tbuckley/cabot-search huggingface dataset:
SAT0493 Maintaining sufficient serum vitamin d levels over two years is associated with improved knee structural and symptomatic outcomes in people with knee osteoarthritis: a post hoc analysis of the video trial
Authors: S Zheng, X Jin, F Cicuttini, X Wang, Z Zhu, A Wluka, W Han, T Winzenberg, BE Antony, D Aitken, L Blizzard, G Jones, C Ding
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To describe whether maintaining sufficient serum vitamin D levels in people with knee osteoarthritis (OA) and baseline vitamin D insufficiency has an association with change in knee structures and symptoms over two years. <h3>Methods</h3> Participants (n=413, age 63.2; 50% females) with symptomatic knee OA and vitamin D insufficiency were enrolled in a clinical trial. 340 participants (82.3%) completed the study with 25-hydroxyvitamin D [25(OH)D] measurements at month 0, 3 and 24. Participants were classified as consistently insufficient (serum 25(OH)D ≤50nmol/l at month 3 and 24, n=45), fluctuating (25(OH)D &gt;50nmol/l at either point, n=68) and consistently sufficient (25(OH)D &gt;50nmol/l at month 3 and 24, n=226) vitamin D groups. Knee cartilage volume, cartilage defects, bone marrow lesions (BMLs) and effusion-synovitis volume were assessed using MRI at baseline and month 24. Knee symptoms were assessed at baseline, month 3, 6 12 and 24 using Western Ontario and McMaster Universities Arthritis Index (WOMAC). <h3>Results</h3> The consistently sufficient group had significantly less loss of tibial cartilage volume (β: 2.1%, 95 CI%: 0.3%, 3.9%), less increase in effusion-synovitis volume (β: -2.5ml, 95 CI%: -4.7, -0.2) and less loss of WOMAC physical function (β: -94.2, 95% CI: -183.8, -4.5) compared to the consistently insufficient group in multivariable analyses. In contrast, there were no significant differences in these outcomes between the fluctuating and consistently insufficient groups. Changes in tibiofemoral cartilage defects, BMLs and knee pain were similar between groups. <h3>Conclusions</h3> This post hoc analysis suggests beneficial effects of maintaining vitamin D sufficiency on cartilage loss, effusion-synovitis and physical function in people with symptomatic knee OA. <h3>References</h3> Cao, Y., et al., Vitamin D supplementation in the management of knee osteoarthritis: study protocol for a randomized controlled trial. Trials 2012;13:131. Jin, X., et al., Effect of Vitamin D Supplementation on Tibial Cartilage Volume and Knee Pain Among Patients With Symptomatic Knee Osteoarthritis: A Randomized Clinical Trial. JAMA 2016; 315(10):1005–13. <h3>Acknowledgements</h3> We specially thank the participants who made this study possible, and we gratefully acknowledge the role of Vitamin D Effect on Osteoarthritis Study staff and volunteers in collecting the data. We thank the research assistants Jodi Barling, Kay Nguo, Judy Hankin and Alice Noone who were involved in the coordination of this study. <h3>Disclosure of Interest</h3> None declared
Abstract 1392: Smoking Cessation Through a Simulated Teachable Moment: Early Results of a Novel Modification Technique Using Personal Identification
Authors: Geoffrey H Tofler, Robin J May, Roger Bartrop, Paul Heinrich, John Baird, Simon deBurgh
Journal: Circulation (2009)

Background: Experiencing a myocardial infarction (MI) can be a “teachable moment” that results in smoking cessation where prior efforts have failed. Purpose: To determine the feasibility of creatin...
