tbuckley/cabot-search huggingface dataset:
Alcohol-Related Mortality in Patients With Psoriasis
Authors: Rosa Parisi, Roger T. Webb, Matthew J. Carr, Kieran J. Moriarty, C. Elise Kleyn, Christopher E. M. Griffiths, Darren M. Ashcroft
Journal: JAMA Dermatology (2017)

People diagnosed with psoriasis have an increased risk of premature mortality, but the underlying reasons for this mortality gap are unclear.To investigate whether patients with psoriasis have an elevated risk of alcohol-related mortality.An incident cohort of patients with psoriasis aged 18 years and older was delineated for 1998 through 2014 using the Clinical Practice Research Datalink (CPRD) and linked to Hospital Episode Statistics (HES) and Office for National Statistics (ONS) mortality records. Patients with psoriasis were matched with up to 20 comparison patients without psoriasis on age, sex, and general practice.Alcohol-related deaths were ascertained via the Office for National Statistics mortality records. A stratified Cox proportional hazard model was used to estimate the cause-specific hazard ratio for alcohol-related death, with adjustment for socioeconomic status.The cohort included 55 537 with psoriasis and 854 314 patients without psoriasis. Median (interquartile) age at index date was 47 (27) years; 408 230 of total patients (44.9%) were men. During a median (IQR) of 4.4 (6.2) years of follow-up, the alcohol-related mortality rate was 4.8 per 10 000 person-years (95% CI, 4.1-5.6; n = 152) for the psoriasis cohort, vs 2.5 per 10 000 (95% CI, 2.4- 2.7; n = 1118) for the comparison cohort. The hazard ratio for alcohol-related death in patients with psoriasis was 1.58 (95% CI, 1.31-1.91), and the predominant causes of alcohol-related deaths were alcoholic liver disease (65.1%), fibrosis and cirrhosis of the liver (23.7%), and mental and behavioral disorders due to alcohol (7.9%).People with psoriasis have approximately a 60% greater risk of dying due to alcohol-related causes compared with peers of the same age and sex in the general population. This appears to be a key contributor to the premature mortality gap. These findings call for routine screening, identification and treatment, using the Alcohol Use Disorders Identification Test (AUDIT-C) in both primary and secondary care to detect alcohol consumption and misuse among people diagnosed with psoriasis.
Whole-Genome Sequencing Reveals Breast Cancers with Mismatch Repair Deficiency
Authors: Helen Davies, Sandro Morganella, Colin A. Purdie, Se Jin Jang, Elin Borgen, Hege Russnes, Dominik Glodzik, Xueqing Zou, Alain Viari, Andrea L. Richardson, Anne-Lise Børresen-Dale, Alastair Thompson, Jorunn E. Eyfjord, Gu Kong, Michael R. Stratton, Serena Nik-Zainal
Journal: Cancer Research (2017)

Mismatch repair (MMR)-deficient cancers have been discovered to be highly responsive to immune therapies such as PD-1 checkpoint blockade, making their definition in patients, where they may be relatively rare, paramount for treatment decisions. In this study, we utilized patterns of mutagenesis known as mutational signatures, which are imprints of the mutagenic processes associated with MMR deficiency, to identify MMR-deficient breast tumors from a whole-genome sequencing dataset comprising a cohort of 640 patients. We identified 11 of 640 tumors as MMR deficient, but only 2 of 11 exhibited germline mutations in MMR genes or Lynch Syndrome. Two additional tumors had a substantially reduced proportion of mutations attributed to MMR deficiency, where the predominant mutational signatures were related to APOBEC enzymatic activity. Overall, 6 of 11 of the MMR-deficient cases in this cohort were confirmed genetically or epigenetically as having abrogation of MMR genes. However, IHC analysis of MMR-related proteins revealed all but one of 10 samples available for testing as MMR deficient. Thus, the mutational signatures more faithfully reported MMR deficiency than sequencing of MMR genes, because they represent a direct pathophysiologic readout of repair pathway abnormalities. As whole-genome sequencing continues to become more affordable, it could be used to expose individually abnormal tumors in tissue types where MMR deficiency has been rarely detected, but also rarely sought.
