tbuckley/cabot-search huggingface dataset:
SAT0471 Abnormal nailfold capillaroscopic patterns are common in underweight subjects with raynaud’s phenomenon
Authors: A. Eman Abdulle, A.M. van Roon, M.M. Habing, A.J. Stel, A.J. Smit, H. van Goor, D.J. Mulder
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Despite the extensive research on this subject, the exact pathogenesis of RP still remains incompletely understood. The current view on this rather complex phenomena is that the imbalance between vasoconstriction and vasodilatation is purely functional and that structural vascular changes do not occur in PRP patients Although RP is a frequently occurring problem in underweight patients, microvascular changes have never been (structurally) investigated. <h3>Objectives</h3> The aim of the current study was to investigate the relationship between microvascular abnormalities and body mass index (BMI) in subjects with Raynaud's phenomenon (RP), without an underlying connective tissue disease. <h3>Methods</h3> Nailfold capillaroscopic patterns (NCP) were retrospectively assessed in 352 RP patients, without an underlying systemic disease (e.g. negative serology tests, and no signs of organ involvement). Patient characteristics were obtained and patients were divided by BMI category: underweight (BMI &lt;18.5 kg/m²), normal weight (BMI 18.5–24.99 kg/m²), and overweight (BMI ≥25 kg/m²). Patterns were deemed abnormal if the mean capillary count was &lt;20 per 3 mm, or mean number of dilated capillaries per finger was &gt;3, or any giant capillaries were observed. <h3>Results</h3> Approximately 70% of the underweight patients showed an abnormal NCP. This was irrespective of age and smoking behaviour. Underweight RP patients had the highest mean count of dilated capillaries (5.14 for BMI &lt;18.5 kg/m<sup>2</sup>; 4.17 BMI for 18.5–24.99 kg/m²; 2.61 for BMI ≥25 kg/m², p=0.002) and giant capillaries (1.01 for BMI &lt;18.5 kg/m<sup>2</sup>; 0.48 BMI 18.5–24.99 kg/m²; 0.23 BMI ≥25 kg/m², p=0.024). However capillary loss was not found to be significantly different (p=0.458). Furthermore, mean number of capillaries (r=0.260, p&lt;0.001), mean number of dilated capillaries (r=−0.225, p&lt;0.001) and mean number of giant capillaries (r=−0.221, p&lt;0.001) were found to be associated with BMI. <h3>Conclusions</h3> Our findings indicate NCP abnormalities are more frequently observed in underweight individuals, indicating that microvascular changes may occur independently of an underlying connective tissue disease. These findings may alert clinicians that (perivascular) adipose tissue may play a crucial role in the occurrence of Raynaud's phenomenon. <h3>Disclosure of Interest</h3> None declared
Gene therapy targeting SARM1 blocks pathological axon degeneration in mice
Authors: Stefanie Geisler, Shay X. Huang, Amy Strickland, Ryan A. Doan, Daniel W. Summers, Xianrong Mao, Jiwoong Park, Aaron DiAntonio, Jeffrey Milbrandt
Journal: The Journal of Experimental Medicine (2019)

Axonal degeneration (AxD) following nerve injury, chemotherapy, and in several neurological disorders is an active process driven by SARM1, an injury-activated NADase. Axons of SARM1-null mice exhibit greatly delayed AxD after transection and in models of neurological disease, suggesting that inhibiting SARM1 is a promising strategy to reduce pathological AxD. Unfortunately, no drugs exist to target SARM1. We, therefore, developed SARM1 dominant-negatives that potently block AxD in cellular models of axotomy and neuropathy. To assess efficacy in vivo, we used adeno-associated virus-mediated expression of the most potent SARM1 dominant-negative and nerve transection as a model of severe AxD. While axons of vehicle-treated mice degenerate rapidly, axons of mice expressing SARM1 dominant-negative can remain intact for >10 d after transection, similar to the protection observed in SARM1-null mice. We thus developed a novel in vivo gene therapeutic to block pathological axon degeneration by inhibiting SARM1, an approach that may be applied clinically to treat manifold neurodegenerative diseases characterized by axon loss.
