tbuckley/cabot-search huggingface dataset:
Lenvatinib versus sorafenib for first-line treatment of unresectable hepatocellular carcinoma: patient-reported outcomes from a randomised, open-label, non-inferiority, phase 3 trial
Authors: Arndt Vogel, Shukui Qin, Masatoshi Kudo, Yun Su, Stacie Hudgens, Tatsuya Yamashita, Jung-Hwan Yoon, Laetitia Fartoux, Krzysztof Simon, Carlos López, Max Sung, Kalgi Mody, Tatsuroh Ohtsuka, Toshiyuki Tamai, Lee Bennett, Genevieve Meier, Valery Breder
Journal: The Lancet. Gastroenterology & hepatology (2021)
Intestinal cDC1 drive cross-tolerance to epithelial-derived antigen via induction of FoxP3 <sup>+</sup> CD8 <sup>+</sup> T <sub>regs</sub>
Authors: Thorsten Joeris, Cristina Gomez-Casado, Petra Holmkvist, Simon Tavernier, Aaron Silva-Sanchez, Luisa Klotz, Troy Randall, Allan Mowat, Knut Kotarsky, Bernard Malissen, William Agace
Journal: Science Immunology (2021)

Intestinal cDC1 drive the generation of FoxP3 + CD8 + T regs to maintain tolerance to epithelial-derived self-antigen.
POS1369 ADULT-ONSET STILL’S DISEASE: A SINGLE-CENTER EXPERIENCE
Authors: B. Egeli, S. Ugurlu
Journal: Annals of the Rheumatic Diseases (2021)

Background: Adult-Onset Still’s disease (AOSD) is an autoinflammatory condition characterized by fever, rash, and arthritis. The diagnosis of AOSD is made by excluding common causes of fever of unknown origin which are infections, malignancies, autoimmune conditions and medication adverse effects. As it is a diagnostic challenge, further data on highlighting clinical and laboratory findings are necessary on guiding clinicians. Objectives: Our main objective is to present our single tertiary center experience of patients diagnosed with AOSD. Methods: This retrospective study was conducted at a tertiary rheumatology center. Patients were diagnosed with AOSD using Yamaguchi’s criteria and followed between 2007 and 2020. Demographic, clinical and laboratory information was retrieved from the patient chars. Treatment-related and prognostic information were also noted with additional information from phone call interviews. Results: The study includes 69 patients (23 M, 46 F). The mean age of diagnosis was 33.86±14.3. The presenting signs and symptoms of the patients are shown in Figure 1. The laboratory findings supporting the diagnosis at initial encounter are summarized in Table 1. The mean corticosteroid dose at initial diagnosis was 29.7±18 mg. In addition to corticosteroid treatment these patients were followed with different glucocorticoid-sparing agents. Methotrexate was the choice of treatment in 54 patients with the mean dose of 14.5±3.43 mg. Eight patients were treated with leflunomide, seven with anti-TNF agents, seven with tocilizumab, nineteen with anakinra and four with canakinumab. Figure 1. The presenting signs and symptoms of the patients Conclusion: In conclusion, the most common presenting symptoms in our AOSD cohort were fever and salmon-colored rash. In the differential diagnosis of fever of unknown origin especially with rash, AOSD should be considered. Corticosteroid was the main treatment modality. In patients who are unresponsive to conventional immunosuppressive treatment, biologic agents can be an alternative. Table 1. The laboratory findings at initial encounter Mean ± Standard Deviation Ferritin (ng/mL) 3179.46±6503.56 ESR (mm/h) 77.43±28.47 CRP (mg/L) 102.29±70.39 Leukocyte Count (cells/L) 13147.3±4640.9 ESR (mm/h) 80±28.48 CRP (mg/L) 105.15±54.67 Leukocyte Count (cells/L) 12427.14±6530.43 Disclosure of Interests: None declared
Collagen V Maintains Experimental Pulmonary Fibrosis In Il17-dependent And -Independent Pathways
Authors: A. T. Fabro, P. Q. Silva, W. S. Zocolaro, M. S. Almeida, I. O. Minatel, E. C. Prando, C. A. Rainho, A. P. Velosa, W. R. Teodoro, E. R. Parra-Cuentas, H. H. Popper, V. L. Capelozzi
Journal: American Journal of Respiratory and Critical Care Medicine (2013)
Nonadhesive massive coiling endoscopic ultrasound-guided embolization in a single session for treatment of gastric varices: learning points of a technical variant
Authors: Albert Garcia-Sumalla, Sandra Maisterra, Alberto Amador-Navarrete, Jose Castellote, Joan B. Gornals
Journal: Endoscopy (2021)

