tbuckley/cabot-search huggingface dataset:
Abstract 21129: Arterial Anatomy and Functional Performance in Peripheral Artery Disease: Cardiovascular Cell Therapy Research Network Patients With Intermittent Claudication Injected With ALDH Bright Cells: CCTRN PACE
Authors: Bharath Ambale Venkatesh, Tomoki Fujii, Emerson Perin, Michael P Murphy, Phillip C Yang, Timothy D Henry, Lemuel A Moye, Judith L Bettencourt, Ray F Ebert, Joao A Lima
Journal: Circulation (2017)

Introduction: Claudication is characterized by the presence of a stenosis or occlusion of arteries in the lower extremities that limits walking endurance compared with healthy individuals. Magnetic Resonance (MR) based assessments of leg arterial anatomy may enable improved understanding of the underlying causes of functional impairment. Hypothesis: The severity of stenosis in the lower extremity arteries and collateral vessel density is associated with functional impairment. Methods: A total of 82 participants with claudication and infrainguinal PAD were recruited across 9 US sites as part of the National Heart, Lung, and Blood Institute-sponsored CCTRN PACE clinical trial. Baseline (pre-treatment) data for 78 participants were used for this analysis. Functional performance was assessed by treadmill test measures of peak walking time (PWT) and claudication onset time (COT). Contrast-enhanced time-resolved magnetic resonance angiography was used to assess maximum stenosis of the superficial femoral artery (SFA) in each leg. The extent of arterial collateralization at the thigh (nTC) and calf (nCC) was measured by counting the number of vessels that bypassed a stenosis and reconstituted the main conduit vessel. Linear regression was used to evaluate the association between PWT and COT as the dependent variable and maximum stenosis, nTC and nCC as independent variables. Results: The participants were 66±9 years old, 27% female. The mean pre-exercise ankle brachial index in the more symptomatic leg was 0.61± 0.12. Participants were primarily Rutherford 2 (54%) and 3 (44%). At baseline, mean PWT was 5.0±2.6 min, COT was 1.6±0.9 min, nTC was 3.4±3.3 and nCC was 1.1±1.9. The maximum thigh stenosis was ≥75% in 77/78 and 99-100% in 66/78 participants. In linear regression models, maximum stenosis and nTC were not associated with PWT or COT. The nCC was associated with the COT (beta=0.08, p=0.008), and weakly associated with PWT (beta= 0.16, p=0.07). The association with COT remained after adjustment for thigh stenosis and nTC (beta=0.08, p=0.01). Conclusions: In patients with claudication and significant SFA stenosis, calf collateralization was associated with superior functional performance.
Should we stop using electroconvulsive therapy?
Authors: John Read, Sue Cunliffe, Sameer Jauhar, Declan M McLoughlin
Journal: BMJ (2019)

Electroconvulsive therapy has no long term benefits compared with placebo and often causes brain damage, say <b>John Read</b> and <b>Sue Cunliffe</b>. But <b>Sameer Jauhar</b> and <b>Declan M McLoughlin</b> argue that evidence shows ECT is effective and safe in depression and that adverse side effects can be managed
FRI0463 A new computed tomography index for quantification of interstitial lung disease in systemic sclerosis is associated with lung function parameters in the short term follow-up
Authors: S. Vettori, M. Bocchino, D. Bruzzese, M. D’Alto, P. Argiento, V. Giacco, E. Romeo, A. Capaccio, G. Rea, T. Valente, A. Sanduzzi-Zamparelli, G. Valentini
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> New computer-assisted methods for the objective quantification of interstitial lung disease (ILD) at computed tomography (CT), based on the evaluation of mean lung attenuation (MLA), skewness and kurtosis have been recently investigated in Systemic Sclerosis (SSc). We developed a computerised integrated index (CII) based on a weighted evaluation of MLA, skewness and kurtosis and investigated its reliability for the quantitative assessment of SSc-ILD and its associations with lung function parameters in a cross-sectional study. <h3>Objectives</h3> To identify the CII cut off value with the highest sensitivity and specificity for CT-detected ILD and to investigate its impact on lung function parameters over-time of baseline assessed CII. <h3>Methods</h3> SSc patients meeting the new ACR/EULAR classification criteria, who had undergone a volumetric lung CT study from July 1 st 2014 to June 30th 2015, had been evaluated at baseline for ILD quantification by Goh et al. method and the previously referred dedicated software and had their CII calculated, were enrolled in a prospective study including complete clinical, serological, and functional assessment at baseline and at 1 year follow-up (FU). <h3>Results</h3> Thirty-nine out of 83 (47%) SSc patients (79 females, 4 males; mean age 56.4±11.3 years; median disease duration 12 years;<sup>2–54</sup> 18 diffuse cutaneous and 65 limited cutaneous SSc) had evidence of ILD as assessed by volumetric CT of the