tbuckley/cabot-search huggingface dataset:
Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update
Authors: Katherine S. Virgo, R. Bryan Rumble, Ronald de Wit, David S. Mendelson, Thomas J. Smith, Mary-Ellen Taplin, James L. Wade, Charles L. Bennett, Howard I. Scher, Paul L. Nguyen, Martin Gleave, Scott C. Morgan, Andrew Loblaw, Sean Sachdev, David L. Graham, Neha Vapiwala, Amy M. Sion, Virgil H. Simons, James Talcott
Journal: Journal of Clinical Oncology (2021)

PURPOSE Update all preceding ASCO guidelines on initial hormonal management of noncastrate advanced, recurrent, or metastatic prostate cancer. METHODS The Expert Panel based recommendations on a systematic literature review. Recommendations were approved by the Expert Panel and the ASCO Clinical Practice Guidelines Committee. RESULTS Four clinical practice guidelines, one clinical practice guidelines endorsement, 19 systematic reviews with or without meta-analyses, 47 phase III randomized controlled trials, nine cohort studies, and two review papers informed the guideline update. RECOMMENDATIONS Docetaxel, abiraterone, enzalutamide, or apalutamide, each when administered with androgen deprivation therapy (ADT), represent four separate standards of care for noncastrate metastatic prostate cancer. Currently, the use of any of these agents in any particular combination or series cannot be recommended. ADT plus docetaxel, abiraterone, enzalutamide, or apalutamide should be offered to men with metastatic noncastrate prostate cancer, including those who received prior therapies, but have not yet progressed. The combination of ADT plus abiraterone and prednisolone should be considered for men with noncastrate locally advanced nonmetastatic prostate cancer who have undergone radiotherapy, rather than castration monotherapy. Immediate ADT may be offered to men who initially present with noncastrate locally advanced nonmetastatic disease who have not undergone previous local treatment and are unwilling or unable to undergo radiotherapy. Intermittent ADT may be offered to men with high-risk biochemically recurrent nonmetastatic prostate cancer. Active surveillance may be offered to men with low-risk biochemically recurrent nonmetastatic prostate cancer. The panel does not support use of either micronized abiraterone acetate or the 250 mg dose of abiraterone with a low-fat breakfast in the noncastrate setting at this time. Additional information is available at www.asco.org/genitourinary-cancer-guidelines .
Audio Interview: A Covid-19 Conversation with Anthony Fauci
Authors: Eric J. Rubin, Lindsey R. Baden, Anthony S. Fauci, Stephen Morrissey
Journal: New England Journal of Medicine (2021)

A Covid-19 Conversation with Anthony Fauci In this audio interview conducted on January 27, 2021, the editors are joined by Dr. Anthony Fauci, U.S. Chief Medical Advisor, to discuss Covid-19 testin...
SAT0297 DIFFERENTIAL PHENOTYPES OF DISEASE-SPECIFIC AUTO-REACTIVE B CELL RESPONSES IN PATIENTS WITH SYSTEMIC SCLEROSIS
Authors: C. Wortel, N. Van Leeuwen, M. Boonstra, R. Toes, T. Huizinga, J. De Vries-Bouwstra, H. U. Scherer
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic Sclerosis (SSc) carries the highest mortality burden among the rheumatic diseases. &gt;95% of SSc patients harbor autoantibodies. Anti-topoisomerase antibodies (ATA) and anti-centromere antibodies (ACA) are most prevalent, mutually exclusive in individual patients, associate with distinct disease phenotypes and predict disease. Whether and how these auto-reactive B cell responses contribute to disease, however, is currently unclear. Objectives: To delineate phenotypic and functional characteristics of anti-topoisomerase and anti-centromere specific B cell responses in individual patients with SSc. Methods: Peripheral blood mononuclear cells (PBMC) obtained from ATA- and ACA-positive SSc patients were cultured without stimulation or in the presence of CD40L-expressing fibroblasts, IL-21 and BAFF. In addition, PBMC were depleted of circulating plasmablasts (CD19+CD20-CD27++) by fluorescence activated cell sorting (FACS), and isolated plasmablasts were cultured separately. ATA- and ACA-IgG and -IgA were measured in culture supernatants by ELISA. B cell subsets were defined by flow cytometry. Healthy donors and patients with rheumatoid arthritis served as controls. Results: We observed that ATA- and ACA-positive SSc patients harbour circulating B cells that secrete either ATA-IgG or ACA-IgG upon stimulation, depending on their serotype. In addition, we noted