tbuckley/cabot-search huggingface dataset:
AB1187 What imaging detected pathologies are associated with shoulder symptoms and their persistence? a systematic literature review
Authors: G. Tran, P. Cowling, T. Smith, A. Lucas, E. Hensor, A. Barr, S. Kingsbury, P. Conaghan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Shoulder pain is a very common musculoskeletal complaint and a significant contributor to disability and morbidity. Recovery can be slow and over 50% continue to have pain at 18 months. Shoulder pain has a significant negative impact on quality of life and poses a significant economic burden, with costs estimated to be €345 million per year in the UK alone. Modern imaging modalities can accurately detect soft-tissue pathologies and are increasingly used, but the relationship of imaging findings to patient symptoms remain unclear. <h3>Objectives</h3> Our aim was to systematically review the literature to determine what imaging features are associated with symptoms and their progression. <h3>Methods</h3> A systematic review using Medline, EMBASE, Cochrane and grey literature was conducted to April 2017. The cross-sectional and longitudinal relationships between imaging-detected abnormalities and symptoms were analysed and associations qualitatively characterised by a best evidence synthesis based on study design, covariate adjustment and the Grade of Recommendations Assessment, Development and Evaluation (GRADE). Modalities included ultrasound, magnetic resonance imaging (MRI), radiographs, positron emission tomography (PET), bone scintigraphy and computerised tomography (CT). <h3>Results</h3> 6569 abstracts were screened and 56 papers were included. 50 studies did not adjust for covariates. The majority of studies showed conflicting findings. There was no significant association between most imaging features (rotator cuff tears, tendinopathies, subacromial bursal pathologies, osteoarthritis, calcification, acromial pathologies and adhesive capsulitis) and symptoms amongst high quality, cross-sectional studies. There was low-quality evidence suggesting that enhancement of the joint capsule on MRI and increased uptake of the rotator cuff interval, anterior joint capsule or axillary recess on PET was associated with symptoms in adhesive capsulitis. Based on high-quality, unadjusted longitudinal studies, enlarging rotator cuff tears was associated with an increased incidence of pain. 20 out of 56 studies evaluated more than one pathology, but only one study examined the association of symptoms with a combination of pathologies. <h3>Conclusions</h3> There were conflicting results on the association of imaging features with shoulder symptoms and its persistence and the existing evidence was very low in quality. There may be some imaging features associated with adhesive capsulitis symptoms and increasing RC tear may be associated with incident shoulder symptoms. Further high quality studies are required to understand the relationship between imaging and symptoms. <h3>Disclosure of Interest</h3> None declared
Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis
Authors: Nathan Kuppermann, Simona Ghetti, Jeff E. Schunk, Michael J. Stoner, Arleta Rewers, Julie K. McManemy, Sage R. Myers, Lise E. Nigrovic, Aris Garro, Kathleen M. Brown, Kimberly S. Quayle, Jennifer L. Trainor, Leah Tzimenatos, Jonathan E. Bennett, Andrew D. DePiero, Maria Y. Kwok, Clinton S. Perry, Cody S. Olsen, T. Charles Casper, J. Michael Dean, Nicole S. Glaser
Journal: New England Journal of Medicine (2018)

Diabetic ketoacidosis in children may cause brain injuries ranging from mild to severe. Whether intravenous fluids contribute to these injuries has been debated for decades.
