tbuckley/cabot-search huggingface dataset:
AB0888 Tenofovir induced osteomalacia: a profile based on three patients with low phosphorus and normal levels of vitamin d and parathyroid hormone
Authors: M Lovy
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Tenofovir can induce proximal renal tubular changes that result in varying expression of Fanconi syndrome<sup>1,2</sup>. Less commonly, osteomalacia related to hypophosphatemia<sup>2,3</sup> can occur and has been documented with bone biopsy<sup>3</sup>. The clinical details of 28 reported cases of tenofovir induced osteomalacia, some of whom had vitamin D deficiency and secondary hyperparathyroidism, was recently summarized<sup>3</sup>. <h3>Objectives</h3> To describe the clinical presentation and course of three HIV patients with tenofovir induced hypophosphatemic osteomalacia and compare to cases previously reported. <h3>Methods</h3> The clinical, laboratory, and radiologic features of three HIV patients referred for evaluation of pain and osteoporosis were reviewed. <h3>Results</h3> All three patients were male, had diffuse pain, suffered multiple clinical fractures, and were on combination long and short acting opioids at the time of presentation. Two were in wheelchairs and two had neuropathy. All patients had hypogonadism and proteinuria and case 1 had glycosuria. All patients had normal 25-OH vitamin D, vitamin B12, PTH, serum protein electrophoresis, magnesium, CBC, calcium, CPK, sedimentation rate, TSH. Case 1 had fractures of the hip, sacrum, and humerus; case 2 hip and ribs; and case 3 ribs, pelvis and knee. The technetium bone scan showed a similar pattern of increased uptake in multiple ribs, calcaneus, metatarsal bones, knees, and sacrum in all three patients. A MRI of the knee showed bone marrow edema in case 2 and an atypical longitudinal fracture of the femur in case 3. Tenofovir was withdrawn, oral phosphates given, and resolution of pain and biochemical changes occurred in 4–8 months. Bone mineral density in case 1 repeated 1 year after presentation increased 16% in the femoral neck and 19% in the lumbar spine. The laboratory and clinical features in our cases shared with those previously reported include long duration of HIV and tenofovir treamtent, severe pain and disability, low BMI, neuropathy, hypogonadism in men, elevation of alkaline phoshatase and varying degrees of renal tubular dysfunction. <h3>Conclusions</h3> Long term tenofovir therapy in HIV patients can induce a devastating disabling osteomalacia caused by hypophosphatemia with features of Fanconi syndrome with or without vitamin D deficiency. A long standing history of HIV infection, low BMI, neuropathy, and hypogonadism in male patients may predispose or be associated with this complication. A serum phosphorus, alkaline phosphatase, and urinalysis should be followed regularly in all tenofovir treated patients to avoid the consequences of osteomalacia. <h3>References</h3> Karras A, et al, Clin Infect Dis 2003; 36:1070–1072. Earle KE, et al, J Bone Miner Dis 2004; 19:714–721. Mateo L, et al, Clin Rheumatol 2016; 35:1271–1279. <h3>Disclosure of Interest</h3> None declared
Preexisting Cardiovascular Risk and Subsequent Heart Failure Among Non-Hodgkin Lymphoma Survivors
Authors: Talya Salz, Emily C. Zabor, Peter de Nully Brown, Susanne Oksberg Dalton, Nirupa J. Raghunathan, Matthew J. Matasar, Richard Steingart, Andrew J. Vickers, Peter Svenssen Munksgaard, Kevin C. Oeffinger, Christoffer Johansen
Journal: Journal of Clinical Oncology (2017)

Purpose The use of anthracycline chemotherapy is associated with heart failure (HF) among survivors of non-Hodgkin lymphoma (NHL). We aimed to understand the contribution of preexisting cardiovascular risk factors to HF risk among NHL survivors. Methods Using Danish registries, we identified adults diagnosed with aggressive NHL from 2000 to 2010 and sex- and age-matched general-population controls. We assessed HF from 9 months after diagnosis through 2012. We used Cox regression analysis to assess differences in risk for HF between survivors and general population controls. Among survivors only, preexisting cardiovascular factors (hypertension, dyslipidemia, and diabetes) and preexisting cardiovascular disease were ascertained. We used multivariable Cox regression to model the association of preexisting cardiovascular conditions on subsequent HF. Results Among 2,508 survivors of NHL and 7,399 controls, there was a 42% increased risk of HF among survivors compared with general population controls (hazard ratio [HR], 1.42; 95% CI, 1.07 to 1.88). Among survivors (median age at diagnosis, 62 years; 56% male), 115 were diagnosed with HF during follow-up (median years of follow-up, 2.5). Before NHL diagnosis, 39% had ≥ 1 cardiovascular risk factor; 92% of survivors were treated with anthracycline-containing regimens. In multivariable analysis, intrinsic heart disease diagnosed before lymphoma was associated with increased risk of HF (HR, 2.71; 95% CI, 1.15 to 6.36), whereas preexisting vascular disease had no association with HF ( P > .05). Survivors with cardiovascular risk factors had an increased risk of HF compared with those with none (for 1 v 0 cardiovascular risk factors: HR, 1.63; 95% CI, 1.07 to 2.47; for ≥ 2 v 0 cardiovascular risk factors: HR, 2.86; 95% CI, 1.56 to 5.23; joint P < .01). Conclusion In a large, population-based cohort of NHL survivors, preexisting cardiovascular conditions were associated with increased risk of HF. Preventive approaches should take baseline cardiovascular health into account.
