tbuckley/cabot-search huggingface dataset:
FRI0616 Eye manifestations of patients with muckle-wells syndrome
Authors: S Cekic, O Yalcinbayir, SS Kilic
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> CAPS is a rare autoinflammatory disease associated with mutations in the <i>CIAS1</i> gene, encoding for NLRP3 that result in overactivation of the inflammasome and systemic inflammation. Muckle-Wells syndrome (MWS) is a rare autosomal dominant disease which causes episodic fever attacks, sensorineural deafness, recurrent hives, arthritis and eye involvement. <h3>Objectives</h3> Here we present the findings of eye involvement in a family whose 11 members have MWS. <h3>Methods</h3> Clinical data was collected during the course of ongoing patient care. <h3>Results</h3> We evaluated the clinical features of 11 patients who were referred to a tertiary care center. The median age of the patients was 25 years (range: 9–65). The ratio of females /males was 1.2 (6/5). All patients had arthritis with exacerbation on exposure to cold and recurrent episodes of pink eye. The median age of onset of ocular involvement was 8 years (2–45). We observed severe eye involvement in 36% of our cases, including band keratopathy, severe damage of corneal stroma and neovascularization. Corneal involvement and clouding was detected in four patient. Two of those had the diagnosis of keratoconus as well. Patients with keratoconus had corneal scarring due to corneal hydrops verified with corneal topography. The other two patients with corneal clouding had bant keratopathy. One of those patient was a 17 year old girl who had recurrent uveitis with hypopyon which necessiated the use of intravitreal dexamethasone implant. She also had posterior synechia of the iris to the lens. The other eye of that patient had signs of phthisis bulbi. The other patient with bant keraopathy was 46 years old male who had optic atrophy and tractional fibrovascular membranes at the posterior pole of the eye. Anakinra was used for treatment of 5 cases, and canakinumab of 3 cases. It was observed that the frequency of conjunctivitis decreased after anti IL-1 therapy. There was no mutation detected in the study of MEFV (all exons), TNFRSF1A (exons 2 to 7), MVK (all exons), NLRP3 (all exons), NOD2 (exons 4, 8 and 9) and PSTPIP1 (exons 10 and 11) genes. <h3>Conclusions</h3> In this study, it has been shown that eye findings related to MWS can vary from conjunctivitis to severe uveitis. We want to emphasize that ocular involvement in MWS should be carefully assessed, since it can lead to visual impairment. <h3>Disclosure of Interest</h3> None declared
Phase II study of cabozantinib in recurrent/metastatic endometrial cancer (EC): A study of the Princess Margaret, Chicago and California Phase II Consortia.
Authors: Neesha C. Dhani, Hal W. Hirte, Marcus O. Butler, Stephanie Lheureux, Julie Burnier, Michelle K. Wilson, Angela Jain, Mihaela C. Cristea, Stephen Welch, Waldo Jimenez, Daniela Matei, Katia Sonia Tonkin, Erica Stringer, Carolyn Johnston, Judy Quintos, Christine Tran, Katherine Karakasis, Lisa Wang, John Joseph Wright, Amit M. Oza
Journal: Journal of Clinical Oncology (2016)

5586 Background: Cabozantinib is a multi-targeted kinase inhibitor against MET, VEGFR, TIE2, RET, AXL and KIT, influencing mitogenic/angiogenic epithelial-stromal cross-talk. It is a rational strategy in endometrial cancer (EC) where the transient benefit of VEGF-targeting is related to signaling through MET/HGF, TIE2 & AXL. The correlation of MET/HGF with EC pathogenesis also supports evaluating cabozantinib in recurrent/metastatic EC, a poor prognosis disease with no standard 2nd line therapy. Methods: PHL86/NCI#9322/NCT01935934 is a multi-centre, phase II trial of cabozantinib (60mg oral daily on a 28-day cycle) in patients (pts) with EC recurring within a year of adjuvant chemotherapy, or with progression after 1 line of chemotherapy for metastatic disease. Enrollment to experimental (E) cohort is stratified by histology (serous (SER) vs endometroid (END)) in a Simon two-stage design for a co-primary endpoint of response rate ( > 30%) or 12- week progression-free-survival (PFS) ( > 55%). Observation of > 8 partial responses (PRs) or > 16 instances of 12 wk-PFS (in 36 pts) would be considered a signal of activity. Pts are also enrolled to an exploratory (ex) cohort of rare histology EC. Results: From May 2013 to Dec 2015, 79 pts (E: 61 (25 SER, 36 END); ex: 18) have been treated; toxicity/outcome data on 71 pts is reported. Prior treatment included chemotherapy (52pts: 1 line; 18 pts: 2 lines) & radiation (28 pts). Most common Grade 3 (G3) toxicity was hypertension (16/71 pts), other relevant G3 events were bowel perforation/fistula (2 pts), GI bleed (1 pt). Common toxicities also included GI disturbance, biochemical abnormalities, cytopenias and palmer-plantar erythrodysesthesia. In endometroid histology pts (n = 36), 4 PRs and 17 instances of > 12-wk PFS have been observed. Mutational profiling (miSeq) demonstrated more mutations (PTEN, CTNNB1) in END vs SER histology EC, with more p53 mutations in SER EC. Conclusions: Cabozantinib is well-tolerated and met its predefined activity endpoint in previously treated END-EC. Correlations between mutational status and response are being investigated. The current data justify further evaluation of this agent in EC. Clinical trial information: NCT01935934.