lungs at baseline. CII in patients with ILD was significantly lower than in those without ILD (−0.4929±0.9933 versus 0.4145±0.8059 HU; p&lt;0.0001). ROC analysis revealed that the best discriminating CII value for ILD was 0.1966: sensitivity 0.81 (95% C.I. 0.68 to 0.92); specificity 0.66 (95% C.I. 0.52 to 0.80). Out of the 44 ILD negative patients, 22 (50%) presented a CII value lower than the cut-off, and 13 of them (59%) were found to have a diffusing lung capacity for CO (DLCO)&lt;80% of predicted. At 1 year FU, the CII was significantly correlated with total lung capacity -TLC (r=0.45, p=0.004) and DLCO (r=0.29, p=0.045). Out of the 22 patients with a CII &lt;0.1966 but no ILD at visual evaluation, 11 (50%) developed a FVC decline at 1 year, and 8 (36.7%) a DLCO decline. <h3>Conclusions</h3> Here we confirm that quantitative computer-assisted CT of the lungs could be a reliable method for SSc-ILD evaluation and found that it could also be useful in predicting the evolution of lung function in the short-term FU. <h3>Disclosure of Interest</h3> None declared
An Analysis of a Multidisciplinary Lymphoma Virtual Tumor Board with Regional and International Participation
Authors: Thomas M. Habermann, Ruth A Lentz, John J Schmitz, Alexander G von Bormann, Jason Young, Christopher H Hunt, Grzegorz S. Nowakowski, Kristen McCullough, Pedro Horna, Adam J Wood, William R. Macon, Paul J Kurtin, Scott L Stafford, Usha Sree Chamarthy, Faraz Khan, Stephen M. Ansell, Rebecca L King
Journal: Blood (2018)
AB0181 Enhanced therapeutic efficacy of apoptotic cell treated mesenchymal stem cells in lupus prone mrl/lpr mice
Authors: Z. Zhang, H. Chen, L. Sun
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Mesenchymal stem cells (MSCs) exhibit promising therapeutic potential in systemic lupus erythematosus (SLE). Increased apoptotic cells (ACs) were observed in SLE and our previous study showed MSC transplantation reduced AC levels in patients with SLE. Yet the effects of ACs on MSCs are not clear. <h3>Objectives</h3> This study aims to investigate the effects of ACs on MSCs and efficacy of AC treated MSCs (AC-MSCs) in SLE. <h3>Methods</h3> Jurkat T cells were irradiated by ultraviolet ray to induce apoptosis and then co-cultured with umbilical cord derived MSCs. Then, ACs were removed and MSCs were further co-cultured with human peripheral blood mononuclear cells (PBMCs). The inhibition of MSCs on PBMC proliferation was detected by flow cytometry. MSCs and AC-MSCs were infused into lupus prone MRL/lpr mice respectively to compare their therapeutic effects. <h3>Results</h3> The suppression of MSCs on PBMC proliferation was significantly enhanced after co-culture with ACs. <i>In vivo</i> study showed that AC-MSCs significantly increased the survival rate of MRL/lpr mice and decreased urine protein as early as one week after treatment, while MSCs decreased urine protein eight weeks post infusion. Moreover, AC-MSCs remarkably reduced the number of splenic plasma cells and serum anti-dsDNA levels, whereas MSCs only showed decreased tendency. <h3>Conclusions</h3> ACs enhanced therapeutic effects of MSC transplantation in lupus mice, which provides new insights into MSC modification in the treatment of SLE. <h3>Disclosure of Interest</h3> None declared
Author Correction: PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1
Authors: Gang Chen, Yong Ho Kim, Hui Li, Hao Luo, Da-Lu Liu, Zhi-Jun Zhang, Mark Lay, Wonseok Chang, Yu-Qiu Zhang, Ru-Rong Ji
Journal: Nature Neuroscience (2019)
SP0029 Fine structure analysis to detect bone pores
Authors: M. Gunzer
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> The blood supply is essential for the many functions of bones. The bone marrow as well as blood cells generated within are particularly dependent on a functional circulation. Despite this fact there is a remarkable logical gap in our understanding of a closed circulatory loop in long bones. We have discovered a previously unknown type of blood vessels in long bones of mice that forms an intense connexion of bone marrow with the external circulation outside of the bone. These blood vessels transport the majority of blood into and out of bones and hence constitute an essential structural component of bone physiology. I will present a detailed characterisation of these vessels and also show evidence for similar structures in man. <h3>Disclosure of Interest</h3> None declared
Multiplex Quantitative Analysis of Tumor-Infiltrating Lymphocytes and Immunotherapy Outcome in Metastatic Melanoma
Authors: Pok Fai Wong, Wei Wei, James W. Smithy, Balazs Acs, Maria I. Toki, Kim R.M. Blenman, Daniel Zelterman, Harriet M. Kluger, David L. Rimm
Journal: Clinical Cancer Research (2019)

Because durable response to programmed cell death 1 (PD-1) inhibition is limited to a subset of melanoma patients, new predictive biomarkers could have clinical utility. We hypothesize that pretreatment tumor-infiltrating lymphocyte (TIL) profiles could be associated with response.
