tbuckley/cabot-search huggingface dataset:
THU0612 Bone sarcoidosis: a retrospective multicenter study of 27 cases
Authors: C. Glanowski, R. Mestiri, L. Bialé, T. Carmoi, D. Lechevalier, G. Leroux, D. Saadoun, C. Chapelon-Abric, P. Cacoub
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Studies on bone involvement of sarcoidosis (BS) are scarse. <h3>Objectives</h3> To analyse in depth main features, treatments and follow up of patients presenting a BS. <h3>Methods</h3> Among 926 patients with a proved sarcoidosis from four tertiary hospitals in Paris (France) seen between 2000 and 2015, all cases of BS were retrospectively analysed for demography, clinical features, biological tests and imaging results. Inclusion criteria were a) a bone biopsy with epithelioid granuloma and no casein necrosis, or b) radiological evidence of BS, after exclusion of other diagnoses. <h3>Results</h3> 27 out 926 (2.9%) sarcoidosis patients fullfilled inclusion criteria for BS. Most patients were caucasian (56%), M/F sex ratio 1.5, 30% were active smokers, mean age at sarcoidosis diagnosis was 39±12 years and at BS diagnosis 43±11 years. Extra-osseous involvement of sarcoidosis was found in lymph nodes (93%), lungs (78%), skin (52%), CNS (33%), ENT (33%), and heart (19%). BS was symptomatic in 15/27 (56%) patients i.e. bone pain (15/15), local inflammation (5/15), bone deformation (3/15), arthritis (4/15), and myalgia (5/15). BS was never the revealing symptom of sarcoidosis. BS was more frequently symptomatic when it was a Perthes-Jüngling osteitis and an appendicular skeletton involvement. On imaging exams, BS lesions were found at the spine skeletton alone (14/27, 52%), appendicular skeletton alone (10/27, 37%) or both (3/27, 11%). BS lesions had an aspect of pseudo-metastasis (59%), micro-cysts (Perthes-Jungling, 37%) or Paget disease (4%). Bone lesion was unique in 22% and 26% of patients had more than 10 lesions. When a bone biopsy was done it always confirmed the diagnosis (n=9); in all other cases extra-osseous biopsies confirmed the diagnosis of sarcoidosis. Nine patients received a treatment for BS, i.e. prednisone (n=8, 0.25–1 mg/kg/day), hydroxychloroquine (n=8), and methotrexate (n=5). Response to treatment was complete (n=3), partial (n=4) or nul (n=2). Of note, 21 out of 27 patients received an immunosuppressant for a severe form of systemic sarcoidosis (n=11) or for a steroid-sparing effect (n=10). A relapse of BS was noted in 13 patients, with a mean number of relapse of 2.<sup>1–24</sup> After a mean follow up of 49 months, BS was in complete remission (8/27, 30%), partial remission (16/27, 59%) or remained active (3/27, 11%). <h3>Conclusions</h3> Bone involvement remains a rare manifestation of sarcoidosis. It was symptomatic in 56% of patients, mainly when Perthes-Jüngling osteitis and appendicular skeletton involvement were present. Extra-osseous involvement of sarcoidosis were always present at the time of BS diagnosis. Treatment remains difficult with frequent relapses. <h3>Disclosure of Interest</h3> None declared
SAT0588 Rheumatologic immune-related adverse effects of checkpoint inhibitor therapy: a single centrecohort of 29 patients
Authors: M.D. Richter, C.S. Crowson, L.A. Kottschade, H.D. Finnes, S.N. Markovic, U. Thanarajasingam
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Immune checkpoint inhibitors for advanced malignancy are associated with a wide range of autoimmune phenomena known as immune-related adverse effects (irAEs).<sup>1</sup> Knowledge of irAEs resembling rheumatologic diseases is limited to case reports and small case series, and there are currently no specific guidelines on how to diagnose or manage these patients. <h3>Objectives</h3> To describe the prevalence, clinical presentation, and management of patients with rheumatologic irAEs from checkpoint inhibitor therapy. <h3>Methods</h3> We retrospectively studied all patients who received a checkpoint inhibitor for any malignancy at Mayo Clinic Rochester, Minnesota between January 1 st, 2011 and November 1 st, 2017. From these patients we identified those with possible rheumatologic irAEs using diagnostic codes, search terms, and the presence of specific laboratory testing. <h3>Results</h3> Of the 1216 patients who received any checkpoint inhibitor, we identified 29 who were clinically diagnosed with a rheumatologic irAE. The diagnosis was confirmed by a rheumatologist in all but 3 cases. Mean follow up time from irAE diagnosis was 1.5 years (±1.1). Seven patients had a pre-existing autoimmune disease with one of these being a rheumatologic disease (Giant-cell arteritis). irAEs included inflammatory arthritis,<sup>15</sup> sicca syndrome,<sup>3</sup> systemic sclerosis,<sup>3</sup> myositis,<sup>3</sup> vasculitis,<sup>3</sup> spondylitis,<sup>1</sup> and polymyalgia rheumatica.<sup>1</sup> Only one irAE represented a disease flare. Mean time from initiation of checkpoint inhibitor therapy to onset of irAE symptoms was 15.0 weeks (±10.8). 