tbuckley/cabot-search huggingface dataset:
Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis
Authors: Xavier Bossuyt, Jan-Willem Cohen Tervaert, Yoshihiro Arimura, Daniel Blockmans, Luis Felipe Flores-Suárez, Loïc Guillevin, Bernhard Hellmich, David Jayne, J. Charles Jennette, Cees G. M. Kallenberg, Sergey Moiseev, Pavel Novikov, Antonella Radice, Judith Anne Savige, Renato Alberto Sinico, Ulrich Specks, Pieter van Paassen, Ming-hui Zhao, Niels Rasmussen, Jan Damoiseaux, Elena Csernok
Journal: Nature Reviews Rheumatology (2017)

In this Consensus Statement, a group of experts propose that high-quality immunoassays, rather than indirect immunofluorescence, should be used as the primary screening method for detecting anti-neutrophil cytoplasmic antibodies when diagnosing patients with suspected granulomatosis with polyangiitis or microscopic polyangiitis. Anti-neutrophil cytoplasmic antibodies (ANCAs) are valuable laboratory markers used for the diagnosis of well-defined types of small-vessel vasculitis, including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). According to the 1999 international consensus on ANCA testing, indirect immunofluorescence (IIF) should be used to screen for ANCAs, and samples containing ANCAs should then be tested by immunoassays for proteinase 3 (PR3)-ANCAs and myeloperoxidase (MPO)-ANCAs. The distinction between PR3-ANCAs and MPO-ANCAs has important clinical and pathogenic implications. As dependable immunoassays for PR3-ANCAs and MPO-ANCAs have become broadly available, there is increasing international agreement that high-quality immunoassays are the preferred screening method for the diagnosis of ANCA-associated vasculitis. The present Consensus Statement proposes that high-quality immunoassays can be used as the primary screening method for patients suspected of having the ANCA-associated vaculitides GPA and MPA without the categorical need for IIF, and presents and discusses evidence to support this recommendation.
Inflammatory Cardiomyopathic Syndromes
Authors: Barry H. Trachtenberg, Joshua M. Hare
Journal: Circulation Research (2017)

Inflammatory activation occurs in nearly all forms of myocardial injury. In contrast, inflammatory cardiomyopathies refer to a diverse group of disorders in which inflammation of the heart (or myocarditis) is the proximate cause of myocardial dysfunction, causing injury that can range from a fully recoverable syndrome to one that leads to chronic remodeling and dilated cardiomyopathy. The most common cause of inflammatory cardiomyopathies in developed countries is lymphocytic myocarditis most commonly caused by a viral pathogenesis. In Latin America, cardiomyopathy caused by Chagas disease is endemic. The true incidence of myocarditis is unknown to the limited utilization and the poor sensitivity of endomyocardial biopsies (especially for patchy diseases such as lymphocytic myocarditis and sarcoidosis) using the gold-standard Dallas criteria. Emerging immunohistochemistry criteria and molecular diagnostic techniques are being developed that will improve diagnostic yield, provide additional clues into the pathophysiology, and offer an application of precision medicine to these important syndromes. Immunosuppression is recommended for patients with cardiac sarcoidosis, giant cell myocarditis, and myocarditis associated with connective tissue disorders and may be beneficial in chronic viral myocarditis once virus is cleared. Further trials of immunosuppression, antiviral, and immunomodulating therapies are needed. Together, with new molecular-based diagnostics and therapies tailored to specific pathogeneses, the outcome of patients with these disorders may improve.