spontaneous secretion of ATA-IgG and, more remarkably, extensive secretion of ATA-IgA in ATA-positive patients. This degree of spontaneous, antigen-specific IgA secretion was specific for the ATA response in ATA-positive patients, while spontaneous ACA-IgA secretion was undetectable in the ACA-positive patient group. FACS experiments showed that spontaneously ATA-IgA secreting B cells were primarily present in the plasmablast compartment. Conclusion: Our findings demonstrate that ATA-positive SSc patients harbour an activated ATA-IgG and ATA-IgA B cell response, as indicated by the spontaneous secretion of both ATA isotypes by circulating plasmablasts. Remarkably, the ACA B cell response was far less active and lacked the active IgA component which suggests a difference in the triggers driving these autoreactive B cell responses in patients. Moreover, the remarkable ATA-IgA secretion points towards a potential mucosal origin of the ATA response. Disclosure of Interests: Corrie Wortel: None declared, Nina van Leeuwen: None declared, Maaike Boonstra: None declared, Rene Toes: None declared, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Jeska de Vries-Bouwstra: None declared, Hans Ulrich Scherer Grant/research support from: Bristol Myers Squibb, Sanofi, Pfizer, Speakers bureau: Pfizer, Lilly, Roche, Abbvie
Progress and Challenges in the Biology of FNDC5 and Irisin
Authors: Steffen Maak, Frode Norheim, Christian A Drevon, Harold P Erickson
Journal: Endocrine Reviews (2021)

In 2002, a transmembrane protein-now known as FNDC5-was discovered and shown to be expressed in skeletal muscle, heart, and brain. It was virtually ignored for 10 years, until a study in 2012 proposed that, in response to exercise, the ectodomain of skeletal muscle FNDC5 was cleaved, traveled to white adipose tissue, and induced browning. The wasted energy of this browning raised the possibility that this myokine, named irisin, might mediate some beneficial effects of exercise. Since then, more than 1000 papers have been published exploring the roles of irisin. A major interest has been on adipose tissue and metabolism, following up the major proposal from 2012. Many studies correlating plasma irisin levels with physiological conditions have been questioned for using flawed assays for irisin concentration. However, experiments altering irisin levels by injecting recombinant irisin or by gene knockout are more promising. Recent discoveries have suggested potential roles of irisin in bone remodeling and in the brain, with effects potentially related to Alzheimer's disease. We discuss some discrepancies between research groups and the mechanisms that are yet to be determined. Some important questions raised in the initial discovery of irisin, such as the role of the mutant start codon of human FNDC5 and the mechanism of ectodomain cleavage, remain to be answered. Apart from these specific questions, a promising new tool has been developed-mice with a global or tissue-specific knockout of FNDC5. In this review, we critically examine the current knowledge and delineate potential solutions to resolve existing ambiguities.
SAT0172 Osteoporosis prophylaxis in patients receiving corticosteroids
Authors: RJ Davies, T Walton, M Carulli, G Kingsley, V Hajela
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Approximately 2% of all general medical outpatients are taking corticosteroids.<sup>1</sup> The link between corticosteroid consumption and osteoporosis with subsequent fracture is strong<sup>2</sup> and national guidelines have been drawn up for the prevention of corticosteroid induced osteoporosis (CSIO).<sup>3</sup> <h3>Objectives</h3> To determine by means of re-audit whether management of CSIO improved following two education sessions and the distribution of guidelines to all general medical physicians, after the initial audit in July 1997. <h3>Methods</h3> The standard used was the National Osteoporosis Society (NOS) guidelines for the management of CSIO. The notes of all patients attending rheumatology, gastroenterology and respiratory clinics at University Hospital Lewisham during July 1997 for the initial audit and April and May 2000 for the re-audit were examined. Education and guidelines about CSIO were given to all relevant departments and a re-audit undertaken 2 years later. <h3>Results</h3> HIGH RISK GROUPS; age &gt; 65 years and on &gt; 7.5 mg/d prednisolone or &lt; 65 years and on &gt; 15 mg/d prednisolone. Initial audit 67% (57/85) were in this group, 5.2% had lifestyle advice, 15.7% BMD and 