The procedure is performed under orotracheal intubation. The echoendoscope is positioned in the distal esophagus or in the gastric fundus to visualize the gastric varices; if necessary, water may be instilled into the fundus to improve visualization. Detection of the feeding vessel is unnecessary owing to the complexity of the vessel network and is time-consuming.
AB0632 СOMORBIDITIES AND DRUG-INDUCED LIVER INJURY DUE TO NSAIDS INTAKE IN PATIENTS WITH GOUT
Authors: E. Mikhnevich, P. Tatsiana, R. Tatsiana, H. Diana
Journal: Annals of the Rheumatic Diseases (2021)

Background: One of the side effects of NSAIDs is hepatotoxicity or Drug-Induced Liver Injury (DILI). Despite the short course of NSAIDs, the patients with gout may develop DILI. At the same time, besides NSAIDs, there are additional factors that affect the functional state of the liver: demography, comorbidities or concomitant medication (1). Objectives: To determine comorbidities associated with the risk of DILI when taking NSAIDs during the attack of gouty arthritis. Methods: Our retrospective study included 200 patients with GA. Inclusion criteria for the study: presence of gout (ACR, 1977), initially normal serum ALT level, NSAIDs as anti-inflammatory drugs in gout. Exclusion criteria: presence of a known liver disease. All patients were divided into 2 groups: those who developed DILI (n = 86) and the control group without cytolysis during NSAID treatment (n = 114). The severity of the cytolytic syndrome was revealed as follows: mild form (2-3-fold excess of the ALT norm) in 81,4 % (n = 70); moderate (3-5 times higher ALT) in 15.1% (n = 13); severe (5-10 fold excess of ALT) in 3.4% (n = 3). The mean age of 55 (49-60) years and 54 (44-59.5) years as well as the sex distribution (men made 90.1% and 93.3%, respectively) were compatible in both groups (р&gt;0,05). When studying the age distribution, statistical differences were revealed in the groups under 52 years (p&lt;0,05), so, this parameter was included into logistic regression model. During the follow-up period, all patients took NSAIDs above average doses. Patients in both groups were comparable in duration of gout. The following parameters were compared: AH, IHD, diabetes mellitus, obesity, dyslipidemia, metabolic syndrome according to ATPIII, CKD, alcohol abuse, age under 52. Results: After conducting logistic regression analysis, the next comorbidities have been revealed to be statistically significant: obesity (OR – 2,15; 95%CI 1,16-3,98), dyslipidemia (OR – 3,41; 95% CI 1,56-7,44) and alcohol abuse (OR – 2,45; 95%CI 1,22-4,91). Worth to note that age under 52 was also a risk factor for DILI (OR – 2,14; 95%CI 1,13-4,04). Thus, among our patients, the younger ones with an unhealthy lifestyle and no serious comorbidities, including cardiovascular, were at a greater risk for developing DILI while taking NSAIDs during the gout attack. Conclusion: In the study group of patients with gout, the hepatotoxicity (cytolysis syndrome) risk due to NSAIDs intake increased in younger patients in the presence of signs of metabolic syndrome (obesity, dyslipidemia) and alcohol abuse. References: [1]European Association for the Study of the Liver. EASL Clinical Practice Guidelines Drug-induced liver injury. J. of Hepatology. 2019; 30: 1-40. Disclosure of Interests: None declared.
Siltuximab downregulates interleukin-8 and pentraxin 3 to improve ventilatory status and survival in severe COVID-19
Authors: Giuseppe Gritti, Federico Raimondi, Barbara Bottazzi, Diego Ripamonti, Ivano Riva, Francesco Landi, Leonardo Alborghetti, Marco Frigeni, Marianna Damiani, Caterina Micò, Stefano Fagiuoli, Ferdinando Luca Lorini, Lucia Gandini, Luca Novelli, Jonathan P. Morgan, Benjamin M. J. Owens, Karan J. K. Kanhai, Gordana Tonkovic Reljanovic, Marco Rizzi, Fabiano Di Marco, Alberto Mantovani, Alessandro Rambaldi
Journal: Leukemia (2021)
Samplot: a platform for structural variant visual validation and automated filtering
Authors: Jonathan R. Belyeu, Murad Chowdhury, Joseph Brown, Brent S. Pedersen, Michael J. Cormier, Aaron R. Quinlan, Ryan M. Layer
Journal: Genome biology (2021)