Re: Haripriya et al.: Endophthalmitis reduction with intracameral moxifloxacin prophylaxis: an analysis of 600 000 surgeries ( Ophthalmology . 2017;124:768-775)
Authors: Nidhi Relhan, Stephen G. Schwartz, Andrzej Grzybowski, Harry W. Flynn
Journal: Ophthalmology (2017)
OP0153 Recurrent infections in rheumatoid arthritis patients, results from the bsrbr
Authors: S Subesinghe, AI Rutherford, R Byng-Maddick, JB Galloway
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) patients have an increased susceptibility to infection. <h3>Objectives</h3> 1.To establish the rate of recurrent infection in RA patients recruited to the British Society of Rheumatology Biologics Registry Rheumatoid Arthritis (BSRBR-RA).2.To establish whether the organ class of index infection predicted future serious infection. <h3>Methods</h3> The BSRBR-RA is a prospective observational cohort, previously described. Patients with at least one episode of serious infection requiring hospitalisation were included if they occurred whilst on anti-rheumatic drug therapy or within 5 drug half-lives of stopping. Infections were coded by MedDRA classification in to 7 categories. Infections occurring over 14 days after the first index infection were considered as new events. Event rates were calculated and compared using a Cox proportional hazards model with adjustments made for age, gender, disease duration, baseline DAS28 score, smoking status and seropositivity. <h3>Results</h3> See Table 1. In total, 21,943 subjects with 115,423 patient-years follow up were studied, 5365 subjects reported at least one serious infection. Comparing organ classes of prior infection at baseline, each group had comparable age, disease duration, baseline DAS28 and HAQ scores. The cohort characteristics are tabulated. The baseline annual rate of first serious infection was 4.6% (95% CI 4.5–4.7). Following an index infection, the annual rate of serious infection was 12.7% (95% CI 12.1–13.3). Respiratory infections were the most common (41.4% of all events). The system class of index infection was associated with the risk of a recurrent event; subjects who experienced sepsis had the highest risk of subsequent serious infection within 12 months:19.7%. Compared to an index respiratory tract infection, sepsis conferred a 33% increased hazard for recurrent serious infection within a year (HR 1.33, 95% CI 1.01–1.76). Increasing age was a significant predictor of infection recurrence. <h3>Conclusions</h3> There is a high risk of recurrent infection in RA patients with past serious infection. Work is ongoing to determine whether organ class of recurrent infection event mirrors index events and the impact of biologic treatment decisions following the index infection. <h3>Disclosure of Interest</h3> None declared
Abstract 15003: Prevalence of Coronary Sinus and Left Circumflex Artery Overlap: Considerations for Percutaneous Treatment of Mitral Regurgitation
Authors: Julianne H Spencer, Garrett Prahl, Paul A Iaizzo
Journal: Circulation (2013)

Background:  Treatment of mitral valve regurgitation using an indirect percutaneous approach through the coronary sinus has been under development. Therefore, detailed characterization of where the circumflex artery tends to cross between the coronary sinus and the mitral valve is important for the prevention of serious arterial complications.   Methods:  Magnetic resonance images were obtained for 65 perfusion-fixed human hearts. Using Mimics Software (Materlise, Leuven, Belgium), reconstructions of the anatomical orientations of the coronary sinus, circumflex artery, and mitral valve annulus were generated. The prevalence and location of sites where the circumflex artery coursed between the coronary sinus and mitral valve were assessed.   Results:  Overall, the circumflex coursed between the coronary sinus and mitral valve in 88% of specimens. The figure depicts where these overlaps most often occurred. More specifically, the figure shows the percentage of specimens with an overlap in specific anatomical regions of the mitral valve. In addition, the coronary sinus did not lie in the plane of the mitral annulus in roughly 20% of the hearts in this study.   Conclusions:  In general, overlaps between the circumflex artery and coronary sinus are less prevalent more proximal to the coronary sinus ostium. This suggests considerations for the development of an annuloplasty device that would be delivered in the proximal region of the coronary sinus. The results of this study also stress the importance of imaging individual patient cardiac anatomy before performing indirect percutaneous mitral valve annuloplasty to avoid impairment to the circumflex artery.
