tbuckley/cabot-search huggingface dataset:
AB0735 Nailfold capillary counts correlate most with complications of systemic sclerodema in japanese patients
Authors: A. Kondo, H. Dobashi, T. Kameda, M. Izumikawa, S. Nakashima, H. Shimada, R. Wakiya, M. Kato, N. Kadowaki
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Connective tissue diseases (CTD) patients have various clinical manifestation including pulmonary hypertension (PH) and digital ulcer (DU). Especially, Raynaud's phenomenon (RP) is one of the common symptoms. On the other hand, "abnormal nailfold capillaries" are important as the findings that suggest RP associated with CTD. They are included in one of the items of classification criteria for Sclerderma (SSc) in 2013 Classification Criteria for Systemic Sclerosis (ACR/EULAR) <sup>1)</sup>. Recently, some reports presented the usefulness of nailfold capillaroscopy (NFC) in SSc <sup>2)</sup>. NFC findings showed enlarged/giant capillaries, fresh or old haemorrhages, avascular areas, ramified/bushy capillaries. These findings are known as "scleroderma pattern" features. Additionally, there are some reports that nailfold capillary density in SSc related with DU, PH and interstitial pneumonia (IP). In this study, we clarify the association between nailfold capillary density and clinical manifestation by analysis of the case in our institution. <h3>Objectives</h3> To clarify the association between nailfold capillary density and clinical manifestation. <h3>Methods</h3> We enrolled Japanese SSc patients from May 2016 to May 2017 in our institution. We measured total nailfold capillary count per 1 µm from second to fifth finger by NFC "OptiPiX Capillaroscopy Clinic 1.7.x". In addition, we investigated relationship with NFC findings and clnical manifestation such as current and previous DU, PH and IP. <h3>Results</h3> We enrolled 42 SSc patients. Total nailfold capillary counts significantly decreased, especially in SSc patients with, previous DU (ρ=−0.4122, p=0.0054), and PH (ρ=−0.3226, p=0.0023). In addition, there is significant difference between DU and existence of giant capillaries (ρ=0.3019 p=0.0464), existence of avascular areas (ρ=0.4057 p=0.0063). On the other hand, there is no significant difference between IP, PH and other "scleroderma pattern" features. <h3>Conclusions</h3> Our study revealed that total nailfold capillary counts were associated with PH and DU in SSc patients. We suggest that nailfold capillary density may most predict complications with SSc patients. <h3>References</h3> [1] Markus Mueller, et al. Relation of Nailfold Capillaries and Autoantibodies to Mortality in Patients With Raynaud Phenomenon. Circulation. 133:509–517, 2016. [2] Maurizio Cutolo, et al. Nailfold Videocapillaroscopic Features and Other Clinical Risk Factors for Digital Ulcers in Systemic Sclerosis. Arthritis &amp; Rheumatology. 68 (10): 2527–2539, 2016. <h3>Disclosure of Interest</h3> None declared
THU0052 A circulating protein signature correlates with synovial pathotypes in rheumatoid arthritis patients
Authors: C. Ruiz-Romero, F. Picchi, P. Fernández-Puente, L. González-Rodríguez, R. Hands, V. Calamia, M. Camacho-Encina, C. Bessant, C. Pitzalis, F.J. Blanco
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is a disease characterised by high clinical variability and an underlying cellular and molecular heterogeneity. Efforts to find tools for the classification of the different disease phenotypes and patient stratification are essential to develop tailored therapies and improve its management. According to this, specific pathological phenotypes of synovial tissue (pathotypes) have emerged as associated with diverse clinical evolution and response to therapy.<sup>1</sup> <h3>Objectives</h3> To identify signatures of circulating proteins associated with specific synovial pathotypes in RA patients. <h3>Methods</h3> A proteomic analysis was carried out on samples from patients enrolled in the Pathobiology of Early Arthritis Cohort. Ultrasound-guided synovial biopsies from these patients allowed their classification into three groups: lymphoid (L), myeloid (M) or fibroid (F), according to the pathotype. The study was performed using 54 serum samples at baseline. Sera were analysed by nanoliquid chromatography coupled to mass spectrometry using a SWATH strategy on a tripleTOF (Sciex). The proteomic data were processed using ProteinPilot and PeakView. A two-stage support vector machine (TSSVM) with RBF kernel and 10 cross-fold validation for each meta-model was applied using the Classyfire, e1071 and caret R packages. <h3>Results</h3> The proteomic analysis led to the identification and quantification of 229 proteins in all samples. A screening was performed on a group of 30 samples (Train set: 10 L, 10 M and 10 F). Data were pre-processed by PCA for dimension reduction. Then, application of machine learning tools led to the identification of a panel of 11 proteins whose different abundance is associated with a specific synovial phenotype (either L, M or F) in RA patients. As shown in the table 1, a very high accuracy and Kappa coefficient were achieved with this classification tool. The results were confirmed on an independent validation set of 24 samples (12 L, 8 M and 4 F) with also good performance. This protein signature allowed the correct classification of the samples into the three pathotypes with very high sensitivity and specificity (see table 1). <h3>Conclusions</h3> A signature of 11 circulating proteins has been identified as associated with synovial pathotypes in RA patients. The putative correlation of this signature with the clinical evolution and/or response to therapy of the patients remains to be elucidated. <h3>Reference</h3> [1] New learnings on the pathophysiology of RA from synovial biopsies. Pitzalis C, Kelly S, Humby F. Curr Opin Rheumatol. 2013May;25(3):334–44. <h3>Disclosure of Interest</h3> None declared
SP0137 Prevention of rmds – what have we learned?