AB0243 Real world clinical trial comparing the patient reported outcomes measurement information system short forms and profiles to cdai disease classification in rheumatoid arthritis patients
Authors: J. Curtis, S. Schwartzman, S. Kafka, D. Parenti, S. Black, S. Xu, W. Langholff, C.O. Bingham
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Pt reported outcomes (PROs) play a role in disease evaluation, therapeutic assessment and care of RA pts. The Pt Reported Outcomes Measurement Information System (PROMIS [P]) questionnaires developed by NIH have been used in RA clinical practice and studies.<sup>Bartlett 2015</sup> AWARE (Comparative and Pragmatic Study of Golimumab Intravenous [IV] Versus Infliximab in RA) is a noninterventional, multi-centre US-based, study of golimumab IV (GLM) vs. infliximab (IFX) in RA and will assess disease activity (DA) and use PROs. <h3>Objectives</h3> 1. PRO assessments of Pt response to treatment using PROMIS-29 Profile v2.0 (P29v2), P Pain Interference Short Form-6b (PISF) and P Fatigue Short Form-7a (FSF), and Clinical DA Index (CDAI), and 2. assess relationship between PROMIS T-score and CDAI category. <h3>Methods</h3> AWARE is a 1200 adult pt study enrolling pts on initiation of treatment w/GLM or IFX. We report an interim analysis (IA) of 747 pts' baseline PROMIS questionnaire and CDAI scores. PROMIS results are normalised to the US population, reported as a "T-score" (mean=50, SD=10) w/higher scores indicating more of the trait measured. PROMIS T–scores were compared between High DA (HDA) w/Moderate DA (MDA), low DA (LDA) and remission. Data shown are mean ±SD. Statistical testing compared T-scores across CDAI categories using ANOVA for these data (before drug admin). Data from GLM and IFX pts are combined. <h3>Results</h3> Mean baseline CDAI score was 32.5±15.4, w/71.7% of pts in HDA, 22.5% in moderate MDA, 5.2% in LDA and 0.7% in remission. PROMIS T-scores were compared to 4 CDAI categories. HDA Pt T-scores were (*, p&lt;0.05) different from those of MDA, LDA and Remission pts (except between HDA and remission for Anxiety, Depression and Sleep Disturbance domains). <h3>Conclusions</h3> Our interim findings demonstrate the feasibility of using PROMIS short forms and profiles to evaluate RA Pts in clinical trials. These results confirm the domain validity of PROMIS measures according to CDAI DA category. PROMIS measures show the range of impact across multiple domains of physical, emotional, and social health experienced by RA Pts. <h3>Disclosure of Interest</h3> J. Curtis Grant/research support from: Janssen Scientific Affairs, LLC, S. Schwartzman Grant/research support from: Janssen Scientific Affairs, LLC, S. Kafka Employee of: Janssen Scientific Affairs, LLC, D. Parenti Employee of: Janssen Scientific Affairs, LLC, S. Black Employee of: Janssen Scientific Affairs, LLC, S. Xu Employee of: Janssen Research and Development, LLC, W. Langholff Employee of: Janssen Research and Development, LLC, C. Bingham III Grant/research support from: Janssen Scientific Affairs, LLC
SP0033 Delay in treatment from the gp perspective
Authors: B. Fautrel
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Inflammatory joint disease (IJD), i.e., rheumatoid arthritis, psoriatic arthritis or spondyloarthritis, require rapid referral to rheumatologists to get optimal specialised care, since early diagnosis and early treatment are 2 key prognosis factors. To achieve this objective, education of general practioners (GP) is of dramatic importance, since they have to detect early IJD symptoms which are sometimes partial and non specific. The lecture will identify the key elements that have to be communicated to GPs to improve their skills in detecting IJD at very steps, as well as the most important elements to make rheumatologist appointment available to them. <h3>Disclosure of Interest</h3> None declared
FRI0090 Association of body composition with disease activity and disability in rheumatoid arthritis
Authors: K.M. Son, S.Y. Lee, S.H. Kang, Y.I. Seo, H.A. Kim