24 patients (83%) were treated with corticosteroids and 8 patients (28%) received additional therapy with disease modifying drugs. Mean treatment duration for these 24 patients was 19.5 weeks (±21.7), and 8 patients (33%) had complete symptom resolution within the study period. Rheumatologic irAEs resulted in discontinuation of checkpoint inhibitor therapy in 7 patients (24%). <h3>Conclusions</h3> Our study represents one of the largest cohorts of rheumatologic irAEs to date. Most patients required long courses of treatment with only a minority achieving complete symptom resolution. Prospective, multicenter studies are necessary to determine the optimal management of these emerging disorders. <h3>Reference</h3> [1] Michot JM, Bigenwald C, Champiat S, Collins M, Carbonnel F, Postel-Vinay S, et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. European journal of cancer2016;54:139–48. <h3>Disclosure of Interest</h3> None declared
THU0709 Reumaheart – a portuguese population based study on cardiovascular risk factors
Authors: V. M, Da Silva Domingues, A. Rodrigues, S. Dias, J. Branco, H. Canhão
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Individuals diagnosed with rheumatic diseases have shown an increased risk of developing several comorbid conditions, of which cardiovascular (CV) comorbidities are the most common and have the greatest effect on mortality. <h3>Objectives</h3> Our global aim is to assess the impact of Inflammatory Rheumatic Diseases (IRD) in the development of cardiovascular diseases controlling for traditional CV risk factors in a Portuguese national-wide population-based cohort. <h3>Methods</h3> This study used data from a population-based longitudinal cohort study – the EpiDOC cohort. IRD participants ere selected according to Rheumatoid Arthritis (RA), Systemic Lupus Erythematous (SLE), Ankylosing Spondylitis (SpA) and polymyalgia rheumatic (PMR) diagnosis criteria fulfilment. Outcome was defined as a composite of myocardial infraction or angor pectoris (ischaemic heart disease), arrhythmias, valvular disease, stroke or transient ischaemic attack and peripheral artery disease. Multivariate logistic regression models were used to assess predictors of CV events in IRD participants. Calibration and discrimation of a predictive model were assessed by goodness-of-fit and area under receiver operating characteristic curve. <h3>Results</h3> In a national cohort of 10 661 people, patients with RA (n=61), SLE (n=13), SpA (n=92), PMR (n=8) were identified. Patients with IRD had similar age as non-IRD (mean age 55 vs 53 years-old; 72,1% female), with a predominance of dyslipidaemia diagnosis (40.7% vs 31.4%; p=0,033) and sedentary lifestyle (exercise practise 22.7% vs 33%; p=0,016). IRD participants were followed by a median follow-up of 2.6 years compared with 2.4 years in the non-IRD group (p&lt;0,01). Cardiovascular events were proportional in both populations, leading ischaemic heart disease on IRD group (34.6%) and arrhythmias in controls (29.4%). After adjustment for risk factors, the odd of cardiovascular event is high (OR 1.64, 95% CI: 1.04–2.58; p=0.03). A stepwise approach to find the best predictive model attained that gender, age, history of hypertension, body mass index, IRD and follow-up time are the most important predictive variables of CV event, with an area under ROC of 0,80. <h3>Conclusions</h3> We report an increase odd of major CV events in inflammatory rheumatic disease in Portugal adjusting for potential modifiers. This study brings forward a contemporary awareness of physicians and patients with IRD for a premature identification and control of higher risk patients among this population. <h3>Disclosure of Interest</h3> None declared
Causes and Patterns of Dementia: An Update in the Era of Redefining Alzheimer's Disease
Authors: Bryan D. James, David A. Bennett
Journal: Annual Review of Public Health (2019)

The burden of dementia continues to increase as the population ages, with no disease-modifying treatments available. However, dementia risk appears to be decreasing, and progress has been made in understanding its multifactorial etiology. The 2018 National Institute on Aging-Alzheimer's Association (NIA-AA) research framework for Alzheimer's disease (AD) defines AD as a biological process measured by brain pathology or biomarkers, spanning the cognitive spectrum from normality to dementia. This framework facilitates interventions in the asymptomatic space and accommodates knowledge that many additional pathologies (e.g., cerebrovascular) contribute to the Alzheimer's dementia syndrome. The framework has implications for how we think about risk factors for "AD": Many commonly accepted risk factors are not related to AD pathology and would no longer be considered risk factors for AD. They may instead be related to other pathologies or resilience to pathology. This review updates what is known about causes, risk factors, and changing patterns of dementia, addressing whether they are related to AD pathology/biomarkers, other pathologies, or resilience.