AB0848 Four years of delay in the diagnosis of sapho syndrome: single tertiary centre experience
Authors: A. Erden, M. Ekici, B. Armagan, A. Sari, G.K. Yardımcı, L. Kilic, S. Apras Bilgen, A. Akdogan, O. Karadag, S. Kiraz, I. Ertenli, U. Kalyoncu
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> SAPHO syndrome is a chronic disease with bone, joint and skin involvement characterised by synovitis, acne, pustulosis, hyperostosis and osteitis. It is a rare disease and its diagnosis may depend on detailed clinical examination as well as radiological evaluation <h3>Objectives</h3> In this study, we aim to present clinical features and diagnostic course of patients with SAPHO syndrome who are followed in our tertiary referral clinic. <h3>Methods</h3> All patients with SAPHO syndrome diagnosed since February 2014 have been registered with a standard form. Patients are prospectively monitored since then. Diagnosis was based on the criteria by Benhamou et al..<sup>1</sup> In the questionnaire, demographic data (age, sex, duration of illness), clinical features (skin and joint involvement), laboratory characteristics (acute phase reactants, HLA-B27), radiological imaging (bone scintigraphy (increased activity in the sternum, bilateral sternoclavicular joints and clavicles), MRI) disease activity parameters (BASDAI, BASFI) were questioned. There were 24 patients with SAPHO syndrome. The data of 21 patients were presented because the clinical findings of 3 patients were insufficient. <h3>Results</h3> Data of 21 patients with SAPHO syndrome were available and 11 (52.4%) patients were female. Mean age at diagnosis was 39.9±12.9, mean age of symptom onset was 35.2±12.9, mean follow-up duration was 18.1±25.1 months. The mean delay time of diagnosis SAPHO syndrome was calculated as 49.0±82.5 months. Thirteen patients (61.9%) were followed up with another clinical diagnosis before SAPHO diagnosis. The clinical characteristics of the patients are shown in Figure 1. HLA-B27 was positive in 3 of 13 patients. Mean activity scores of our patients at initial visit were; BASDAI: 4.8±2.8, BASFI: 4.6±2.2, CRP2.3±4.2 mg/dL and erythrocyte sedimentation rate 23.8±22.6 mm/h. Scintigraphy findings were positive in 16 (94.1%) of 17 patients. The diagnosis of 2 patients was supported by MRI. The remaining 2 patients were diagnosed with X-ray and clinic findings. PPP: palmoplantar pustulosis, IBP: Inflammatory Back pain <h3>Conclusions</h3> There is a certain diagnostic problem in the SAPHO syndrome. Delay of SAPHO diagnosis was almost 4 years and 62% of patients had wrong diagnosis before SAPHO syndrome. Anterior chest wall involvement with dermatological findings should be alerting to the physicians. Bone scintigraphy can be helpful to diagnose SAPHO syndrome. It is important to distinguish SAPHO syndrome from other spondyloarthritis and/or psoriatic arthritis because of the potential different treatment strategies. <h3>Reference</h3> [1] Benhamou CL, Enjolras O, Delrieu F, Prier A, Camus JP, Amor B. Pseudoseptic arthritis and bacterid of Andrews [in French]. Rev Rhum Mal Osteoartic. 1984;51(4):229–231. <h3>Disclosure of Interest</h3> None declared
AB0114 Modulation of endothelial function by proinflammatory cytokines involved in rheumatoid arthritis. focus on il-17a, il-20, il-23 and il-9
Authors: P. Totoson, D. Wendling, C. Prati, C. Demougeot
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid Arthritis (RA) is the most common inflammatory rheumatic disease, characterised by high circulating of pro-inflammatory cytokines. RA is associated with an increased cardiovascular risk secondary to the accelerated atherogenesis which is the consequence of endothelial dysfunction (ED) <sup>1</sup>. In addition to the well-known cytokines (TNF-α, IL-1β and IL-6), emerging data identified new cytokines such as IL-17A, IL-20, IL-23 and IL-9 as putative key-players of the pathogenesis of RA. To date, whether these cytokines might contribute to RA-associated endothelial dysfunction is not known. <h3>Objectives</h3> This study investigated the effect of IL-17A, IL-20, IL-23 and IL-9 on endothelium-dependent relaxation in response to acetylcholine (Ach) in rat aortic rings. <h3>Methods</h3> Experiments were conducted on thoracic aortic rings from male Lewis rats (11 week old), incubated for 1 hour or 24 hour at 37°C with 2 concentrations of each cytokine (IL-17A: 250 pg/ml and 10 ng/ml; IL-20: 500 pg/ml and 5 ng/ml; IL-23: 80 pg/ml and 10 