tbuckley/cabot-search huggingface dataset:
AB1208-HPR Psoriasis induced by tnf antagonist therapy. analysis of 13 cases
Authors: À Martinez-Ferrer, A Mateu Puchades, C Vergara Dangond, M Aguliar Zamora, L Montolio, S Santos, È Valls Pascual, D García Ybáñez, JJ Alegre Sancho
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Tumor necrosis factor (TNF) antagonist drugs have been shown to be effective in different inflammatory arthropathies and autoimmune pathologies, including psoriasis. However, an unexpected side effect has been observed: the new occurrence or worsening of psoriatic lesions. <h3>Objectives</h3> The aim of this study is to describe the cases of induction or worsening of psoriasis in patients treated with TNF antagonist therapy in our center. <h3>Methods</h3> Retrospective observational study, review of cases of new or worsening psoriasis in patients with TNF antagonist at the University Hospital Dr. Peset from October 2008 to November 2016. A total of 13 cases were obtained. <h3>Results</h3> Thirteen patients, 8 females and 5 males with mean age 46 years (± 16). 38% of patients received treatment for Crohn9s disease, 31% for rheumatoid arthritis (RA), 31% for psoriatic arthropathy (APs), 8% for ankylosing spondylitis (AE) and another 8% for psoriasis. Two patients were diagnosed of more than one pathology: Crohn9s disease associated with APs and Crohn9s disease associated with RA. Sixty one percent had no known personal history of psoriasis, in one of them the family history of psoriasis was recorded. Infliximab was used in 38.5% of cases, followed by adalimumab and golimumab in 23% each and etanercept in 15.4%. The mean latency time since drug introduction was 9.3 months (2–26). There were 12 cases of psoriasis and 1 case of pityriasis lichenoides (histologically confirmed). Lesion morphology included pustular psoriasis in 91%, scalp psoriasis in 25%, guttate lesions in 25%, plaque psoriasis in 8%, and inverse psoriasis in 8%; 58% experienced lesions of more than one type. There were no cases of nail, mucosal or erythrodermic psoriasis. The psoriasiform lesions resolved without interruption of TNF antagonist therapy in 53.85%. Of the 6 patients who required discontinuation, 3 patients were switched to another anti-TNF drug (adalimumab, golimumab and certolizumab) and all 3 had recurrence of the lesions, in 2 patients the anti-TNF was replaced by a non-anti-TNF biological. Topical treatment was used in all cases, one patient also required systemic treatment with methotrexate. <h3>Conclusions</h3> TNF antagonist induced psoriasis is a well-described adverse event. Pustular psoriasis is the most frequent presentation. In most cases there is no personal or family history of psoriasis. Topical therapy may be effective but some patients require discontinuation of the drug. Skin lesions can reappear when switching to another anti-TNF drug. <h3>Disclosure of Interest</h3> None declared
FRI0615 Sarcoidosis and cancer: different patterns of association in a multicenter cohort from southern europe
Authors: R Pérez-Alvarez, B Kostov, A García González, R Gόmez De La Torre, M Lopez Dupla, B De Escalante, A Alguacil, J Chara, J Velilla, J Rascόn, JS Garcia Morillo, C Tolosa, E Fonseca, M Bonet, JL Callejas, G de la Red, E Calvo, A Gόmez Lozano, E Peral, JF Gόmez Cerezo, G Cruz, P Perez, S Fernández Rodríguez, B Pinilla, A Gato, M Akasbi, A Robles, I Ojeda, MJ Vives, C Morcillo, M Penadés, M De Vicente, M Ramos-Casals, L Pallarés, P Brito-Zerόn
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To evaluate the temporal association between the diagnosis of neoplasia and sarcoidosis in a large cohort of Spanish patients with sarcoidosis. <h3>Methods</h3> In January 2016, the Autoimmune Diseases Study Group (GEAS-SEMI) created a national registry (SARCOGEAS) of patients with sarcoidosis. Sarcoidosis was diagnosed with the criteria proposed by the ATS/ERS/WASOG 1999 statement, and extrathoracic disease by the 2014 WASOG instrument. Diagnosis of neoplasia was recorded before and after the diagnosis of sarcoidosis. <h3>Results</h3> The cohort included 1082 patients (82% biopsy-proven, 618 women, mean age 47yrs). Association with neoplasia was detected in 135 (13%) patients who developed 140 neoplasms (110 solid and 30 hematological neoplasia). The neoplasia more frequently reported were breast (n=18), lymphoma (n=16), non-melanoma skin (n=15) and colon (n=15). Association with neoplasia was more frequent in patients born in Spain (97% vs 86%, p&lt;0.001, OR 4.06), older patients (55 vs 46yrs, p&lt;0.001, OR 1.03) and those with bone marrow involvement (14% vs 4%, p&lt;0.001, OR 3.64). Patients in whom cancer preceded the diagnosis of sarcoidosis had a higher frequency of sarcoidosis diagnosed incidentally (20% vs 4%, p=0.011) and a lower frequency of ocular