Authors: S.M. Verstappen
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Rheumatic and Musculoskeletal Diseases (RMDs) cause the greatest burden of disability in Europe and is increasing. The WHO Europe Action Plan for the Prevention and Control of Non-communicable Diseases recently recognised this burden and recommends action to promote prevention and improve health in the general population and those with musculoskeletal health. Targeted screening and prevention in individuals at high-risk of developing RMDs will only be successful if there is a good understanding of the underlying mechanisms of the disease and of possible genetic and environmental risk factors associated with the risk of developing RMDs. The main focus of this presentation is on the evidence of the association between modifiable lifestyle factors and the risk of developing RMDs and the effectiveness of drugs administered during the preclinical phase of RMDs. <h3>Disclosure of Interest</h3> None declared
SAT0546 Sensorineural hearing loss in takayasu’s arteritis
Authors: U. Kimyon, S.N. Esatoglu, E. Kara, A. Atas, E.E. Gunay, E. Karaman, E.D. Gozen, V. Hamuryudan, H. Yazici, E. Seyahi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Sensorineural hearing loss has been reported to be increased in several chronic autoimmune and non-autoimmune diseases such as systemic lupus erythematosus (SLE), progressive systemic sclerosis, rheumatoid arthritis, small vessel vasculitides, ankylosing spondylitis and Behçet's syndrome. We had sporadically noted several degrees of sensorineural hearing loss among our Takayasu's arteritis (TA) patients. While some revealed this in their past history, others had relapsing attacks of hearing loss independent of or associated with vascular relapses. <h3>Objectives</h3> We formally investigated the frequency and type of hearing loss among TA patients and suitable controls. <h3>Methods</h3> The study was done in two parts. In the first part, consecutive TA and SLE patients seen at outpatient clinic along with apparently healthy controls were administered a standardised questionnaire that assessed hearing loss, tinnitus, and episodic vertigo. In the second part, previously registered TA and SLE patients for another study were called to specifically for otological examination and audiometry tests that included pure-tone air and bone conduction, speech audiometry and acoustic reflex threshold test. <h3>Results</h3> In the first part, 73 patients with TA, 107 patients with SLE and 133 healthy controls were studied as shown in table 1. The frequency of those with hearing deficit/loss, tinnitus and vertigo were significantly more common among both TA and SLE patients (table 1). While the frequency of those with hearing deficit/loss was similar in TA and SLE, those with tinnitus and vertigo were significantly more common in TA. In the second part, 50 patients with TA, 22 patients with SLE and 32 healthy controls were studied as shown in table 2. Audiometry tests revealed that several degrees of hearing loss were present in 36% of the patients with TA, 18% of the patients with SLE and 6.3% of the healthy controls (p&lt;0.05). This was mostly due to sensorineural hearing loss in TA patients (13/18) and high –frequency type was the most common pattern. Moreover, those TA patients with sensorineural hearing loss did not show any specific vascular pattern. <h3>Conclusions</h3> We are unaware of previous surveys of sensorineural hearing loss in TA. Our study shows that audiovestibular system is considerably affected in TA, similar to that observed in SLE. The fact that there was no clear vascular pattern among patients with hearing loss, suggest that small vessel vasculitis was probably the cause of this hearing loss. <h3>Disclosure of Interest</h3> None declared
FRI0037 Characteristics of recent elderly-onset rheumatoid arthritis patients