Eosinophil Biology in COPD
Authors: Christine F McDonald
Journal: New England Journal of Medicine (2017)

Chronic obstructive pulmonary disease (COPD) is a lethal disease that is predicted to become the third leading cause of death globally within 3 years.1 Recent research has highlighted the heterogeneity of the pathologic characteristics of COPD, indicating that disease mechanisms are complex. Inflammatory pathways implicating neutrophils have been emphasized,2 but attention has recently focused on the persistent blood and airway eosinophilia that is found in up to 40% of patients with COPD, even in the absence of a history of asthma; such patients have a higher risk of exacerbations than patients without eosinophilia.3,4 Guidelines have generally recommended a “one size . . .
Mitosis-Mediated Intravasation in a Tissue-Engineered Tumor–Microvessel Platform
Authors: Andrew D. Wong, Peter C. Searson
Journal: Cancer Research (2017)

Abstract Intravasation involves the migration of tumor cells across the local endothelium and escape into vessel flow. Although tumor cell invasiveness has been correlated to increased intravasation, the details of transendothelial migration and detachment into circulation are still unclear. Here, we analyzed the intravasation of invasive human breast cancer cells within a tissue-engineered microvessel model of the tumor microenvironment. Using live-cell fluorescence microscopy, we captured 2,330 hours of tumor cell interactions with functional microvessels and provide evidence for a mitosis-mediated mechanism where tumor cells located along the vessel periphery are able to disrupt the vessel endothelium through cell division and detach into circulation. This model provides a framework for understanding the physical and biological parameters of the tumor microenvironment that mediate intravasation of tumor cells across an intact endothelium. Cancer Res; 77(22); 6453–61. ©2017 AACR.
Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial
Authors: Paresh Dandona, Chantal Mathieu, Moshe Phillip, Lars Hansen, Steven C Griffen, Diethelm Tschöpe, Fredrik Thorén, John Xu, Anna Maria Langkilde, Joseph Proietto, Stephen Stranks, Roger Chen, David O'Neal, Alexia Pape, Mark Forbes, Claire Morbey, Anton Luger, Ursula Hanusch, Christoph Schnack, Evelyn Fliesser-Goerzer, Bertram Hoelzl, Christoph Ebenbichler, Rudolf Prager, Luc Van Gaal, Chris Vercammen, Andre Scheen, Chantal Mathieu, Francis Duyck, Frank Nobels, Johannes Ruige, Naresh Aggarwal, Vincent Woo, Bruno St-Pierre, Richard Dumas, Irene Hramiak, Thomas Elliott, Troels Krarup Hansen, Jan Erik Henriksen, Jeppe Gram, Aina Lihn, Jens Bruun, Juha Saltevo, Jyrki Taurio, Jorma Strand, Timo Valle, Sakari Nieminen, Kirsi Pietilainen, Bruno Guerci, Samy Hadjadj, Bertrand Cariou, Bruno Verges, Sophie Borot, Alfred Penfornis, Thomas Schaum, Diethelm Tschoepe, Cornelia Marck, Thomas Horacek, Ludger Rose, Gerhard Klausmann, Joerg Luedemann, Steffi Appelt, Ulrich Aigner, Rolf Goebel, Thomas Behnke, Anette-Gabriele Ziegler, Eva Peterfai, Zsuzsanna Kerenyi, Tamas Oroszlan, Gyula G. Kiss, Laszlo Konyves, Gyorgyi Piros, Moshe Phillip, Ofri Mosenzon, Naim Shehadeh, Faiad Adawi, Julio Wainstein, Francesco Dotta, Piermarco Piatti, Stefano Genovese, Agostino Consoli, Paolo Di Bartolo, Edoardo Mannucci, Carla Giordano, Annunziata Lapolla, Carlos Aguilar, Alberto Esteban, Bazzoni Ruiz, Guillermo Mondragon Ramirez, Emilia Pelayo Orozco, Carlos Alejandro, Stobschinski de Alba, Carlos Medina Pech, Jose Garza Ruiz, Leobardo Sauque Reyna, Guillermo Llamas Esperon, Luis Alejandro Nevarez Ruiz, Maricela Vidrio Velazquez, Fernando Flores Lozano, Jose Gerardo Gonzalez Gonzalez, Pedro Alberto Garcia-Hernandez, Roberto Araujo-Silva, Efrain Villeda - Espinosa, Cristina Mistodie, Daniela Popescu, Ciprian Constantin, Alina Nicolau, Bogdan Popa, Romulus Timar, Cristian Serafinceanu, Ella Pintilei, Alfonso Soto, Margarita Gimenez, Juan Francisco Merino-Torres, Cristobal Morales, Pedro Mezquita, Johan Jendle, Bengt-Olov Tengmark, Jan Eriksson, Magnus Londahl, Bjorn Eliasson, Anthony Gunstone, Simon