AB1428-HPR Two-year follow-up of the therapeutic exercise program for patients with rotator cuff tendinopathy: a single group study to investigate the effects on pain and disability
Authors: E Turgut, I. Duzgun
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Although exercise training is accepted as one of the important and active treatment approach for the shoulder-related musculoskeletal problems,<sup>1</sup> the scientific rationale and long-term results for the inclusion of specific progressive exercises are less clear. <h3>Objectives</h3> This longitudinal, single group study aims to investigate the effects of a therapeutic exercise program on pain and disability in patients with the rotator cuff tendinopathy. <h3>Methods</h3> Twenty-eight participants with chronic non-traumatic unilateral shoulder pain diagnosed with rotator cuff tendinopathy (28.6±5.4 years old, symptoms duration 3.2±1.5 months) were included. The appropriate patient education and criteria-based, supervised exercise program including scapular and rotator cuff neuromuscular control exercises were performed. We evaluated self-reported shoulder pain and disability status by using Shoulder Pain and Disability Index (SPADI)<sup>2</sup> at baseline, after 6 week, 12 week training, at one-year-follow-up, and two-year-follow-up. Repeated measures ANOVA used for statistical analysis. <h3>Results</h3> Comparisons showed that there was significantly less SPADI-pain and SPADI-disability score reported starting from six-week after baseline and at two-year-follow-up (p&lt;0.05). <h3>Conclusions</h3> The findings of the study showed that pain and disability gains can be achieved with 6 week progressive exercise training for participants with rotator cuff tendinopathy. Therefore, the progressive exercise training should be recommended to apply starting from early shoulder rehabilitation program. <h3>References</h3> [1] Cools AM, Struyf F, De Mey K, Maenhout A, Castelein B, Cagnie B. Rehabilitation of scapular dyskinesis: from the office worker to the elite overhead athlete. British journal of sports medicine. 2013; 48:675–676. [2] Williams JJ, Holleman JD, Simel D. Measuring shoulder function with the Shoulder Pain and Disability Index. The Journal of rheumatology. 1995; 22(4):727–732. <h3>Disclosure of Interest</h3> None declared
SP0180 Communication skills, an essential competency to make the difference in daily practice
Authors: N. Nigil Haroon, E. Szabo, A.M. CHEUNG, R. Inman
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Ankylosing spondylitis (AS) is associated with high risk of fractures. BMD, bone microarchitecture and strength are negatively affected in AS. TNF inhibitors such as etanercept, adalimumab, golimumab and infliximab are the mainstay of treatment in AS. However no data is available on the effect of TNF inhibitors on bone microarchitecture and strength. <h3>Objectives</h3> This study aimed to assess the effect of TNF inhibitors on bone microarchitecture in patients with AS. <h3>Methods</h3> AS was defined by Modified New York criteria. Areal BMD was measured by DXA. Volumetric BMD (vBMD) and bone microarchitecture were measured using highresolution peripheral quantitative CT (HRpQCT) at the radius and tibia at baseline and after one year of treatment with TNF inhibitors. Intake of calcium and vitamin D were optimised. <h3>Results</h3> There were 31 subjects (58% men). Mean (+SD) age and BASDAI were 40+14 years and 4.1+2.1 respectively. Median duration of disease was 14 (IQ: 6.5–25.5) years. Mean duration of follow-up was 15 months. Areal BMD (n=22) at lumbar spine (1.053+0.235 vs. 1.049+0.202,p=0.89), total hip (0.944+0.152 vs. 0.912+0.164,p=0.5), and femoral neck (0.955+0.151 vs. 0.954+0.191,p=0.2) did not change significantly. HRpQCT (n=31) on follow-up demonstrated that total, trabecular and cortical volumetric BMD were unchanged at both radius and tibia (table 1). Also, HRpQCT based trabecular parameters such as trabecular number, thickness and separation, BV/TV and cortical parameters such as cortical porosity and thickness remained stable (table 1). FEA estimates of bone stiffness and stress tended to be lower at the radius on follow-up however these parameters were not significantly different at the tibia (table 1). <h3>Conclusions</h3> This is the first study to document the changes in bone strength in AS patients with the use of TNF inhibitors. Treatment with TNF inhibitors might maintain bone microarchitecture at cortical and trabecular sites in patients with AS. <h3>Disclosure of Interest</h3> N. Nigil Haroon Consultant for: AMGEN Canada, E. Szabo: None declared, A. CHEUNG Consultant for: AMGEN, ELI LILLY, R. Inman Grant/research support from: AMGEN, Consultant for: AMGE, ABBVIE, NOVARTIS, JANNSEN, MERCK