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic form of inflammatory arthritis characterised by multiple joint involvement and significant disability. Previous studies showed that RA is associated with considerable changes in body composition, lipid profile, adipokines and insulin sensitivity <h3>Objectives</h3> To explore the association of body composition with pain, disease activity and disability in rheumatoid arthritis (RA) <h3>Methods</h3> Three hundred thirty five patients with RA visiting the Hallym University Sacred Hospital underwent body composition measurement with inbody analyzer and examined the disease activity score (DAS28). The association of body mass index (BMI), body fat mass and skeletal muscle mass with DAS28, DAS28-P (an index derived to measure subjective component of DAS28), pain VAS and disability measured with the health assessment questionnaire (HAQ) was explored. Obesity was defined as BMI ≥25 kg/m<sup>2</sup>. Pain VAS was dichotomized as ≤40 and&gt;40. Low HAQ score was defined as ≤0.5. Logistic regression was divided in female versus male. <h3>Results</h3> Mean age of patients was 56±11.9 years and 84.8% were female. The median(IQR) disease durations was 6 (3.5–9) years and mean DAS28 score was 3.55±1.14. Mean BMI was 23.6±3.7 kg/m<sup>2</sup> and 109 patients (32.5%) were obese. Obese patients had higher CRP level (1.68 ml/dL vs 0 ml/dL, p=0.013), ESR level (25 mm/hr vs 18 mm/hr, p=0.032), pain VAS score (40 vs 35, p=0.045), and higher DAS28-ESR score (3.75±1.18 vs 3.46±1.11, p=0.031), than non obese patients. In multivariable regression analysis, DAS28 score in female was positively associated with current steroid dose, HAQ and body fat mass. In univariable logistic regression, higher pain VAS category in female was associated with older age, higher BMI and higher body fat mass. In multivariable logistic regression analysis, higher HAQ score in female was associated with older age, higher DAS28, higher body fat/skeletal muscle ration and lower skeletal muscle mass. In multivariable regression analysis, DAS28-P score in female was positively associated with higher body fat/skeletal muscle ratio and negatively associated with positivity of anti-CCP. <h3>Conclusions</h3> Body compositions such as body fat mass and skeletal muscle mass are significantly associated with pain and disability in RA patients <h3>Disclosure of Interest</h3> None declared
Residential greenness and mortality in oldest-old women and men in China: a longitudinal cohort study
Authors: John S Ji, Anna Zhu, Chen Bai, Chih-Da Wu, Lijing Yan, Shenglan Tang, Yi Zeng, Peter James
Journal: The Lancet Planetary Health (2019)

BackgroundExposure to natural vegetation, or greenness, might affect health through several pathways, including increased physical activity and social engagement, improved mental health, and reductions in exposure to air pollution, extreme temperatures, and noise. Few studies of the effects of greenness have focused on Asia, and, to the best of our knowledge, no study has assessed the effect on vulnerable oldest-old populations. We assessed the association between residential greenness and mortality in an older cohort in China.MethodsWe used five waves (February, 2000–October, 2014) of the China Longitudinal Healthy Longevity Survey (CLHLS), a prospective cohort representative of the general older population in China. We assessed exposure to greenness through satellite-derived Normalised Difference Vegetation Index (NDVI) values in the 250 m and 1250 m radius around the residential address for each individual included in the study. We calculated contemporaneous NDVI values, cumulative NDVI values, and changes in NDVI from the start of the study over time. The health outcome of the study was all-cause mortality, excluding accidental deaths. Mortality rate ratios were estimated with Cox proportional hazards models, adjusted for age, sex, ethnicity, marital status, geographical region, childhood and adult socioeconomic status, social and leisure activity, smoking status, alcohol consumption, and physical activity.FindingsAmong 23 754 individuals (mean age at baseline 93 years [SD 7·5]) totaling 80 001 person-years, we observed 18 948 deaths during 14 years of follow-up, between June, 2000, and December, 2014. Individuals in the highest quartile of contemporaneous NDVI values had 27% lower mortality than those in the lowest quartile for the 250 m radius (hazard ratio [HR] 0·73, 95% CI 0·70–0·76), and 30% lower mortality for the 1250 m radius (0·70, 0·67–0·74). No clear association was observed for cumulative NDVI measurements and mortality. We did not detect an association between area-level changes in NDVI and mortality.InterpretationOur research suggests that proximity to more green space is associated with increased longevity, which has policy implications for the national blueprint of ecological civilisation and preparation for an ageing society in China.FundingBill & Melinda Gates Foundation, US National Institute on Aging, US National Institute of Health, Natural Science Foundation of China, UN Population Fund, China Social Sciences Foundation, and Hong Kong Research Grants Council.
