tbuckley/cabot-search huggingface dataset:
FRI0651 Quantitative chest ct predicts 8-years-mortality and comorbidity in systemic sclerosis
Authors: A. Ariani, M. Silva, E. Bravi, M. Saracco, S. Parisi, F. De Gennaro, L. Idolazzi, M. De Santis, F. Girelli, F. Lumetti, A. Volpe, D. Santilli, F. Mozzani, G. Lucchini, D. Giuggioli, V. Seletti, E. Bacchini, C. Benini, E. Arrigoni, F. C. Bodini, G. Paolazzi, D. Imberti, E. Fusaro, C. A. Scirè, N. Sverzellati
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Interstitial Lung Disease (ILD) is the main cause of death in Systemic Sclerosis (SSc). Serious lung involvement increase the hospitalization rate and sometimes oxygen therapy is required. An prompt treatment in ILD-SSc patients is essential, but nowadays there is not a feasible method to identify patients with poor prognosis. Although chest Computed Tomography (CT) is the gold standard to detect ILD, there is no standardized assessment of its severity. Quantitative CT (QCT) is an innovative and operator independent method to assess ILD-SSc extent and severity. An increasing number of evidences confirm that QCT is extremely useful for detecting SSc-ILD with the worst prognosis. However is not well established if QCT can predict death or comorbidity associated to ILD. <h3>Objectives:</h3> The main aim of this study is to verify if QCT predict 8-years mortality or clinical worsening (i.e. hospitalization for respiratory complications or chronic oxygen therapy) in SSc. <h3>Methods:</h3> Consecutive SSc patients (according to ACR/EULAR classification criteria) from ten different centers underwent a chest CT. Their clinical history was carefully recorded in the following 96 months. A rheumatologist post-analyzed every CT with an open source DICOM viewer in order to obtain QCT indexes. Patients were clustered in two subgroups: according to QCT indexes' cutoff previously found (see Ariani et al., 2017). The survival time of each patient was considered the time interval between the CT date and death, hospitalization related to lung worsening, beginning of chronic oxygen therapy or last medical examination <h3>Results:</h3> We enrolled 342 patients; during the 8-years follow-up 15.5% (53/342) died and 4,4% (15/342) had a clinical worsening. The Kaplan-Meier survival analysis demonstrates a worse survival in patients with QCT indexes above or below the previously observed cutoffs. (p&lt;0.01). In particular the QCT index cutoff which the best performance was total lung kurtosis (tKurt) equal to 4.89 (p&lt;0.0001). <h3>References:</h3> The QCT indexes' cutoffs previously found (see Ariani, et al., 2017) identify the SSc-ILD subjects with an high risk of 8-years mortality and comorbidity. These findings suggest that QCT could became a pivotal assessment in SSc management because its role in identifying patients with poor prognosis and who deserve an early aggressive treatment. <h3>Disclosure of Interest:</h3> None declared
AB1125 Urinary soluble cd25 as a biomarker of active lupus nephritis in egyptian children with juvenile systemic lupus erythematosus
Authors: W.A. Hassan, M.Y. Mahgoup, E.G. Behiry
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Lupus nephritis (LN) is more prevalent and severe in children than adult and considered a major predictor of poor outcome. Thus, early diagnosis and treatment is associated with better outcome. Soluble CD25 (sCD25), also known as Interleukin-2 receptor alpha chain, is a type I transmembrane protein present on activated T lymphocytes that play important role in the pathogenesis LN[.<sup>1</sup> <h3>Objectives</h3> This study aimed to measure urinary levels of sCD25 in children with juvenile systemic lupus erythematosus (JSLE) and to investigate its role as a potential biomarker of activity in LN. <h3>Methods</h3> We measured sCD25 using enzyme-linked immunosorbent assay in urine samples from 53 JSLE patients and in urine samples from 30 healthy controls and these levels were normalised to creatinine excretion in urine. All JSLE patients underwent thorough clinical examination and disease activity assessment using Systemic Lupus Erythematous Disease Activity Index (SLEDAI). Systemic Lupus International Collaborating Clinics (SLICC) renal activity score<sup>2</sup> was used to assess activity of LN. <h3>Results</h3> Urinary sCD25 normalised levels were highly significantly increased in JSLE patients (278.38±133.68 pg/mg) compared to urinary level in the healthy controls (187.33±83.59 pg/mg),p&lt;0.001. Also, patients