Authors: T. Oshige, Y. Kaneko, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Elderly-onset rheumatoid arthritis (EORA) has been increasing along with the ageing society. EORA is believed to be different from young-onset RA (YORA) in clinical characteristics, however, it is unknown whether the characteristics of recent EORA are similar with those in the past. <h3>Objectives</h3> To elucidate recent characteristics of recent EORA patients. <h3>Methods</h3> Consecutive patients who were newly diagnosed with RA in our institution from November 2015 until May 2017 (group 1), and those from February 2011 until December 2012 (group 2) were enrolled. Each group was divided into EORA and YORA according to the onset age of 65 years old. Clinical data were collected from their medical records and compared. <h3>Results</h3> In group 1, 176 patients with newly diagnosed RA were identified; EORA 37% and YORA 63%. The mean age was 74.0±1.5 and 46.3±2.4 years old, and female was 73.9% and 84.7%, respectively. The duration from onset to first visit was significantly shorter in the EORA compared to the YORA (4.7±3.0 to 13.9±5.9 months; p=0.038). Disease activity was significantly higher in EORA than the YORA (DAS28-CRP; 4.47±0.35 vs 3.49±0.27, p&lt;0.001; CDAI, 20.5±3.6 vs 15.1±2.2, p=0.009). Inflammatory biomarkers at the first visit were also significantly higher in the EORA than the YORA; CRP (2.6±0.7 vs 1.2±0.5 mg/dl, p&lt;0.001), ESR (68±9 vs 38±6 mm/hr, p&lt;0.001), and serum ferritin (173.3±36.7 vs 102.3±18.8 ng/ml, p&lt;0.001). RF and anti-CCP antibody were less positive in EORA than in YORA (RF 55.4 vs 72.1%, p=0.024; anti-CCP 40.0 vs 63.1%, p=0.003). Large joints were more involved in EORA, but small joint involvement was not different between EORA and YORA. In group 2, 255 patients with newly diagnosed RA were enrolled, EORA 44% and YORA 56%, and female was 85.3% and 84.6%, respectively. The mean age at onset of RA was not different between group 1 and group 2 (58.3±2.4 vs 58.9±2.0, p=0.512). <h3>Conclusions</h3> EORA developed more rapidly and showed severer inflammatory signs with more large joints involved. Conflicting with previous reports, the age at onset of RA did not increase between the patients in 2015–2017 and in 2011–2012. <h3>Disclosure of Interest</h3> None declared
“Only outcome is erasure,” says judge about doctor who was suspended for lying about chaperone
Authors: Clare Dyer
Journal: BMJ (2019)

A High Court judge has ordered a doctor who performed aesthetic procedures in the private sector to be struck off the UK medical register after quashing an “illogical and flawed” medical practitioners’ tribunal decision to suspend him for 12 months.

Mrs Justice Lambert said that the tribunal’s decision in March 2018 “made no sense” and allowed the General Medical Council’s appeal against it.

She said this was one of the rare cases where the correct result was so clear that a judge need not send the case back to a tribunal to take the decision again, but could substitute the court’s own decision on sanction.

Xavier Mmono qualified …
Outcomes of Patients with Relapsed/Refractory Double Expressor B Cell Lymphoma As Defined By Multicenter Pathology Review Treated with Ibrutinib Monotherapy
Authors: Daniel J. Landsburg, Mitchell E. Hughes, Alexa Koike, David A. Bond, Kami J. Maddocks, Ling Guo, Allison M. Winter, Brian T. Hill, Sarah L. Ondrejka, Eric D. Hsi, Sunita Dwivedy Nasta, Jakub Svoboda, Stephen J. Schuster, Agata M. Bogusz
Journal: Blood (2018)
Television News Coverage of Public Health Issues and Implications for Public Health Policy and Practice
Authors: Sarah E. Gollust, Erika Franklin Fowler, Jeff Niederdeppe
Journal: Annual Review of Public Health (2019)

Television (TV) news, and especially local TV news, remains an important vehicle through which Americans obtain information about health-related topics. In this review, we synthesize theory and evidence on four main functions of TV news in shaping public health policy and practice: reporting events and information to the public (surveillance); providing the context for and meaning surrounding health issues (interpretation); cultivating community values, beliefs, and norms (socialization); and attracting and maintaining public attention for advertisers (attention merchant). We also identify challenges for TV news as a vehicle for improving public health, including declining audiences, industry changes such as station consolidation, increasingly politicized content, potential spread of misinformation, and lack of attention to inequity. We offer recommendations for public health practitioners and researchers to leverage TV news to improve public health and advance health equity.
