tbuckley/cabot-search huggingface dataset:
THU0155 Impact of baseline modified rheumatic disease comorbidity index (MRDCI) on drug survival and effectiveness of biological drugs in patients affected with rheumatoid arthritis (RA), spondyloarthritis (SPA), and psoriatic arthritis (PSA) in real-world settings
Authors: M Fornaro, M Di Carlo, S Gentileschi, MG Giannotta, L Cantarini, F Salaffi, G Lapadula, F Iannone
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The overall assessment of patients with systemic arthritis can not exclude comorbidities, which may impact therapeutic outcomes. <h3>Objectives</h3> To assess the impact of baseline modified rheumatic disease comorbidity index<sup>1</sup> (mRDCI) on drug survival and effectiveness of biological drugs in patients affected with Rheumatoid arthritis (RA), Spondyloarthritis (SpA), and Psoriatic Arthritis (PsA) in real-world settings. <h3>Methods</h3> Patients (nr. 635) with RA (nr. 214), SpA (nr. 213), and PsA (nr. 208) starting a biological drug were retrospectively analysed. mRDCI was scored at baseline, and disease characteristics were recorded at entry and at last observation. Drug retention was analysed using Kaplan–Meier curves. Cox-regression models were used to estimate the association of mRDCI with drug discontinuation and clinical outcomes, the achievement of clinical remission based on 28 joint-Disease Activity Score (DAS28) &lt;2.6 for RA and PsA, and on Ankylosing Spondylitis-C-reactive protein Disease Activity Score (ASDAS-CRP) &lt;1.3 for SpA. <h3>Results</h3> Baseline mRDCI significantly correlated with the number of biological drug switches (rho 0.47). Drug persistence was significantly higher in patients with mRDCI=0 (96.4%), than in those with mRDCI ≥2 (83.9%). Compared to mRDCI ≥2 patients, those without comorbidities showed significantly higher drug survival rate in PsA (p=0.0001) or SpA (p=0.02), but not in RA (Figure 1). mRDCI was also found to be a predictor of definitive drug discontinuation (HR 1.53) and of failure to achieve DAS28 based remission in RA (HR 0.66) or PsA (HR 0.77), and ASDAS-CRP driven remission in SpA (HR 0.43). <h3>Conclusions</h3> This study provided evidence that baseline mRDCI negatively impacts the persistence on biologic treatments and the clinical outcomes in patients with RA, SpA, and PsA in real-life settings. <h3>References</h3> Staetgens et al. Content and construct validity of the Rheumatic Diseases Comorbidity Index in patients with gout. Rheumatology (2015)Sep;54(9):1659–1663. <h3>Disclosure of Interest</h3> None declared
AB0914 Cutaneous leishmaniasis in patients treated with biological therapy
Authors: J Lluch, M Lόpez de Recalde, X Michelena, J Marcoval, X Juanola
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Leishmaniasis is a chronic protozoal disease endemic in several areas of the world. In the Mediterranean basin cutaneous leishmaniasis is caused by <i>Leishmania infantum</i> and usually produces localized skin lesions. Biological therapy (BT) may increase the risk of reactivation or development of infections such as tuberculosis, mycoses and protozoan diseases. However, there is scarce literature on <i>Leishmania</i> infections in patients treated with anti-TNF drugs. We have diagnosed five cases of cutaneous leishmaniasis in patients treated with anti-TNF drugs in the last four years. <h3>Objectives</h3> To show the clinical characteristics and the evolution of cutaneous leishmaniasis in patients treated with BT at a tertiary level hospital. <h3>Methods</h3> We reviewed the clinical characteristics, previous treatments, the complementary tests used for the diagnosis, the main disease, the therapy used for the treatment of the infection, the clinical evolution and the reintroduction of the BT. <h3>Results</h3> In the last four years we have diagnosed five cases of cutaneous leishmaniasis in patients treated with BT. Four of them were men and one a woman, the age range was 35 to 61 years old. In four of them the symptoms were only cutaneous, but one of them also had systemic impairment, basically hepatosplenomegaly. For the diagnosis skin biopsy, positive PCR for <i>Leishmania</i> DNA from skin samples, serology and response to treatment were all needed. Three cases were patients treated with adalimumab and two treated with infliximab. Three patients had Crohn9s disease, one psoriatic arthritis and the other ankylosing spondylitis. The diagnostic delay was between 5 and 24 months. All patients were treated with EV liposomal amphotericin B, and two of them also received intralesional injections of meglumine antimoniate. In all cases resolution was achieved, and there have been no relapses to date after reintroduction of BT. <h3>Conclusions</h3> We have to consider cutaneous leishmaniasis in patients with BT who present compatible skin lesions, especially in endemic areas. It is important to be aware of this type of condition in order to make a fast and accurate diagnosis. <h3>References</h3> Alvar J, Vélez ID, Bern C, et al. WHO Leishmaniasis Control Team. Leishmaniasis worldwide and global estimates of its incidence. PLoS One 2012; 7:e35671. Dujardin JC, Campino L, Cañavate C et al. Spread of vector-borne diseases and neglect of Leishmaniasis, Europe. Emerg Infect Dis 2008; 14:1013–8. <h3>Disclosure of Interest</h3> None declared