Abstract Visual validation is an important step to minimize false-positive predictions from structural variant (SV) detection. We present Samplot, a tool for creating images that display the read depth and sequence alignments necessary to adjudicate purported SVs across samples and sequencing technologies. These images can be rapidly reviewed to curate large SV call sets. Samplot is applicable to many biological problems such as SV prioritization in disease studies, analysis of inherited variation, or de novo SV review. Samplot includes a machine learning package that dramatically decreases the number of false positives without human review. Samplot is available at https://github.com/ryanlayer/samplot .
AB0778 VENOUS THROMBOSIS IN UNUSUAL SITES
Authors: A. Fraj, O. Berriche, S. Arfa, O. Jomaa, W. Romdhane, H. Sfar
Journal: Annals of the Rheumatic Diseases (2021)

Background: Unusual site venous thrombosis (USVT), which includes venous thromboses of the upper limbs, digestive tract, cellar and brain, are rarely observed compared to those of the lower limbs and require both an etiological approach and a rigorous management. Objectives: Our objective is to identify the epidemiological, clinical, therapeutic and evolutionary characteristics of USVT. Methods: Retrospective study including 33 patients files with USVT followed in The Internal Medicine Departments at Tahar Sfar University Hospital Mahdia TUNISIA over a period of 10 years. Results: They were 21 females (63.6 %) and 12 males (36.4%) with an average age of 45.2 ± 18 years. Cerebral venous thrombosis was the most frequent localization identified in 10 patients (30.3%), followed by gastrointestinal thrombosis in 9 cases (27.3%), vena cava thrombosis in 9 cases (27.3%) and upper limb thrombosis in 5 cases (15.2%). The risk factors were respectively: age (42.4%), obesity (42.4%), smoking (30%), prolonged downtime (24.2%), surgical interventions (6.1%) and pregnancy (3%). An etiology was identified in 21 patients (66.6%), dominated by constitutional thrombophilia (27.3%), followed by BVL (15.1%) and Behçet’s disease (16.4%). Rare causes were neoplasia in one case (3%), scleroderma in one case (3%) and inflammatory bowel disease in one case (3%). The etiological investigation was negative in 36.3% of cases. Treatment was based on heparin therapy followed by vitamin K therapy. Progression was favourable without accident or recurrence in 25 patients (75.5%). Complications were dominated by recurrence in 12.1% of cases, post-thrombotic disease in 6% of cases and pulmonary embolism in 3% of cases. We reported one death related to a hemorrhagic event. Conclusion: USVT is a multifactorial pathology that involves both acquired and constitutional risk factors. Heparin therapy with an early relay by antivitamin K remains the treatment of choice today. The duration of treatment depend on the etiology, the recurrence of venous thrombosis and the risk of hemorrhagic complications. Disclosure of Interests: None declared
OP0186 CHANGES IN CIRCULATING B CELL LEVELS AND IMMUNOPHENOTYPE ARE ASSOCIATED WITH DEVELOPMENT OF ARTHRITIS FOLLOWING TREATMENT WITH CHECKPOINT INHIBITORS
Authors: M. Gatto, S. Bjursten, C. Jonell, C. Jonsson, S. Mcgrath, A. Rudin, M. Levin, I. Gjertsson
Journal: Annals of the Rheumatic Diseases (2021)

