tbuckley/cabot-search huggingface dataset:
AB0264 Trend in hospital admissions in rheumatoid arthritis in spain: a national observational cohort study (1999–2015) (trend-ar study)
Authors: M. Espinosa Malpartida, C. Barbadillo, H. Godoy, C. Martínez Prada, V. Villaverde, C. Morado Quinoa, J. Quirós, E. Perez-Fernandez, M. Peña, C. Macía Villa, A. García-Vadillo, N. Crespi, J.L. Morell Hita, M. Fernández-Prada, M. Galindo, O. Guzón Illescas, Á. Herranz, R. Mazzucchelli
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> There have been significant changes in the management of rheumatoid arthritis (RA) during the past 20 years. The potential impact of these strategies on hospitalisation trend is unknown. <h3>Objectives</h3> To analyse the incidence and trend of hospital admissions in patients with RA in Spain from 1999 to 2015. <h3>Methods</h3> This is a population based study. We analysed a national administrative database that includes a Minimum Basic Data Set (MBDS) of hospital admissions of patients with RA during the period 1999–2015. The admission cases in patients with RA were identified by the presence in primary and secondary diagnosis of the ICD9 codes (714.0–714.9). The population at risk was estimated through the population census of the National Institute of Statistics, with an estimated prevalence for RA of 0.5%, with crudes and adjusted admission rates being calculated. The trend was analysed using Generalised Linear Models (GLM). <h3>Results</h3> There were a total of 3 38 343 hospital admissions in RA patients during the study period, accounting for a total of 1 76 097 patients (1 17 985 women and 58 112 men). The mean age at admission was 68 years (67.8 in women and 68.5 in men), with a linear increase throughout the study period from 65.3 in 1999 until 70.5 in 2015 (p&lt;0.001). The main admission code was for Osteoarticular and connective tissue diseases (20%) followed by Circulatory system diseases (16.8%). There were a total of 18 641 intrahospital deaths (5.5% of all the admissions). The age-adjusted admission rate was 12.03/100 RA patients*yr (9,12 for women and 1.88 for men). The age-adjusted admission rate increased from 1999 to 2015 (in both genders). An annual increase of admission rate of 3.7% is estimated. When adjusting by age, the largest increase is observed in patients older than 80 years, with an estimated annual increase of 7.5%. <h3>Conclusions</h3> In Spain, despite the improvement in RA management, there is a global tendency to the increase of admissions during the period of 1999–2015, mainly in &gt;60 year, especially in &gt;80 year. <h3>Disclosure of Interest</h3> None declared
FRI0227 Risk factors for skin reactions to allopurinol in the kinh population of vietnam
Authors: T. Bardin, L.G. Le, T.M.K. Buy, A.D. Do, H. Le, M.D. Do, V.A. Hoang, A.N. Le, Q.D. Nguyen, N.H. Le, P. Richette, M. Resche-Rigon, T.P. Mai
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Allopurinol (ALLO) exposes to mild (M) and severe (S) cutaneous adverse reactions (CARs). SCARS have been associated with HLA*B58 01 with various strength of across ethnicities. Little is known about ALLO tolerance in Vietnam (VN). <h3>Objectives</h3> The aim of this ongoing prospective study was to investigate risk factors, including HLA*B-58 01, for MCARs and SCARs in the predominant Kinh ethnicity of VN <h3>Methods</h3> All included patients were Kinh Vietnamese. SCARs were recruited at Ho Chi Minh City hospitals, MCARs from the same departments and from the Vien Gut clinic at HCMC (specialised in gout care), and tolerant gouty patients (no skin reaction after at least 3 months from the last increment in ALLO dose) at the Vien Gut clinic. Clinical data were prospectively collected and HLA*B-58 01 typing used the PG5801 DNA detection kit (Pharmigene-Taiwan). Fisher exact test for categorical variables and Kruskal/Wilkonson test for quantitative variables were used for statistics. <h3>Results</h3> 10 patients experienced a non-fatal SCAR. Toxic necrotic epidermolysis, Stevens-Johnson syndrome and mixed syndrome were diagnosed in 1, 8 and 1 patients respectively. 54 patients stopped ALLO because of MCAR.112 ALLO tolerant patients were recruited. Table 1 shows the main features of interest in the 3 groups. The Odds ratio of HLA*B-58 01 positive patients to develop SCARs was calculated at 171.2 (95% CI: 20; 7889) <h3>Conclusions</h3> HLA*B-58 01 was significantly associated with SCARs to ALLO in the VN Kinh population. Other known factors but not high ALLO dose were also associated. The only association with MCARs was lack of ALLO titration. <h3>Acknowledgements</h3> ART Viggo <h3>Disclosure of Interest</h3> None declared