Assessing Microvascular Function in Humans from a Chronic Disease Perspective
Authors: Alfons J.H.M. Houben, Remy J.H. Martens, Coen D.A. Stehouwer
Journal: Journal of the American Society of Nephrology (2017)

Microvascular dysfunction (MVD) is considered a crucial pathway in the development and progression of cardiometabolic and renal disease and is associated with increased cardiovascular mortality. MVD often coexists with or even precedes macrovascular disease, possibly due to shared mechanisms of vascular damage, such as inflammatory processes and oxidative stress. One of the first events in MVD is endothelial dysfunction. With the use of different physiologic or pharmacologic stimuli, endothelium-dependent (micro)vascular reactivity can be studied. This reactivity depends on the balance between various mediators, including nitric oxide, endothelin, and prostanoids, among others. The measurement of microvascular (endothelial) function is important to understand the pathophysiologic mechanisms that contribute to MVD and the role of MVD in the development and progression of cardiometabolic/renal disease. Here, we review a selection of direct, noninvasive techniques for measuring human microcirculation, with a focus on methods, interpretation, and limitations from the perspective of chronic cardiometabolic and renal disease.
FRI0315 Clinical characteristics of vascular involvement in behcet's disease
Authors: A Ateş, M Torgutalp, E Okatan, E Uslu, B Dinçer, E Yayla, M Turgay, G Kınıklı
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Behçet9s disease (BD) is a multisystemic inflammatory disorder classified as vasculitis, which can affect all types of vessels. The prevalence of vascular involvement has been reported at rates ranging from 15 to 50%. <h3>Objectives</h3> In this study, we aimed to determine the characteristics of vascular involvement in patients with BD. <h3>Methods</h3> Six hundred and ninety-two patients with BD, who applied to the multidisciplinary BD policlinic between 2006–2016, were retrospectively analyzed. The diagnosis of vascular involvement was made on clinical signs, by Doppler ultrasonography and/or angiography using computed tomographic or magnetic resonance techniques where appropriate. <h3>Results</h3> One hundred and seventy-six patients (%25.4) had vascular involvement. The mean age of patients with vascular involvement (n=176) and non-vascular involvement (n=516) was similar to 42.5±12.3 and 42.2±12.2 years, respectively, while male sex frequency was significantly higher in patients with vascular involvement (72% to %42, p&lt;0.001). Uveitis (45%) and erythema nodosum (EN) (47.7%) were significantly higher in patients with vascular involvement than those without vascular involvement (for Uveitis OR: 1.7, p=0.003/for EN: OR: 2.5, p&lt;0.001) (Table 1). Deep vein thrombosis was detected in 142 (80.7%) of the patients with vascular involvement and this was the most common type of vascular involvement (Table 2). Arterial involvement was detected in 52 (29.5%) of 176 patients with vascular involvement. Deep venous thrombosis alone was present in 125 (71%) patients, arterial involvement alone in 12 (6.8%) patients, arterial and venous involvement together detected in 40 (22.7%) patients. Arterial involvement was most commonly seen as pulmonary artery involvement in 45 (25.6%) patients [pulmonary artery thrombosis 35 (20%), aneurysm 10 (5.7%) and thrombosis + aneurysm 6 (3.4%) patients]. Twenty (11.3%) patients had other arterial involvement except pulmonary, 8 of them had thrombosis and 12 had aneurysm. <h3>Conclusions</h3> Vascular involvement in Behçet9s disease is commonly seen in males. Deep vein thrombosis is the most common form of vascular involvement. Arterial involvement is important because of its higher risk of mortality (especially pulmonary artery aneurysm). The incidence of EN and uveitis is higher in patients with vascular involvement. <h3>Disclosure of Interest</h3> None declared
SP0060 Biomarkers are required for remission: pro
Authors: R Van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2017)

1. Conceptually, remission is thought of as a state where the disease is absent. As we approach a better understanding of the underlying pathophysiological process of a disease, it becomes more and more relevant to include in a definition of remission appropriate biochemical markers of that process. 2. From a practical point of view, definitions of remission in RA have been built upon clinical parameters of disease activity, supplemented in some cases with a single biomarker. However, it is clear that in practice these definitions are insufficiently precise: held against a gold standard of expert opinion, they perform at around 80–90%, misidentifying one or two out of every ten patients. And while there is an understandable and in many ways desiriable development of more patient-reported emphasis in outcomes, it has considerable practical value to be able to objectify an important disease state such as remission. 3. There is convincing evidence to show that biomarkers can be employed succesfully to predict some aspects of RA. In the day-to-day care of patients with this disease, the most important prediction may be whether the effective drug can be tapered or not. Current evidence indicates that biomarkers may be invaluable at helping clinicians and their patients make this important decision. <h3>Disclosure of Interest</h3> None declared