SAT0621 Agreement between semiquantitative and quantitative doppler scoring systems for the assessment of synovial pathological vascularization in rheumatoid arthritis
Authors: E Naredo, IM Rutigliano, I Janta, C Scirocco, L Valor, F Figus, L Carreño, J Garrido, A Iagnocco
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To compare power Doppler (PD) vs colour Doppler (CD) semiquantitative and quantitative scoring of synovial vascularization (RA) and to evaluate the relationship between semiquantitative and quantitative scores in patients with rheumatoid arthritis (RA). <h3>Methods</h3> One hundred RA patients underwent B-mode, PD, and CD assessments of 12 joints at two European centres. Each joint with synovial hypertrophy detected on B-mode was semiquantitatively scored (0–3) for PD (SPD score) and CD (SCD score) synovial signal. PD and CD synovial signal were also quantitatively scored (0–100%) (QPD and QCD scores, respectively) using a software for counting the colour fraction. <h3>Results</h3> We found SH in 184 joints. SPD and SCD agreed in 92.3% (95% CI: 88.4; 96.2%) of paired scores, with Kendall rank correlation coefficient tau-b=0.95. Significant differences between marginal distributions of SPD and SCD were not found (p=0.565). QPD and QCD scores were highly correlated (Pearson9s coefficient=0.70) but Blamd-Altman plot showed insufficient agreement, being the QCD scores systematically slightly higher than the QPD scores. The distribution of QPD and QCD values between SPD and SCD scores, respectively, showed significant differences between grade 0 and grade 1 (p&lt;0.001), and grade 2 and grade 3 (p=0.042 and p=0.007, respectively) but not between grade 1 and 2 (p=0.154 and p=0.150, respectively). <h3>Conclusions</h3> SPD and SCD scores were concordant and QPD and QCD scores highly correlated although were not concordant. There was consistency between SPD and SCD moderate and severe scores and QPD and QCD scores. There was an overlapping between SPD and SCD mild and moderate scores regarding QPD and QCD scores. <h3>Disclosure of Interest</h3> None declared
Human CD40 ligand–expressing type 3 innate lymphoid cells induce IL-10–producing immature transitional regulatory B cells
Authors: Zsolt I. Komlósi, Nóra Kovács, Willem van de Veen, Anna Isabella Kirsch, Heinz Benedikt Fahrner, Marcin Wawrzyniak, Ana Rebane, Barbara Stanic, Oscar Palomares, Beate Rückert, Günter Menz, Mübeccel Akdis, György Losonczy, Cezmi A. Akdis
Journal: Journal of Allergy and Clinical Immunology (2017)
AB0517 Predictive factors for infection in systemic lupus erythematosus
Authors: M Kechida, N Lorenzo, R Klii, S Hammami, I Khochtali
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> it9s known that infection could complicate the course of systemic lupus erythematosus (SLE) because of the immune status or the long term steroids and immunosuppressors. <h3>Objectives</h3> This study was aiming at determining the prevalence of infectious complications during SLE and their predictive factors. <h3>Methods</h3> A retrospective bi-centric analyzes of 289 patients diagnosed as SLE between January 2004 and December 2016 according to the ARA criteria of 1997 was conducted. A descriptive analysis of infectious complications was first made, then a comparative study between patients with (group 1) and without (group 2) infectious complications was performed to detect predictive factors. <h3>Results</h3> Mean age was 84.6±13 years (14–72 years) with a sex ratio F/M=6. Cardiac involvement and lupus nephritis (LN) were developed in 20% of patients. About 13.75% of patients had neurological manifestations, 26.5% articular complications, 16% vascular involvement and 10% of them developed infectious complications. Eight percent of these infections were diagnosed concomitantly with the diagnosis of SLE and 92% of them after the diagnosis of lupus with an average of 25 months. About 52.9% of the patients developed more than 2 episodes of infection. The spectrum of infectious complications was: pulmonary in 33.3%, urinary in 22.2% and cutaneous in 13.9%. Tuberculosis was the most frequent infection 12.5%. Lupus flare complicated the infection in 28.6% of patients with mean SLEDAI score at 10. Comparative study between group 1 and group 2 revealed that LN, corticosteroids and immunosuppressors were associated with a high risk of infection (p=0.002, p=0.017 and p=0.034 respectively). In multivariate analysis only LN was an independent predictive factor (OR=3.5, 95% CI=1.06- 12.87, p=0.049). <h3>Conclusions</h3> Infections may complicate the course of SLE with flares presenting in 1/3 of cases. Half of the patients had more than 2 episodes of infection during their follow up. The presence of LN represents a predictive factor of such complication. <h3>Disclosure of Interest</h3> None declared
AB0876 Osteomalacia: modalities of presentation and etiology of 20 cases
Authors: H Mouanaa, Z Saoussen, A Arfa, M Jguirim, I Bejia, M Touzi, N Bergaoui