Heller, Ken Darzy, Peter Mansell, Melanie Davies, Rory Reed, Duncan Browne, Hamish Courtney, Wayne Turner, Mark Blagden, Rory McCrimmon, Richard Bergenstal, Wendy Lane, Kathryn Lucas, Alexander White, Shichun Bao, Judith White, Curtis Jantzi, Neda Rasouli, William Ervin, Lorena Lewy-Alterbaum, Yehuda Handelsman, Bresta Miranda-Palma, Alan Cleland, Raymond Fink, Helena Rodbard, Samer Nakhle, Craig Greenberg, Alan Schorr, Harold Bays, Debra Simmons, Eric Klein, Laurie Kane, Norman Fishman, Eli Ipp, Satish Garg, Anuj Bhargava, Michelle Zaniewski Singh, Julio Rosenstock, James Thrasher, Mark Warren, Laura Young, Vanita Aroda, Jeremy Pettus, David Liljenquist, Robert Busch, Paresh Dandona, Jonathan Wise, David Kayne, William Biggs
Journal: The Lancet Diabetes & Endocrinology (2017)
AB0482 Elevation of serum proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations and its correlation with C-reactive protein, but not atherogenic lipids in patients with systemic lupus erythematosus
Authors: C Fang, L Huang, T Luo, X Chen, L Lin
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patients with systemic lupus erythematosus (SLE) have a tendency of accelerated atherosclerosis with controversial benefits from statin. This phenomenon can only partly be explained by traditional risk factors for cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease associated with cardiovascular risk that not only regulates cholesterol metabolism, but acts as a critical regulator of inflammatory reaction. PCSK9 inhibitors were also highly promising drugs bringing added cardiovascular benefit when administered with statin [1] [2]. <h3>Objectives</h3> The present study firstly aimed to compare serum PCSK9 levels in SLE patients and healthy controls. The association between PCSK9 concentrations with atherogenic lipids and C-reactive protein (CRP) in SLE patients was also analyzed. <h3>Methods</h3> 77 individuals encompassed; 47 patients with SLE and 30 age- and sex-matched controls. Serum PCSK9, lipoproteins concentrations and CRP levels were assessed in patients and controls. Individuals with history of smoking, diabetes, infection, tumor and statin use were excluded. <h3>Results</h3> Serum PCSK9 levels were significantly elevated in patients with SLE, compared with healthy controls (p=0.034). PCSK9 positively correlated with serum levels of CRP (r<sub>s</sub>=0.351, p=0.016); The tendency seemed more significant in female patients (r<sub>s</sub>=0.487, p=0.001); No correlation with statistical significance between PCSK9 levels with disease activity (SLEDAI) or serum lipids parameter was found (p&gt;0.05, all) (Table 1). <h3>Conclusions</h3> Elevation of PCSK9 was observed in patients with SLE and correlated with CRP but not atherogenic lipids, particularly in female patients. The result was indicative of pathogenic role of PCSK9 in the low-grade inflammation which promotes the atherogenic process in SLE patients. <h3>References</h3> Giugliano RP, Sabatine MS. Are PCSK9 Inhibitors the Next Breakthrough in the Cardiovascular Field?. J Am Coll Cardiol. 2015 Jun 23;65(24):2638–51. Walley KR, Thain KR, Russell JA, et al. PCSK9 is a critical regulator of the innate immune response and septic shock outcome.Sci Transl Med. 2014 Oct 15;6(258):258ra143. <h3>Acknowledgements</h3> The authors thank Qiulan Li for the excellent technical assistance. <h3>Disclosure of Interest</h3> None declared
Survey of Compounds Which Have Been Tested for Carcinogenic Activity. Jonathan L. Hartwell, associate chemist, National Cancer Institute, National Institute of Health, United States Public Health Service. 371 pp. (Multilithed) 1941. Available for free distribution
Authors: Harold L. Stewart
Journal: JNCI Journal of the National Cancer Institute (1942)

Survey of Compounds Which Have Been Tested for Carcinogenic Activity. Jonathan L. Hartwell, associate chemist, National Cancer Institute, National Institute of Health, United States Public Health Service. 371 pp. (Multilithed) 1941. Available for free distribution Get access Harold L. Stewart Harold L. Stewart Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 6, June 1942, Pages 634–635, https://doi.org/10.1093/jnci/2.6.634 Published: 01 June 1942