ROC-king onwards: intraepithelial lymphocyte counts, distribution &amp; role in coeliac disease mucosal interpretation
Authors: Kamran Rostami, Michael N Marsh, Matt W Johnson, Hamid Mohaghegh, Calvin Heal, Geoffrey Holmes, Arzu Ensari, David Aldulaimi, Brigitte Bancel, Gabrio Bassotti, Adrian Bateman, Gabriel Becheanu, Anna Bozzola, Antonio Carroccio, Carlo Catassi, Carolina Ciacci, Alexandra Ciobanu, Mihai Danciu, Mohammad H Derakhshan, Luca Elli, Stefano Ferrero, Michelangelo Fiorentino, Marilena Fiorino, Azita Ganji, Kamran Ghaffarzadehgan, James J Going, Sauid Ishaq, Alessandra Mandolesi, Sherly Mathews, Roxana Maxim, Chris J Mulder, Andra Neefjes-Borst, Marie Robert, Ilaria Russo, Mohammad Rostami-Nejad, Angelo Sidoni, Masoud Sotoudeh, Vincenzo Villanacci, Umberto Volta, Mohammad R Zali, Amitabh Srivastava
Journal: Gut (2017)

Objectives Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive ‘normal’ IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on &gt;400 mucosal biopsy specimens. Design The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected. Results The mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2–88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion. Conclusion Our ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose–response by IEL to environmental (gluten) antigenic influence.
AB0799 Decreased ratio of TIMP1/MMP-9 is associated with higher pain sensitivity in a subset of osteoarthritic patients with low mechanistic target of rapamicin gene expression in the peripheral blood
Authors: EV Tchetina, GA Markova, EA Taskina, NG Kashevarova, EP Sharapova, LI Alekseeva
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Progression of osteoarthritis (OA) produces loss of articular cartilage that may culminate in pain, loss of joint function, and disability. Osteoarthritic changes in articular cartilage are associated with progressive proteolytic degradation of the extracellular matrix due to excessive expression of metalloproteinases (MMPs) over their tissue inhibitors (TIMPs). At the same time, decrease in TIMP concentration versus MMP has been previously associated with an increase in pain sensitivity. <h3>Objectives</h3> Here we hypothesized that imbalance in TIMP1 and MMP-9 gene and protein expressions in the peripheral blood might contribute to pain perception in OA patients. <h3>Methods</h3> We examined whole blood of 65 OA outpatients and 27 healthy subjects. Clinical testing comprised physical examination, radiographic and WOMAC scoring, and ultrasonography. Total RNA isolated from the whole blood was used for gene expression examination of mTOR, mechanistic target of rapamycin, a major regulator of cell growth and proliferation, metalloproteinase MMP-9, and tissue inhibitor of metalloproteinase, TIMP1 using quantitative Real-time RT-PCR. p70-S6K (mTOR read-out), MMP-9, and TIMP1 protein levels were quantified by ELISA. <h3>Results</h3> 23 OA outpatients exhibited significant downregulation of mTOR gene expression (subset "Low mTOR") while other 42 OA outpatients have demonstrated upregulation of mTOR gene expression (subset "High mTOR") in the peripheral blood compared to healthy controls. Although both OA outpatient subsets had comparable radiographic severity according to Kellgren-Lawrence grading, similar age, disease duration, and body mass index, "Low mTOR" patients experienced significantly higher pain at joint function versus "High mTOR" subset. This was associated with a significant upregulation of MMP-9 gene expression in "Low mTOR" patients versus healthy subjects while TIMP1 expression remained equal to controls. In a "High mTOR" subset, both gene expressions were significantly upregulated. p70-S6K and TIMP1 protein concentrations measured in the peripheral blood mononuclear cells were significantly lower in "Low mTOR" patients versus that in "High mTOR" while MMP-9 protein expression was significantly higher compared to healthy subjects in both examined OA subsets. <h3>Conclusions</h3> Our results show that TIMP1 and MMP-9 gene expressions measured in the peripheral blood might be associated with pain sensitivity in OA outpatients while low level of TIMP1/MMP-9 ratio indicates increased pain perception. <h3>Disclosure of Interest</h3> None declared
Abstract 007: Platelet Derived Growth Factor-AA Promotes Migration of Resident Cardiac Stem Cells
Authors: Severina Windmolders, Astrid De Boeck, Remco Koninckx, Annick Daniëls, Karen Hensen, Olivier De Wever, Marc Bracke, Marc Hendrikx, Jean-Luc Rummens