sarcoidosis (3% vs 16%, p=0.016). Patients with associated hematological neoplasia had a higher frequency of ENT (13% vs 1%, p=0.009) and bone marrow (33% vs 9%, p=0.002) involvements in comparison with patients with associated solid neoplasia. <h3>Conclusions</h3> Association between sarcoidosis and cancer was found in 13% of patients (80% solid and 20% hematologic malignancies). Elderly patients and those born in Spain were at high risk of having associated cancer. Asymptomatic sarcoidosis was more frequently observed in those patients with a previous history of neoplasia, while the association with hematological neoplasms was linked to a higher frequency of sarcoidosis involving ENT and bone marrow. <h3>Disclosure of Interest</h3> None declared
AB0809 Fall risk and related factors in knee osteoarthritis
Authors: M Alkan Melikoglu, A Kul
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Balance, as a complex task, may be affected in knee osteoarthritis (KOA) and this may cause postural instability and fall risk. <h3>Objectives</h3> The aim of this study was to determine the fall risk in patients with KOA with an objective computerized technique and to evaluate the potential risk factors for falls in these patients. <h3>Methods</h3> Patients with KOA and controls were included in this cross-sectional study. Gender, age, and body mass index (BMI) were recorded. Pain was evaluated with a visual analog scale (VAS). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess the patients and the Falls Efficacy Scale International (FES-I) was used for the evaluation of fall efficacy. Knee radiographs were recorded with the Kellgren–Lawrence grading scale. Fall risk analysis was performed by using the Tetrax Interactive Balance System, which is a computerized posturography device. <h3>Results</h3> One hundred patients with KOA and 30 controls were included. The age, gender, and BMI scores were similar between the groups. FES-I scores were significantly higher in the cases than in the controls (p&lt;0.000). Using a computerized system, significantly higher fall risk results (p&lt;0.000) and significantly low, moderate, and high fall risk distribution were recorded in the cases than in the controls (p&lt;0.000). Fall risk was significantly related to age, pain, and the WOMAC scores of the patients. <h3>Conclusions</h3> Using an objective computerized technique, our study demonstrated a higher fall risk in patients with KOA than in healthy individuals. This higher risk was shown even in the early radiographic phases of the disease related to age, pain, and dysfunction. An understanding of factors on postural control seems to be critical in successful fall prevention in these patients. <h3>Disclosure of Interest</h3> None declared
AB0585 Vasculitis damage index in limited and systemic granulomatosis with poliangiitis in mexican patients
Authors: O Vera-Lastra, AG Angulo-Gonzalez, J Sepulveda-Delgado
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Granulomatosis with polyangiitis (GPA) has been transformed from life-threatening conditions to chronic relapsing long-term diseases as a result of significant advances in immunosuppressive therapy. Structured clinical assessment using Vasculitis Damage Index (DVI) should form the basis of a treatment plan and be used to document progress. <h3>Objectives</h3> To investigate the Vasculitis Damage Index and clinical manifestations in localized and systemic granulomatosis with poliangiitis in Mexican patients <h3>Methods</h3> We enrolled 61 patients with GPA according to The American College of Rheumatology (ACR) criteria at a referral hospital during the period from 2005 to 2015. Clinical and laboratory data, organ involvement and the Vasculitis Damage Index (VDI) were recorded at baseline. Patients were divide into systemic and localized form for their analysis. <h3>Results</h3> They were 61 GPA (34 men and 27 women) mean age 42 years old at diagnosis. Systemic form was observed in 53% and localized form 47%. Chronic sinusitis was the most frequent manifestation in 33% followed by otologic in 26%. Subglottic stenosis 4 patients, alveolar hemorrhage 1%. Of the patients with the systemic form 22 presented focal and segmental glomerulonephritis and 10 patients (32%) rapidly progressive glomerulonephritis. Distal-symmetric polyneuropathy and cranial neuropathy were present in 24%; scleritis 24.5% and proptosis in 18%, palpable purpura 26.2% and ulcers in 9 patients (14.8%). The VDI score in the systemic form was 3.8 and in the localized 2.6, p= NS. The disease related damage was pronounced in kidneys and upper airways. The majority of patients in the induction to remission phase received steroids plus cyclophosphamide, 7 patients also received plasmapheresis and in maintenance phase they were treated with methotrexate or azathioprine. <h3>Conclusions</h3> In this cohort of patients with GPA, a high chronic damage was found which was similar in both systemic and localized forms of this vasculitis. The VDI was more prominent in kidneys and upper airways in GPA patients <h3>References</h3> Bhamra K, et al. Damage assessment in ANCA-associated vasculitis. Curr Rheumatol Rep. 2012; 14:494–50. Kamali S, et al. Predictors of damage and survival in patients with Wegener9s granulomatosis: analysis of 50 patients, J Rheumatol 2010;37:374–78. Luqmani R, et al. State of the art in the treatment of systemic vasculitides. Front Immunol 2014;5:471. <h3>Disclosure of Interest</h3> None declared
