tbuckley/cabot-search huggingface dataset:
PB2430 CHANGES OF TPA AND PAI‐1 IN PATIENTS WITH CORONARY ARTERY DISEASE.
Authors: Y. Tyravska, V. Lizogub, T. Vovk, O. Savchuk
Journal: HemaSphere (2019)

Background: Impaired fibrinolysis, with imbalance between the key enzyme of plasminogen to plasmin activation, tissue plasminogen activator (tPA), and its main endogenous inhibitor, plasminogen activator inhibitor‐1 (PAI‐1), is shown to play a crucial role in thrombi formation which is an essential process in acute coronary syndrome (ACS). Most studies exist regarding myocardial infarction (MI). Limited investigations include patients with unstable angina (UA). However, no data is found concerning types of UA, namely, new‐onset angina (NUA) and progressive angina (PUA). Consequently, we investigated concentrations of tPA, PAI‐1 and tPA/PAI‐1 ratio in patients with above‐mentioned types of coronary artery disease (CAD). Aims: to compare the concentration of tPA and PAI‐1, tPA/PAI‐1 ratio in patients with different types of CAD (including NUA and PUA). Methods: In this cross‐sectional study, we collected blood samples in 94 patients with CAD ‐ 10 patients with MI, 57 patients with UA (38 patients with PUA and 19 patients with NUA), 27 patients with chronic coronary disease (stable angina (SA)). Concentrations of tPA and PAI‐1 were determined by standart method ELISA. Ratio tPA/PAI‐1 was calculated. There were no significant difference between groups of patients with respect of age, gender and body mass index. Results: In our study, we observed significant difference in tPA concentration (p = 0,0001) and tPA/PAI‐1 ratio (p = 0,004). However, PAI‐1 did not differ significantly in groups (p = 0,326), though it tended to be higher in patients with ACS in comparison with SA (0,392 (0,324‐0,472) U/ml vs 0,321 (0,284‐0,456) U/ml, p = 0,100). Unexpectedly, we identified the highest PAI‐1 concentration in UA group. Both tPA and tPA/PAI‐1 were significantly lower in ACS in contrast to SA (0,226 (0,173‐0,233) U/ml and 0,514 (0,432‐0,625) vs 0,234 (0,222‐0,295) U/ml and 0,619 (0,505‐0,997), p = 0,016 and p = 0,039, respectively). We detected significantly lower tPA concentration and tPA/PAI‐1 in patients with UA in comparison with SA (0,219 (0,173‐0,230) U/ml vs 0,234 (0,222‐0,256) U/ml, p = 0,002, and 0,485 (0,427‐0,597) vs 0,619 (0,505‐0,811), p = 0,021, respectively). Finally, we revealed significant difference in tPA concentration and tPA/PAI‐1 between NUA and PUA (p = 0,0001 and p = 0,001, respectively). Moreover, there were no difference between tPA concentration and tPA/PAI‐1 in MI and NUA (p = 0,071 and p = 0,756, respectively) as well as SA and PUA (p = 0,153 and p = 0,188, respectively). Additionally, the lowest tPA/PAI‐1 ratio was in NUA group. Summary/Conclusion: We have established imbalance between concentrations of tPA and PAI‐1 depending on CAD type. Thus, the highest thrombotic activity was detected in UA group while the lowest fibrinolytic activity was in NUA group. These findings call for further studies within types of UA as well as MI. image
Association of Conventional Cardiovascular Risk Factors With Cardiovascular Disease After Hypertensive Disorders of Pregnancy
Authors: Eirin B. Haug, Julie Horn, Amanda R. Markovitz, Abigail Fraser, Bjørnar Klykken, Håvard Dalen, Lars J. Vatten, Pål R. Romundstad, Janet W. Rich-Edwards, Bjørn O. Åsvold
Journal: JAMA Cardiology (2019)

<h3>Importance</h3> Women with a history of hypertensive disorders of pregnancy (HDP) have higher risk of cardiovascular disease (CVD). It is not known how much of the excess CVD risk in women with a history of HDP is associated with conventional cardiovascular risk factors. <h3>Objective</h3> To quantify the excess risk of CVD in women with a history of HDP and estimate the proportion associated with conventional cardiovascular risk factors. <h3>Design, Setting, and Participants</h3> Prospective cohort study with a median follow-up of 18 years. Population-based cohort of women participating in the Nord-Trøndelag Health Study in Norway. We linked data for 31 364 women from the Nord-Trøndelag Health Study (1984-2008) to validated hospital records (1987-2015), the Cause of Death Registry (1984-2015), and the Medical Birth Registry of Norway (1967-2012). A total of 7399 women were excluded based on selected pregnancy characteristics, incomplete data, or because of emigrating or experiencing the end point before start of follow-up, leaving 23 885 women for study. Data were analyzed between January 1, 2018, and June 6, 