43.8% were prescribed prophylaxis. Re-audit 46.2% (37/80) were in this group, 24.3% had lifestyle advice, 51.3% BMD and 67.6% were prescribed prophylaxis. MEDIUM RISK GROUPS; age &lt; 65 years, prednisolone dose &gt; 7.5 mg/d &lt;15 mg/d. Initial audit 7% (6/85) were in this group, 16.6% had lifestyle advice, 50% BMD and 66.6% were receiving prophylaxis. Re-audit 32.5% (26/80) were in this group, 30.8% had lifestyle advice, 50% BMD and 42.3% were receiving prophylaxis. LOW RISK GROUPS; prednisolone &lt; 7.5 mg/d. Initial audit 25.8% (22/85) were in this group, none had received lifestyle advice, 22.7% BMD and 27.2% were receiving prophylaxis. Re-audit 21.2% (17/80) were in this group, none received lifestyle advice, 23.5% BMD and 52.9% were receiving prophylaxis. <h3>Conclusion</h3> Education and distribution of NOS guidelines lead to an increase in the number of high risk patients receiving appropriate treatment. The percentage of patients receiving prophylaxis in July 1997 was 41.1% and 56.2% in the re-audit. Clarity is needed in the management of low risk groups. Patients receiving lifestyle advice remains unacceptably low. There is a reluctance to prescribed calcium and vitamin D to medium risk patients and those awaiting DEXA scan results. <h3>References</h3> Bell R, Carr A, Thompson PW. Managing corticosteroid induced osteoporosis. J R Coll Phys. 1997;31:158–61 American College of Rheumatology Task Force on Osteoporosis Guidelines. Recommendations for the prevention and treatment of glucocorticoid induced osteoporosis. Arthritis Rheumatol. 1996;39:1791–801 Eastell R, <i>et al</i>. A UK Consensus Group on management of glucocorticoid induced osteoporosis: an update. J Intern Med. 1998;244:271–92
FRI0131 Incidence of renal flares and their prognostic significance in diffuse proliferative glomerulonephritis
Authors: M Mosca, W Bencivelli, R Neri, A Pasquariello, R Puccini, V Batini, S Bombardieri
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Diffuse Proliferative Glomerulonephritis (DPGN) is considered one of the most important factors influencing the long term prognosis of SLE patients. Renal flares are considered important risk factors influencing the outcome of renal involvement. <h3>Objectives</h3> The aim of this study was to evaluate the occurrence of renal flares and their prognostic significance for the renal outcome in a population of SLE patients with DPGN. <h3>Methods</h3> The clinical, laboratory and histological data of 91 SLE patients (8 males and 83 females) followed at the Rheumatology Unit of the University of Pisa, were retrospectively evaluated. <h3>Results</h3> Fourty-nine patients (54%) presented a renal flare a mean of 42 months after the renal biopsy. Twenty-eight flares (57%) were proteinuric, twenty-one (43%) were nephritic flares. A young age at the time of the renal biopsy and treatment with steroids alone, were significantly correlated with the occurrence of renal flares, furthermore a high Activity Index (AI &gt;9) and the presence of karyorrhexis on renal histology were correlated with the occurrence of nephritic flares. A poor renal outcome occurred in 27% of the patients; serum creatinine levels at the time of renal biopsy, the presence of karyorrhexis and the composite Chronicity Index (CI) as well as all of its component on renal histology, the number of renal flares (both proteinuric and nephritic), the occurrence of nephritic flares and early proteinuric flares (i.e. in the first 17 months after the renal biopsy), were correlated with a poor renal outcome. <h3>Conclusion</h3> In conclusion, the analysis of our patients has showed that nephritic flares and early proteinuric flares are important risk factors for the occurrence of a poor renal outcome. Since young patients with an elevated AI and karyorrhexis are at increased risk for renal flares, they should be candidated for a more aggressive and prolonged treatment. <h3>References</h3> Moroni G, <i>et al</i>. Kidney Int. 1996;50:2047–53 Ponticelli C, <i>et al</i>. Lupus 1998;7:635–8 Ciruelo, <i>et al</i>. Arthritis Rheum. 1996;39:2028–34
SAT0013 Seronegative b27 negative undifferentiated oligoarthritis: large follow-up study of 40 cases
Authors: IA Ferraz-Amaro, A Arteaga, E Trujillo, A Alvarez, JJ Bethancourt, S Bustabad, F Diaz-Gonzalez, M Gantes, T Gonzalez