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Osteomalacia is a defect of mineralization of the protein framework of the skeleton. <h3>Objectives</h3> We try through our series to determine the presentation modalities and the various causes of this fragile benign osteopathy. <h3>Methods</h3> It is a descriptive retrospective study of cases collected in our rheumatology department between 2001 and 2016, concerning patients with osteomalacia <h3>Results</h3> Twenty patients were collected: 13 women and 7 men with an average age of 53±19 years [22 years, 80 years]. The mean duration of the disease is 45 months [5–172]. The findings were: bone pain in 55% of cases, pelvic pain in 45% of cases, a waddling gait in 5 cases (25%), fractures with low energy in 40% of cases, Functional impotence of the lower limbs in 35% of cases and a biological discovery in 2 cases (10%). Hypocalcemia, phosphorus deficiency and hypocalciuria were found in 14 cases, ie 70%. Alkaline phosphatases were elevated in 12 cases, with a variable rate of 2 to 7 times normal.The PTH, performed in 17 cases, was elevated in 53% of the cases. In our series, all patients had hypovitaminosis D. In addition, an associated iron deficiency anemia was detected in 50% of the cases, biological stigma of digestive malabsorption in 40% of the cases and renal insufficiency in 15% of the cases. Standard radiographs showed diffuse demineralization in 90% of cases, Looser-Milkman streaks in 40% of cases and fractures in 30% of cases. Bone scintigraphy among 8 patients revealed diffuse hyperfixation in 4 cases (50%), localized hyperfixation in 3 cases (37%) and non conclusive images in only one case (12.5%). Bone densitometry performed in 5 patients showed secondary osteoporosis in 80% of cases. The diagnosis of osteomalacia was retained in 2 cases, celiac disease in 5 cases, renal insufficiency in 1 case, phosphate diabetes in 3 cases including Fanconi syndrome, hypophosphatasia in one case and tubular involvement as part of ankylosing spondylitis In one case. Etiology was a neoplastic cause in 4 cases including multiple myeloma. All the patients had a vitamin-calcium treatment (calcium intake between 500mg and 2g per day with an average of 2.5 cp/d, phosphorus in 3 cases and an etiological treatment in 3 cases. The resection of the tumor was the reason behind a clinical-biological improvement in the case of thyroid tumors. The outcome was favorable in the short term for all cases. <h3>Conclusions</h3> Osteomalacia is a generalized benign osteopathy, essentially linked to a deficiency in vitamin D often unrecognized. The diagnosis is simple and the treatment is easy, but the ignorance of the etiological forms can be responsible for an unfavorable evolution. <h3>Disclosure of Interest</h3> None declared
Cemiplimab (REGN2810): A fully human anti-PD-1 monoclonal antibody for patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC)—Initial safety and efficacy from expansion cohorts (ECs) of phase I study.
Authors: Kyriakos P Papadopoulos, Taofeek Kunle Owonikoko, Melissa Johnson, Irene Brana, Marta Gil Martin, Raymond P. Perez, Victor Moreno, April K. Salama, Emiliano Calvo, Nelson S Yee, Howard Safran, Antonio Gonzalez Martin, Raid Aljumaily, Daruka Mahadevan, Kosalai Kal Mohan, Jingjin Li, Elizabeth Stankevich, Israel Lowy, Matthew G. Fury, Jade Homsi
Journal: Journal of Clinical Oncology (2018)

195 Background: There is no established standard of care for unresectable locally advanced or metastatic CSCC. UV-induced DNA damage causes hypermutation in most CSCCs. Therefore, these tumors may be responsive to PD-1 checkpoint blockade. In the dose escalation portion of the phase 1 study of cemiplimab (REGN2810), a durable (19 + months) radiologic complete response was observed in a patient (pt) with metastatic CSCC (ASCO 2015, #3024). Methods: ECs enrolled pts with distantly metastatic (EC 7) and locally advanced (EC 8) CSCC. All patients received cemiplimab 3 mg/kg by intravenous infusion over 30 minutes every 2 weeks for up to 48 weeks. Research biopsies were performed at baseline and Day 29 (and at progression, if possible). Tumor measurements were performed every 8 weeks according to RECIST 1.1 to determine overall response rate (ORR). Data cutoff date was 31 Jan 2017. Results: 26 pts were enrolled (10 in EC 7 and 16 in EC 8): median age, 72.5 y (range, 56–88y); median PS 1 (range, 0–1); 21M:5F; median number of prior systemic therapy regimens, 1 (range, 0–2). Median exposure to cemiplimab was 7 doses (range, 1–22). The most common treatment-related adverse event of any grade was fatigue (19.2%). Each of the following ≥ Grade 3 related AEs occurred once: AST elevation, ALT elevation, arthralgia, and rash. ORR (PR + CR, including unconfirmed) and disease control rate (ORR+SD) were 52% (12/23; 4uPR, 5 PR, 2CR, 1 uCR) and 70% (16/23, including 4SD), respectively. Three patients are not yet evaluable. Median PFS and OS have not been reached, and only one patient has experienced PD during cemiplimab treatment after initial response. Correlative studies are in process, including PD-L1 status and whole exome tumor DNA sequencing. Conclusions: Cemiplimab is well tolerated and produces antitumor activity in patients with advanced CSCC. A pivotal trial of cemiplimab for patients with advanced CSCC is enrolling patients. Clinical trial information: NCT02383212.