THU0282 The impact of comorbidities on physical function in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PSA) attending rheumatology clinics
Authors: C. Fernández-Carballido, M. Martín-Martínez, C. García-Gómez, S. Castañeda, C. González-Juanatey, F. Sánchez, R. García-Vicuña, C. Erausquin, J. Lopez-Longo, M. Sánchez-González, A. Corrales, E. Quesada, E. Chamizo, C. Barbadillo, J. Bachiller, T. Cobo, A. Turrión, E. Giner, J. Llorca, M. González-Gay
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Regardless of disease activity, functional status gets worse in patients with rheumatoid arthritis (RA) with comorbidities. However, the impact of comorbidities on physical function in ankylosing spondylitis (AS) and psoriatic arthritis (PsA) is less known. <h3>Objectives</h3> To assess the impact of comorbidities on physical function (PF) in patients with AS and PsA. <h3>Methods</h3> Analysis of the baseline visit from the ongoing multicentric, observational, prospective, CARMA study. Data from patients with AS and PsA were analysed. Two different adjusted multivariate models were performed, where PF was the dependent variable (BASFI in AS and HAQ in PsA) and the following independent variables: comorbidities, a proxy for the Charlson index (ChI) (minimum 0; maximum 11), sociodemographic, disease activity (ESR, CRP and BASDAI in AS; while SJC, TJC, CRP, ESR, DAS, dactylitis count and PASI in PsA) and duration, radiographic damage and treatments. Results are presented as β coefficients and p-values. <h3>Results</h3> 738 patients with AS and 721 with PsA included (mean age at inclusion 48.1±11.7 and 51.8±12 years, respectively). AS patients: median BASFI 3.1 [interquartile range (IQR): 1.3–5.2], BASDAI 3.5 [IQR: 1.7–5.3], mean ChI 1.32±0.73. PsA patients: HAQ 0.4 [IQR: 0.0–0.9], DAS28 2.9 [IQR: 2.0–3.8], mean ChI 1.30±0.66. A ChI &gt;1 found in 21% of the patients. Hypertension in 25.7% and 29.5%; hypercholesterolemia in 27% and 35.6% and diabetes in 7.6% and 9.2% of the patients with AS and PsA, respectively. Cardiovascular events occurred in 7.6% AS and 7.2% PsA, in most cases after the rheumatic disease diagnosis. Only patients with PsA with higher ChI showed worse adjusted physical function (β: 0.09; p=0.03). Also female sex (β: 0.03; p=0.001), obesity (β: 0.09; p=0.04), disease duration (β: 0.01; p=0.009), NSAIDs (β: 0.1; p=0.02), corticosteroids (β: 0.12; p=0.02) and biologics (β: 0.15; p=0.07) were associated with worse function in patients with PsA. In contrast, a higher educational level was associated with less disability. In patients with AS, thyroid disease (β: 1.19, p=0.002) and raised ESR (β: 0.01, p=0.010) were independently associated with function. <h3>Conclusions</h3> The presence of comorbidities in patients with PsA is independently associated with worse physical function, similar to what happens in RA. Early detection and control may yield an integral management of the disease and better final outcomes. <h3>Disclosure of Interest</h3> None declared
Intrahepatic fibrin(ogen) deposition drives liver regeneration after partial hepatectomy in mice and humans
Authors: Dafna Groeneveld, David Pereyra, Zwanida Veldhuis, Jelle Adelmeijer, Petra Ottens, Anna K. Kopec, Patrick Starlinger, Ton Lisman, James P. Luyendyk
Journal: Blood (2019)
Abstract 19090: Identification and Classification of Descending Aorta Re-entry Sites in Type I Aortic Dissection
Authors: Konstantinos Tsagakis, Daniel S Dohle, Rolf A Jánosi, Thomas Schlosser, Jaroslav Benedik, Daniel Wendt, Matthias Thielmann, Raimund Erbel, Heinz Jakob
Journal: Circulation (2015)