AB0369 Vitamin d status and disease activity in patients with rheumatoid arthritis
Authors: V Povoroznyuk, O Synenky, N Balatska
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The purpose of the study was to define the associations between serum level of 25-hydroxyvitamin D (25(OH)D) and disease activity in patients with rheumatoid arthritis (RA). <h3>Objectives</h3> The study group comprised 93 patients aged 27–80 years suffering from RA (74.2% women) and 93 controls. <h3>Methods</h3> The levels of rheumatoid factor (RF) and C-reactive protein (CRP) were measured by immunoturbidimetric assay. Erythrocyte sedimentation rate (ESR) was measured by Westergren method. Serum 25(OH)D<sub>total</sub> level was determined by electrochemiluminescence (ECL) method. The optimal vitamin D status was defined when serum 25(OH)D level was 30–50 ng/ml. <h3>Results</h3> In general, 54.8% of RA patients revealed vitamin D deficiency, and 37.6% - vitamin D insufficiency. No significant difference was found when mean serum 25(OH)D levels in RA patients and healthy controls where compared. 25(OH)D levels appeared markedly lower in patients with the highest activity of RA compared to values noted in patients with the minimal RA activity (16.55±9.26 vs 22.59±9.74 ng/ml, p&lt;0.05). In RA patients 25(OH)D levels were significantly and negatively associated with markers of disease activity (DAS28-ESR (β = -0.33; 95% CI =0.05, -0.01), CRP (β = -0.23; 95% CI = -0.72; 0.00), and ESR (β = -0.26; 95% CI = -0.78; -0.10). All these associations remained statistically significant after adjustment for gender, age and BMI. <h3>Conclusions</h3> Vitamin D deficiency should be considered as an important predictor of the high RA activity (AUROC =0.67; 95% CI =0.513–0.83, P=0.05). <h3>Disclosure of Interest</h3> None declared
AB0300 Association of vitamin d status with rheumatoid arthritis disease activity and uv index
Authors: C Lopes, JL Gomes, T Costa, M Mateus, F Pimentel-Santos, JC Branco
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Lower serum vitamin D levels have been shown to be associated with various autoimmune disorders, including Rheumatoid Arthritis (RA). Vitamin D deficiency is common in RA patients, despite profiting from a sunny country. <h3>Objectives</h3> The aim of the study is to evaluate (1) – the association between vitamin D serum levels and disease activity in patients with RA; (2) – seasonal distribution of vitamin D levels. <h3>Methods</h3> Patients fulfilling the 2010 EULAR/ACR Rheumatoid Arthritis Classification Criteria, which had serum vitamin D [25(OH)D3] levels measured between January 2013 and December of 2016 were included. Demographic data, disease activity scores, including DAS283v-CRP and DAS283v-ESR, vitamin D supplementation with cholecalciferol and other therapeutic approaches were recorded. Vitamin D insufficiency was considered between 25–75 nmol/L and deficiency if &lt;25 nmol/L. According to the national agency for the study of sea and atmosphere, UV Index levels were grouped into low UV Index 3–6 (October to April) and high UV Index 9–10 (May to September). Correlation between variables was analyzed using Spearman9s rho. <h3>Results</h3> A sample composed by 95 patients, 79 females (83.16%), with an average age (SD) of 68.57 (11.92) years within 40–88 years range were included. Average disease duration was 13.46 (11.41) years. The average age at diagnosis was 57.10 (14.25) years. The average vitamin D levels were 78.13 (60.98) nmol/L in a range between 20–400 nmol/L. Vitamin D levels were not significantly different in male <i>vs</i>. females patients. The prevalence of vitamin D insufficiency and deficiency was 53.68% and 8.42% respectively, despite 57.89% of the patients taking supplementation (average 6141 (4800) UI/week). The univariable analysis showed that albeit vitamin D levels presented a negative poor correlation with DAS283v-CRP (rho=-0.348, p-value&lt;0.001) and DAS283v-ESR (rho=-0.271, p-value&lt;0.01), there was a direct reduction in dispersion of the vitamin D values for increasing values of DAS283v-CRP and ESR. It was observed that vitamin D levels increase with patient age and decrease with disease duration. Sazonality and supplementation didn9t affect vitamin D levels in our population. <h3>Conclusions</h3> Vitamin D insufficiency/deficiency was frequent among RA patients (62.1%), independently of seasonality or supplementation. An interesting pattern behavior was observed in this study, which indicates that the likelihood of encountering a very narrowband of vitamin D values for patients with high disease activity is very high, and thus, the forecast capability of vitamin D values for patients with increasingly active disease is quite good. Future research will aim at strengthening the statistical parameters of relevance, identifying and characterizing the more specific behaviours of this global pattern. <h3>Disclosure of Interest</h3> None declared