Radiologic Aspects of Operable Heart Disease
Authors: HERBERT L. ABRAMS
Journal: Circulation (1956)

Patent ductus arteriosus and coarctation of the aorta are common causes of congestive heart failure in infancy, yet are more difficult to diagnose than in later life. Retrograde brachial aortography is a relatively simple method of establishing the diagnosis with assurance. A description ofthe technic is followed by a discussion of the normal aortogram in infancy. A relatively large series of cases, in which a high diagnostic yield was obtained, is analyzed. The hazards of the procedure are few if highly concentrated media are avoided and careful attention is paid to details of technic.
Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt+ Regulatory T Cells and Exacerbate Colitis in Mice
Authors: Graham J. Britton, Eduardo J. Contijoch, Ilaria Mogno, Olivia H. Vennaro, Sean R. Llewellyn, Ruby Ng, Zhihua Li, Arthur Mortha, Miriam Merad, Anuk Das, Dirk Gevers, Dermot P.B. McGovern, Namita Singh, Jonathan Braun, Jonathan P. Jacobs, Jose C. Clemente, Ari Grinspan, Bruce E. Sands, Jean-Frederic Colombel, Marla C. Dubinsky, Jeremiah J. Faith
Journal: Immunity (2019)
Comprehensive Analysis of 343 Genes Using Targeted Sequencing Panel By Next-Generation Sequencer in 77 Pediatric AML Patients with Normal and Complex Karyotypes: Jccg Study, JPLSG AML-05
Authors: Taeko Kaburagi, Genki Yamato, Norio Shiba, Kenichi Yoshida, Yusuke Hara, Yuichi Shiraishi, Kentaro Ohki, Manabu Sotomatsu, Hirokazu Arakawa, Hidemasa Matsuo, Akira Shimada, Nobutaka Kiyokawa, Daisuke Tomizawa, Takashi Taga, Keizo Horibe, Satoru Miyano, Seishi Ogawa, Souichi Adachi, Yasuhide Hayashi
Journal: Blood (2018)
Abstract 18460: Mesenchymal Stem/stromal Cell Delivery Through Cardiopulmonary Bypass for Reduction In Systemic- and Neuro-inflammation in a Juvenile Porcine Model
Authors: Kamil Sarkislali, Fahad Somaa, Gary R Stinnet, Paul D Morton, Bobbi Lewis, Mark M Nuszkowski, Erin K Montague, Karuna Panchapakesan, Lauren Roesch, Patrick J Hanley, Joseph A Frank, Richard A Jonas, Nobuyuki Ishibashi
Journal: Circulation (2017)

Introduction: Neurodevelopmental impairment is emerging as one the most important current challenges for survivors after pediatric cardiac surgery. Cardiopulmonary bypass (CPB) can cause substantial systemic inflammation and trigger prolonged microglial activation in the brain. Mesenchymal stem/stromal cells (MSCs) have significant immunomodulatory properties and regulate microglia activation. We hypothesize that intra-arterial MSC delivery through CPB is neuroprotective by modulating systemic and brain-specific inflammatory responses. Methods: Two-week old piglets (n=12) were randomly assigned to one of 3 groups: (1) Control, (2) Deep hypothermic circulatory arrest (DHCA), (3) DHCA followed by MSC administration. In group 3, superparamagnetic iron oxide (SPIO)-labeled MSCs (10 x 106 per kg) were delivered through the aortic cannula during the rewarming period. Animals were sacrificed 3hrs after CPB. Distribution of MSCs was examined with MRI and immunohistochemistry. Plasma cytokine/chemokine levels were...