SAT0023 Direct-acting antiviral-based therapy restores immune tolerance in hepatitis c-induced cryoglobulinemia vasculitis
Authors: C Comarmond, M Garrido, A-C Desbois, M Costopoulos, M Garff-Tavernier Le, SN Si Ahmed, L Alric, H Fontaine, B Bellier, A Maciejewski, M Rosenzwajg, D Klatzmann, L Musset, T Poynard, P Cacoub, D Saadoun
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> Interferon-free direct-acting antiviral (DAA)-based therapy has proven to be very effective in patients with hepatitis C virus-cryoglobulinemia vasculitis (HCV-CV). However, their mechanisms of action and their effects on cellular immunity remain poorly defined. <h3>Methods</h3> 27 HCV-CV patients treated with DAA therapy, 12 healthy donors (HD) and 12 HCV were included. We investigated the effects of DAA-based therapy on cellular and cytokine abnormalities in HCV-CV patients by flow cytometry, cytokine Multiplex and enzyme-linked immunosorbent assay. <h3>Results</h3> Compared with HD and HCV, pre-DAA abnormalities in HCV-CV patients included a decreased percentage of CD4<sup>+</sup>CD25<sup>hi</sup>FoxP3<sup>+</sup> regulatory T cells (P&lt;0.01) with increases in IgM<sup>+</sup>CD21<sup>-/low</sup> memory B cells (P&lt;0.05), CD4<sup>+</sup>IFNγ<sup>+</sup> (P&lt;0.01), CD4<sup>+</sup>IL17A<sup>+</sup> (P&lt;0.01) and CD4<sup>+</sup>CXCR5<sup>+</sup>IL21<sup>+</sup> follicular helper T cells (Tfh) (P&lt;0.01). IgM<sup>+</sup>CD21<sup>-/low</sup> memory B cells were negatively correlated with regulatory T cells (Tregs) (P=0.03), and positively correlated with Tfh (P=0.03) and serum cryoglobulin levels (P=0.01). DAA-based therapy was associated with an increase in Tregs frequency (1.5% ± 0.18% versus 2.1% ± 0.18%), and decreased IgM<sup>+</sup>CD21<sup>-/low</sup> memory B cells and Tfh percentage (35.7% ± 6.1% versus 14.9% ± 3.8%, and 12% ± 1.3% versus 8% ± 0.9%, respectively). B lymphocyte stimulator receptor 3 and programmed death-ligand 1 staining expression on B cells increased in HCV-CV after DAA-based therapy (MFI 37±2.4 versus 47±2.6, P&lt;0.01; and 29±7.3 versus 48±9.3, P&lt;0.05 respectively). <h3>Conclusions</h3> Our results indicate that DAA-based therapy effectively normalizes many of the disturbances in peripheral B and T lymphocyte homeostasis of HCV-CV patients. <h3>Disclosure of Interest</h3> None declared
Endoscopic management of chronic pancreatitis with a fully covered self-expanding metal stent and laser lithotripsy
Authors: Aleksey Novikov, Ming-ming Xu, Amy Tyberg, Michel Kahaleh
Journal: Endoscopy (2017)

The patient was a 58-year-old man with a long-standing history of alcohol abuse and chronic pancreatitis leading to multiple hospitalizations. He continued to have pain despite conservative management, pain control, and alcohol cessation. His chronic pancreatitis and pancreatic duct (PD) stones resulted in a tight PD stricture at the head of the pancreas. Multiple prior attempts at conventional endoscopic retrograde cholangiopancreatography (ERCP) had failed. He presented to our institution seeking advanced therapy after extracorporeal shock wave lithotripsy (ESWL). At our index ERCP we could not get conventional transpapillary access to the PD. Instead, given his stone burden, after ESWL, we chose to treat him with an EUS-guided pancreaticogastrostomy, and placement of a fully covered self-expanding metal stent (FCSEMS) followed by a pancreatoscopy with holmium laser lithotripsy ([Fig. 1] and [Fig. 2]). The patient responded to treatment, with resolution of his pain at 12 months after the intervention.