Abstract 12450: Myocardial Fibrosis Burden Predicts Left Ventricular Ejection Fraction and is Modified by Age and Steroid Treatment Duration in Duchenne Muscular Dystrophy
Authors: Animesh Tandon, Chet R Villa, Kan N Hor, John L Jefferies, Zhiqian Gao, Jeffrey A Towbin, Brenda L Wong, Wojciech Mazur, Robert J Fleck, Joshua J Sticka, Dudley W Benson, Michael D Taylor
Journal: Circulation (2014)

Background: Patients with Duchenne muscular dystrophy (DMD) typically exhibit progressive cardiac and skeletal muscle dysfunction, and are commonly treated with corticosteroids to prolong ambulation. Myocardial fibrosis and steroid treatment may modulate the progression of cardiac dysfunction in DMD patients. We aimed to longitudinally characterize the impact of myocardial fibrosis and steroid treatment on the progression of cardiac dysfunction using cardiac magnetic resonance (CMR) in a large DMD cohort. Methods: Serial CMR studies performed on DMD patients were reviewed for LVEF and late gadolinium enhancement (LGE) status, a marker for myocardial fibrosis. LVEF was modeled by examining effects of patient age, steroid treatment duration, LGE status, and myocardial fibrosis burden, as assessed by the number of LGE positive (LGE+) LV segments. Results: We analyzed 469 CMR studies from 99 DMD patients with ≥4 CMRs. Patient age at time of CMR ranged from 6.6 to 29.4 (median 12.3) years. There were 146 (31.1%) LGE+ studies and 59 studies (12.6%) that demonstrated depressed LVEF (LVEF&lt;55%). An age-only model demonstrated that LVEF declined 0.58±0.10%/yr (p&lt;0.0001, r 2 =0.067). Univariate modeling showed significant associations between LVEF and steroid treatment duration, presence of LGE, and number of LGE+ LV segments; multivariate modeling showed that LVEF declined by 0.93±0.09% for each LGE+ LV segment (p&lt;0.0001, r 2 =0.171), while age and steroid treatment duration were no longer significant. The number of LGE+ LV segments increased with age by 1.2 segments/year (95% confidence interval 1.1-1.2), and steroid treatment partially mitigated this increase (interaction term β=-0.01±0.005, p=0.010). Conclusions: Progressive myocardial fibrosis, as imaged by LGE on CMR, is a strong marker for the decline in LVEF in DMD patients. Steroid treatment partially attenuates the age-related increase in myocardial fibrosis burden.
Excess Burden of Mental Illness and Hospitalization in Young-Onset Type 2 Diabetes
Authors: Calvin Ke, Eric Lau, Baiju R. Shah, Thérèse A. Stukel, Ronald C. Ma, Wing-Yee So, Alice P. Kong, Elaine Chow, Philip Clarke, William Goggins, Juliana C.N. Chan, Andrea Luk
Journal: Annals of Internal Medicine (2019)

Type 2 diabetes (T2D) increases hospitalization risk. Young-onset T2D (YOD) (defined as onset before age 40 years) is associated with excess morbidity and mortality, but its effect on hospitalizations is unknown.To determine hospitalization rates among persons with YOD and to examine the effect of age at onset on hospitalization risk.Prospective cohort study.Hong Kong.Adults aged 20 to 75 years in population-based (2002 to 2014; n = 422 908) and registry-based (2000 to 2014; n = 20 886) T2D cohorts.All-cause and cause-specific hospitalization rates. Negative binomial regression models estimated effect of age at onset on hospitalization rate and cumulative bed-days from onset to age 75 years for YOD.Patients with YOD had the highest hospitalization rates by attained age. In the registry cohort, 36.8% of YOD bed-days before age 40 years were due to mental illness. The adjusted rate ratios showed increased hospitalization in YOD versus usual-onset T2D (onset at age ≥40 years) (all-cause, 1.8 [95% CI, 1.7 to 2.0]; renal, 6.7 [CI, 4.2 to 10.6]; diabetes, 3.7 [CI, 3.0 to 4.6]; cardiovascular, 2.1 [CI, 1.8 to 2.5]; infection, 1.7 [CI, 1.4 to 2.1]; P < 0.001 for all). Models estimated that intensified risk factor control in YOD (hemoglobin A1c level <6.2%, systolic blood pressure <120 mm Hg, low-density lipoprotein cholesterol level <2.0 mmol/L [<77.3 mg/dL], triglyceride level <1.3 mmol/L [<115.1 mg/dL], waist circumference of 85 cm [men] or 80 cm [women], and smoking cessation) was associated with a one-third reduction in cumulative bed-days from onset to age 75 years (97 to 65 bed-days).Possible residual confounding.Adults with YOD have excess hospitalizations across their lifespan compared with persons with usual-onset T2D, including an unexpectedly large burden of mental illness in young adulthood. Efforts to prevent YOD and intensify cardiometabolic risk factor control while focusing on mental health are urgently needed.Asia Diabetes Foundation.