AB1130 Late onset tumour necrosis factor receptor (TNFR)–associated periodic syndrome (TRAPS) caused by somatic tnfrsf1 mosaicism
Authors: A. Kontzias, S. Zarabi, C. Calabrese, Y.-W. Cheng
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Tumour necrosis factor receptor (TNFR)–associated periodic syndrome (TRAPS) is an autosomal-dominant disease caused by gain-of-function mutations in the TNFRSF1A gene, which encodes the 55-kd TNFR type I (TNFRI) protein. Mosaicism has been identified in a single patient.1 A 60 year old male presented with a 6 year history of intermittent fever as high as 103.5, lasting 3–4 weeks with associated peritoneal symptoms, arthralgias, myalgias, lymphadenopathy, bilateral episcleritis, erythematous rash in his torso. Prednisone up to 60 mg daily and colchicine was ineffective where he responded fully to canakinumab at a dose of 150 mg every 4 weeks. <h3>Objectives</h3> To identify the extent of mosaicism in a patient with adult onset TRAPS phenotype. <h3>Methods</h3> DNA was extracted from the patient‘s whole blood, saliva and hair root. The TNFRSF1A gene was analysed by Sanger sequencing in all tissues, whole blood and fractionated cell subsets. <i>In silico</i> molecular modelling was performed to predict the structural and functional consequences of the tumour necrosis factor receptor (TNFR) type I protein mutation. <h3>Results</h3> Sanger sequencing revealed differential tissue and hematopoietic cell presence of a misense mutation at c.265 T&gt;C p.Phe89Leu (F89L) Chr12(GRCh37):g.6442960A&gt;G ex3 rs104895245. The mutant allele was present in whole blood and buccal mucosa and absent in hair root, supporting the presence of somatic TNFRSF1A mosaicism. Additionally, quantitave analysis revealed allele frequency of 50% in B cells, 30% in NK cells and 30% in neutrophils. The mutation was absent in T cells and monocytes. <i>In silico</i> prediction modelling with SIFT and PolyPhen2 suggested that this mutation led to numerous structural rearrangements which resulted in changes in the protein surface profile. <h3>Conclusions</h3> This is the second reported case of TNFRSF1A mosaicism in a patient with TRAPS, which was attributable to a <i>de novo</i> mosaic missense mutation in the TNFRSF1A gene. (c.265 T&gt;C) p.Phe89Leu (F89L). Our results point to a late-onset mutational event at the level of a multipotent hematopoietic stem cell. <h3>Reference</h3> [1] Rowczenio, et al. Association of Tumor Necrosis Factor Receptor–Associated Periodic Syndrome With Gonosomal Mosaicism of a Novel 24-Nucleotide TNFRSF1A Deletion Arthritis and Rheumatology, Vol. 68, No. 8, August 2016, pp 2044–2049 <h3>Disclosure of Interest</h3> None declared
Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10
Authors: Morgan L. Maeder, Michael Stefanidakis, Christopher J. Wilson, Reshica Baral, Luis Alberto Barrera, George S. Bounoutas, David Bumcrot, Hoson Chao, Dawn M. Ciulla, Jennifer A. DaSilva, Abhishek Dass, Vidya Dhanapal, Tim J. Fennell, Ari E. Friedland, Georgia Giannoukos, Sebastian W. Gloskowski, Alexandra Glucksmann, Gregory M. Gotta, Hariharan Jayaram, Scott J. Haskett, Bei Hopkins, Joy E. Horng, Shivangi Joshi, Eugenio Marco, Rina Mepani, Deepak Reyon, Terence Ta, Diana G. Tabbaa, Steven J. Samuelsson, Shen Shen, Maxwell N. Skor, Pam Stetkiewicz, Tongyao Wang, Clifford Yudkoff, Vic E. Myer, Charles F. Albright, Haiyan Jiang
Journal: Nature Medicine (2019)
AB0150 Diminished expression of pd-l1 by activated b cells is characteristic of sle
Authors: A.-L. Stefanski, A. Wiedemann, K. Reiter, A.C. Lino, T. Dörner
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Programmed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2 are known to play an important role in immune response regulation via a co-inhibitory signal during T cell activation. Genome-wide association studies in humans and the fact that PD-1 knock-out mice develop a lupus-like pathology point toward the involvement of the PD-1 pathway in the pathogenesis of systemic lupus erythematosus (SLE).