“One-Pot” Fabrication of Highly Versatile and Biocompatible Poly(vinyl alcohol)-porphyrin-based Nanotheranostics
Authors: Yan Luo, Hao Wu, Caihong Feng, Kai Xiao, Xixiao Yang, Qiangqiang Liu, Tzu-yin Lin, Hongyong Zhang, Jeffrey H. Walton, Yousif Ajena, Yide Hu, Kit S. Lam, Yuanpei Li
Journal: Theranostics (2017)

Nanoparticle-based theranostic agents have emerged as a new paradigm in nanomedicine field for integration of multimodal imaging and therapeutic functions within a single platform. However, the clinical translation of these agents is severely limited by the complexity of fabrication, long-term toxicity of the materials, and unfavorable biodistributions. Here we report an extremely simple and robust approach to develop highly versatile and biocompatible theranostic poly(vinyl alcohol)-porphyrin nanoparticles (PPNs). Through a "one-pot" fabrication process, including the chelation of metal ions and encapsulation of hydrophobic drugs, monodispersenanoparticle could be formed by self-assembly of a very simple and biocompatible building block (poly(vinyl alcohol)-porphyrin conjugate). Using this approach, we could conveniently produce multifunctional PPNs that integrate optical imaging, positron emission tomography (PET), photodynamic therapy (PDT), photothermal therapy (PTT) and drug delivery functions in one formulation. PPNs exhibited unique architecture-dependent fluorescence self-quenching, as well as photodynamic- and photothermal- properties. Near-infrared fluorescence could be amplified upon PPN dissociation, providing feasibility of low-background fluorescence imaging. Doxorubicin (DOX)-loaded PPNs achieved 53 times longer half-life in blood circulation than free DOX. Upon irradiation by near infrared light at a single excitation wavelength, PPNs could be activated to release reactive oxygen species, heat and drugs simultaneously at the tumor sites in mice bearing tumor xenograft, resulting in complete eradication of tumors. Due to their organic compositions, PPNs showed no obvious cytotoxicity in mice via intravenous administration during therapeutic studies. This highly versatile and multifunctional PPN theranostic nanoplatform showed great potential for the integration of multimodal imaging and therapeutic functions towards personalized nanomedicine against cancers.
Long-Term Prognostic Value of Gasping During Out-of-Hospital Cardiac Arrest
Authors: Guillaume Debaty, Jose Labarere, Ralph J. Frascone, Marvin A. Wayne, Robert A. Swor, Brian D. Mahoney, Robert M. Domeier, Michael L. Olinger, Brian J. O’Neil, Demetris Yannopoulos, Tom P. Aufderheide, Keith G. Lurie
Journal: Journal of the American College of Cardiology (2017)
Conduction Disturbances After Transcatheter Aortic Valve Replacement
Authors: Vincent Auffret, Rishi Puri, Marina Urena, Chekrallah Chamandi, Tania Rodriguez-Gabella, François Philippon, Josep Rodés-Cabau
Journal: Circulation (2017)

Transcatheter aortic valve replacement (TAVR) has become a well-accepted option for treating patients with aortic stenosis at intermediate to high or prohibitive surgical risk. TAVR-related conduction disturbances, mainly new-onset left bundle-branch block and advanced atrioventricular block requiring permanent pacemaker implantation, remain the most common complication of this procedure. Furthermore, improvements in TAVR technology, akin to the increasing experience of operators/centers, have translated to a major reduction in periprocedural complications, yet the incidence of conduction disturbances has remained relatively high, with perhaps an increasing trend over time. Several factors have been associated with a heightened risk of conduction disturbances and permanent pacemaker implantation after TAVR, with prior right bundle-branch block and transcatheter valve type and implantation depth being the most commonly reported. New-onset left bundle-branch block and the need for permanent pacemaker implantation may have a significant detrimental association with patients’ prognosis. Consequently, strategies intended to reduce the risk and to improve the management of such complications are of paramount importance, particularly in an era when TAVR expansion toward treating lower-risk patients is considered inevitable. In this article, we review the available evidence on the incidence, predictive factors, and clinical association of conduction disturbances after TAVR and propose a strategy for the management of these complications.