ng/ml; and IL-9: 300 pg/ml and 10 ng/ml). Incubation with 10 ng/ml TNF-α was used as a positive control and with vehicle as negative control. At the end of the incubation period, endothelial function was studied by assessing concentration-response curves to Ach (10–1<sup>1–1</sup>0–4 mol/L) after phenylephrine (PE, 10–5 mol/L) or KCl (30 mmol/L) -induced contractions. <h3>Results</h3> As described in the literature<sup>2</sup>, a 24h- but not 1h-incubation with TNF-α reduced Ach-induced relaxation. The same result was obtained with IL-17A (10 ng/mL). By contrast, IL-20 did not change Ach-induced relaxation whatever the concentration and the incubation time. Impairment in vascular relaxation was observed after exposure to IL-9 (10 ng/mL), both after 1h- and more severely after 24h-incubation. As regards IL-23, an effect was observed only after 1 hour incubation and with high concentration. <h3>Conclusions</h3> Our data demonstrated that IL-17A, IL-23 and IL-9 but not IL-20 induced endothelial dysfunction, with different kinetics profiles. Among the cytokines evaluated, IL-9 exhibited the most important effect thus revealing a new putative role of this pleiotropic cytokine in RA-associated cardiovascular risk. Further studies are needed to confirm these data on animal models of diseases. <h3>References</h3> [1] Steyers CM 3rd, Miller FJ Jr. Endothelial dysfunction in chronic inflammatory diseases. Int J Mol Sci. 2014Jun;15(7):11324–49. [2] Hilgers, et al. Acute O-GlcNAcylation prevents inflammation-induced vascular dysfunction. Am J Physiol Heart Circ Physiol2012Sept;303(5):H513–22. <h3>Disclosure of Interest</h3> None declared
PTH-038 Management of biliary complications following liver transplantation: 10 years experience
Authors: Vinod Hegade, Theodoros Tsirlis, Sandra Latimer, Derek Manas Richard, Manu Nayar, Kofi Oppong, Mark Hudson, John Leeds
Journal: Endoscopy (2018)

<h3>Introduction</h3> Biliary complications after liver transplantation (LT) are common and some risk factors have been identified. Optimum endoscopic management including use of fully covered self-expanding metal stents (fcSEMS) in patients following LT requires evaluation. We aimed to identify risk factors for biliary complications following LT and present our experience of endoscopic management. <h3>Methods</h3> Retrospective analysis of adult LT's performed at our centre. Patient demographics, donor characteristics, transplantation data (including graft type; donation after brain death (DBD) or cardiac death (DCD)), biliary complications and subsequent management were recorded and the DRI calculated. The cohort consisted of all LT performed between 2007 and 2016. Univariate and multivariable analysis was used to identify risk factors for biliary complications and ascertain factors associated with biliary stricture resolution. <h3>Results</h3> A total of 353 (n=322 DBD and n=31 DCD) patients were included of which 80 (22.7%) patients developed biliary complications. DCD patients had a higher prevalence of biliary complications compared to DBD patients (16/31 vs 64/322, OR 4.3, 95% CI 2.0–9.2, p=0.0002). Biliary leak rate was not significantly different (DCD 9.7% vs DBD 8.1%) but biliary strictures were more common in DCD patients compared to DBD (12/31 vs 36/322, OR 5.0, 95% CI 2.3–11.2, p=0.0001). Biliary strictures were also associated with higher DRI (1.97 vs 1.76, p=0.015). Hepatic artery thrombosis rate was the same in both groups (9.3% vs 7.2%, p=0.74). Multivariable analysis showed that only DCD was independently associated with biliary strictures (adjusted OR 4.6, 1.9–11.2, p=0.0007). 21/80 with biliary complications underwent surgical (n=8), radiological (n=8) or conservative (n=5) management. The remainder underwent ERCP; 42 patients had 116 procedures for strictures, 19 patients had 35 procedures for biliary leak and 12 had 20 procedures for stone disease (some multiple indications). There were no differences in stricture resolution between DCD and DBD (6/10 vs 21/32, p=ns). Per stent analysis showed higher stricture resolution rates following fcSEMS insertion compared to plastic stents (18/20 (90%) vs 17/69 (24.6%) respectively, p&lt;0.0001). <h3>Conclusion</h3> Biliary complications are associated with DCD livers. Endoscopic management of biliary complications leads to high resolution rates but patients undergo a high volume of procedures for strictures. fcSEMS had a higher stricture resolution rate compared to plastic stents.