In HF with secondary mitral regurgitation, percutaneous mitral valve repair did not improve 1-year clinical outcomes
Authors: Anthony Donato, Eric Elgin
Journal: Annals of Internal Medicine (2019)

Source Citation Obadia JF, Messika-Zeitoun D, Leurent G, et al; MITRA-FR Investigators. Percutaneous repair or medical treatment for secondary mitral regurgitation. N Engl J Med. 2018;Aug 27. [Epub ahead of print.] 30145927
Uncoupling protein 2 reprograms the tumor microenvironment to support the anti-tumor immune cycle
Authors: Wan-Chen Cheng, Yao-Chen Tsui, Simone Ragusa, Viktor H. Koelzer, Marco Mina, Fabien Franco, Heinz Läubli, Benjamin Tschumi, Daniel Speiser, Pedro Romero, Alfred Zippelius, Tatiana V. Petrova, Kirsten Mertz, Giovanni Ciriello, Ping-Chih Ho
Journal: Nature Immunology (2019)
Type 2 Diabetes and Hypertension
Authors: Dianjianyi Sun, Tao Zhou, Yoriko Heianza, Xiang Li, Mengyu Fan, Vivian A. Fonseca, Lu Qi
Journal: Circulation Research (2019)

Rationale: In observational studies, type 2 diabetes mellitus (T2D) has been associated with an increased risk of hypertension, and vice versa; however, the causality between these conditions remains to be determined. Objectives: This population-based prospective cohort study sought to investigate the bidirectional causal relations of T2D with hypertension, systolic and diastolic blood pressure (BP) using Mendelian randomization (MR) analysis. Methods and Results: After exclusion of participants free of a history of heart failure, cardiovascular disease, cardiac procedures, and non-T2D diabetes mellitus, a total of 318 664 unrelated individuals with qualified genotyping data of European descent aged 37 to 73 from UK Biobank were included. The genetically instrumented T2D and hypertension were constructed using 134 and 233 single nucleotide polymorphisms, respectively. Seven complementary MR methods were applied, including inverse-variance weighted method, 2 median-based methods (simple and weighted), MR-Egger, MR-robust adjusted profile scores, MR-Pleiotropy Residual Sum and Outlier, and multivariate MR. The genetically instrumented T2D was associated with risk of hypertension (odds ratio, 1.07 [95% CI, 1.04–1.10], P =3.4×10 −7 ), whereas the genetically determined hypertension showed no relationship with T2D (odds ratio, 0.96 [0.88–1.04], P =0.34). Our MR estimates from T2D to BP showed that the genetically instrumented T2D was associated with a 0.67 mm Hg higher systolic BP (95% CI, 0.41–0.93, P =5.75×10 –7 ) but not with a higher diastolic BP. There was no clear evidence showing a causal effect of elevated systolic BP or diastolic BP on T2D risk. Positive pleiotropic bias was indicated in the hypertension→T2D relation (odds ratio, of MR-Egger intercept 1.010 [1.004–1.016], P =0.001) but not from T2D to hypertension (1.001 [0.998–1.004], P =0.556). Conclusions: T2D may causally affect hypertension, whereas the relationship from hypertension to T2D is unlikely to be causal. These findings suggest the importance of keeping an optimal glycemic profile in general populations, and BP screening and monitoring, especially systolic BP, in patients with T2D.