AB0884 Prevalence of ultrasonographic gout specific signs of hand and fingers joints
Authors: MA Mahdi, H Rkain, M Erraoui, R Watfeh, S Aktaou, L Tahiri, R Bahiri, F Allali, N Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To evaluate the prevalence of ultrasonographic gout specific signs of hand and fingers joints. <h3>Methods</h3> This is a cross-sectional study which includes 15 patients with chronic gout, defined according to the American College of Rheumatology criteria (ACR 1977). Ultrasound (US) examination was performed using a high-frequency linear probe (Toshiba Xario®, frequency (8–14 MHz)) in B mode. 540 articular sites were studied at their dorsal surface. The ultrasound has objectified the presence of two signs: hyperechoic band over the superficial margin of the articular cartilage described as a double contour (DC) and the tophaceous deposits at the joint cavity. <h3>Results</h3> The mean age at onset was 54.7±12,6 years, and the median diagnosis duration was 0 (0.3) years). The results of the US examination are summarized in Table 1. <h3>Conclusions</h3> This study showed a predilection for the gout specific ultrasound signs (DC and tophaceous deposits) of the wrist and MCP joints. The contribution of musculoskeletal ultrasound seems to be very interesting to objectify the presence of gout specific signs in the hand and fingers joints. <h3>Disclosure of Interest</h3> None declared
SP0115 Neurotransmitters and innervation in synovium
Authors: RH Straub
Journal: Annals of the Rheumatic Diseases (2017)

The synovial tissue is innervated by nociceptive sensory nerve fibers and sympathetic postganglionic nerve fibers. While sensory nerve fibers have afferent (by transmitting pain to the CNS) and efferent functions (by local release of neuropeptides), sympathetic nerve fibers exert mainly efferent vasoregulatory, energy-regulating and immunomodulating roles. In synovial tissue of patients with rheumatoid arthritis (RA), the major proinflammatory neuropeptide of sensory nerve fibers is substance P, which is upregulated relative to anti-inflammatory calcitonin gene-regulated peptide (CGRP). In addition, sensory nerve fibers undergo a sprouting response leading to sensory hyperinnervation of RA synovial tissue. Removal of sensory nerve fibers exerts anti-inflammatory effects, and it is thought that this elimination is beneficial during hemiplegia, which can spare the paralytic limb from developing RA. Therapeutic neutralization of substance P was not successful, most probably due to vast receptor redundancy. Furthermore, the sensory nervous system undergoes a sensitization response (aggravation of pain and inflammation) in the synovial tissue, the dorsal root ganglion, the spinal cord, and more central in the brain. Chemical sympathectomy or suppression of adrenergic signaling significantly reduce inflammatory processes in the initial acute state of inflammation whereas the same procedures may increase inflammation at later stages. These findings indicate that the sympathetic nervous system supports the development of inflammation but can reduce inflammation at more chronic stages. During chronic inflammation, the density of sympathetic nerve fibers in synovial tissue is reduced but other tyrosine hydroxylase-positive cells secreting noradrenaline appear in the inflamed joint. In addition to local vascular effects in the joint, the sympathetic nervous system influences numerous immune processes in the joint and in lymphoid organs. Hence the net effect of the sympathetic nervous system on inflamed tissue results from local sympathetic effects in the joint as well as from sympathetic influences on major systemic immune processes and energy regulation. This lecture summarize the central aspects of the two nervous systems. <h3>Disclosure of Interest</h3> None declared
Plakin Family Autoantibodies in Bronchiolitis Obliterans Following Hematopoietic Stem Cell Transplantation As Useful Biomarkers and the Target for Rituximab Therapy
Authors: Eri Nishikawa, Yoshinao Muro, Nozomu Kawashima, Shinsuke Kataoka, Motoharu Hamada, Daisuke Ichikawa, Daiei Kojima, Norihiro Murakami, Kyogo Suzuki, Yuko Sekiya, Yusuke Okuno, Rieko Taniguchi, Atsushi Narita, Hideki Muramatsu, Nobuhiro Nishio, Asahito Hama, Seiji Kojima, Masashi Akiyama, Yoshiyuki Takahashi
Journal: Blood (2016)
SAT0377 Reliability of a new automated system for absolute capillary number counting (AUTOCAPI) on systemic sclerosis nailfold videocapillaroscopic images
Authors: M Cutolo, K Melsens, AC Trombetta, C Pizzorni, E Deschepper, A Sulli, V Smith