AB0278 Ultrasound examination in diagnosis of early rheumatoid arthritis
Authors: W Hamdi, S Miladi, K Matallah, M Bouaziz, D Kaffel, I Zouch, MM Kchir
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Fortunately, management of RA at the early stage has become possible thanks to both the emergence of new biotherapies and the strategy treat to target. Musculoskeletal ultrasound (US) is a potent tool for the detection of synovitis, effusion and bone erosion in RA. <h3>Objectives</h3> The aim of this study was to assess the contribution of US in diagnosing RA at the early stage of the disease. <h3>Methods</h3> A cross-sectional study was performed during 2 years. Patients with a history of inflammatory joint pain for ≥6 weeks and ≤2 years with synovitis of at least one joint were enrolled in this study. All patients underwent clinical assessement, laboratory tests and plain radiography of hands and feet.US was assessed within one week of clinical examination. Synovitis and erosion were defined according to the OMERACT. <h3>Results</h3> One hundred patients were included in this study with an average age of 51,8±14,6 years-old. Female outnumbered male with a sex ratio of 3,8. The mean duration of the disease was 10,9±7,4 months. When admitted to our department and after clinical examination it was found that 31% of patients presented polyarthritis, 4% had oligoarthritis and 7% suffered from monoarthritis. <i>US findings:</i> US was found to be more sensitive than clinical examination to detect synovitis. Among the 2200 joints assessed by US, a synovitis was detected in 81% patients, an intra-articular effusion in 36% patients and PD signals in 51% patients. Also, flexor tenosynovitis were present in 55% patients and extensor tenosynovitis in 59% patients. Erosions were more detected in plain radiography (70%) than in US (41%). Clinical parameters (VAS, duration of morning stiffness, number of night awakens, TJC) were not correlated with most US findings. Nevertheless, correlation was detected for US effusion (r=0,250, p=0,028) and for US Doppler (r=0,289, p=0,011) with SJC. PDUS examination correlated with CRP results (r=0,302, p=0,023) but not with ESR results. A significant, positive correlation was observed between erosions in X-rays or US assessment (r=0,342, p=0,002). The US detected synovitis in 25% of patients who had no swollen joint at the clinical examination when admitted to our department and had detected erosions in 9% of patients having negative plain X rays. <h3>Conclusions</h3> Ultrasound appears as a sensitive tool to detect subclinical synovitis (25%) and infra- radiological erosions (9%). It helps us to make an early diagnosis and start appropriate treatment before the onset of irreversible joint destruction. <h3>Disclosure of Interest</h3> None declared
Safety and Long-Term Efficacy of AAV4 Gene Therapy in Patients with RPE65 Leber Congenital Amaurosis
Authors: Guylène Le Meur, Pierre Lebranchu, Fanny Billaud, Oumeya Adjali, Sébastien Schmitt, Stéphane Bézieau, Yann Péréon, Romain Valabregue, Catherine Ivan, Christophe Darmon, Philippe Moullier, Fabienne Rolling, Michel Weber
Journal: Molecular Therapy (2017)

The aim of this study was the evaluation of the safety and efficacy of unilateral subretinal injection of the adeno-associated vector (AAV) serotypes 2 and 4 (AAV2/4) RPE65-RPE65 vector in patients with Leber congenital amaurosis (LCA) associated with RPE65 gene deficiency. We evaluated ocular and general tolerance and visual function up to 1 year after vector administration in the most severely affected eye in nine patients with retinal degeneration associated with mutations in the RPE65 gene. Patients received either low (1.22 × 1010 to 2 × 1010 vector genomes [vg]) or high (between 3.27 × 1010 and 4.8 × 1010 vg) vector doses. An ancillary study, in which six of the original nine patients participated, extended the follow-up period to 2–3.5 years. All patients showed good ophthalmological and general tolerance to the rAAV2/4-RPE65-RPE65 vector. We observed a trend toward improved visual acuity in patients with nystagmus, stabilization and improvement of the visual