AB0792 Autoimmune and inflammatory disturbances in patients with pulmonary arterial hypertension associated with systemic sclerosis
Authors: N. Yudkina, A. Volkov, T. Martynyuk, E. Nikolaeva, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The prognosis of patients with pulmonary arterial hypertension associated with systemic sclerosis (SSc-PAH) is significantly worse, than other forms of PAH, and mechanisms of this phenomenon are unknown. Therefore, the isolation of autoimmune disorders is of great importance for early diagnosis and differential diagnosis, as well as the search for new therapeutic targets. <h3>Objectives</h3> To identify the autoimmune disorders in patients with SSc-PAH. <h3>Methods</h3> The study includes 52 pts with idiopathic pulmonary arterial hypertension (IPAH), 51 pts with SSc-PAH, 65 pts with SSc without PAH. Serum concentrations of the C-reactive protein (CRP), anticentromere antibodies (ACA) and antibodies to topoisomerase-I (anti-Scl-70) were routinely measured. The control group consists of 146 volunteers. Statistical analysis includes univariable logistic regression, ROC analysis and Kaplan-Mayer method. <h3>Results</h3> The average age of patients with IPAH was 37.9±10.5 years, SSc-PAH – 52.3±12.7 years, SSc without PAH – 51.2±13.2. Patients did not differ in functional class (FC), which was the main criterion of comparability. Mean values of FC in groups with SSc-PAH and IPAH also did not differ (2.7±0.8 and 2.6±0.7, respectively). ACA was associated with a 15.2-fold increased odds of developing PAH in SSc (OR 15.2, 95% CI 5.4–43.0), on the contrary, presense of anti-Scl-70 associated with low risk of PAH (OR 0.5, 95% CI 0.01 to 0.21). The level of CRP in the serum was significantly higher in patients with PAH than in the control group: 4.1 (1.9, 10.0) and 0.61 (0.25, 1.9), p&lt;0.000001, and also in comparison with patients without PAH (1.9 (0.8, 6.4), p=0.02). In pts with PAH, the level of CRP correlated with FC and right atrium pressure and 6 min walk test distance. The level of CRP was significantly higher in patients with FC III-IV compared with FC I-II and in non-surviving patients. The Kaplan-Mayer analysis showed that pts with CRP level more than 4.75 mg/L at the time of diagnosis of PAH had a significantly lower survival rate (median 48 months) than pts with normal values (median 91 months) (p&lt;0.005), with 67% sensitivity and 61% specificity. <h3>Conclusions</h3> SSc-PAH is a unique phenotype combining the manifestations of SSc and PAH, the pathogenetic mechanisms of which modify the course of these states. It is based on a feature of autoimmunity with the predominance of ACA and a low occurrence of anti-Scl-70. An increase in the concentration of CRP, as well as the effect of its baseline level on survival, attests to the significant role of autoimmunity and inflammation in the pathogenesis of this fatal SSc complication. <h3>Disclosure of Interest</h3> None declared
Clusterin Impairs Hepatic Insulin Sensitivity and Adipocyte Clusterin Associates With Cardiometabolic Risk
Authors: David Bradley, Alecia Blaszczak, Zheng Yin, Joey Liu, Joshua J. Joseph, Valerie Wright, Kajol Anandani, Bradley Needleman, Sabrena Noria, David Renton, Martha Yearsley, Stephen T.C. Wong, Willa A. Hsueh
Journal: Diabetes Care (2019)

OBJECTIVE Components of the adipose tissue (AT) extracellular matrix (ECM) are recently discovered contributors to obesity-related cardiometabolic disease. We identified increased adipocyte expression of ECM-related clusterin (apolipoprotein J) in obese versus lean women by microarray. Our objective was to determine 1) whether subcutaneous AT adipocyte (SAd) clusterin and serum clusterin are associated with insulin resistance (IR) and known markers of cardiometabolic risk and 2) how clusterin may contribute to increased risk. RESEARCH DESIGN AND METHODS We validated increased clusterin expression in adipocytes from a separate group of 18 lean and 54 obese individuals. The relationship of clusterin gene expression and plasma clusterin with IR, cardiovascular biomarkers, and risk of cardiovascular disease (CVD) was then determined. Further investigations in human cultured cells and in aged LDLR−/− mice prone to development of obesity-associated complications were performed. RESULTS SAd clusterin correlated with IR, multiple CVD biomarkers, and CVD risk, independent of traditional risk factors. Circulating human clusterin exhibited similar associations. In human adipocytes, palmitate enhanced clusterin secretion, and in human hepatocytes, clusterin attenuated insulin signaling and APOA1 expression and stimulated hepatic gluconeogenesis. LRP2 (megalin), a clusterin receptor, highly expressed in liver, mediated these effects, which were inhibited by LRP2 siRNA. In response to Western diet feeding, an increase in adipocyte clusterin expression was associated with a progressive increase in liver fat, steatohepatitis, and fibrosis in aged LDLR−/− mice. CONCLUSIONS Adipocyte-derived clusterin is a novel ECM-related protein linking cardiometabolic disease and obesity through its actions in the liver.