Introduction: False lumen patency along the downstream aorta after proximal aortic surgery for acute type I aortic dissection (AD) is associated with poor prognosis. We visualized and evaluated intraoperatively the position and morphology of distal re-entry sites in type I/III AD patients for treatment definition. Methods: From 01.2008 - 05.2015 212 patients underwent surgery for AD via median sternotomy. In 124, acute (n=87) or chronic (n=37) type I/ III AD, a flexible videoscope, called angioscope, was used during the open arch repair for visualization of the descending aorta. The procedure was performed under isolated selective cerebral perfusion and hypothermic circulatory arrest distally. The position of the distal intimal lesions was defined according to the distance to left subclavian artery (LSA) origin. The lesions were classified as disrupted intercostal arteries, vertical- and oval- shaped lesions and circumferential obliteration of the intimal wall. The information was used for ad hoc extension of the aortic treatment. Results: In 102/124 a total of 188 intimal lesions were identified, mean±SD 1.47±1.22/patient. In 22 no re-entry was found. Within 5cm, 6-10cm, 11-15cm and 16-20cm distal from the LSA reentries were found in 73%, 31%, 14% and 11% of the patients, respectively. Disrupted intercostal arteries were found in 42%, vertical in 36% and oval in 19%. A circumferential obliteration of the intimal wall was identified in 3% and only in chronic AD. Re-entries were excluded using the frozen elephant trunk (FET) technique in 94/124 obtaining a false lumen thrombosis in 94%. The angioscopy rescued the FET procedure from severe complication in 7 and guided antegradely a FET extension by a second graft in 2 patients. Conclusions: The angioscopy of the downstream aorta enables the identification and classification of re-entries in patients underwent open arch surgery for AD. Visualization of the descending aorta pathology warrants the safety of endovascular treatment via the open arch.
Immunotherapy for the First-Line Treatment of Patients with Metastatic Non–Small Cell Lung Cancer
Authors: Pablo Martinez, Solange Peters, Timothy Stammers, Jean-Charles Soria
Journal: Clinical Cancer Research (2019)

Immunotherapy has fundamentally changed the treatment landscape for many patients with cancer. mAbs targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen-4 immune checkpoints have received regulatory approval across a wide range of tumor types, including non-small cell lung cancer (NSCLC). Indeed, treatment approaches for a majority of patients with newly diagnosed metastatic NSCLC are evolving rapidly. Only for the small proportion of patients with metastatic NSCLC and genomic-driven tumors with EGFR or anaplastic lymphoma kinase (ALK)-sensitizing mutations (5%-15%), and possibly BRAF mutations and ROS rearrangements, have initial treatment recommendations remained unchanged, with specific tyrosine kinase inhibitors as the preferred therapy. For the remaining patients, an immunotherapy-based regimen alone or in combination with chemotherapy is now the preferred option based on high-level evidence obtained from randomized controlled trials and in accordance with all available guidelines. Deciding between therapeutic options can be difficult due to the lack of direct cross-comparison studies, differences in chemotherapies and stratification factors, and differences in study populations resulting from inclusion criteria such as histology, PD-L1 expression, or tumor mutational burden (TMB). In an attempt to aid the decision-making process, we discuss and summarize the most recent data from studies using immunotherapies for the treatment of patients with previously untreated metastatic NSCLC.