AB0345 Psychiatric disorders related to hyperleptinemia and rheumatoid arthritis clinical activity measured by das28
Authors: M Vázquez-Del Mercado, A-M Rodrígez-Ramírez, E Chavarria-Avila, F Sandoval-García, B-T Martin-Marquez, R-E Navarro-Hernandez, F Corona-Meraz, E Gomez-Bañuelos
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Leptin is an adipose-derived hormone with a role in depression related to chronic stress, anxiety and pain disorders, disturbs with a high prevalence in RA patients. In previous studies, it has been demonstrated the role of leptin in the pathogenesis of RA, in particular, its association with anti-CCP. The purpose of this study was to evaluate the psychiatric disorders risk related to serum soluble leptin (sLep) levels with clinical activity in RA patients. <h3>Objectives</h3> To evaluate the association between psychiatric disorders and serum leptin (sLep) levels and RA disease activity <h3>Methods</h3> 76 outpatients diagnosed with RA (ACR1987/ ACR/ EULAR2010) were evaluated with clinical, laboratory and image assessment. Disease activity was measured using DAS28 CRP, the Mini International Neuropsychiatric Interview Plus (M. I. N. I. Plus) was used for the psychiatric evaluation. sLep levels were measured by ELISA method. <h3>Results</h3> sLep levels were significantly higher in RA patients M.I.N.I. plus (+) (<i>P</i>&lt;0.001). DAS28 CRP score was significantly higher in patients with a present psychiatric disorder (<i>P=</i>0.006) with an odds ratio of 1.6 ([1.04–2.46] <i>P=</i>0.03) for present psychiatric comorbidity. After adjustment with age and years of RA diagnosis, the odds ratio increased to 1.72 ([1.08–2.73] <i>P=</i>0.02). Also, DAS28 CRP had a moderate correlation with the number of psychiatric diagnosis present, past and for lifetime (r=0.485, <i>P</i>&lt;0.001, IC95% [0.99–0.636]). <h3>Conclusions</h3> sLep levels and DAS28-CRP were associated with symptoms of depression, such as anxiety and pain disorder in RA patients. <h3>Disclosure of Interest</h3> None declared
FRI0326 Recommendations for the management of neuro-behÇet disease by japanese research committee for behÇet disease
Authors: H Kikuchi, T Sawada, M Okada, M Takeno, M Kuwana, Y Ishigatsubo, I Kawachi, H Mochizuki, S Kusunoki, S Hirohata
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Central nervous system involvement is one of the most serious complications in Behçet9s disease (BD). This condition is referred to as neuro-Behçet9s disease (NB) and can be classified into acute type (ANB) and chronic progressive type (CPNB) based upon differences in the clinical course and responses to corticosteroid treatment. Diagnostic criteria were generated in 2013 based on a multicenter clinical survey performed by the Behçet9s Disease Research Committee of the Ministry of Health, Labor and Welfare of the Japanese Government. Although "Guidelines for Treatment of NB" was also proposed based on the survey, it is still preliminary. <h3>Objectives</h3> The aim of the current study is to develop evidence-based recommendations for the management of NB supplemented by expert opinions where necessary. <h3>Methods</h3> First, clinical questions (CQs) on NB were extracted from a literature search for problem areas and related keywords, and draft CQs and a flow chart were prepared. The expert committee, a task force of the research subcommittee for NB, consisted of 7 board-certified rheumatologists (one was also a board-certified neurologist) and 3 board-certified neurologists. A systematic literature search was performed using Medline and the Japan Medical Abstract Society databases from 1997 to 2016. A total of 15 initial CQs were generated. These yielded the final recommendations developed from 3 blind Delphi rounds, in which the rate of agreement scores on CQs (range 1 [disagree]–5 [strongly agree]) was determined though voting by the whole committee. <h3>Results</h3> Thirteen recommendations were developed for the management of NB (general 1, ANB 7, CPNB 5). The strength of each recommendation was established based on the evidence level as well as rate of agreement. There was excellent concordance between the level of agreement of rheumatologists and that of neurologists. Based on these recommendations, a flow chart was established for the management for ANB and CPNB (Figure). <h3>Conclusions</h3> The recommendations generated in this study are mainly based not only on expert opinions but on the results of uncontrolled evidence from open trials and retrospective cohort studies. Guidelines that can be used for international studies are needed, for which verification by further properly designed controlled clinical trials is required. <h3>Disclosure of Interest</h3> None declared