field, and cortical activation along visual pathways during fMRI analysis. OCT analysis after vector administration revealed no retinal thinning, except in cases of macular detachment. Our findings show that the rAAV2/4.RPE65.RPE65 vector was well tolerated in nine patients with RPE65-associated LCA. Efficacy parameters varied between patients during follow-up. The aim of this study was the evaluation of the safety and efficacy of unilateral subretinal injection of the adeno-associated vector (AAV) serotypes 2 and 4 (AAV2/4) RPE65-RPE65 vector in patients with Leber congenital amaurosis (LCA) associated with RPE65 gene deficiency. We evaluated ocular and general tolerance and visual function up to 1 year after vector administration in the most severely affected eye in nine patients with retinal degeneration associated with mutations in the RPE65 gene. Patients received either low (1.22 × 1010 to 2 × 1010 vector genomes [vg]) or high (between 3.27 × 1010 and 4.8 × 1010 vg) vector doses. An ancillary study, in which six of the original nine patients participated, extended the follow-up period to 2–3.5 years. All patients showed good ophthalmological and general tolerance to the rAAV2/4-RPE65-RPE65 vector. We observed a trend toward improved visual acuity in patients with nystagmus, stabilization and improvement of the visual field, and cortical activation along visual pathways during fMRI analysis. OCT analysis after vector administration revealed no retinal thinning, except in cases of macular detachment. Our findings show that the rAAV2/4.RPE65.RPE65 vector was well tolerated in nine patients with RPE65-associated LCA. Efficacy parameters varied between patients during follow-up.
AB1012 Clinical utility of antihistone antibodies: a descriptive study
Authors: D Boveda-Ruiz, B Vilas-Pio, M Freire-Dapena, R Lorenzo-Castro, A Soto-Peleteiro, S Mirete-Bachiller, A Rivera-Gallego
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Antihistone antibodies (AHA) have been linked to Drug-Induced Lupus Erythematosus (DILE) for decades<sup>1</sup>. However, for some authors this relationship is not so clear and sugest that the presence of these autoantibodies is related to other autoimmune diseases more frequently<sup>2,3,4</sup>. <h3>Objectives</h3> The main objetive of this work was to study the association of AHA with different autoimmune entities (including DILE) and secondarily, look into which clinical manifestations and which autoantibodies are more frequently related to AHA. <h3>Methods</h3> We performed a descriptive study. A database was constituted using all patients with AHA+ in any blood analysis between years 2000 and 2016 in the University Hospital Complex of Vigo. The variables of the study were: presence of autoimmune disease, clinical manifestations and related autoantibodies. <h3>Results</h3> None of the 73 patients AHA+ developed DILE while almost the 50% of them suffer any other autoimmune disease. We found a high percentage of AHA+ patients with lupus erythematous complications such as arthritis and hematological abnormalities. AntiDNAds antibody was the more frequent coexpressed autoantibody. <h3>Conclusions</h3> AHA detection is not useful as DILE screening. AHA+ sugest the presence of other autoimmune disease rather than DILE. AHA+ may be related to lupus erythematous systemic complications. <h3>References</h3> Fritzler MJ, Tan EM. Antibodies to histone in drug-induced and idiopathic lupus erythematosus. J Clin Invest. 1978;62:560–567. Peng SL, Craft J. Antinuclear antibodies. In: Ruddy S, Harris ED, Sledge CB, eds. Kelley9s Textbook of Rheumatology. 6th ed. Philadelphia, Pa: WB Saunders; 2001:166. Kubo M, Ihn H, Yasawa N, et al. Prevalence and antigen specificity of antihistone antibodies in patients with polymyositis/dermatomyositis. J Invest Dermatol. 1999;112:711–715. Zirwas MJ, Kress DW, Deng JS. The Utility of Antihistone Antibody Screening in the Diagnosis of Drug-Induced Lupus Erythematosus. Arch Dermatol Apr 2004; VOL 140: 494–495. <h3>Disclosure of Interest</h3> None declared
Spinal Metastasis Characterized on FDG PET/CT in Head and Neck Squamous Cell Carcinoma