<sup>1 2</sup> However, little is known regarding the role of this pathway in B cells from patients with SLE. <h3>Objectives</h3> This study addressed the kinetics of PD-1, PD-L1 and PD-L2 expression on B cells from patients with SLE. <h3>Methods</h3> Blood samples were obtained from healthy donors (HD) and SLE patients. PBMCs from HD and SLE patients were stimulated with IL2/IL10, aBCR (IgG/IgM/IgA), CpG oligodeoxynucleotides (CpG) and CD40L alone or in combination. The membrane expression of PD-1, PD-L1 and PD-L2 on CD19 +CD20+B cells was measured by FACS at baseline and after 48 hour stimulation. <h3>Results</h3> At baseline, the expression of PD-1, PD-L1 and PD-L2 on B cells between HD and SLE patients was similar. Notably, 48 hour stimulation of B cells with IL2/IL10, aBCR, CpG and CD40L gave rise to twofold reduced expression of PD-L1 by SLE compared to HD B cells. Interestingly, PD-L1 expression by SLE B cells was increased only in presence of CD40L, whereas in HD the mix of CpG, aBCR, and IL2/IL10 led also to a significant increase in PD-L1 expression. <h3>Conclusions</h3> The data suggest that activation of B cells from SLE patients require CD40/CD40L interaction to increase PD-L1 expression, which is, however, reduced compared to HD. Diminished PD-L1 expression upon B cell stimulation is consistent with impaired inhibition of T cells in SLE (figure 1). <h3>References</h3> [1] Nishimura H, et al. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity1999;11(2):141–151. [2] Prokunina L, et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet2002;32(4):666–9. <h3>Disclosure of Interest</h3> None declared
Development of hepatopulmonary syndrome during combination therapy for portopulmonary hypertension
Authors: Karen M. Olsson, Katrin Meyer, Dominik Berliner, Marius M. Hoeper
Journal: European Respiratory Journal (2019)

Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome (HPS) are rare pulmonary vascular complications of portal hypertension [1]. In PoPH, pulmonary vascular resistance (PVR) is elevated, resulting in heightened right ventricular workload which may lead to right-sided heart failure. HPS is characterised by progressive hypoxaemia due to diffusion–perfusion mismatching caused by regional, mostly basilar, intrapulmonary vascular dilatations of capillary and pre-capillary vessels. The exact pathogenesis of both conditions is unclear, as is the underlying predisposition causing a small proportion of patients with liver disease to develop PoPH or HPS. Patients with portopulmonary hypertension may develop hepatopulmonary syndrome during treatment with pulmonary vasodilators <http://ow.ly/brHB30mOIWn>
Endoscopic scar assessment after colorectal endoscopic mucosal resection scars: when is biopsy necessary (EMR Scar Assessment Project for Endoscope (ESCAPE) trial)
Authors: Pujan Kandel, Eelco Christiaan Brand, Joe Pelt, Colleen T Ball, Wei-Chung Chen, Ernest P Bouras, Victoria Gomez, Massimo Raimondo, Timothy A Woodward, Michael B Wallace
Journal: Gut (2019)

Objective It is unclear whether endoscopic assessment of scars after colorectal endoscopic mucosal resection (EMR) has to include biopsies, even if endoscopy is negative. Vice versa, endoscopic diagnosis of recurrent adenoma may not require biopsy before endoscopic reinterventions. We prospectively analysed various endoscopic modalities in the diagnosis of recurrence following EMR. Design We conducted a prospective study of patients undergoing colonoscopy after EMR of large (≥20 mm) colorectal neoplasia. Endoscopists predicted recurrence and confidence level with four imaging modes: high-definition white light (WL) and narrow-band imaging (NBI) with and without near focus (NF). Separately, 26 experienced endoscopists assessed offline images. Results Two hundred and thirty patients with 255 EMR scars were included. The prevalence of recurrent adenoma was 24%. Diagnostic values were high for all modes (negative predictive value (NPV) ≥97%, positive predictive value (PPV) ≥81%, sensitivity ≥90%, specificity ≥93% and accuracy ≥93%). In high-confidence cases, NBI with NF had NPV of 100% (95% CI 98% to 100%) and sensitivity of 100% (95% CI 93% to 100%). Use of clips at initial EMR increased diagnostic inaccuracy (adjusted OR=1.68(95% CI 1.01 to 2.75)). In offline assessment, specificity was high for all imaging modes (mean: ≥93% (range: 55%–100%)), while sensitivity was significantly higher for NBI-NF (82%(72%–93%)%)) compared with WL (69%(38%–86%); p&lt;0.001), WL-NF (68%(55%–83%); p&lt;0.001) and NBI (71%(59%–90%); p&lt;0.001). Conclusion Our study demonstrates very high sensitivity and accuracy for all four imaging modalities, especially NBI with NF, for diagnosis of recurrent neoplasia after EMR. Our data strongly suggest that in cases of high confidence negative optical diagnosis based on NBI-NF, no biopsy is needed to confirm absence of recurrence during colorectal EMR follow-up. A high confidence positive optical diagnosis can lead to immediate resection of any suspicious area. In all cases of low confidence, biopsy is still required. Trial registration number NCT02668198 .