with active LN had significantly higher normalised urinary sCD25 levels (402.69±139.58 pg/mg) compared to urinary level in active JSLE patients without LN (262.18±98.35 pg/mg),p=0.002 and inactive JSLE patients (192.7±66.4 pg/mg), p&lt;0.001. In JSLE patients, urinary sCD25 normalised levels significantly correlated with SLEDAI (r=0.48, p&lt;0.05), renal SLEDAI (r=0.61, p&lt;0.001), SLICC renal activity score (r=0.68, p&lt;0.001) and C3 (r=−0.48, p&lt;0.001). <h3>Conclusions</h3> JSLE patients have significantly increased urinary levels of sCD25 especially in those with active LN. Urinary sCD25 levels are remarkably correlated with the renal disease activity scores suggesting that it could be a useful marker to reflect active renal involvement in JSLE patients. <h3>References</h3> [1] - Gupta R, Yadav A, Misra R, Aggarwal A. Urinary sCD25 as a biomarker of lupus nephritis disease activity. Lupus2015; Mar;24(3):273–9. [2] - Petri M, Kasitanon N, Lee SS, Link K, Magder L, Bae SC, et al. Systemic Lupus International Collaborating Clinics (008) Systemic lupus international collaborating clinics renal activity/response exercise. Development of a renal activity score and renal response index. Arthritis Rheum2008; 58(6):1784–88. <h3>Disclosure of Interest</h3> None declared
AB1249 An analysis of inpatient referrals to rheumatology in an irish tertiary referral hospital
Authors: K. Murray, N. Rutledge, Q. Shah, D.J. Veale
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Reviewing patients under other services is an important part of the service we deliver in our hospital's rheumatology department. <h3>Objectives</h3> In order to improve quality of the inpatient consult service and relevance of teaching delivered to rheumatology trainees, we wanted to examine the nature of referrals to our service. <h3>Methods</h3> All available consults (n=81) were reviewed. The age, gender, urgency and referral source were recorded. The most likely reason for referral as decided by our specialist registrar (research fellow) were determined. <h3>Results</h3> 49% of patients were 70 years of age or older. 30% of patients were 70–79 years old. 68% were female. There was a wide range of referrals, 21% were vasculitides (including polymyalgia and giant cell arteritis), 20% inflammatory arthritides, 19% crystal arthropathies, 16% connective tissue disease, 14% osteoarthritis, 3% septic arthritis, 3% fibromyalgia, 3% pyrexia of unknown origin, 1% sarcoid, 1% antphospholipid syndrome and 1% osteoporosis. 59% of consults came from general medical teams, 14% from acute medicine, 14% from surgery, 3% from psychiatry and 11% from other inpatient services (including haematology, oncology etc). 36% of consults were considered urgent (to be seen within 24 hours) by the referring team, 64% were routine (to be seen within 48 hours). <h3>Conclusions</h3> Almost half of referrals were over 70 years of age. Most referrals came from medical teams. The majority of consults were women and referred due to a vasculitis, inflammatory arthritis or connective tissue disease. 3% were septic arthritis. Our trainee teaching will now focus primarily on these topics. 3% of referrals were for fibromyalgia, which could perhaps be managed on an outpatient basis. This may improve utilisation of limited inpatient hospital resources. <h3>Disclosure of Interest</h3> None declared
Blockade of Mer By the Small Molecule Inhibitor R992 Inhibits Multiple Myeloma and Its Associated Bone Disease By Restoring the Perturbed Bone Homeostasis
Authors: Janik Engelmann, Isabel Ben Batalla, Hanna Taipaleenmäki, Kristoffer Riecken, Victoria Gensch, Sarina Paesler, Nikolaus Berenbrok, Maria Elena Vargas, Jonas Waizenegger, Boris Fehse, Klaus Pantel, Ihab S Darwish, Somasekhar Bhamidipati, Esteban Masuda, Carsten Bokemeyer, Eric Hesse, Sonja Loges
Journal: Blood (2018)
THU0260 The uveitis impact study: a survey by the spondylitis association of america
Authors: J.T. Rosenbaum, R. Howard, L.M. Savage
