Unfortunately, their burden of cardiovascular disease in general and acute ST-segment–elevation myocardial infarction (STEMI) in particular is increasing at an unprecedented rate. Compounding the problem, outcomes remain suboptimal because of a lack of awareness and a severe paucity of resources. Guideline-based treatment has dramatically improved the outcomes of STEMI in high-income countries. However, no such focused recommendations exist for LMICs, and the unique challenges in LMICs make directly implementing Western guidelines unfeasible. Thus, structured solutions tailored to their individual, local needs, and resources are a vital need. With this in mind, a multicountry collaboration of investigators interested in LMIC STEMI care have tried to create a consensus document that extracts transferable elements from Western guidelines and couples them with local realities gathered from expert experience. It outlines general operating principles for LMICs focused best practices and is intended to create the broad outlines of implementable, resource-appropriate paradigms for management of STEMI in LMICs. Although this document is focused primarily on governments and organizations involved with improvement in STEMI care in LMICs, it also provides some specific targeted information for the frontline clinicians to allow standardized care pathways and improved outcomes.
Uridine Triacetate for Severe Fluoropyrimidine Cardiotoxicity in a Patient With Thymidylate Synthase Gene Variants
Authors: Inbar Raber, Morgan B. Frazer, Jessica A. Zerillo, Aarti Asnani
Journal: JACC CardioOncology (2020)

A 56-year-old woman with history of hypertension, inadequately controlled on hydrochlorothiazide and nebivolol, presented with colorectal cancer with metastases to the liver in 2019. Genotypic testing revealed that her colorectal cancer was KRAS/NRAS wild-type and microsatellite stable. FOLFOX was
Re: Gregory T. Chesnut, Emily A. Vertosick, Nicole Benfante, et al. Role of Changes in Magnetic Resonance Imaging or Clinical Stage in Evaluation of Disease Progression for Men with Prostate Cancer on Active Surveillance. Eur Urol 2020;77:501–7
Authors: Benjamin S. Simpson, Lina M. Carmona Echeverria, Joseph M. Norris, Hashim U. Ahmed, Caroline M. Moore, Hayley C. Whitaker
Journal: European Urology (2020)
Serum cytokine concentrations and asthma persistence to middle age
Authors: Jingwen Zhang, Eugene H. Walters, Mimi L. K. Tang, Adrian J. Lowe, Caroline J. Lodge, Dinh Bui, Rangi Kandane‐Rathnayake, Bircan Erbas, Garun S. Hamilton, Bruce R. Thompson, Michael J. Abramson, Graham G. Giles, Jennifer L. Perret, Shyamali C. Dharmage
Journal: Allergy (2020)

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109P Updated Results of the Bolero-2 Phase Iii Trial Evaluating Everolimus (Eve) for Postmenopausal Women with Advanced Breast Cancer (Abc)
Authors: H. Rugo, M. Piccart, G. Hortobagyi, S. Noguchi, M. Gnant, M. Campone, H. Bauly, P. Mukhopadhyay, T. Sahmoud, J. Baselga
Journal: Annals of Oncology (2012)
When You Hear Hoofbeats in the Distance But Find Zebras
Authors: Miguel A. Arias, Alberto Puchol, Marta Pachón
Journal: Circulation (2020)

A 29-year-old woman with a short history of paroxysmal palpitations and documented wide QRS complex tachycardia was referred to our institution for an electrophysiologic study.The patient had no previous history of cardiovascular disease.Her chest radiograph and transthoracic echocardiogram showed no abnormalities.
HDAC6-specific inhibitor suppresses Th17 cell function via the HIF-1α pathway in acute lung allograft rejection in mice
Authors: Wenyong Zhou, Jun Yang, Gaowa Saren, Heng Zhao, Kejian Cao, Shijie Fu, Xufeng Pan, Huijun Zhang, An Wang, Xiaofeng Chen
Journal: Theranostics (2020)

Background: Previous animal experiments and clinical studies indicated the critical role of Th17 cells in lung transplant rejection. Therefore, the downregulation of Th17 cell function in lung transplant recipients is of great interest. Methods: We established an orthotopic mouse lung transplantation model to investigate the role of histone deacetylase 6-specific inhibitor (HDAC6i), Tubastatin A, in the suppression of Th17 cells and attenuation of pathologic lesions in lung allografts. Moreover, mechanism studies were conducted in vitro. Results: Tubastatin A downregulated Th17 cell function in acute lung allograft rejection, prolonged the survival of lung allografts, and attenuated acute rejection by suppressing Th17 cell accumulation. Consistently, exogenous IL-17A supplementation eliminated the protective effect of Tubastatin A. Also, hypoxia-inducible factor-1α (HIF-1α) was overexpressed in a lung transplantation mouse model. HIF-1α deficiency suppressed Th17 cell function and attenuated lung allograft rejection by downregulating retinoic acid-related orphan receptor γt (ROR γt) expression. We showed that HDAC6i downregulated HIF-1α transcriptional activity under Th17-skewing conditions in vitro and promoted HIF-1α protein degradation in lung allografts. HDAC6i did not affect the suppression of HIF-1α-/- naïve CD4+ T cell differentiation into Th17 cell and attenuation of acute lung allograft rejection in HIF-1α-deficient recipient mice. Conclusion: These findings suggest that Tubastatin A downregulates Th17 cell function and suppresses acute lung allograft rejection, at least partially, via the HIF-1α/ RORγt pathway.
Abstract 32: Data-driven inference of crosstalk in the tumor microenvironment
Authors: Umesh Ghoshdastider, Marjan Naeini, Neha Rohatgi, Sundar Solai, Tin Nguyen, Egor Revkov, Anders Skanderup
Journal: Clinical Cancer Research (2020)

Abstract Signaling between cancer and nonmalignant (stromal) cells in the tumor microenvironment (TME) is key to tumorigenesis, yet challenging to decipher from tumor transcriptomes. Here, we report an unbiased, data-driven approach to deconvolute bulk tumor transcriptomes and predict crosstalk between ligands and receptors on cancer and stromal cells in the TME of 20 solid tumor types. Our approach recovers known transcriptional hallmarks of cancer and stromal cells and is concordant with single-cell and immunohistochemistry data, underlining its robustness. Pan-cancer analysis reveals previously unrecognized features of cancer-stromal crosstalk. We find that autocrine cancer cell crosstalk varied between tissues but often converged on known cancer signaling pathways. In contrast, many stromal crosstalk interactions were highly conserved across tumor types. Interestingly, the immune checkpoint ligand PD-L1 was overexpressed in stromal rather than cancer cells across all tumor types. Moreover, we predicted and experimentally validated aberrant ligand and receptor expression in cancer cells of basal and luminal breast cancer, respectively. Collectively, our findings validate a data-driven method for tumor transcriptome deconvolution and establish a new resource for hypothesis generation and downstream functional interrogation of the TME in tumorigenesis and disease progression. Citation Format: Umesh Ghoshdastider, Marjan Naeini, Neha Rohatgi, Sundar Solai, Tin Nguyen, Egor Revkov, Anders Skanderup. Data-driven inference of crosstalk in the tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 32.
Minding the epistemic gap in covid-19 and beyond
Authors: Sandy J Goldbeck-Wood
Journal: BMJ (2020)

It is heartening to see The BMJ publishing information based on lived experience of covid-19. Perspectives such as Boyes’s are vital in understanding its harms, along with other qualitative data.1

Boyes extends knowledge in two ways—flagging issues such as memory loss, sleep difficulties, and fear, which might prove generalisable as part of the clinical picture of covid-19, and offering lessons about …