AB0341 How common is discordance in das components in patients with rheumatoid arthritis
Authors: M Shaikh
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Chronic pain remains a significant problem for patients with rheumatoid arthritis (RA) despite advances in the management of joint inflammation (1–3). Pain that persists in the absence of significant inflammatory disease activity is thought to arise from sensitisation of the central nervous system. Composite scores such as DAS28, combine both objective and subjective aspects of disease. This may overestimate inflammatory disease in patients in whom pain occurs independently and has implications for treatment. However, the proportions of patients with such discordance is not clear. <h3>Objectives</h3> 1. To assess the degree of discordance between objective and subjective components of the DAS28 score in patients attending rheumatology clinics in a teaching hospital in Cambridge. 2. To assess the association between such discordance and the DAS28-P measure <h3>Methods</h3> A retrospective review of clinic notes was conducted of patients attending the rheumatology department at Addenbrooke9s Hospital, Cambridge. Patients attending the early arthritis clinic, nurse practitioner follow up clinic and biologics clinic were included. Demographic information was collected including age, gender, current use of synthetic and biologic DMARDs. DAS28 scores and the individual components were retrieved and analysed. DAS28P was calculated as well as the difference between tender and swollen joint count (TJC-SJC) which has also been noted to be a measure of discordance between subjective and objective symptoms. <h3>Results</h3> 120 patients with RA were studied. The mean age was 59.4 years (range 27–86). 74% (89) were female. 88% (106) were on synthetic DMARDs: MTX 48% (58), HCQ 37% (45), SSZ 12% (15), LEF 3% (4), Gold 0.8% (1). 30% (36) were on biologic DMARDs: RTX 30% (11), ETA 30% (11), TOCI 17% (6), ADA 14% (5), ABA 6% (2). Mean DAS28 was 3.42, SD 1.39. Mean TJC 4, mean SJC 2. Mean PGA 43, SD 24. DAS28-P was calculated as per previous studies (3). Mean TJC-SJC was 2, median 1. PGA and TJC-SJC (r=0.33) and TJC-SJC and DAS28P were correlated (r=0.44). <h3>Conclusions</h3> Discordance between subjective and objective components of DAS scores is relatively frequent in patients with RA. This can lead to confounding of DAS scores. There is currently no formal system of assessing the degree of such discordance which can have implications for treatment of inflammatory disease as compared to pain management strategies. <h3>References</h3> Taylor, P. et al., 2010. J. Int. Med. Res. 38, 1213–1224. Strand, V. et al., 2015. J. Rheumatol. 42, 2046–2054. McWilliams, D.F. et al., 2012. Arthritis Care Res. 64, 1505–1513. <h3>Disclosure of Interest</h3> None declared
FRI0165 Serum free light chains of immunoglobulins in rheumatoid arthritis: correlation with interstitial lung disease
Authors: S Belghali, S Lataoui, S Ferchichi, K Baccouche, N Elamri, K Limam, H Zeglaoui, E Bouajina
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Lungs in Rheumatoid arthritis (RA) seem to play an important role, not only as an extra-articular manifestation but also as a site of initiation of the disease and activation for the immune response. B lymphocytes are thought to be involved in the pathophysiology of RA and interstitial lung disease (ILD). The encouraging results of the use of Anti-CD20 treatments to stabilize articular symptoms and lung involvement reinforce this theory. Serum Free immunoglobulin Light Chains (FLC) might represent, in this context, an interesting marker of B lymphocytes activation during this disease. <h3>Objectives</h3> To determine the serum FLC levels in RA patients with and without ILD and to study their possible association with disease characteristics and activity. <h3>Methods</h3> Fifteen RA patients with clinically symptomatic interstitial lung disease, confirmed