2018. <h3>Exposures</h3> Experiencing 1 or more pregnancies complicated by HDP before age 40 years vs only experiencing normotensive pregnancies. <h3>Main Outcomes and Measures</h3> We used Cox proportional hazards models to estimate the hazard ratios (HRs) for the association between HDP and CVD. The proportion of excess risk associated with conventional cardiovascular risk factors was estimated using an inverse odds ratio weighting approach. <h3>Results</h3> Our study population consisted of 23 885 parous women from Nord-Trøndelag County, Norway. A total of 21 766 women had only normotensive pregnancies, while 2199 women experienced ever having an HDP. From age 40 to 70 years, women with history of HDP had an increased risk of CVD compared with women with only normotensive pregnancies (HR, 1.57; 95% CI, 1.32-1.87) but not at older age (β = 0.98; 95% CI, 0.96-1.00;<i>P</i>for interaction by age = .01). Blood pressure and body mass index were associated with up to 77% of the excess risk of CVD in women with history of HDP, while glucose and lipid levels were associated with smaller proportions. <h3>Conclusion and Relevance</h3> In this study, the risk of excess CVD in women with history of HDP was associated with conventional cardiovascular risk factors, indicating that these risk factors are important targets for cardiovascular prevention in these women.
AB0230 CYTOKINE SIGNATURE DOES NOT CORRELATE WITH PAIN OR DISEASE ACTIVITY IN WELL CONTROLLED ERA
Authors: Anna Radziszewska, Corinne Fisher, Timothy Bray, Vera Choida, Debajit Sen, Margaret Hall-Craggs, Coziana Ciurtin
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Inflammation is a mediator and primary driver of joint damage in juvenile idiopathic arthritis (JIA). Musculoskeletal pain can be experienced in the presence or absence of inflammation. Enthesitis related arthritis (ERA) is a subtype of JIA characterised by inflammation of the spine, enthesis, and peripheral joints. Cytokines and numerous other regulatory molecules are implicated in pain and inflammation, yet, to date, no reliable biomarkers have been identified. <h3>Objectives</h3> To assess if cytokine profiles correlate with pain or disease activity in patients with ERA. <h3>Methods</h3> 42 patients, with either a prior diagnosis of JIA or back pain, agreed to have a standard clinical MRI scan of lumbar spine, sacroiliac joints, and pelvis and to donate serum. Serum was also collected from 12 volunteer age matched healthy controls. Serum was analysed using a bead-based multiplex assay (Luminex) for the concentrations of the following analytes: IL-6, IL-12, IL-17, IL-23, IL-27, TNFα, IFNγ, MIF, OPG, SOST, GM-CSF, VEGF, DKK-1, S100A8, MMP-3 and CRP. To assess pain levels, patients indicated on a scale of 0-10 the amount of back pain experienced at night and separately the amount of back pain experienced at any time during the last week. They also completed a Bath Ankylosing Spondylitis Disease activity Index (BASDAI) questionnaire to assess disease activity. Cytokine concentrations in patients with ERA were compared with those of controls. The levels were also correlated with the two measures of back pain as well as individual questions from the BASDAI questionnaire. <h3>Results</h3> Of all 54 samples tested, 11 patients and 5 controls cross-reacted with the negative control for the assay and thus were excluded from analysis. Based on MRI scan results, 14 patients had ERA, 8 had biomechanical pain, 7 had other subtypes of JIA, and 2 had non-specific features of spinal inflammation. The median overall back pain and the total BASDAI scores for the ERA group were 2.4 (IQR=1.45-5.55) and 2.5 (IQR= 0.75-6.25) respectively, suggesting well controlled disease on treatment and minimal residual symptoms. There was no statistical difference between cytokine levels in the ERA group compared to controls when corrected for multiple testing, with the exception of IL-12 which was significantly higher in controls (p=0.003). No correlation was found between cytokines and pain scores (at night or overall during the last week) or with the overall BASDAI score or any of the sub-component questions of the BASDAI questionnaire. <h3>Conclusion</h3> Well-controlled ERA patients on treatment have similar cytokine profiles as healthy controls and they do not correlate with clinical pain scores or disease activity. <h3>Disclosure of Interests</h3> None declared
PS1546 IS IT BETTER TO MOBILIZE HEMATOPOIETIC STEM CELLS FROM HEALTHY DONORS AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION WITH PEGFILGRASTIM?