Ambient Pollution–related Reprogramming of the Human Small Airway Epithelial Transcriptome
Authors: Sarah L. O’Beirne, Sushila A. Shenoy, Jacqueline Salit, Yael Strulovici-Barel, Robert J. Kaner, Sudha Visvanathan, Jay S. Fine, Jason G. Mezey, Ronald G. Crystal
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Epidemiologic studies have demonstrated that exposure to particulate matter ambient pollution has adverse effects on lung health, exacerbated by cigarette smoking. Particulate matter less than or equal to 2.5 μm in aerodynamic diameter (PM
Apache: An open label, randomized, phase 2 study of durvalumab (Durva), alone or in combination with tremelimumab (Treme), in patients (pts) with advanced germ cell tumors (GCT): Results at the end of first stage.
Authors: Daniele Raggi, Patrizia Giannatempo, Luigi Mariani, Maurizio Colecchia, Giuseppina Calareso, Roberto Salvioni, Siraj Mahamed Ali, Jeffrey S. Ross, Jon Chung, Andrea Necchi
Journal: Journal of Clinical Oncology (2018)

4547 Background: The prognosis of chemorefractory GCT pts is dismal. Durva is an anti-PD-L1 monoclonal antibody (mAb). Treme is anti-CTLA4 mAb. We aimed to investigate the activity of Durva, alone or with Treme, in these pts. Methods: Apache (NCT03081923) is an open-label, randomized, 3-stage, phase 2 study. Pts who have failed ≥2 chemotherapy (CT) regimens receive Durva, 1.5 gr q4w, x 13 cycles (arm A) or Durva plus with Treme, 75 mg q4w, x 4 cycles, followed by Durva alone x total 13 cycles (arm B). Serum tumor markers (STM), and radiologic assessments are repeated q8 weeks. The primary endpoint is the modified objective response-rate (mORR = RECIST 1.1 complete or partial response [PR] or stable disease [SD]+STM reduction > 10%). H0: mORR rate ≤10%, H1: mORR ≥25%, type I and II error rates at 10%. The total sample size of 120 pts is split into 3 stages: in stage 1, according to Gehan’s rule, each arm is terminated whenever no response is observed. Biomarker analyses include: IHC PD-L1 expression on immune cells (Ventana SP142) and genomic sequencing with FoundationOne assay (Foundation Medicine Inc., Cambridge, MA, USA). Results of first stage are presented. Results: From 02/17-11/17, 18 pts were enrolled (17M, 1F), 9 per arm. 14 had gonadal and 4 extragonadal GCT, 15 had received ≥3 prior CT regimens. Median tumor mutational burden (TMB) was 4 mutations (mut)/mb. One pt (5.6%) had reversible G3 irAE (pneumonitis) in arm B. In arm A, 100% of pts had disease progression (PD), all with features of hyperprogression (hyper-PD): 4 had clinical PD and death before restaging, median increase in sum of tumor diameters (RECIST 1.1) was 146%, median increase in the elevated STM was 462%. In arm B, 2 responses (22.2%, 1 RECIST-PR in seminoma and 1 SD with STM reduction in nonseminoma) were observed. PD features were similar to arm A. PD occurred in both arms regardless of PD-L1 expression and TMB (PR case: PD-L1 negative and 4 mut/mb). Conclusions: Single-agent durvalumab should not be pursued further in GCT; conversely, combination immunotherapy showed signals of activity and will be expanded to 2nd stage. Response biomarkers are urgently required. Clinical trial information: NCT03081923.