Mass spectrometry-assisted gel-based proteomics in cancer biomarker discovery: approaches and application
Authors: Rongrong Huang, Zhongsi Chen, Lei He, Nongyue He, Zhijiang Xi, Zhiyang Li, Yan Deng, Xin Zeng
Journal: Theranostics (2017)

There is a critical need for the discovery of novel biomarkers for early detection and targeted therapy of cancer, a major cause of deaths worldwide.In this respect, proteomic technologies, such as mass spectrometry (MS), enable the identification of pathologically significant proteins in various types of samples.MS is capable of high-throughput profiling of complex biological samples including blood, tissues, urine, milk, and cells.MS-assisted proteomics has contributed to the development of cancer biomarkers that may form the foundation for new clinical tests.It can also aid in elucidating the molecular mechanisms underlying cancer.In this review, we discuss MS principles and instrumentation as well as approaches in MS-based proteomics, which have been employed in the development of potential biomarkers.Furthermore, the challenges in validation of MS biomarkers for their use in clinical practice are also reviewed.
WP1066, a potent inhibitor of Jak2/STAT3 pathway inhibits pancreatic tumor growth both in vitro and in vivo
Authors: Sushovan Guha, Arup Chakraborty, Slawomir Szymanski, Izabela Fokt, James Abbruzzese, Reza Kazerooni, Timothy Madden, Waldemar Priebe
Journal: Cancer Research (2007)

2393  Background: Pancreatic cancer is now the fourth leading cause of cancer-related mortality in United States. Its intransigence to current chemotherapy regimens stimulated our interest to explore novel targets for therapeutic development. Constitutive activation of Signal Transducer and Activator of Transcription-3 (STAT3) in pancreatic cancer cells is associated with VEGF expression, and when suppressed, leads to inhibition of VEGF expression, angiogenesis, tumor growth, and subsequent metastasis in vivo. In addition to VEGF expression, STAT3 activation also promotes tumor cell proliferation and survival pathways in vivo. EGF and IL-6 mediated mitogenic signaling pathways can also induce Jak2/STAT3 phosphorylation in pancreatic cancer. Thus, JAK2/STAT3 proteins are potential novel therapeutic targets in pancreatic cancer.  Currently available Jak2/STAT3 pathway inhibitors including AG490 can block STAT3 phosphorylation at concentrations of 50-100 µM but are not active in vivo. The striking similarity of AG490 to the natural products of the caffeic acid family, and our comparison of caffeic acid benzyl ester to AG490, showing no additional benefit for AG490 in vitro led us to the design of novel potent inhibitors. We have discovered a new class of compounds that inhibits IL-6 induced Jak2 and STAT3 phosphorylation and suppression of related downstream signaling pathways. Next, we selected compound WP1066 for more detailed evaluation in pancreatic cancer.  Aim: Determine the effects of novel Jak2/STAT3 inhibitor WP1066 on pancreatic cancer cells both in vitro and in vivo.  Methods and Results: WP1066 significantly inhibited proliferation and induced apoptosis of pancreatic cancer cells including Colo357FG and MIA PaCa-2 with IC50 of 2.5 μM. WP1066 potently blocked constitutive and IL-6 induced STAT3 phosphorylation in Colo357FG cells in a dose-dependent manner with maximal effects noted at 5 μM. WP1066 (5 μM) also suppressed expression of STAT3 dependent antiapoptotic proteins including Bcl-xL and survivin. Next, we evaluated in vivo effects of WP1066 in athymic nu/nu murine subcutaneous xenograft model for pancreatic cancer. WP1066 was injected intraperitoneally thrice weekly for 4 weeks at 40 mg/kg per mouse. WP1066 was well tolerated and no adverse events were noted. WP1066 significantly inhibited Colo357FG tumor growth by 4 fold after 4 weeks of treatment (p  Conclusion: Our studies show that targeting Jak2/STAT3 pathway with novel drugs including WP1066 significantly blocked pancreatic cancer cell proliferation in vitro and tumor growth in vivo. Thus drugs including WP1066 should be potentially considered as one of the future strategies for treatment of pancreatic cancer.