Tob1 suppresses invasive phenotype of human breast cancer
Authors: Chunmin Ge, Yan Jiao, Qinghui Meng, Saijun Fan
Journal: Cancer Research (2008)

4547  TOB1 has been shown to function as an anti-cell proliferation gene and a promising candidate tumor-suppressor gene. Here we show that the loss of TOB1 expression in highly metastatic breast cancer cell lines compared to normal breast epithelial cell lines and non-metastatic breast cancer cell lines. Overexpression of TOB1 caused a significant reduction of cell invasion and a decreased clonogenicity in soft (0.3%) and hard (0.9%) agar in the metastatic human breast carcinoma cell line MDA-MB-435. By injected into the mammary fat pads of athymic nude mice, MDA-MB-435 tumors with high expression of TOB1 reduced metastatic potential by 90% compared to control tumors. Increased expression of TOB1 significantly induce higher cell surface levels of alpha5- and alpha3-containing integrins and reduced levels of alpha2-, alpha4-, alpha6-, alpha(v)-, and some beta1-containing integrins. Analysis of human breast cancer specimens revealed that loss of TOB1 expression occurred most frequently in advanced and metastatic cancers. These studies suggest TOB1 may play an important role in the metastatic cascade of breast cancer and could be a useful target for therapeutic intervention.
THU0481 Physical performance factors influencing gait speed in patients surgically treated for osteoporotic hip fractures
Authors: B.R. Kim
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> This study was undertaken to determine physical performance factors associative of gait speed in patients surgically treated for hip fractures. <h3>Methods</h3> Fifty eight patients (16 males and 42 females; average age 79.1±9.1 years) who underwent a hip surgery due to hip fractures participated in this study. Patients completed 10 metre walk test (10MWT) to assess gait speed. Additional physical performance tests included Timed up and go test (TUG), Berg balance scale (BBS), one repetitive maximum (1RM) of leg extension, leg curl, hip abduction of surgical and nonsurgical sides, and instrumental gait analysis for spatio-temporal parameters. <h3>Results</h3> In the bivariate analyses, postoperative 10WMT had a significant positive correlation with the postoperative TUG (r=0.85, p&lt;0.01), age (r=0.57, p&lt;0.01), swing phase duration (r=0.35, p&lt;0.01), gait cycle duration (r=0.49, p&lt;0.01) and significant negative correlation with the postoperative BBS (r=−0.69, p&lt;0.01), 1RM of surgical leg extension (r=−0.35, p=0.01), 1RM of nonsurgical leg extension (r=−0.40, p&lt;0.01), 1RM of surgical leg curl (r=−0.44, p&lt;0.01), 1RM of nonsurgical leg curl (r=−0.41, p&lt;0.01), 1RM of hip abduction (r=−0.32, p=0.02), cadence (r=−0.53, p&lt;0.01), stance phase duration (r=−0.26, p=0.04). In addition, a presence of dementia was significantly correlated with 10WMT (44.2 s vs 22.4 s, p=0.02). In the linear regression analyses, the postoperative TUG (β=0.85, p&lt;0.01) was a factor associative of the postoperative 10MWT. <h3>Conclusions</h3> This study revealed that the presence of dementia, the postoperative balance ability, muscle strength of surgical and nonsurgical legs were significantly associated with postoperative gait speed 1 month after hip surgery due to hip fractures. Therefore, these results could be importance in planning various postoperative rehabilitative programs to improve gait speed early after hip surgery due to hip fractures. <h3>Disclosure of Interest</h3> None declared
A wearable cardioverter–defibrillator did not reduce arrhythmic death in MI with reduced ejection fraction
Authors: Kristen Sullivan, Harriette G.C. Van Spall
Journal: Annals of Internal Medicine (2019)