Authors: Shahroz Khan, Hannah Son
Journal: Clinical Nuclear Medicine (2017)

Spinal metastases are rare in head and neck cancer. We present a rare case of vocal cord squamous cell cancer that metastasized to the spinal cord and cauda equina. A 63-year-old man presented with acute back pain and bilateral leg weakness 5 months after having a surgical treatment for moderately differentiated vocal cord squamous cell cancer (T2 N0 M0). Restaging F-FDG PET examination demonstrated a soft tissue mass with intense hypermetabolism in the distal spinal cord and a hypermetabolic leptomeningeal metastatic deposit at the L3 level. The findings were confirmed on MRI prior to treatment.
AB0947 Characteristics of a transition clinic for young people with rheumatic diseases
Authors: B Serrano-Benavente, JC Lόpez-Robledillo, D Clemente, I Monteagudo, JC Nieto-González
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Paediatric rheumatologic diseases can still be active in the adulthood. Transitional care units are very important for the transition from paediatric to adult health care system. <h3>Objectives</h3> To describe the demographic characteristics, paediatric rheumatologic diseases distribution and active treatments in a Rheumatologic Transitional Care Unit (RTCU). <h3>Methods</h3> We included all new patients who attended the RTCU of a tertiary level hospital from 1st September 2015 until 31st December 2016. These patients were remitted from the paediatric rheumatology unit of two tertiary level hospitals. We retrospectively analyzed their demographic, laboratory and treatment characteristics. The connective tissue diseases (CTD) group included systemic lupus erythematosus, Behçet disease, dermatomyositis and scleroderma. Patients were considered active according to the physician opinion. <h3>Results</h3> We attended 81 new patients. 59 were female (72.8%) and the median age (range) was 19 years (18.1–20.7). 65.43% were diagnosed with Juvenile Idiopathic Arthritis (JIA) and 12.35% with CTD. Table 1 shows the main baseline characteristics of the patients. In the first visit at the unit, half of the patients did not have any systemic treatment (41 patients [50.62%]). From the remaining 40 patients with systemic treatment, 16 patients (40%) were under biologic treatment, mostly anti-TNFα. In any of the two first appointments, 20 patients (24.7%) were active, most of them from the JIA group. Seven (35%) of these patients increased or changed the treatment, 6 of them initiating a biologic treatment. <h3>Conclusions</h3> Our RTCU received mostly JIA patients. Median age at arriving was slightly higher than expected. A fourth of patients were active in the transition moment. All this data highlights the need of an strict control of these patients in the transitional period. <h3>References</h3> Foster HE. Ann Rheum Dis 2016;0:1–8. Calvo I. Rheumatol Int (2015) 35:1615–1624. <h3>Disclosure of Interest</h3> None declared
SAT0518 Association between grip strength and hand and knee radiographic osteoarthritis in older adults: data from the dong-gu study
Authors: J-E Kim, J-H Kang, K-E Lee, D-J Park, S-S Lee
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> Although some studies have shown a negative relationship between grip strength and hand osteoarthritis (OA), little is known about how grip strength is related to specific radiographic features of hand OA, such as osteophytes, joint space narrowing, and erosion. In addition, no reported study has examined whether grip strength, as a measure of muscle activity, is related to knee OA, which may also show a one-way effect of reduced muscle strength on OA. In this large, population-based cohort study, we took advantage of the availability of subjects without hand pain to evaluate the effect of grip strength on OA using a novel, semi-quantitative grading system. We also examined whether grip strength was related to detailed radiographic features of OA. <h3>Methods</h3> Data from 2,251 subjects enrolled in the Dong-gu study, who had no hand joint pain, were analyzed to investigate the relationship between grip strength and OA. Hand grip strength was measured using a