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Uveitis is the most common clinically apparent concomitant of ankylosing spondylitis. The implications of developing uveitis in association with AS could help to understand this association and assist both clinicians and patients. <h3>Objectives</h3> To compare survey responses from patients with AS and no history of uveitis to those with AS and a history of uveitis. <h3>Methods</h3> Patients associated with the Spondylitis Association of America (SAA) participated in a web based survey with telephone follow-up performed for a subset. <h3>Results</h3> 716 respondents replied that a physician had made a diagnosis of AS. 30.4% of these patients had a history of uveitis. Patients with a history of uveitis tended to be older (median age 31 versus 23 years) and the median age for onset of uveitis was 18 years. Although patients with uveitis did not differ from patients without uveitis on many measures of function, medication, or disability, patients with uveitis were more likely to have heel pain (56% v.45%, p&lt;0.005), rib pain (60% v. 50%, p=0.02), gut inflammation (37% v 23%, p=0.0001), hypertension (42% v 33%, p=0.02), fibromyalgia (18% v 12%, p=0.03), psoriatic arthritis (11% v 6%, p=0.02), or acid reflux (57% v 48%, p=0.03). Patients with uveitis were more like to be negatively impacted in the past week for the ability to concentrate (18% v 12%, very limited, p=0.03); the ability to read, listen, or watch TV (15% v 9%, very limited, p=0.01); and the ability to enjoy family life or friends (6% v 2%, totally limited, p=0.005). Prednisone was more commonly used by those with uveitis (16% v 7%, p=0.0002); and while sulfasalazine was more commonly used previously (41% v 24%, p&lt;0.001), it was less commonly used currently (7% v. 10%). Etanercept, which is less effective in preventing uveitis than monoclonal anti-TNF inhibitors, was used equally in the two groups (11% v 12%). <h3>Conclusions</h3> This survey suggests associations between uveitis and clinical manifestations such as heel pain, bowel disease, and skin disease. It is one of the first reports to suggest that uveitis affects quality of life such as the ability to enjoy family or friends. Although medications differentially affect uveitis, our study did not indicate an impact on therapy resulting from uveitis except for the current use of prednisone and a prior history of the use of sulfasalazine. <h3>Acknowledgements</h3> Funded by the Spondylitis Association of America <h3>Disclosure of Interest</h3> J. Rosenbaum Shareholder of: Novartis, Grant/research support from: Pfizer, Consultant for: Abbvie, UCB, Novartis, Regeneron, Gilead, R. Howard: None declared, L. Savage: None declared
SP0047 Challenges in the management of different rheumatologic disorders during pregnancy: lessons from the registries
Authors: R. Fischer-Betz
Journal: Annals of the Rheumatic Diseases (2018)

Sexual health is rarely addressed by health professionals (HP), and it is as a rule not spontaneously reported by patients.HPs may feel awkward to intrude into the intimate sphere of a patient, and patients may feel ashamed of revealing their sexual dysfunction.A first step to improve the physician-patient communication in this area is to include sexuality in the curriculum of health professionals teaching how to address and evaluate sexual function.Assessment of sexual function by validated instruments includes both frequency of intercourse as well as sexual desire, arousal, orgasm, and sexual satisfaction.In women vaginal lubrication and in men erectile function and ejaculation are part of the evaluation.Assessment of disease activity and comorbidities helps to detect physical components of sexual dysfunction.Barriers regarding communication on sexual activity should be identified and overcome.Assessment of sexual function may be assigned to a specially trained nurse, an occupational therapist or a psychologist of the interdisciplinary team.Referral to specialists in urology, gynaecology or sexual medicine may also help patients to get a better sex life.A major point for restoring sexual and reproductive health in patients of both genders is to achieve optimal disease control.
OP0050 Gene polymorphisms of the glucocorticoid receptor and 11Β-hydroxysteroid dehydrogenase type 1 affect relevant clinical outcomes in anca associated vasculitis
Authors: A.C. Hessels, J. Tuin, J.S.F. Sanders, M.G. Huitema, E.F.C. van Rossum, F.J.W. Koper, A.P. van Beek, C.A. Stegeman, A. Rutgers