A Combination RNAi-Chemotherapy Layer-by-Layer Nanoparticle for Systemic Targeting of KRAS/P53 with Cisplatin to Treat Non–Small Cell Lung Cancer
Authors: Li Gu, Zhou J. Deng, Sweta Roy, Paula T. Hammond
Journal: Clinical Cancer Research (2017)

Purpose: Mutation of the Kirsten ras sarcoma viral oncogene homolog (KRAS) and loss of p53 function are commonly seen in patients with non-small cell lung cancer (NSCLC). Combining therapeutics targeting these tumor-defensive pathways with cisplatin in a single-nanoparticle platform are rarely developed in clinic.Experimental Design: Cisplatin was encapsulated in liposomes, which multiple polyelectrolyte layers, including siKRAS and miR-34a were built on to generate multifunctional layer-by-layer nanoparticle. Structure, size, and surface charge were characterized, in addition to in vitro toxicity studies. In vivo tumor targeting and therapy was investigated in an orthotopic lung cancer model by microCT, fluorescence imaging, and immunohistochemistry.Results: The singular nanoscale formulation, incorporating oncogene siKRAS, tumor-suppressor stimulating miR-34a, and cisplatin, has shown enhanced toxicity against lung cancer cell line, KP cell. In vivo, systemic delivery of the nanoparticles indicated a preferential uptake in lung of the tumor-bearing mice. Efficacy studies indicated prolonged survival of mice from the combination treatment.Conclusions: The combination RNA-chemotherapy in an LbL formulation provides an enhanced treatment efficacy against NSCLC, indicating promising potential in clinic. Clin Cancer Res; 23(23); 7312-23. ©2017 AACR.
Disease modification and Neuroprotection in neurodegenerative disorders
Authors: Jeffrey Cummings
Journal: Translational Neurodegeneration (2017)

Disease modifying therapies (DMTs) are urgently needed for neurodegenerative diseases (NDD) such as Alzheimer's disease (AD) and many other disorders characterized by protein aggregation and neurodegeneration. Despite advances in understanding the neurobiology of NDD, there are no approved DMTs.Defining disease-modification is critical to drug-development programs. A DMT is an intervention that produces an enduring change in the trajectory of clinical decline of an NDD by impacting the disease processes leading to nerve cell death. A DMT is neuroprotective, and neuroprotection will result in disease modification. Disease modification can be demonstrated in clinical trials by a drug-placebo difference in clinical outcomes supported by a drug-placebo difference on biomarkers reflective of the fundamental pathophysiology of the NDD. Alternatively, disease modification can be supported by findings on a staggered start or delayed withdrawal clinical trial design. Collecting multiple biomarkers is necessary to support a comprehensive view of disease modification.Disease modification is established by demonstrating an enduring change in the clinical trajectory of an NDD based on intervention in the fundamental pathophysiology of the disease leading to nerve cell death. Supporting data are collected in clinical trials. Effectively defining a DMT will assist in NDD drug development programs.
SAT0385 Similarities and differences between patients fulfilling non-radiographic axial spondyloarthritis and undifferentiated spondyloarthritis criteria: results from the esperanza cohort
Authors: A Juan Mas, X Juanola Roura, E de Miguel Mendieta, E Estévez Collantes, JC Quevedo Abeledo, E Blanco-Morales Alonso, V Navarro-Compán
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patients with spondyloarthritis (SpA) were classified in five subgroups: ankylosing spondylitis (AS), psoriatic arthritis, arthritis associated with inflammatory bowel disease, reactive arthritis and undifferentiated SpA (uSpA). ASAS criteria classify patients in peripheral SpA and axial SpA (axSpA), being the latest classified in two groups: classical AS and non-radiographic axSpA (nr-axSpa). Whether or not patients with nr-axSpA represent the same group of patients that used to be classified as uSpA remains unclear. <h3>Objectives</h3> To evaluate the similarities and differences between patients with predominant axial disease classified currently as nr-axSpA versus those traditionally classified as uSpA. <h3>Methods</h3> Baseline data from the ESPeranza program (a multicenter national initiative to early diagnose SpA between 2008 and 2011) was used. Inclusion criteria for this program were: age &lt;45 years and inflammatory back pain plus ≥1 SpA features with symptoms duration between 3 and 24 months. Demographic, clinic, laboratory and image results were compared between two groups: 182 patients with nr-axSpA and 166 patients classified as uSpA. In order to get a deeper knowledge of the differences between nr-axSpA and uSpA, we also compared: i) 88 patients only classified as nr-axSpA, ii) 72 patients only classified as uSpA; iii) 94 patients fulfilling both criteria. Student-t test for continuous variables and Pearson Chi-square test for categorical variables were used. <h3>Results</h3> Compared to patients classified as uSpA patients with nr-axSpA were younger, had HLA-B27 positive more frequently and higher values of CRP. On the other hand, they had history of SpA less frequently and lower values for BASDAI, BASFI and ASQoL (table). No differences were observed for gender, work incapacity, dactilitis, enthesitis, Pt9s and Phy9s VAS, BASMI and BASRI. <h3>Conclusions</h3> Compared with patients traditionally classified as uSpA, patients who are currently classified as nr-axSpA are diagnosed earlier, are more frequently HLA-B27 carriers and have higher disease activity according to objective parameters. On the other hand, they report lower values for patient reported outcomes. <h3>Disclosure of Interest</h3> None declared
Dreams Deferred — The Public Health Consequences of Rescinding DACA
Authors: Atheendar S. Venkataramani, Alexander C. Tsai
Journal: New England Journal of Medicine (2017)

The evidence indicates that rescinding the Deferred Action for Childhood Arrivals (DACA) program will have profound adverse population-level effects on mental health — effects that may be potentiated by the broader hostile political climate surrounding immigration.