Journal: Circulation Research (2013)

Bone marrow mesenchymal stem cells modulate cardiac healing via the release of paracrine factors. Although the exact mechanisms are not yet understood, one promising approach is through the mobilization of endogenous cardiac stem cells. Recently, we reported the existence of a new type of cardiac stem cell, named Cardiac Atrial appendage Stem Cells (CASCs), that is characterized by a high aldehyde dehydrogenase expression. In this study, we hypothesized that conditioned medium from mesenchymal stem cells (MSC-CM) is able to promote migration of resident cardiac stem cells. Therefore, human cardiac fragments were cultured inside a collagen type I matrix and subjected to serum-free DMEM (control) or MSC-CM. By analysis of cell counts, perimeter and area measurements, we found that MSC-CM promoted migration of cells from cardiac fragments throughout the matrix. These migrating cells possessed stem cell properties, as shown by a clonogenicity of 21.6±4.3% (n=3) and pluripotency associated genes like Oct-4, Nanog, Dppa-3, Tbx-3, c-Myc and Klf-4. Flow cytometrical analysis showed that these cells expressed a CSC-phenotype. Further investigation demonstrated that, comparable to CASCs, migrating cells had a high aldehyde dehydrogenase activity and were able to differentiate towards cardiomyocytes. In addition, we demonstrated an extensive activation of the platelet derived growth factor receptor-α (PDGFRα) in migrating cells subjected to MSC-CM. Subsequent collagen assays indicated that pure PDGF-AA was sufficient to produce migration effects similar to MSC-CM, albeit higher PDGF-AA concentrations than measured in MSC-CM were necessary. Imatinib mesylate, a PDGFR inhibitor, was partially able to attenuate MSC-CM induced migration, pointing out that PDGF-AA might work synergistically with other factors to promote migration. In conclusion, these data demonstrate that MSC-CM stimulates migration of resident CASCs. PDGF-AA is an important paracrine factor in this process, although the synergic role of other growth factors has to be further investigated. These findings contribute to the development of future therapies in which paracrine agents can be utilized to activate the endogenous repair system of the heart.
THU0767-HPR Advanced practice musculoskeletal physiotherapy services: a national evaluation
Authors: O Fennelly, C Blake, O Fitzgerald, R Breen, A Brennan, J Ashton, C Cunningham
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patients with musculoskeletal (MSK) disorders may remain on lengthy hospital outpatient waiting lists to be reviewed by a consultant doctor, although medical or surgical intervention may not be required (1,2). In 2012, a waiting list initiative saw the introduction of Advanced Practice Physiotherapists (APPs) across 16 hospitals in Ireland. APPs triage and manage patients awaiting a consultant doctor appointment, who are deemed non-urgent or unlikely to require surgery on screening of referral letters. APP scope of practice generally involves some traditionally medical-controlled acts such as: administering injections, ordering investigations/imaging, surgical listing and onward referral to hospital specialities; and depending on consultant doctor availability, their input may be sought on clinical decisions if required. <h3>Objectives</h3> Profile the national APP patient caseload Establish the clinical outcomes of APP consultations <h3>Methods</h3> A national database was established with all APPs (n=22) submitting patient data for 2014. These data were analysed using descriptive statistics. <h3>Results</h3> Data showed that APPs assessed 13,981 new patients, who presented most commonly with MSK disorders of the knee (n=3,096), lumbar spine (n=2,926) and shoulder (n=1,945) (Fig. 1) and the median wait time was 167 days (IQR 91–316). Including an additional 2,596 return appointments, the most common clinical outcomes were physiotherapy and/or clinical investigations (Table 1), and clinical decisions were made independently by the APP in 77% (n=11,728) of recorded cases (n=15,189). <h3>Conclusions</h3> APP services provide a more efficient MSK clinical pathway and reduce demands on the Consultant Doctor services. Collection of National Data enables ongoing service evaluation and monitoring of key performance indicators. <h3>References</h3> Wood, L., Hendrick, P., Boszczyk, B. &amp; Dunstan, E. 2016. A review of the surgical conversion rate and independent management of spinal extended scope practitioners in a secondary care setting. Ann R Coll Surg Engl, 1–5. Desmeules, F., Toliopoulos, P., Roy, J. S., Woodhouse, L.J., Lacelle, M., Leroux, M., Girard, S., Feldman, D.E. &amp; Fernandes, J. C. 2013. Validation of an advanced practice physiotherapy model of care in an orthopaedic outpatient clinic. BMC Musculoskelet Disorders, 14, 162. <h3>Acknowledgements</h3> I would like to thank the National Clinical Programmes and Health Service Executive for their funding and support of this project. <h3>Disclosure of Interest</h3> None declared