Developing Allogeneic Double-Negative T Cells as a Novel Off-the-Shelf Adoptive Cellular Therapy for Cancer
Authors: Jong Bok Lee, Hyeonjeong Kang, Linan Fang, Cheryl D'Souza, Oyedele Adeyi, Li Zhang
Journal: Clinical Cancer Research (2019)

Abstract Purpose: To expand clinical-grade healthy donor-derived double-negative T cells (DNT) to a therapeutically relevant number and characterize their potential to be used as an “off-the-shelf” adoptive cellular therapy (ACT) against cancers. Experimental Design: We developed methods to expand DNTs under GMP conditions and characterized their surface molecule expression pattern using flow cytometry–based high-throughput screening. We investigated the off-the-shelf potential of clinical-grade DNTs by assessing their cytotoxicity against various cancer types and their off-tumor toxicity in vitro and in xenograft models and determining the effect of cryopreservation under GMP conditions on cell viability and cytotoxicity. Further, we determined the susceptibility of DNTs to conventional allogeneic T cells in vitro and in vivo. Results: Clinical-grade DNTs expanded 1,558 ± 795.5-fold in 17 days with &amp;gt;90% purity. Expanded DNTs showed potent in vitro cytotoxic activity against various cancer types in a donor-unrestricted manner. DNTs enhanced the survival of mice infused with a lethal dose of EBV-LCL and significantly reduced leukemia engraftment in xenograft models. Expanded DNTs cryopreserved using GMP-compliant reagents maintained viability and anticancer functions for at least 600 days. Live allogeneic DNTs did not induce cytotoxicity of alloreactive CD8+ T cells in vitro, and coinfusion of DNTs with peripheral blood mononuclear cells (PBMC) from a different donor into mice resulted in coengraftment of DNTs and PBMC-derived allogeneic conventional T cells in the absence of cytotoxicity toward DNTs, suggesting the lack of host-versus-graft reaction. Conclusions: We have established a method to generate therapeutic numbers of clinical-grade DNTs that fulfill the requirements of an off-the-shelf ACT.
Risk of Death, Relapse or Progression, and Loss of Life Expectancy at Different Progression-Free Survival Milestones in Primary Central Nervous System Lymphoma
Authors: Jorne Lionel Biccler, Kerry J Savage, Peter de Nully Brown, Judit Jørgensen, Thomas Stauffer Larsen, Christian Bjørn Poulsen, Danny Stoltenberg, Lasse H. Jakobsen, Martin Bøgsted, Diego Villa, Tarec C. El-Galaly
Journal: Blood (2018)
Comparing Costs and Consequences of Eltrombopag Plus IST Versus IST Alone for First-Line Treatment in Severe Aplastic Anemia: Results from a Responder Analysis
Authors: Gabriel Tremblay, Qayyim Said, Beilei Cai, Shan Ashton Garib, Dimitrios Tomaras, Anna Forsythe, Anuja Roy
Journal: Blood (2018)
Thrombin-Mediated Activation of PAR-1 Contributes to Microvascular Stasis in Mouse Models of Sickle Cell Disease Via Increased Endothelial Expression of P-Selectin and VWF
Authors: Erica Sparkenbaugh, Chunsheng Chen, Julia Nguyen, Shaobin Wang, Gregory M. Vercellotti, John D Belcher, Rafal Pawlinski
Journal: Blood (2018)