AB1263 Finnish healthvillage.fi-rheumaticdiseases.fi: a specialised care service unit developed together with patients to offer on-line information and treatment for patients in a modern way
Authors: R.A. Luosujärvi, K. Taimen, S. Lindqvist, R. Roiha, O. Kaipiainen-Seppanen, H. Mäkinen, P. Isomaki, L. Pirila, A. Karjalainen, T. Valiviita, S. Viinikainen, K. Eklund, S. Arvonen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Finnish on-line Health village environment, so-called HUS-MAP©, was used to develop on-line information for rheumatic patients. <h3>Objectives</h3> To face the challenge of increasing demand for rheumatological care without additional resources a new virtual client-orientated service was developed. <h3>Methods</h3> In Finland, an on-line Health village environment, so-called HUS-MAP©, has been developed to offer virtual digital information to citizens, patients, and healthcare professionals. By using this HUS-MAP© environment, we provide information and support to citizens and patients who need information on different rheumatic diseases and various unspecified aches and musculoskeletal pains. The study group consisted of participants from every university hospital in Finland, from local authorities; rheumatologists, other specialists, general practitioners, nurses, special professionals such as physical therapists, and patients. Information provided was based on updated international and Finnish guidelines on rheumatic diseases. After the information was reviewed and accepted by our study group, it was fed into a special program and published on-line in the Health village environment. <h3>Results</h3> E-service for citizens and patients was opened in March 2017. Detailed description of symptoms, diagnosis and therapy of various rheumatic diseases, such as rheumatoid arthritis, spondyloarthritis, connective tissue diseases and vasculitis are available. Early diagnosis and treatment to remission when possible is emphasised. The service aids to identify, by using symptom navigator and questionnaires for back pain, as well as swollen and painful joints those who may have a rheumatic disease and guide patients to find medical services without delay. Already 60 500 persons have visited our website. <h3>Conclusions</h3> Finnish e-service, rheumaticdiseases.fi, offers an easy way to reach people and increase citizen’s awareness on their own health. By guiding people to search for care the service may reduce delays in diagnosis of rheumatic diseases and the onset of therapy <h3>Acknowledgements</h3> To patients and healthcare professionals workin in Finnish Helathvillage.fi-rheumaticdisease.fi <h3>Disclosure of Interest</h3> None declared
FRI0545 Risk factors predicting radiological progression of knee osteoarthritis
Authors: L. Alekseeva, S. Anikin, N. Kashevarova, E. Sharapova, E. Taskina, T. Korotkova, T. Raskina, E. Otteva, A. Dubikov, E. Zonova, I. Vinogradova
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Currently a number of risk factors (RF) are considered to be responsible for radiological progression of knee osteoarthritis (OA), nevertheless key predictors of OA progression have not yet been established. <h3>Objectives</h3> To identify RF predicting radiological progression of knee joint osteoarthritis (OA) in a 5 year multicenter prospective study. <h3>Methods</h3> This study of RF predicting knee OA progression was the first with multicenter prospective design ever conducted in Russia. The study included 344 female patients 40–75 y.o with primary stage I-III knee OA (ACR criteria) from 6 centres. Radiological stage was identified by Kellgren J.