THU0048 Pro-inflammatory il-17a-producing ccr6+ t helper memory cells change into anti-inflammatory cells with regulatory capacity upon exposure to active vitamin d
Authors: W. Dankers, N. Davelaar, J.P. van Hamburg, J. van de Peppel, E.M. Colin, E. Lubberts
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In autoimmune diseases such as rheumatoid arthritis (RA), an important therapeutic goal is to normalise the imbalance between pro- and anti-inflammatory cells. In RA, especially pro-inflammatory CCR6 +T helper (Th) memory cells, characterised by IL-17A production and RORC expression, are elevated and more activated compared to healthy controls. Therefore, modulating these cells to become anti-inflammatory could contribute to restoring the immunological balance. Interestingly, the active vitamin D metabolite 1,25(OH)<sub>2</sub>D<sub>3</sub> inhibits pro-inflammatory cytokine production by CCR6 +Th memory cells. <h3>Objectives</h3> We investigated whether 1,25(OH)<sub>2</sub>D<sub>3</sub> can induce an anti-inflammatory phenotype in these memory CCR6 +Th cells. <h3>Methods</h3> CCR6 +Th memory cells, excluding Tregs, were sorted from treatment-naïve early RA patients or healthy controls and cultured with or without 1,25(OH)<sub>2</sub>D<sub>3</sub>. Effects were analysed using microarray, RT-PCR, ELISA or flow cytometry. Functional properties were assessed via suppression and chemotaxis assays. <h3>Results</h3> 1,25(OH)<sub>2</sub>D<sub>3</sub> inhibits pro-inflammatory cytokines such as IL-17A, IL-17F and IL-22 in CCR6 +Th memory cells from both healthy controls and RA patients. This is accompanied by induction of anti-inflammatory factors, including IL-10 and CTLA4. Interestingly, these formerly pathogenic cells suppress proliferation of autologous CD3 +T cells, similar to classical Tregs. Importantly, the modulated memory cells still migrate towards the site of inflammation, modelled by synovial fluid, and retain their suppressive capacity in this environment. <h3>Conclusions</h3> Committed pro-inflammatory IL-17A-producing CCR6 +Th memory cells shift towards anti-inflammatory cells with functional regulatory capacities upon exposure to active vitamin D. This process can contribute to restoring the immunological balance and inhibiting synovial inflammation in RA. <h3>Disclosure of Interest</h3> None declared
CD70 defines a subset of proinflammatory and CNS-pathogenic TH1/TH17 lymphocytes and is overexpressed in multiple sclerosis
Authors: Tessa Dhaeze, Laurence Tremblay, Catherine Lachance, Evelyn Peelen, Stephanie Zandee, Camille Grasmuck, Lyne Bourbonnière, Sandra Larouche, Xavier Ayrignac, Rose-Marie Rébillard, Josée Poirier, Boaz Lahav, Pierre Duquette, Marc Girard, Robert Moumdjian, Alain Bouthillier, Catherine Larochelle, Alexandre Prat
Journal: Cellular and Molecular Immunology (2019)
Abstract 17274: The Number of Risk Factors Stratifies the Quality of Exercise Performance in the Euro-ex Trial: A Population Based Trial in Apparently Healthy Individuals
Authors: Pietro L Laforgia, Francesco Bandera, Marco Guazzi
Journal: Circulation (2017)

Background: Exercise performance at CPET is a valuable tool to stratify prognosis in heart failure (HF) patients. Despite a strong rationale, less is known about the role of CPET in the general pop...