OP0062 Assessment of biotherapies' efficacy in blau syndrome: data from an international retrospective cohort of 23 cases
Authors: O Fogel, A Cantagrel, K Ikeda, P Sève, E Hachulla, R Cimaz, P Sfriso, L Punzi, C Pajot, E Grouteau, S Tellier, C Galeotti, S Grotto, J Sibilia, B Bodaghi, I Touitou, C Miceli-Richard
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Blau Syndrome (BS) is a rare autosomal dominant inflammatory disease characterized by early-onset granulomatous arthritis, dermatitis and recurrent uveitis (1). Mutations in the nucleotide-binding domain (NBD) of <i>CARD15/NOD2</i> gene (mainly R334W, R334Q and L469F) have been identified in Blau syndrome (2). Despite advances in BS knowledge, patients9 functional prognosis remains uncertain, BS potentially leading to visual impairment or joint deformities. Optimal treatments have not been determinated yet. <h3>Objectives</h3> To assess the efficacy of several biologic agents in this affection <h3>Methods</h3> We conduct an observational, international, retrospective cohort of BS collecting clinical, biological and histological data. <h3>Results</h3> Among the twenty-three patients included in the cohort, 14 patients were treated by one or several lines of biologic agents, mostly by TNF blockers (80%), IL1 blockers (16%) or treatment targeting CTLA-4 (4%). Fifty-seven percent of patients achieved remission after almost two lines of treatment (1.75 lines; [0.8–2.7]). Association with csDMARDs did not significantly improved response to biologics. Considering the 3 mains symptoms independently, TNF blockers were associated with a better response in case of articular or skin features but less effective in case of ocular involvement, a clinical situation in which IL-1 targeting should be preferentially chosen. <h3>Conclusions</h3> Biologic treatments appeared to be effective in BS but additional data prospectively collected are still needed in order to define their place in the therapeutic strategy in order to minimize functional consequences. <h3>References</h3> Blau EB. Familial granulomatous arthritis, iritis, and rash. The Journal of pediatrics. 1985 Nov;107(5):689–93. PubMed PMID: 4056967. Epub 1985/11/01. eng. Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Hafner R, et al. CARD15 mutations in Blau syndrome. Nature genetics. 2001 Sep;29(1):19–20. PubMed PMID: 11528384. Epub 2001/08/31. eng. <h3>Disclosure of Interest</h3> None declared
When Is a Little Breast Tissue Too Much?