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> High doses of exogenous glucocorticoids (e.g., prednisolone) are a standard part of treatment for ANCA-associated vasculitis.<sup>1</sup> Efficacy and toxicity of glucocorticoid treatment differ widely between individuals.<sup>2</sup> We hypothesised that this can be partly explained by genetic polymorphisms of the glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) that influence glucocorticoid sensitivity. <h3>Objectives</h3> To investigate whether five haplotypes of the Glucocorticoid Receptor gene (NR3C1) and a single nucleotide polymorphism of 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) are associated with treatment efficacy and toxicity in ANCA associated vasculitis. <h3>Methods</h3> A total of 241 ANCA associated vasculitis patients were genotyped for five polymorphisms of the glucocorticoid receptor gene and one polymorphism of the HSD11B1 gene. Glucocorticoid receptor gene haplotypes were predicted based on genotyping results. Relapse free survival, mortality, renal survival, metabolic adverse events and infections were compared between carriers and non-carriers of glucocorticoid receptor haplotypes and the HSD11B1 genotype. <h3>Results</h3> Carriers of the ER22/23EK haplotype of the glucocorticoid receptor had a significantly higher risk of 10 year mortality (Hazard Ratio (HR) 3.0, 95% confidence interval, CI: 1.2 to 7.3), more frequently required plasmapheresis treatment (p=0.04) and had a higher risk of developing end-stage renal disease (HR 7.4, 95% CI: 1.9 to 28.7). Carriers of a minor variant of HSD11B1 more frequently experienced relapse (HR 2.5, 95% CI: 1.5 to 4.1), except if they also carried the <i>Bcl</i>I haplotype of the glucocorticoid receptor. Homozygous carriers of the <i>Bcl</i>I haplotype had a higher risk of developing hypertension (HR 2.7, 95% CI: 1.2 to 5.7) and dyslipidemia (HR 4.1, 95% CI: 1.8 to 9.6). Occurrence of infections neither differed between GR haplotypes, nor between HSD11B1 genotypes. <h3>Conclusions</h3> The ER22/23EK and <i>Bcl</i>I haplotype of the glucocorticoid receptor and a polymorphism of the gene for HSD11B1 are associated with clinically relevant inflammatory and metabolic outcomes in ANCA associated vasculitis. <h3>References</h3> [1] Yates M, Watts RA, Bajema IM, Cid MC, Crestani B, Hauser T, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis2016Sep;75(9):1583–1594. [2] Quax RA, Manenschijn L, Koper JW, Hazes JM, Lamberts SW, van Rossum EF, et al. Glucocorticoid sensitivity in health and disease. Nat Rev Endocrinol2013Nov;9(11):670–686. <h3>Disclosure of Interest</h3> None declared
Coagulation Profile of Sickle Cell Patients with Leg Ulcers
Authors: Ugochi Olivia Ogu, Ashley Buscetta, Elena Crouch, Shuo You, Christopher Bradford, Moonseong Heo, Khadijah Abdallah, Giacomo Vinces, Vence L. Bonham, Caterina Minniti
Journal: Blood (2018)
Abstract LB-239: An rnai sensitization screen identifies compensatory IKKα activation during IKKβ inhibition
Authors: Lloyd T Lam, R. Eric Davis, Vu Ngo, George Wright, Georg Lenz, Hong Zhao, Xin Yu, Lenny Dang, Louis M Staudt
Journal: Cancer Research (2008)

Abstract Introduction: We previously described a subtype of diffuse large B-cell lymphoma (DLBCL) termed activated B-cell-like (ABC) DLBCL that depends on NF-κB activity for survival, and showed that a specific small molecule inhibitor of the upstream kinase IKKβ is selectively toxic to this subgroup of lymphoma. Methods: To identify proteins or pathways whose inhibition may synergize with the toxicity of IKKβ inhibition in ABC DLBCL, we performed an “RNAi sensitization” screen with an RNA interference library, directed against 500 protein kinases, in the presence of the specific IKKβ inhibitor in an ABC DLBCL cell line. Results: Short hairpin RNA (shRNAs) targeting IKKα, a component of the IKK complex, enhanced killing by the IKKβ inhibitor in ABC DLBCL cell lines but not other lymphoma cell lines. Gene expression profiling and NF-κB-specific reporter assays showed that IKKα shRNA affects the classical NF-κB pathway, further inhibiting the phosphorylation of IκBα only in the presence of the specific IKKβ inhibitor. Further studies in physiologic models of lymphocyte stimulation showed that compensatory IKKα activity occurs in other settings. Conclusions: These results demonstrate that loss-of-function screens in the presence of a defined inhibitor can identify therapeutic targets in cancers, providing a rationale for combination therapies targeting multiple pathways critical to an individual cancer.
Former British Cycling doctor faces allegations he hid truth about ordering testosterone
Authors: Clare Dyer
Journal: BMJ (2019)

The former chief doctor for British Cycling faces allegations from the General Medical Council that he obtained a banned substance for an athlete and then cooked up a false story to conceal the truth.

Richard Freeman will confront the accusations when he appears at a medical practitioners’ tribunal in Manchester next month.