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Nailfold capillary density is a useful measure in systemic sclerosis (SSc) classification and evaluation. Its manual detection may be time-consuming, hampering its use in largescale investigations. We evaluated a new automated system to assess the absolute nailfold capillary number. <h3>Objectives</h3> To attest the instrumental reliability of automatic counting in SSc patients using nailfold video capillaroscopy (NVC) images. <h3>Methods</h3> 75 NVC random images, from SSc patients, were blindly analyzed by four raters (2 less and 2 more experienced; raters: 1,2,3,4) from two European centers. Each rater was asked to define the region of interest (ROI) on the NVC images and to manually count the number of capillaries, according to the following instructions: upper bound placed on top of the longest capillary head and lower bound placed on half of the length of that longest capillary (figure 1); if the common branch of an abnormal shape (neoangiogenesis) is in ROI it is counted as being one; if the common branch is out of ROI it is counted as separate capillaries; if the capillary is on the edge of the vertical line of ROI, it is only counted when the head of the capillary is half in ROI; if the capillary head is on the edge of lower bound, it is counted as soon as the "head" part is in the ROI; all "heads" in the ROI are counted (not only distal row). The dedicated automated system (AUTOCAPI-ds medica, IT) also counted the number of capillaries in the same ROI (figure 1). Reliability between the manual and automatic counting was investigated per rater through intraclass correlation coefficient (ICC) and reported with 95% confidence interval (CI). External validation was obtained by multi-rating of the same set of images. Average difference between automated and manual counting per rater was calculated. <h3>Results</h3> The ICC (95% CI) of manual versus automatic counting in ROI was 0.77 (0.61–0.86) for rater 1 (p&lt;0.0001), 0.81 (0.71–0.88) for rater 2 (p&lt;0.0001), 0.65 (0.50–0.76) for rater 3 (p&lt;0.0001) and 0.81 (0.71–0.87) for rater 4 (p&lt;0.0001). The average difference was -0.69 for rater 1, 0.04 for rater 2, -0.03 for rater 3 and 0.16 for rater 4. <h3>Conclusions</h3> This is a first study to attest the reliability of a new automated system to calculate the absolute number of capillaries in a ROI arising from SSc NVC images. High performance of the new automated counting system was confirmed in pathological conditions (SSc). <h3>Disclosure of Interest</h3> None declared
AB0841 Medical and social consequences in hip fractures depending on the method of treatment
Authors: JV Averkieva, T Raskina
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> medical and social significance of osteoporosis is determined by its consequences - fractures of the vertebrae and the bones of the peripheral skeleton leading to high rates of mortality and disability among older adults. Purpose: to follow basic health and social consequences among the surviving patients with hip fractures aged 50 years or older at 6, 24 months. <h3>Objectives</h3> The study included 432 patients (328 women and 104 men) with radiographic evidence of hip fractures that occurred with minimal trauma. <h3>Methods</h3> Surgical treatment was performed in 171 (40,04%) patients, conservative treatment-261(59.96%). <h3>Results</h3> tracked mortality in hip fractures in 432 patients. It was found that in the first 6 months in the surgical treatment of deaths registered in 11 (6,43%) patients and in 84 (32.18%) - the conservative (p&lt;0.0001). After 12 months after fracture increased mortality rate after the surgical treatment and after conservative (12.9% and 44.81%, respectively, p&lt;0.0001). It was revealed that in the first 6 months in patients with surgical treatments bedridden were 10 (8.0%) men and 78 - a group with conservative treatment (66.67%) (p&lt;0.0001). Restriction of physical activity within the room was observed in 86 (68.8%) patients with surgery, and in 30 (25.64%) patients - with conservative treatment (p&lt;0.0001). Aids used after surgical treatment of 105 (84.0%) patients after conservative - 34 (29.0%) (p&lt;0.0001). Social impact showed that after 6 months of observation revealed a low proportion of patients with complete recovery of function after a surgery, or after conservative treatment (8.0% and 5.13%, respectively; p=0.5). After 24 months from the time of the fracture using surgical methods bedridden stayed only 1 (0.4%) and 16 patients (13.68%) - with conservative methods (χ<sup>2</sup> =18,3; p&lt;0.0001). There was a significant decrease in the number of patients with limited motion activity within the room in the group with surgery and in the group with conservative (10.4% and 26.5%, respectively, p=0.002). When surgical treatment aids continued to use 38.4% (48 patients) under conservative treatment - 58.97% (69 people) (χ<sup>2</sup>=10,24; p=0.002). Full restoration of function was observed in 72 (57.6%) and 32 (27.35%) patients who received surgical and conservative treatment, respectively (χ<sup>2</sup> =4,62; p&lt;0.0001). <h3>Conclusions</h3> the obtained during this study data suggest that the immediate and long-term consequences in patients with a fracture of the proximal femur depends on the method of treatment. Surgical treatment is the method of choice for the treatment of patients with this type of fracture. <h3>Disclosure of Interest</h3> None declared