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Undifferentiated arthritis could be an early stage or forme fruste of a definite rheumatic disease. <h3>Objectives</h3> The purpose of this poster is to describe the evolution of 40 patients (&gt;16 years) in our hospital, with seronegative mono-oligoarthritis, HLA B27 negative, without axial involvement, that at the onset of the disease did not meet the criteria to be included in any other defined arthropathy. <h3>Methods</h3> Forty patients (21 females and 19 males) with seronegative undifferentiated oligoarthritis, without axial involvement, that could not be typified as rheumatic disease of the rheumatoid, psoriatic, enteropathic, gouty, or reactive type, were studied retrospectively. In all patients the presence of crystals in their synovial fluid was discared as well as skin or eye symptoms, infectious diseases (Salmonella, Shigella, Yersinia, Ureaplasma and mycobacteria) or associated connective-tissue disease. <h3>Results</h3> The mean age at the onset of oligoarthritis was 42.1 years (44.9 for males and 36.3 for females). The average duration of follow-up was 11.1 years (range 24–1). Eight (28%) of the 40 patients had just one joint affected while the remaining patients presented with 4 or less involved joints. In 8 of our cases (20%) the disease resolved spontaneously. In 12 patients (30%), a definitive diagnosis was made after an average of 4.1 years (range 13–1) from the onset to the final diagnosis. Among these 12 patients, 5 were diagnosed as gout, 2 as arthropathy associated with inflammatory bowel disease, 2 as psoriatic arthritis, 2 as rheumatoid arthritis and one case of SAPHO associated arthropathy. In the remaining patients the disease followed a chronic course and no improvement was detected. Only 16 of the 40 patients received specific antirheumatic drug therapy: 10 of the 20 cases in which the disease took a chronic course and for which no diagnosis was reached. <h3>Conclusion</h3> We would like to stress that no rheumatologist would deny the difficulty implied in diagnosing and managing patients with undifferentiated mono-oligoarthritis that do not fit into any typified rheumatic disease. Nevertheless, although 50% of our patients have not yet been definitively diagnosed after a 6.5 year average follow-up, a final diagnosis has been reached for 30% of the total number in a 4.1-year period on the average.
Relationship between type 2 diabetes mellitus and markers of cutaneous melanoma aggressiveness: an observational multicentric study in 443 patients with melanoma*
Authors: E. Nagore, M.A. Martinez‐Garcia, J.D. Gomez‐Olivas, E. Manrique‐Silva, A. Martorell, J. Bañuls, C. Carrera, P. Ortiz, J. Gardeazabal, A. Boada, E. Eusebio, E. Chiner, C. Gonzalez, A. Pérez‐Gil, D. Cullen, M. Formigón, B. Unamuno, C. Navarro‐Soriano, A. Muriel, D. Gozal
Journal: British Journal of Dermatology (2021)

Some studies have suggested a relationship between type 2 diabetes mellitus (T2DM) and increased incidence of melanoma. Efforts are under way to identify preventable and treatable factors associated with greater melanoma aggressiveness, but no studies to date have examined the relationship between T2DM and the aggressiveness of cutaneous melanoma at diagnosis.To explore potential associations between T2DM, glycaemic control and metformin treatment and the aggressiveness of cutaneous melanoma.We conducted a cross-sectional multicentric study in 443 patients diagnosed with cutaneous melanoma. At diagnosis, all patients completed a standardized protocol, and a fasting blood sample was extracted to analyse their glucose levels, glycated haemoglobin concentration and markers of systemic inflammation. Melanoma characteristics and aggressiveness factors [Breslow thickness, ulceration, tumour mitotic rate (TMR), sentinel lymph node (SLN) involvement and tumour stage] were also recorded.The mean (SD) age of the patients was 55·98 (15·3) years and 50·6% were male. The median Breslow thickness was 0·85 mm. In total, 48 (10·8%) patients were diagnosed with T2DM and this finding was associated with a Breslow thickness > 2 mm [odds ratio (OR) 2·6, 95% confidence interval (CI) 1·4-4·9; P = 0·004)] and > 4 mm (OR 3·6, 95% CI 1·7-7·9; P = 0·001), TMR > 5 per mm2 (OR 4·5, 95% CI 1·4-13·7; P = 0·009), SLN involvement (OR 2·3, 95% CI 1-5·7; P = 0·038) and tumour stages III-IV (vs. I-II) (OR 3·4, 95% CI 1·6-7·4; P = 0·002), after adjusting for age, sex, obesity, alcohol intake and smoking habits. No significant associations emerged between glycated haemoglobin levels, metformin treatment and melanoma aggressiveness.T2DM, rather than glycaemic control and metformin treatment, is associated with increased cutaneous melanoma aggressiveness at diagnosis.