Pak2 as a Novel Therapeutic Target for Cardioprotective Endoplasmic Reticulum Stress Response
Authors: Pablo Binder, Shunyao Wang, Maria Radu, Min Zin, Lucy Collins, Saba Khan, Yatong Li, Karolina Sekeres, Neil Humphreys, Eileithyia Swanton, Adam Reid, Fay Pu, Delvac Oceandy, Kaomei Guan, Susanne S. Hille, Norbert Frey, Oliver J. Müller, Elizabeth J. Cartwright, Jonathan Chernoff, Xin Wang, Wei Liu
Journal: Circulation Research (2019)

Secreted and membrane-bound proteins, which account for 1/3 of all proteins, play critical roles in heart health and disease. The endoplasmic reticulum (ER) is the site for synthesis, folding, and quality control of these proteins. Loss of ER homeostasis and function underlies the pathogenesis of many forms of heart disease.To investigate mechanisms responsible for regulating cardiac ER function, and to explore therapeutic potentials of strengthening ER function to treat heart disease.Screening a range of signaling molecules led to the discovery that Pak (p21-activated kinase)2 is a stress-responsive kinase localized in close proximity to the ER membrane in cardiomyocytes. We found that Pak2 cardiac deleted mice (Pak2-CKO) under tunicamycin stress or pressure overload manifested a defective ER response, cardiac dysfunction, and profound cell death. Small chemical chaperone tauroursodeoxycholic acid treatment of Pak2-CKO mice substantiated that Pak2 loss-induced cardiac damage is an ER-dependent pathology. Gene array analysis prompted a detailed mechanistic study, which revealed that Pak2 regulation of protective ER function was via the IRE (inositol-requiring enzyme)-1/XBP (X-box-binding protein)-1-dependent pathway. We further discovered that this regulation was conferred by Pak2 inhibition of PP2A (protein phosphatase 2A) activity. Moreover, IRE-1 activator, Quercetin, and adeno-associated virus serotype-9-delivered XBP-1s were able to relieve ER dysfunction in Pak2-CKO hearts. This provides functional evidence, which supports the mechanism underlying Pak2 regulation of IRE-1/XBP-1s signaling. Therapeutically, inducing Pak2 activation by genetic overexpression or adeno-associated virus serotype-9-based gene delivery was capable of strengthening ER function, improving cardiac performance, and diminishing apoptosis, thus protecting the heart from failure.Our findings uncover a new cardioprotective mechanism, which promotes a protective ER stress response via the modulation of Pak2. This novel therapeutic strategy may present as a promising option for treating cardiac disease and heart failure.
Which definition of a central tumour is more predictive of occult mediastinal metastasis in nonsmall cell lung cancer patients with radiological N0 disease?
Authors: Sun Hye Shin, Dong Young Jeong, Kyung Soo Lee, Jong Ho Cho, Yong Soo Choi, Kyungjong Lee, Sang-Won Um, Hojoong Kim, Byeong-Ho Jeong
Journal: European Respiratory Journal (2019)

Guidelines recommend invasive mediastinal staging for centrally located tumours, even in radiological N0 nonsmall cell lung cancer (NSCLC). However, there is no uniform definition of a central tumour that is more predictive of occult mediastinal metastasis.A total of 1337 consecutive patients with radiological N0 disease underwent invasive mediastinal staging. Tumours were categorised into central and peripheral by seven different definitions.About 7% (93 out of 1337) of patients had occult N2 disease, and they had significantly larger tumour size and more solid tumours on computed tomography. After adjustment for patient- and tumour-related characteristics, only the central tumour definition of the inner one-third of the hemithorax adopted by drawing concentric lines arising from the midline significantly predicted occult N2 disease (adjusted OR 2.13, 95% CI 1.17-3.87; p=0.013). This association was maintained after excluding patients with pure ground-glass nodules (adjusted OR 2.54, 95% CI 1.37-4.71; p=0.003) or only including those with solid tumours (adjusted OR 2.30, 95% CI 1.08-4.88; p=0.030).We suggest that a central tumour should be defined using the inner one-third of the hemithorax adopted by drawing concentric lines from the midline. This is particularly useful for predicting occult N2 disease in patients with NSCLC.