Authors: J. Li, L. Gao, Y. Liu, Q. Wen, S. Zhou, X. Liu, L. Gao, C. Zhanng, P. Kong, X. Zhang
Journal: HemaSphere (2019)

Background: Granulocyte colony-stimulating factor (G-CSF) has been established for mobilizing allogeneic hematopoietic stem cells from healthy donors as the standard regimen. It has a short elimination half-life and daily subcutaneous injection. The pegylated form of filgrastim (pegfilgrastim) has a longer elimination half-life because of decreased serum clearance and might be a convenient alternative for allogeneic hematopoietic stem cell mobilization. Aims: To observe the efficacy and safety of pegfilgrastim in mobilization of donor stem cells compared with rhG-CSF. Methods: This study was a prospective randomize control single-center trial. 47 normal related donors received pegfilgrastim 12 mg subcutaneously to mobilize peripheral blood stem cells (PBSC) for allogeneic stem cell transplantation. 36 donors received 10 ug/kg granulocyte colony-stimulating factor (G-CSF) for mobilization in conventional filgrastim group. Pegfilgrastim group with inadequate mobilization (blood CD34+ cells 20/uL on day 4) were given additional daily doses of 10 ug/kg conventional filgrastim. Leukapheresis was planned to start 5 days after injection. Results: There were 40/47 donors in pegfilgrastim group who only required single leukapheresis, 29/36 in conventional filgrastim group. These indicated no statistical difference. The maximum concentration of white blood cells (WBC) and circulating CD34 cells occurred 5 days after egfilgrastim injection in two groups had significant statistical difference(P = 0.039,P = 0.02,respectively), median WBC in case group is 511836/ul vs.42.6884/ul in control group; CD34:median 128.33/ul vs.73.68/ul). In 44 out of 47 achieved neutrophil and platelet engraftment in pegfilgrastim group after transplantation,34/36 in conventional filgrastim group, respectively. Median neutrophil and platelet engraftments in the recipients in pegfilgrastim group occurred on day 14 and day 16, day 15 and day 17 in conventional filgrastim group. Pegfilgrastim group was associated with lower incidences of acute graft-versus-host disease(GVHD) (14.9% vs. 30.5%, p < 0.05) compared with conventional filgrastim. The main adverse events were bone pain and headache, the incidence ratio is 14.9% in pegfilgrastim group, 22.2% in conventional filgrastim group. Summary/Conclusion: PBSC mobilization in normal donor with single injection of pegfilgrastim is feasible. Further comparisons to standard G-CSF for allogeneic stem cell mobilization should be conducted in future.
A Non-Human Primate CRISPR/Cas9 Model of Clonal Hematopoiesis of Indeterminate Potential Demonstrates Expansion of TET2-Disrupted Clones
Authors: Kyung-Rok Yu, Cynthia E Dunbar, Marcus Corat, Shirley Chen, Aisha Aljanahi, Eun Jung Baek, Jean-Yves Metais, Hannah Natanson, Thomas Winkler, Robert E Donahue
Journal: Blood (2017)
Digital Manufacturing for Microfluidics
Authors: Arman Naderi, Nirveek Bhattacharjee, Albert Folch
Journal: Annual Review of Biomedical Engineering (2019)

The microfluidics field is at a critical crossroads. The vast majority of microfluidic devices are presently manufactured using micromolding processes that work very well for a reduced set of biocompatible materials, but the time, cost, and design constraints of micromolding hinder the commercialization of many devices. As a result, the dissemination of microfluidic technology-and its impact on society-is in jeopardy. Digital manufacturing (DM) refers to a family of computer-centered processes that integrate digital three-dimensional (3D) designs, automated (additive or subtractive) fabrication, and device testing in order to increase fabrication efficiency. Importantly, DM enables the inexpensive realization of 3D designs that are impossible or very difficult to mold. The adoption of DM by microfluidic engineers has been slow, likely due to concerns over the resolution of the printers and the biocompatibility of the resins. In this article, we review and discuss the various printer types, resolution, biocompatibility issues, DM microfluidic designs, and the bright future ahead for this promising, fertile field.