Authors: Helen M. Johnson, Jan H. Wong
Journal: JAMA Surgery (2017)

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Fistula recurrence, pregnancy, and childbirth following successful closure of female genital fistula in Guinea: a longitudinal study
Authors: Alexandre Delamou, Therese Delvaux, Alison M El Ayadi, Vandana Tripathi, Bienvenu S Camara, Abdoul H Beavogui, Lauri Romanzi, Bethany Cole, Patrice Bouedouno, Moustapha Diallo, Thierno H Barry, Mandian Camara, Kindy Diallo, Alain Leveque, Wei-Hong Zhang, Vincent De Brouwere
Journal: The Lancet Global Health (2017)

Female genital fistula is a devastating maternal complication of delivery in developing countries. We sought to analyse the incidence and proportion of fistula recurrence, residual urinary incontinence, and pregnancy after successful fistula closure in Guinea, and describe the delivery-associated maternal and child health outcomes.We did a longitudinal study in women discharged with a closed fistula from three repair hospitals supported by EngenderHealth in Guinea. We recruited women retrospectively (via medical record review) and prospectively at hospital discharge. We used Kaplan-Meier methods to analyse the cumulative incidence, incidence proportion, and incidence ratio of fistula recurrence, associated outcomes, and pregnancy after successful fistula closure. The primary outcome was recurrence of fistula following discharge from repair hospital in all eligible women who consented to inclusion and could provide follow-up data.481 women eligible for analysis were identified retrospectively (from Jan 1, 2012, to Dec 31, 2014; 348 women) or prospectively (Jan 1 to June 20, 2015; 133 women), and followed up until June 30, 2016. Median follow-up was 28·0 months (IQR 14·6-36·6). 73 recurrent fistulas occurred, corresponding to a cumulative incidence of 71 per 1000 person-years (95% CI 56·5-89·3) and an incidence proportion of 18·4% (14·8-22·8). In 447 women who were continent at hospital discharge, we recorded 24 cases of post-repair residual urinary incontinence, equivalent to a cumulative incidence of 23·1 per 1000 person-years (14·0-36·2), and corresponding to 10·3% (5·2-19·6). In 305 women at risk of pregnancy, the cumulative incidence of pregnancy was 106·0 per 1000 person-years, corresponding to 28·4% (22·8-35·0) of these women. Of 50 women who had delivered by the time of follow-up, only nine delivered by elective caesarean section. There were 12 stillbirths, seven delivery-related fistula recurrences, and one maternal death.Recurrence of female genital fistula and adverse pregnancy-related maternal and child health outcomes were frequent in women after fistula repair in Guinea. Interventions are needed to safeguard the health of women after fistula repair.Belgian Development Cooperation (DGD), Institute of Tropical Medicine of Antwerp (ITM), and Maferinyah Training and Research Center in Rural Health (Guinea).
SAT0569 Outcome of patients with systemic rheumatic diseases admitted in intensive care unit: a prognostic study of 98 patients
Authors: A Malézieux-Picard, H Hivernat, N Martis, J-G Fuzibet, G Bernardin, V Queyrel
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic rheumatic diseases (SRD) are a rare and heterogeneous group of diseases, associated with a high mortality rate due to the natural evolution of the disease and/or consequences of their specific treatments (infections, toxicity). <h3>Objectives</h3> To describe the clinical features, outcomes and prognostic factors for patients with SRD admitted to the intensive care unit (ICU). <h3>Methods</h3> Single-center retrospective observational cohort study of 98 patients with SRD over an 11-year period in an ICU of a French teaching hospital. <h3>Results</h3> Ninety-eight patients (57% women; median age, 57 years [19–81years]) accounted for 108 admissions. Connective tissue disease (primarily systemic lupus erythematosus) and systemic vasculitides (mainly ANCA-associated vasculitides) represented respectively 55% and 30% of SRD. For nineteen patients, diagnosis of SRD was made at admission. Reasons for admission were: SRD exacerbations (43%), isolated infections (34%), SRD exacerbations associated with infections (12%) or other (11%). Respiratory failure was the most common organ dysfunction. Mechanical ventilation was necessary for 43 patients (44%), vasoactive drugs for 47 (48%) and extra-renal replacement therapy for 38 (39%). The ICU mortality rate was 30% and 37% one year after admission. Infection was the main cause of death (69%). The factors significantly associated with mortality in the ICU were (multivariate analysis): diabetes, cardiovascular diseases and immunosuppressive treatments on admission. At 1 year of follow-up, additional risk factors were: number of organ dysfunction at ICU admission and mechanical ventilation. It is to be noted that at 1 year of follow-up, diabetes was not anymore a prognostic factor. <h3>Conclusions</h3> Patients with SRD admitted to the ICU have a severe prognosis. Causes of mortality are mainly infections. Our study points out the importance of vaccination and developing new therapeutic strategies. Diagnosis of SRD in the ICU is not rare and should be systematically considered on admission. Prognostic factors of mortality in the ICU were patient comorbidities and immunosuppressive therapy at admission. In addition, mechanical ventilation and multiple organ failure were risk factors for mortality at 1 year. <h3>Disclosure of Interest</h3> None declared