Profiling T Cell Receptor Repertoires in Phase I/II Clinical Trials of Donor Treg Infusion for the Treatment of Chronic Graft-Versus-Host Disease
Authors: Hans-Jörg Warnatz, Rita I Azevedo, Maria G.D Soares, Ana C Alho, Laura C Ward, Ana C Ribeiro, Clara Juncal, Anabela Rodrigues, Ana Garção, Susana Roncon, Carlos Pinho Vaz, Christine Voigt, Marie-Laure Yaspo, Hans Lehrach, Matthias Edinger, Frédéric Baron, Mario Arpinati, Marta Garcia-Fiñana, Jerome Ritz, João F Lacerda
Journal: Blood (2018)
THU0622 Histopathology and expressions of chemokines, cxcl10, cxcl13, and cxcr3, and an endogenous ligand s100a8/a9 in lymph nodes of patients with adult-onset still’s disease
Authors: H.-A. Kim, J.H. Han
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Adult-onset still's disease (AOSD) is a rare systemic inflammatory disease with several symptoms, such as a persistent high spiking fever, typical rash, and lymphadenopathy. Endogenous factors related to interleukin (IL)−1, such as S100A8/A9 and several chemokines including CXCL10, CXCL13 and CXCR3, could play a potential role in the pathogenesis of AOSD. <h3>Objectives</h3> We aimed to find out typical histopathologic features, expressed pattern of chemokines in lymph nodes (LN) of AOSD patients. <h3>Methods</h3> Formalin-fixed paraffin-embedded excisional LN tissues from 48 AOSD patients and 6 nonspecific reactive hyperplasia were histologically reviewed. The immunohistochemical stain for CXCL10, CXCL13, CXCR3 and S100A8/A9 were done. The clinical and laboratory data of the patients who underwent LN biopsies were reviewed. <h3>Results</h3> The LN specimens were categorised according to four distinctive patterns: follicular (n=2, 4.2%), paracortical (n=19, 39.6%), diffuse (n=9, 18.8%) hyperplasia, or mixed pattern (n=18, 37.5%). The other examined histologic features were presence of necrosis, karyorrhexis, immunoblastic, histiocystic and vascular proliferation. Most of the cases were required to take into differential diagnosis such as dermatopathic lymphadenitis (n=16, 33.3%), lymphoma (n=11, 22.9%) and histiocytic necrotizing lymphadenitis (n=9, 18.8%). The expression of chemokines and S100A8/A9 were higher than that of nonspecific reactive hyperplasia. The expression of chemokines and S100A8/A9 were higher than that of nonspecific reactive hyperplasia. <h3>Conclusions</h3> Histopathologic findings of LN in AOSD patients are diverse enough to be included various differential diagnosis. Because the several chemokines and S100A8/A9 were more expressed in AOSD patients than those of reactive hyperplasia, they may serve as a pathogenesis of AOSD. <h3>Disclosure of Interest</h3> None declared
Highly-Soluble Cyanine J-aggregates Entrapped by Liposomes for <i>In Vivo</i> Optical Imaging around 930 nm
Authors: Dyego Miranda, Haoyuan Huang, Homan Kang, Ye Zhan, Depeng Wang, Yang Zhou, Jumin Geng, Hailey I Kilian, Wesley Stiles, Aida Razi, Joaquin Ortega, Jun Xia, Hak Soo Choi, Jonathan F Lovell
Journal: Theranostics (2019)

Near infrared (NIR) dyes are useful for in vivo optical imaging. Liposomes have been used extensively for delivery of diverse cargos, including hydrophilic cargos which are passively loaded in the aqueous core. However, most currently available NIR dyes are only slightly soluble in water, making passive entrapment in liposomes challenging for achieving high optical contrast. Methods: We modified a commercially-available NIR dye (IR-820) via one-step Suzuki coupling with dicarboxyphenylboronic acid, generating a disulfonated heptamethine; dicarboxyphenyl cyanine (DCP-Cy). DCP-Cy was loaded in liposomes and used for optical imaging. Results: Owing to increased charge in mildly basic aqueous solution, DCP-Cy had substantially higher water solubility than indocyanine green (by an order of magnitude), resulting in higher NIR absorption. Unexpectedly, DCP-Cy tended to form J-aggregates with pronounced spectral red-shifting to 934 nm (from 789 nm in monomeric form). J-aggregate formation was dependent on salt and DCP-Cy concentration. Dissolved at 20 mg/mL, DCP-Cy J-aggregates could be entrapped in liposomes. Full width at half maximum absorption of the liposome-entrapped dye was just 25 nm. The entrapped DCP-Cy was readily detectable by fluorescence and photoacoustic NIR imaging. Upon intravenous administration to mice, liposomal DCP-Cy circulated substantially longer than the free dye. Accumulation was largely in the spleen, which was visualized with fluorescence and photoacoustic imaging. Conclusions: DCP-Cy is simple to synthesize and exhibits high aqueous solubility and red-shifted absorption from J-aggregate formation. Liposomal dye entrapment is possible, which facilitates in vivo photoacoustic and fluorescence imaging around 930 nm.