Abstract 17339: Inspiratory Capacity and NT-pro BNP Predict Key Cardiopulmonary Exercise Measurements but Not Six-Minute Walk Test Distance in Older Patients With Heart Failure
Authors: Marjorie Webb, Ruth Lindquist, Ulf Bronas, Lisa Anderson, Cynthia Gross, Diane Treat-Jacobson
Journal: Circulation (2017)

Introduction: Heart failure (HF) affects more than five million people, half of whom are at least 75 years old. Peak oxygen consumption (VO2peak), Ventilatory efficiency (VE/VCO2 slope) and the Six...
PB1808 THE LEVELS OF SERUM FERRITIN CAN BE A PREDICTIVE FACTOR FOR SURVIVAL OUTCOMES IN DIFFUSE LARGE B CELL LYMPHOMA PATIENTS WITH ANEMIA
Authors: H.S. Lee, J.Y. Jeong, J.‐C. Jo, W.S. Lee, J.H. Lee
Journal: HemaSphere (2019)

Background: There are many clinical and molecular factors used to predict outcomes in patients with malignant lymphomas. Some studies have shown that serum ferritin levels correlated with tumor mass and closely followed disease activity in patients with hematologic malignancies such as malignant lymphoma and acute leukemia. And serum ferritin has frequently been used as a surrogate marker for systemic iron stores, but may also be elevated in specific circumstances without excess iron stores, such as in inflammation. Nevertheless, in actual clinical practice, the patients with malignant lymphoma, who are anemic and have high serum ferritin levels, are considered to suffer from anemia of chronic disease (ACD). To date, no studies have reported the survival differences between the ferritin and Hemoglobin (Hb) levels. Aims: Therefore, we investigated the clinical significance of high serum ferritin level in DLBCL patients with ACD. Methods: A total of 312 patients who were diagnosed with DLBCL between 2010 and 2016 were retrospectively analyzed. Patients were divided into four groups based on their ferritin (&lt;500 and ≥500 ng/ml) and hemoglobin (Hb, &lt;12 and ≥12 g/dL) levels. Progression free survival and Overall survival were calculated with the use of the Kaplan‐Meier methods. Results: In this study, several factors were demonstrated as independent prognostic factors for survival outcomes. IPI risk is an independent prognostic factor for the 5‐year PFS and 5‐year OS (relative risks (RR) = 0.458, 95% confidence interval [CI]: 0.277–0.758, p = 0.002 and RR = 0.297, 95% CI: 0.152–0.578, p &lt; 0.001, respectively). Non‐bulky mass (&lt;10 cm) (RR = 1.995, 95% CI: 1.140–3.448, p = 0.015) and female sex (RR = 1.848, 95% CI: 1.141–2.997, p = 0.013) were independent good prognostic factors for the 5‐year PFS. Low Hb and high ferritin were also independent poor prognostic factor for the 5‐year PFS (RR = 2.411, 95% CI: 1.063–5.473, p = 0.035: compared with high Hb and low ferritin levels and RR = 2.124, 95% CI: 1.072–4.209, p = 0.031: low Hb and low ferritin). Nevertheless, the groups based on Hb and ferritin levels did not significantly differ for 5‐year OS. In addition, the survival outcomes based on the ferritin level in patients with anemia (Hb &lt; 12.0 g/dL) indicated statistically significant difference. The 5‐year PFS values were 59.3% and 40.9% in low and high serum ferritin levels (&lt;500 and ≥500 ng/ml), respectively ( p = 0.01), and the 5‐year OS values were 78.4% and 51.9% in the low and high ferritin levels, respectively ( p = 0.006). Summary/Conclusion: High serum ferritin levels may prove to be efficient predictive markers for survival outcomes in DLBCL patients with anemia looks like ACD. In DLBCL patients with anemia, that is, considered as ACD, high ferritin level may not indicate a simple ACD but may be a prognostic factor for poor survival.