by computed tomography (RA-ILD) (53.3% females; mean age 61,27±6,48 years) and age matched RA patients (66.7% females) with no clinically evident interstitial disease (non-ILD) were studied. Clinical and immunological inflammatory characteristics were assessed for all the patients. FLC levels were quantified by turbidimetry (Freelite TM Kappa and Lambda Kits, The Binding Site, UK). <h3>Results</h3> The mean serum FLC-κ levels (RA-ILD: 40,74±16,94 ng/ml <i>vs</i> non-ILD 24,88±8,87 ng/ml, p=0,003) and FLC-λ levels (RA-ILD: 37,34±16,56 ng/ml <i>vs</i> non-ILD 26,28±7,22 ng/ml, p=0,028) were significantly higher in patients with ILD compared to non-ILD, while the serum FLC-ratioκ/λ (RA-ILD: 1,15±0,38 <i>vs</i> non-ILD 1,00±0,43, p=0,304) were comparable. There was no significant difference for the DAS28 disease activity score between both groups (RA-ILD: 4,6±1,5 vs non-ILD 4,38±1,46, p=0,69). No significant correlations were found between the DAS28-score and FLCκ, FLCλ and FLC-ratioκ/λ (p&gt;0,05). FLC-κ levels correlated significantly with ESR and CRP levels (p&lt;0.001), FLC-λ levels with CRP (p=0,005) but not with ESR (p=0,247) and FLC-ratioκ/λ did not correlate with both ESR and CRP levels. <h3>Conclusions</h3> High levels of serum FLC are associated with RA-ILD and with a higher degree of inflammation, supporting the role of B cell activation in the pathophysiology of RA with ILD. <h3>Disclosure of Interest</h3> None declared
AB0392 Safety and effectiveness of CT-P13 in patients with rheumatoid arthritis: results from 24 months nationwide registry in korea
Authors: SH Park, SS Nah, SH Chang, KJ Kim, KS Park, SS Lee, SR Kwon, SI Lee, CH Suh, SH Kim, CN Son, JK Min, HR Kim, HJ Beak, HS Kim, JY Choe, HI Yang, MK Lim, SJ Hong, YS Kim, JH Lee, J Suh, S Lee
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> CT-P13 is approved in both European Union and United States, and licensed for use in 79 countries around the world as a biosimilar to innovator infliximab (INX). The independent registries of CT-P13 have been conducted in a number of European countries and Korea [1]. <h3>Objectives</h3> To evaluate safety and effectiveness of CT-P13 when administered in a real-life setting in active RA patients. <h3>Methods</h3> This study collected data of patients who were treated with CT-P13 from 2013 December to 2016 June. Efficacy was assessed at baseline and every 6 months thereafter using DAS28 (ESR) and/or DAS28 (CRP) and collection of adverse events (AEs) was performed. Immunogenicity was assessed at baseline, Week 30 and every year during CT-P13 treatment period. <h3>Results</h3> Total 125 patients were enrolled; 104 patients started treatment with CT-P13 (Naïve group) and 21 patients (8 from INX, 13 from other anti-TNFs) switched treatment to CT-P13 (Switching group). The mean (SD) duration since RA diagnosis was 6.5 (±6.85) years for all patients. Of all patients treated with CT-P13, only 4.8% (6/125) of patients changed to other anti-TNFs. Two of six patients changed treatment within 8 month after starting CT-P13. The proportion of patients achieving clinical remission by DAS28 (ESR/CRP) increased gradually (Figure 1). DAS28 (ESR/CRP) value decreased from baseline at 6 months and it maintained thereafter (Table 1). Switching group also showed similar results that remission rate by DAS28 (CRP) was 42.9% (3/7) and mean actual value was 2.85 at 12 months. For Naïve group, 50% (52/104) of patients had at least one positive anti-drug antibody result and it is consistent to other published study [2]. Overall safety summarized as the percentage of patients with at least one treatment emergent AE (TEAE) was similar or lower after switching to CT-P13 (Table 2). No cases of active tuberculosis were reported. <h3>Conclusions</h3> The overall safety profile revealed that CT-P13 is well-tolerated in patients with RA and remission rate for 24 months also showed that CT-P13 is efficacious under real world practice. <h3>References</h3> Glintborg et al. ACR 2016. Krintel et al. Rheumatology 2013. <h3>Disclosure of Interest</h3> None declared