Background: Inflammatory arthritis (IA) is frequent among rheumatic side effects induced by checkpoint inhibitor (CPI) therapy for metastatic malignancies 1 . While T cells are likely to sustain the inflammatory process 2 , fewer data are available concerning the role of B cells 3 . Objectives: To investigate the phenotype of circulating B cells in patients who develop CPI-induced IA (CPI-IA) and to compare it with features of B cells in patients not developing immune-related adverse events (irAE) upon CPI treatment. Methods: B cell subsets at baseline (before CPI initiation) and during CPI treatment were analyzed in CPI-IA patients and in patients receiving CPI but who did not develop irAE (non-irAE). Peripheral blood mononuclear cells (PBMC) were analyzed by flow cytometry and B cells were identified as CD19 + and divided into naïve (CD27 - IgD + ), memory (CD27 + IgD +/- ), double negative (CD27 - IgD - ) and transitional (CD10 + CD24 + CD38 +/hi ) B cells. Levels of CD21, an activation marker on transitional B cells, were also analyzed. Non-parametric tests were used for analysis of differences between groups. Results: Six CPI-IA and 7 non-irAE patients matched for age, gender and CPI treatment were included, who had received CPI treatment due to metastatic melanoma. Flow cytometry revealed a significant increase of circulating B cells (p=0.002) (Figure 1A) and especially of transitional B cells in CPI-IA patients vs. non-irAE (median %, range: 7.8 (4.5-11.4) vs. 3.2 (1.6-4.3),p=0.007) (Figure 1B), while no remarkable changes were seen across other subsets. Transitional B cell levels significantly decreased from active to quiescent CPI-IA in all patients (p=0.008). In two CPI-IA patients for whom baseline sampling was available, the increase of transitional levels occurred early after CPI treatment and before CPI-IA onset. Levels of expression of CD21 on transitional B cells were increased in CPI-IA vs. non-irAE (p=0.01). Conclusion: Transitional B cells are expanded in CPI-IA patients and seem to increase early after start of CPI therapy. Monitoring this B cell subset might lead to closer follow-up and earlier diagnosis of CPI-IA. References: [1]Ramos-Casals M, Brahmer JR, Callahan MK, et al. Immune-related adverse events of checkpoint inhibitors. Nat Rev Dis Primers 2020;6:38 [2]Murray-Brown W, Wilsdon TD, Weedon H, et al. Nivolumab-induced synovitis is characterized by florid T cell infiltration and rapid resolution with synovial biopsy-guided therapy. J Immunother Cancer 2020;8:e000281 [3]Das R, Bar N, Ferreira M, et al. Early B cell changes predict autoimmunity following combination immune checkpoint blockade. J Clin Invest. 2018;128:715-2 Disclosure of Interests: None declared
The cGAS–STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy
Authors: Patrick Kwabena Oduro, Xianxian Zheng, Jinna Wei, Yanze Yang, Yuefei Wang, Han Zhang, Erwei Liu, Xiumei Gao, Mei Du, Qilong Wang
Journal: Acta Pharmaceutica Sinica B (2021)

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS-STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS-STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS-STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases.
The emerging osteo-metabolic phenotype of COVID-19: clinical and pathophysiological aspects
Authors: Luigi di Filippo, Stefano Frara, Andrea Giustina
Journal: Nature Reviews Endocrinology (2021)

An emerging feature of COVID-19 is a clinically relevant osteo-metabolic phenotype characterized by widespread acute hypocalcaemia and chronic hypovitaminosis D with high prevalence of vertebral fractures. This phenotype might have negative effects on disease severity and its components could represent possible targets for prevention of SARS-CoV-2 infection and poor COVID-19 outcomes.
POS1000 COMORBIDITIES ASSOCIATED TO SPONDYLOARTHRITIS
Authors: S. Bouden, L. Kharrat, A. Ben Tekaya, O. Saidane, R. Tekaya, I. Mahmoud, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2021)