Novel insights into the clinical phenotype and pathophysiology underlying low VWF levels
Authors: Michelle Lavin, Sonia Aguila, Sonja Schneppenheim, Niall Dalton, Kenneth L. Jones, Jamie M. O’Sullivan, Niamh M. O’Connell, Kevin Ryan, Barry White, Mary Byrne, Marie Rafferty, Mairead M. Doyle, Margaret Nolan, Roger J. S. Preston, Ulrich Budde, Paula James, Jorge Di Paola, James S. O’Donnell
Journal: Blood (2017)
Effect of counselling on health-care-seeking behaviours and rabies vaccination adherence after dog bites in Haiti, 2014–15: a retrospective follow-up survey
Authors: Melissa Dominique Etheart, Maxwell Kligerman, Pierre Dilius Augustin, Jesse D Blanton, Benjamin Monroe, Ludder Fleurinord, Max Millien, Kelly Crowdis, Natael Fenelon, Ryan MacLaren Wallace
Journal: The Lancet Global Health (2017)

Haiti has an integrated bite case management (IBCM) programme to counsel animal-bite victims on the risk of rabies and appropriate treatment, as well as the Haiti Animal Rabies Surveillance Program (HARSP) to examine the animals. We assessed the usefulness of the IBCM programme to promote best practices for rabies prophylaxis after exposure in a low-income rabies-endemic setting.We did a retrospective follow-up survey of randomly selected bite victims who were counselled by Haiti's IBCM programme between May 15, 2014, and Sept 15, 2015. We classified participants by HARSP decisions of confirmed, probable, suspected, or non-rabies exposures. We compared health-care outcomes in people who sought medical care before IBCM counselling with those in people who sought care after counselling. We used decision trees to estimate the probability of actions taken in the health-care system, and thereby human deaths.During the study period, 1478 dog bites were reported to HARSP for assessment. 37 (3%) were confirmed exposures, 76 (5%) probable exposures, 189 (13%) suspected exposures, and 1176 (80%) non-rabies exposures. 115 of these cases were followed up in the survey. IBCM counselling was associated with a 1·2 times increase in frequency of bite victims seeking medical care and of 2·4 times increase in vaccination uptake. We estimated that there would be four human rabies deaths among the 1478 people assessed by IBCM during the survey period, and 11 in the absence of this programme, which would equate to a 65% decrease in rabies deaths. Among three people dead at the time of the follow-up survey, one was deemed to be due to rabies after a probable rabies exposure.Adherence to medical providers' recommendations might be improved through counselling provided by IBCM programmes.None.
AB1027 The utility of lip biopsy in patients diagnosed of IPAF (interstitial pneumonia with autoimmune features)
Authors: HS Park, P Millan, D Castillo, M Millan, P Moya, B Magallares, A Laiz, C Diaz, JM De Llobet, I Castellvi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The European Respiratory Society/American Thoracic Society Task Force has defined a classification criteria for interstitial pneumonia with features of autoimmunity that does not accord to a specific systemic disease. This criteria combines clinical, serological and radiological domains. The clinical criteria does not include dry syndrome eventhough the serological criteria does include antiRo and antiLa antibodies. It is known that some patients with dry syndrome with antibodies negativity undertake lip biopsy to confirm Sjögren Syndrome (SS). Therefore lip biopsy could be useful to IPAF if SS is suspected. <h3>Objectives</h3> Determine the utility of lip biopsy in patients with interstitial pneumonia that present symptoms suggestive of an autoimmune disease. <h3>Methods</h3> Retrospective study of patients attended between june of 2010 and june of 2016 in a tertiary referral hospital was done. We included 23 Pneumology patients diagnosed of IPAF that were referred to Rheumatology clinic to rule out underlying connective disease. All patients had a complete immunologic study, two pulmonary function test including diffusion capacity of CO and a lip biopsy to confirm SS. The results of the lip biopsy was analysed with different variables. Epidemiologic data, blood test, pulmonary function test and pattern of ILD by high definition CT or lung biopsy were analysed. Changes in therapeutic decisions and pulmonary function test a year after the lip biopsy were also registered. To compare qualitative variables we used Chi Square test or Fisher exact test when necessary. The statistical significance was set up to p-value inferior to 0.05. <h3>Results</h3> 16 of 23 patients with ILD met classification criteria of IPAF (69.6%). 