ACP Journal Club15 January 2019A wearable cardioverter–defibrillator did not reduce arrhythmic death in MI with reduced ejection fractionKristen Sullivan, MD, Harriette G.C. Van Spall, MD, MPH, FRCPCKristen Sullivan, MDMcMaster University, Hamilton, Ontario, Canada (K.S., H.G.V.)Search for more papers by this author, Harriette G.C. Van Spall, MD, MPH, FRCPCMcMaster University, Hamilton, Ontario, Canada (K.S., H.G.V.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2019-170-2-005 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationOlgin JE, Pletcher MJ, Vittinghoff E, et al; VEST Investigators. Wearable cardioverter-defibrillator after myocardial infarction. N Engl J Med. 2018;379:1205-15. https://pubmed.ncbi.nlm.nih.gov/30280654Clinical Impact RatingsCardiology: References1 Hohnloser SH, Kuck KH, Dorian P, et al; DINAMIT Investigators. Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction. N Engl J Med. 2004;351:2481-8. [PMID: 15590950] Google Scholar2 Steinbeck G, Andresen D, Seidl K, et al; IRIS Investigators. Defibrillator implantation early after myocardial infarction. N Engl J Med. 2009;361:1427-36. [PMID: 19812399] Google Scholar3 Tseng ZH, Olgin JE, Vittinghoff E, et al. Prospective countywide surveillance and autopsy characterization of sudden cardiac death: POST SCD Study. Circulation. 2018;137:2689-2700. [PMID: 29915095] Google Scholar Author, Article, and Disclosure InformationAffiliations: McMaster University, Hamilton, Ontario, Canada (K.S., H.G.V.)This article was published at Annals.org on 1 January 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 January 2019Volume 170, Issue 2Page: JC5KeywordsArrhythmiaEjection fractionImplantable cardioverter defibrillatorsMortalityMyocardial infarctionRevascularizationShockSudden cardiac deathTachycardiaThorax ePublished: 15 January 2019 Issue Published: 15 January 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
FRI0330 Rituximab therapy in sle: early retreatment is associated with lower disease activity and a reduction in corticosteroid use
Authors: R.L. Batten, S. Batool, C.E. Kidd, A. Lorenzi, J. Vila, K. Walker, B. Griffiths
Journal: Annals of the Rheumatic Diseases (2018)

Background  The recently published UK guidelines for the management of SLE recommend biologic therapy for severe or refractory disease. The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) has shown rituximab (RTX) to be safe, effective and corticosteroid [CS] sparing when used to treat refractory SLE. In 2013 NHS England published an interim clinical commissioning policy statement with criteria determining when RTX can be used to treat SLE.  Objectives  We evaluated our centre’s RTX retreatment strategy in patients with SLE and the consequent outcomes (disease activity and CS dose).  Methods  Records for the first 50 patients receiving RTX for refractory SLE who consented to join BILAG-BR from our centre between December 2013 and January 2016 were analysed (data cut off July 2016). Demographics, disease activityBILAG 2004/SLEDAI-2K), change in CS dose, retreatment schedules and adverse events were analysed.  Results  Median(IQR) age and disease duration were 42.8 (33–53) years and 9.5 (4–15.8) years respectively. Male: female ratio was 1:25. 80% were Caucasian, 6% Asian, 4% Caribbean and 10% other. All patients met SLICC/ACR classification criteria for SLE. The median(IQR) SLEDAI-2K scores and BILAG 2004 scores reduced from 6 (4–8) to 4 (0–4) (p  30/50 patients received their 1 st course of RTX at BILAG-BR baseline visit. 23 met criteria for active disease (at least 1A or 2Bs), 6 were taking an unacceptably high maintenance CS dose, and 1 was planning pregnancy. Median(IQR) CS dose in this group at baseline was 10 mg(1.5–20), and 5 mg(3–9) at 6 months. 70.8% demonstrated complete response at 6 months. 17 (57%) went on to have retreatment due to active disease, of which 11 (64.7%) had responded at 6 months post retreatment. Median(IQR) time to retreatment was 8 (6–12) months.  20/50 patients had received retreatment at predetermined intervals prior to their baseline BILAG-BR visit. Median(IQR) numbers of previous RTX courses were 3 (2–6). Median(IQR) CS dose was 8.75 mg(0–11.3) at baseline BILAG-BR visit and 5.5 mg(0–10) at 6 months. Median(IQR) time from baseline to retreatment was 6 (6–9.5) months. Median(IQR) sustained response was 18 (13.5–18) months.  Conclusions  Historically, our centre used time from 1 st treatment to flare as a guide to a patient’s future RTX retreatment schedule; patients were, on average, treated 2 months earlier than those treated under the current commissioning policy. Findings suggest that earlier retreatment led to sustained disease control and reduction of CS dose with no increase in adverse events. 11/16 incomplete responders responded following retreatment. Early retreatment may be associated with better outcomes for the patient and further research is needed in this area.  Disclosure of Interest  None declared