The GMC will allege at a month long hearing starting 6 February that in May 2011 Freeman ordered 30 sachets of the testosterone gel Testogel from Fit4Sport Limited to be delivered to the Manchester velodrome. …
AB0636 Damage accrual in systemic lupus erythematosusis not related to sustained hypocomplementemia
Authors: W.D. Raymond, L. Tyack, G. Ø. Eilertsen, J. Nossent
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Hypocomplementemia (HC) represents a significant clinical finding in Systemic Lupus Erythematosus (SLE) as it suggests complement activation by immune-complexes, which can initiate inflammation. As disease activity contributes to damage accrual in SLE patients, we investigated the role of HC as a predictor of subsequent organ damage. <h3>Objectives</h3> Investigate the relationship between HC, disease flares and organ damage accrual in SLE patients. <h3>Methods</h3> Longitudinal cohort study of 102 SLE patients with HC defined as a C3 and/or C4 levels below cut-off during median follow-up of 13.8 years (IQR 7.0, 23.1). Disease activity was scored by time averaged SLEDAI-2K without the serological components (cWAS), flares by SELENA-SLEDAI and damage accrual by SLICC-DI. Analysis included comparisons between normocomplementemic (NC) and hypocomplementemic (HC) patients, and multivariate logistic and Cox regression modelling determined the predictive value of HC on organ damage. <h3>Results</h3> HC occurred in 2/3 of patients overall and was more often due to low C3 (97%) than low C4 (54%). HC patients had a higher prevalence of anti-dsDNA Ab (72% vs 36%, p&lt;0.01) and aPL (74% vs 40%, p&lt;0.01), but HC concurred with anti-dsDNA presence in only 36% of cases. HC patients had higher maximum cSLEDAI scores, but the time adjusted cWAS scores (1.9 vs 1.2, p=0.9) and the frequency and risk of overall damage accrual (SDI&gt;0, n=60) associated with HC was similar as for NC patients (OR 1.08, p&gt;0.20). <h3>Conclusions</h3> Low complement levels occur in 2/3 of SLE patients but have negligible impact on time averaged disease activity and damage accrual in SLE. Discrepancies between low C3, low C4 and anti-dsDNA Ab occurrence indicate that in SLE alternative complement activation occurs frequently and requires further translational study. <h3>Acknowledgements</h3> The Rheumatology Group of UWA (JN) was supported by an unrestricted grant from the Arthritis and Osteoporosis Foundation of Western Australia (AOWA). The AOWA provided WR with a PhD Scholarship in Memory of Johan Donald Stewart. <h3>Disclosure of Interest</h3> None declared
Serum and blister‐fluid elevation and decreased epidermal content of high‐mobility group box 1 protein in drug‐induced Stevens–Johnson syndrome/toxic epidermal necrolysis
Authors: D.F. Carr, C.‐W. Wang, T. Bellón, L. Ressel, G. Nwikue, V. Shrivastava, W. Bergfeld, A.L. Jorgensen, W.‐H. Chung, M. Pirmohamed
Journal: British Journal of Dermatology (2019)

High-mobility group box 1 (HMGB1) is a damage-associated molecular-pattern protein. Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are serious, immune-mediated skin-blistering conditions.To determine serum and/or blister-fluid total HMGB1 levels in SJS/TEN cohorts, and HMGB1 expression in formalin-fixed, paraffin-embedded (FFPE) SJS/TEN skin vs. healthy and maculopapular exanthema (MPE) skin. Methods Serum HMGB1 was quantified in Malawian nevirapine-induced hypersensitivity, Taiwanese SJS/TEN and Spanish SJS/TEN cohorts. FFPE skin (healthy skin, MPE, SJS/TEN) was stained and assessed for HMGB1 expression.Serum total HMGB1 was not significantly elevated in patients with nevirapine-induced SJS/TEN (3·98 ± 2·17 ng mL-1 ), MPE (3·92 ± 2·75 ng mL-1 ) or drug reaction with eosinophilia and systemic symptoms (4·73 ± 3·00 ng mL-1 ) vs. tolerant controls (2·97 ± 3·00 ng mL-1 ). HMGB1 was significantly elevated in Taiwanese patients with SJS/TEN, highest during the acute phase (32·6 ± 26·6 ng mL-1 ) vs. the maximal (19·7 ± 23·2 ng mL-1 ; P = 0·007) and recovery (24·6 ± 25·3 ng mL-1 ; P = 0·027) phases. In blister fluid from Spanish patients with SJS/TEN, HMGB1 (486·8 ± 687·9 ng mL-1 ) was significantly higher than in serum (8·8 ± 7·6 ng mL-1 ; P <0·001). Preblistered SJS/TEN skin showed decreased epidermal nuclear HMGB1 expression in upper epidermis vs. healthy or MPE skin but retained basal/suprabasal expression.Epidermal HMGB1 expression was decreased in SJS/TEN skin. Retained basal/suprabasal epidermal HMGB1 expression may exacerbate localized injury in SJS/TEN.