hand-held dynamometer, and radiographs of the hand and knee were scored according to a semi-quantitative grading system. Multiple linear regressions were used to explore associations between grip strength and radiographic features of OA. <h3>Results</h3> Grip strength in men and women was negatively related to hand (both <i>p</i>&lt;0.001) and knee (men, <i>p</i>&lt;0.001; women, <i>p</i>=0.010) OA after adjusting for confounders. Hand (men, <i>p</i> &lt;0.001; women, <i>p</i>=0.001) and knee (both <i>p</i>&lt;0.001) joint space narrowing showed the strongest associations with low grip strength, regardless of sex. Moreover, the severity of hand osteophytes in women (<i>p</i>=0.001), knee osteophytes in men (<i>p</i>=0.006), hand malalignment (men, <i>p</i>=0.008; women, <i>p</i>=0.041), and subchondral cysts (men, <i>p</i>&lt;0.001; women, <i>p</i> =0.007) was correlated with low grip strength in both sexes. <h3>Conclusions</h3> Among subjects without hand joint pain, low grip strength was associated significantly with hand and knee radiographic OA, regardless of sex. Among all types of OA radiographic damage, low grip strength showed the strongest association with joint space narrowing. <h3>Disclosure of Interest</h3> None declared
AB0241 Relationship between leptin and disease activity in patients with rheumatoid arthritis
Authors: JADJ Batún Garrido, IE Juárez Rojop, M Salas Magaña, Έ Hernández Núñez, F Olán
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Increased concentrations of leptin have been observed during infectious processes and inflammation, in such a way that it plays a role in the inflammatory and the immune response <h3>Objectives</h3> Determine the association between serum leptin and disease activity measured through DAS-28 PCR. <h3>Methods</h3> Patients with the diagnosis of rheumatoid arthritis (RA) according to the ACR/EULAR 2010 criteria were studied. Leptin was determined by enzyme immunoassay (ELISA) with the TECO® Test Kit, the values higher than 17ng/mL were considered as hyperleptinemia. Disease activity was assessed by the DAS-28 PCR, classifying as remission &lt;2.3, low activity ≥2.3 to &lt;3.8, moderate activity as ≥3.8 to &lt;4.9 and high activity ≥4.9. Statistical analysis was performed using the SPSS 22.0 package. A p≤0.05 was considered a significant result. A multivariate logistic regression model was used to determine the association between significant variables and leptin concentrations. <h3>Results</h3> 77 patients were studied, 93,5% were female. The activity of the disease was determined, finding that 40,3% of patients were in remission, 41,6% had low activity, 11,7% had moderate activity and 6,5% had high activity. The 46,8% had obesity, 32,5% were overweight, 18,2% had normal weight and 2,5% were underweight. The 37,7% of the patients studied had metabolic syndrome, being the main factor the presence of an altered abdominal perimeter. The 63,6% had positive rheumatoid factor. The 71,4% had leptin levels ≥17 ng/ml. A multivariate logistic regression was performed with leptin as dependent variable. The results show an independent association between higher concentrations of leptin and disease activity (OR 1,9; 95% CI 1,3–3,8; p=0,045), obesity (OR 3,63; 95% CI 1,1–11,9; p=0,033), the presence of metabolic syndrome (OR 2,74; 95% CI 1,7–10,4; p=0,038), and positive rheumatoid factor (OR 3,5; 95% IC 1,2–11,3; p=0,033). It was also found that at higher disease activity, there were higher concentrations of serum leptin. Patients with severe activity had higher leptin media than patients in remission <h3>Conclusions</h3> There is a positive relationship between the activity of the disease and the serum leptin concentration, likewise this hormone is related to other inflammatory processes such as metabolic syndrome and rheumatoid factor. <h3>References</h3> Tilg H, Moschen A. Adipocytokines: Mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006; 6: 772–83. Otero M, Lago R, Lago F, Casanueva F, Dieguez C, Gόmez J. Leptin, from fat to inflammation: Old questions and new insights. Febs Lett. 2005; 579: 295–301. <h3>Disclosure of Interest</h3> None declared