Background: In contrast to other chronic rheumatic diseases such as rheumatoid arthritis, comorbidities associated to spondyloarthritis (SpA) and their impact on disease outcomes are less well studied. Objectives: The aim of our study was to investigate the prevalence of comorbidities among SpA patients and to determine factors influencing their appearance. Methods: We conducted a retrospective study including patients meeting the Assessment of SpondyloArthritis International Society (ASAS) criteria between 2000 and 2020. The following comorbidities were collected: cardiovascular pathologies and their risk factors (smoking, arterial hypertension, diabetes, dyslipidemia and obesity), neoplasms, osteoporosis, depression, infections, gastrointestinal and pulmonary disorders. Results: We included 138 patients. Sixty-eight per cent of them were males. The mean age was 45.73 ± 12.66 years. The mean age at the disease onset was 28.89 ± 12.54 years. The mean CRP was 33.38 ± 39.65 mg/dL. The mean BASDAI and ASDAS-CRP were 4.21 ±2.23 and 3.06 ± 1.26, respectively. The mean BASFI was 4.77 ± 2.58. Sixty patients had at least one comorbidity (43.5%): 53 patients had one comorbidity (38.4%), 21 accumulated two types of comorbidities (15.2%) and 7 patients accumulated three types or more (5%). Osteoporosis was the most frequent comorbidity, it was present in 23.1% of the cases (n=32), followed by tuberculosis 8.7% (n=12), stomach ulcers 5.1% (n=7), pulmonary superinfection 2.9% (n=4), neoplasia 2.2% (n=3) and then depression 1.4% (n=2). Cardiovascular risk factors were noted in 44 patients (31.9%): hypertension (15.9%), diabetes (12.3%), dyslipidemia (9.4%) and obesity (8.7%). Thirty-seven per cent of our patients were smokers. SpA patients with comorbidities were significantly older than those without (50.2±11.07 versus 42.3±12.8 years, p&lt;0.0001). The presence of comorbidities was significantly associated to a higher disease activity evaluated by BASDAI (p=0.005) and ASDAS-CRP (p=0.002). Furthermore, BASFI was significantly higher among patients with comorbidities (5.47±2.38 versus 4.31±2.62, p=0.028). However, no association was found between presence of comorbidities and smocking or CRP. Conclusion: Our results show that more than 40% of our SpA patients presented with at least one comorbidity. Remarkably, the presence of comorbidities was associated with high disease activity, suggesting that that inflammation might promotes comorbidities. For optimal management of SpA, a systemic screening for comorbidities is essential. Disclosure of Interests: None declared.
Behavioral Counseling Interventions for Healthy Weight and Weight Gain in Pregnancy
Authors: Karina W. Davidson, Michael J. Barry, Carol M. Mangione, Michael Cabana, Aaron B. Caughey, Esa M. Davis, Katrina E. Donahue, Chyke A. Doubeni, Alex H. Krist, Martha Kubik, Li Li, Gbenga Ogedegbe, Lori Pbert, Michael Silverstein, Melissa Simon, James Stevermer, Chien-Wen Tseng, John B. Wong
Journal: JAMA (2021)

<h3>Importance</h3> The prevalence of overweight and obesity is increasing among persons of childbearing age and pregnant persons. In 2015, almost half of all persons began pregnancy with overweight (24%) or obesity (24%). Reported rates of overweight and obesity are higher among Black, Alaska Native/American Indian, and Hispanic women and lower among White and Asian women. Excess weight at the beginning of pregnancy and excess gestational weight gain have been associated with adverse maternal and infant health outcomes such as a large for gestational age infant, cesarean delivery, or preterm birth. <h3>Objective</h3> The USPSTF commissioned a systematic review to evaluate the benefits and harms of behavioral counseling interventions to prevent adverse health outcomes associated with obesity during pregnancy and to evaluate intermediate outcomes, including excess gestational weight gain. This is a new recommendation. <h3>Population</h3> Pregnant adolescents and adults in primary care settings. <h3>Evidence Assessment</h3> The USPSTF concludes with moderate certainty that behavioral counseling interventions aimed at promoting healthy weight gain and preventing excess gestational weight gain in pregnancy have a moderate net benefit for pregnant persons. <h3>Recommendation</h3> The USPSTF recommends that clinicians offer pregnant persons effective behavioral counseling interventions aimed at promoting healthy weight gain and preventing excess gestational weight gain in pregnancy. (B recommendation)