- Lawrence J. grading scale. The follow up (FUP) was 5 years. Individual patients' files described 90 parameters. Instrumental diagnostic methods included plain radiography of knee joints, dual energy X-ray absorptiometry (DEXA) of lumbar spine L1–4, femoral neck and subchondral tibia, ultrasound (US) and MRI examination of knee joints. OA progression was verified based on evolution of radiological stage. At baseline 24 pts (7%) had stage I OA, 227 (66%) – stage II, and 93 (27%) – stage III. Discriminant analysis was applied to verify most reliable RF predicting radiological progression. <h3>Results</h3> Radiological progression was documented in 45% participants during 5 year FUP. The groups with and without progression were comparable in terms of age and disease duration (<i>»</i>&lt;0,05). Pts who progressed suffered more intensive knee pain – 68(52–72) vs 41(30–63) mm, <i>»</i> &lt;0,01, had higher body weight – 82(77–93) vs 72(65–81) kg, <i>»</i> &lt;0,01, had higher rates of knee synovitis (US) 44% vs 26%, <i>»</i>=0,03, (RR=1,67, 95% CI 1,07–2,59) and mid-tibia bone marrow oedema – 60% vs 28%, <i>»</i> &lt;0,01 (RR=2,12, 95% CI 1,34–3,35). The discriminant analysis showed that knee pain, excessive body weight, synovitis and mid-tibia bone marrow oedema (MRI) can be considered as predictors of OA radiological progression. A model capable of predicting OA course in an individual patient with high 88% accuracy, 87.7% sensitivity and 70% specificity has been developed based on identified RF and their coefficients. Area under the ROC-curve 0, 921 (95% CI 0,875–0,966). <h3>Conclusions</h3> Knee pain, excessive body weight, synovitis and bone marrow oedema should be considered as key RF predicting knee OA radiological progression. <h3>Disclosure of Interest</h3> None declared
Fractionated Radiation of Primary Prostate Basal Cells Results in Downplay of Interferon Stem Cell and Cell Cycle Checkpoint Signatures
Authors: Fabian Guggenberger, Harmen J.G. van de Werken, Holger H.H. Erb, Giuseppe Cappellano, Kristina Trattnig, Florian Handle, Sarah Peer, Georg Schäfer, Guido Jenster, Zoran Culig, Ira Skvortsova, Frédéric R. Santer
Journal: European Urology (2018)
Effect of KRAS and P-STAT3 inhibition by SBT-100 on gemcitabine and pancreatic cancer growth in vivo.
Authors: Sunanda Singh, Genoveva Murillo, Avani Singh, Samara Singh, Meenakshi S Parihar, Anjali H Singh, Rajendra Mehta, Ashutosh S Parihar
Journal: Journal of Clinical Oncology (2017)

e15727 Background: Over 90% of pancreatic cancers have KRAS mutations and hyper-expression of P-STAT3 oncoproteins, which if specifically targeted may help treatment of pancreatic cancers. Singh Biotechnology’s proprietary technology engineered SBT-100, a single domain antibody that is bispecific for KRAS &amp; STAT3, which can cross the cell membranes and bind to these intracellular oncoproteins. Combining this targeted therapy with an established chemotherapy, such as gemcitabine, may improve patient’s response to treatment. Methods: Human pancreatic cancer cells (PANC-1 and BX-PC3) were used. Biacore assay demonstrates SBT-100 binding to KRAS, KRAS (G12D), and STAT3. Immunoprecipitation (IP) and western blot analysis confirmed binding to STAT3 by SBT-100. Pancreatic cancer cells were treated at varying doses of SBT-100 ranging from 0µg/ml to 200µg/ml ± gemcitabine, and after 72 hours growth inhibition was determined by a MTT assay. PANC-1 tumors were grown in athymic nude mice, divided into four groups and staged to a range of 100-150mm 3 before treatment. Groups were: vehicle only, SBT-100, gemcitabine, and SBT-100 &amp; gemcitabine. Animals received treatments for 14 days, then monitored for 7 days. Results: Biacore study shows SBT-100 binds KRAS with an affinity of 10 -9 M, KRAS (G12D) with 10 -8 M, and STAT3 with 10 -8 M. IP and western blot analysis demonstrates that SBT-100 binds P-STAT3. MTT assay demonstrates SBT-100 inhibits the growth of PANC-1 and BX-PC3 (p &lt; 0.001). In PANC1 cells a combination of SBT-100 &amp; gemcitabine demonstrates synergism in inhibiting growth of PANC-1, even at 1/8 th the gemcitabine IC 50 concentration. PANC-1 xenograft study demonstrates that combination therapy of SBT-100 &amp; gemcitabine is superior to either SBT-100 or gemcitabine alone. Compared to the vehicle group, SBT-100 &amp; gemcitabine is far superior (p &lt; 0.001) and gives statistically significant suppression of pancreatic cancer growth in vivo. Conclusions: Targeted therapy for KRAS and P-STAT3 expressing tumors with SBT-100 &amp; gemcitabine is synergistic for the treatment of pancreatic cancer. This study suggests that synergism maybe achieved with lower doses of gemcitabine, thereby reducing toxicity in patients.