12 were women (52.2%) with a median age of 77 (from 54 to 87 years). The findings of our group is summarised in table 1. 9 lip biopsies confirmed SS (39.1%) and 7 changed treatment according to result (30.4%). No variables such as sex, smoking, previous lung disease, dry syndrome or Schirmer test showed relation with lip biopsy result. Previous treatment with corticosteroids did not seem to influence the results of lip biopsy eventhough it was not statistically significant (p-value 0.059). No relation with antinuclear antibody or acute phase reactants was observed either. Lip biopsy was most useful to diagnose SS for those with Usual Interstitial Pattern (p&lt;0.02) among other patterns of ILD. <h3>Conclusions</h3> Lip biopsy is a complementary examination to consider for IPAF. In our group the results were significant for UIP. Corticosteroid therapy did not seem influential to the results of lip biopsy eventhough it was not statistically significant. In 39.1% SS was diagnosed and in 30.4% treatment was changed according to results. <h3>Disclosure of Interest</h3> None declared
AB0858 Association of bone mineral density with development of heart failure in diabetic patients
Authors: V Vasilkova, T Mokhort, E Naumenko, M Zmailik
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Diabetes mellitus has shown to be a significant risk factor for the development and prognosis of heart failure (HF) and associated with an increased risk of fractures [1]. Osteoporosis and heart failure are generally considered two distinct diseases, but recent evidence suggests a link between both diseases. <h3>Objectives</h3> The aim of the study was to investigate the association of bone mineral density with the risk of developing heart failure in diabetic patients. <h3>Methods</h3> 85 patients both sexes with type 2 diabetes aged 58.69±9.07 years were studied. Besides standard laboratory parameters, the echocardiographic and BMD measurements were performed. Estimated glomerular filtration rate was measured. <h3>Results</h3> Among diabetic subjects, 8 patients (9.4%) had osteoporosis, 21 (24.8%) had osteopenia and 56 (65.8%) had a normal BMD. Increased serum NT-proBNP (p&lt;0.001) and decreased left ventricular ejection fraction (EF) (p=0.03) were significantly correlated with low T-score L1-L4 cutoff points between groups (normal, osteopenia, and osteoporosis). Multivariate stepwise linear regression analysis of the significant variables revealed that NT-proBNP, EF were independent predictors of lumbar BMD among female patients with diabetes mellitus. After adjusting for age, gender, and related comorbidities, the osteoporosis group was associated with a significantly higher risk of coronary artery disease in women with diabetes. However, no association between BMD and HF was found in men. <h3>Conclusions</h3> Osteoporosis may be an independent factor for HF in women with diabetes mellitus. Our data suggested that early detection of abnormal BMD should warrant for early search of undetected HF in diabetic women. A further study is needed to elucidate the effects of BMD on cardiac function in diabetic patients. <h3>References</h3> Heart failure is a risk factor for orthopedic fracture: a population-based analysis of 16,294 patients. van Diepen S, Majumdar SR, Bakal JA, McAlister FA, Ezekowitz JA Circulation. 2008 Nov 4; 118(19):1946–52. <h3>Acknowledgements</h3> We acknowledged the help from the Republican Research Center for Radiation Medicine and Human Ecology for the technical assistance. <h3>Disclosure of Interest</h3> None declared
Validation of a 52-gene risk profile for outcome prediction in patients with idiopathic pulmonary fibrosis: an international, multicentre, cohort study
Authors: Jose D Herazo-Maya, Jiehuan Sun, Philip L Molyneaux, Qin Li, Julian A Villalba, Argyrios Tzouvelekis, Heather Lynn, Brenda M Juan-Guardela, Cristobal Risquez, Juan C Osorio, Xiting Yan, George Michel, Nachelle Aurelien, Kathleen O Lindell, Melinda J Klesen, Miriam F Moffatt, William O Cookson, Yingze Zhang, Joe G N Garcia, Imre Noth, Antje Prasse, Ziv Bar-Joseph, Kevin F Gibson, Hongyu Zhao, Erica L Herzog, Ivan O Rosas, Toby M Maher, Naftali Kaminski
Journal: The Lancet Respiratory Medicine (2017)