SAT0245 Improvement in health-related quality of life from anakinra therapy in patients with rheumatoid arthritis not using dmards
Authors: P Emery, JM Woolley, WW Chan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate the effect of anakinra on health related quality of life (HRQOL) as measured by the Nottingham Health Profile (NHP), in subjects with rheumatoid arthritis not using DMARDs. <h3>Methods</h3> In a 24-week, multicenter, randomised, double-blind clinical trial conducted in Europe, 473 subjects received either one of three doses of anakinra (30 mg, 75 mg, or 150 mg) or placebo SC QD. Subjects were excluded if they used DMARDs within six weeks of entry, or if they had failed therapy with more than three DMARDs. The NHP was administered in selected countries at baseline and at weeks 12 and 24 (n = 353). The NHP consists of 38 items which assess physical mobility (MOB), pain (PAIN), energy (ENRG), sleep (SLP), emotional reactions (EMO), and social isolation (ISO). The NHP is scored so that lower scores indicate better HRQOL and negative change scores indicate improvements. The mean change in each NHP scale score was compared between subjects receiving anakinra (all doses combined) and those on placebo. All subjects who completed at least one post-baseline assessment were included (n = 328) and the last-observation was carried forward in the case of missing data. <h3>Results</h3> Subjects using anakinra experienced statistically significant improvements in all six NHP scales. These improvements exceeded those for subjects on placebo for all six scales, four of which were statistically significant. <h3>Conclusion</h3> Subjects receiving anakinra experienced statistically significant improvements in their NHP scores that exceeded those for subjects on placebo. These improvements were seen in both physical and psychosocial domains. In subjects who are not receiving DMARD therapy, anakinra leads to improvements in health-related quality of life.
A new player in the game: treatment with antagomiR-21a-5p significantly attenuates histological and echocardiographic effects of experimental autoimmune myocarditis
Authors: Moritz Mirna, Vera Paar, Albert Topf, Theo Kraus, Karl Sotlar, Achim Aigner, Alexander Ewe, Simon Watzinger, Bruno K Podesser, Matthias Hackl, Rudin Pistulli, Uta C Hoppe, Attila Kiss, Michael Lichtenauer
Journal: Cardiovascular Research (2021)

Abstract Aims Myocarditis is associated with formidable symptoms and increased risk of adverse outcomes. Current approaches mostly rely on symptomatic treatments, warranting novel concepts for clinical practice. The aim of this study was to investigate the microRNA (miRNA) expression profile of Balb/c mice with experimental autoimmune myocarditis (EAM), choose a representative miRNA to antagonize after review of available literature and test its effects on myocardial inflammation in vitro and in vivo. Methods and results Phase 1: EAM was induced in 12 male Balb/c mice, 10 animals served as controls. After sacrifice, next-generation sequencing (NGS) of the miRNA expression profile was performed. Based on these results, H9C2 cells and human ventricular cardiac fibroblasts exposed to lipopolysaccharide (LPS) were treated with the selected candidate antagomiR-21a-5p. Phase 2: EAM was induced in 48 animals. Thereof, 24 animals were either treated with antagomiR-21a-5p or negative control oligonucleotide in a nanoparticle formulation. Transthoracic echocardiography (TTE) was performed on Days 0, 7, 14, and 21. Histopathological examination was performed after sacrifice. Phase 1: EAM resulted in a significant up-regulation of 27 miRNAs, including miR-21a-5p (log2FC: 2.23, adj. P = 0.0026). Transfection with antagomiR-21a-5p resulted in a significant reduction of TNFα, IL-6, and collagen I in vitro. Phase 2: Treatment with antagomiR-21a-5p, formulated in polymeric nanoparticles for systemic injection, significantly attenuated myocardial inflammation (P = 0.001) and fibrosis (P = 0.013), as well as myocardial ‘hypertrophy’ on TTE. Conclusions Silencing of miR-21a-5p results in a significant reduction of the expression of pro-inflammatory cytokines in vitro, as well as a significant attenuation of inflammation, fibrosis and echocardiographic effects of EAM in vivo.