AB1017 WHAT IS THE CURRENT SITUATION OF THE PAEDIATRIC RHEUMATOLOGY TRANSITION CARE UNITS?
Authors: José Luis Martín-Varillas, Daniel Clemente, J.C. López Robledillo, Belén Serrano Benavente, Indalecio Monteagudo, Juan Carlos Nieto
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Switching from paediatric rheumatology to the adult rheumatology care units has a negative impact on disease control and adherence in young patients with juvenile idiopathic arthritis (JIA) but also in other chronic diseases. Transitional care services provide the opportunity of being followed-up by an adult rheumatology specialized in juvenile rheumatic diseases. <h3>Objectives</h3> In our study we report the current situation of a rheumatology transition care unit (RTCU). <h3>Methods</h3> We set up an observational and retrospective study of patients followed in our unit between September 2015 and December 2018. We included those patients with a disease beginning at 16 years or younger and those patients who were attended on RTCU for the first time before age 25. Clinical and demographic data and all treatments received by the patients before and after de first visit in the transition care unit were also collected. <h3>Results</h3> 119 patients were attended in our RTCU. After applying the exclusion criteria, 110 patients remained: 78 female/32 male (70.9/29.1%) with a median age of 18.5 [17.9-19.8] years at the first visit. No significant differences in age at the first visit were found between the first (September-2015 to September-2017) and the second stage (October-2017 to December-2018), 18.7 (17.8-20.2) vs. 18.2 (17.9-18.6) years respectively. The most frequent diagnoses are included in the <b>table 1</b>. Of the 75 patients with JIA, 54 were women (72%) with a median age at the disease onset of 6.88 [2.3-12.7] and 21.3% of patients had chronic anterior uveitis. 22 patients (29.3%) presented joint or ocular inflammatory activity or flare at the time of transition first visit but only 1 patient maintained inflammatory activity during the 3 years of follow-up. A total of 64 patients (85.3%) with JIA diagnosis were under treatment with synthetic DMARD, mostly methotrexate (61) or leflunomide (7). In addition, 43 patients (57.3%) required biological DMARD in the past, and 8 of them (10.7%) required more than one. The most frequently used drugs were: etanercept (ETN) (29 patients) and adalimumab (ADA) (19 patients). Tocilizumab (TCZ) (4), abatacept (1) and infliximab (1) were also used. Of these patients, at the time of the first visit on RTCU, 24 (32%) had no treatment, 42 patients (56%) had synthetic DMARD and 34 patients (45.3%) had biologic therapy in monotherapy or combined with DMARDs (19 ETN, 12 ADA, and 3 TCZ). <h3>Conclusion</h3> RTCU assessed mainly patients with JIA and connective tissue diseases. Most patients were inactive during the transfer to the adult unit, but the existence of patients that were still active and/or needed treatment with synthetic and/or biological DMARD reaffirms the need for close control in this period. <h3>Disclosure of Interests</h3> None declared
Imprint of assortative mating on the human genome
Authors: Loic Yengo, Matthew R. Robinson, Matthew C. Keller, Kathryn E. Kemper, Yuanhao Yang, Maciej Trzaskowski, Jacob Gratten, Patrick Turley, David Cesarini, Daniel J. Benjamin, Naomi R. Wray, Michael E. Goddard, Jian Yang, Peter M. Visscher
Journal: Nature Human Behaviour (2018)
OP0091 RISK OF MEDICAL COMPLICATIONS FOLLOWING TOTAL HIP OR KNEE ARTHROPLASTY IN PATIENTS WITH RHEUMATOID ARTHRITIS: A NATIONWIDE REGISTER-BASED COHORT STUDY
Authors: René Cordtz, Lars Erik Kristensen, Anders Odgaard, Søren Overgaard, Lene Dreyer
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Total hip and total knee arthroplasty (THA/TKA) are major surgeries carrying a risk of complications. Patients with rheumatoid arthritis (RA) are at increased risk of venous thromboembolism (VTE), arterial thromboembolic events (ATE), and infections in a non-surgical setting. <h3>Objectives:</h3> To investigate the risk of VTE, ATE, and non-surgical infection following THA/TKA in patients with RA compared with osteoarthritis (OA); and to explore the impact of biologics treatment. <h3>Methods:</h3> In a nationwide register-based study, patients with RA and OA who had elective THA/TKA in 2000-2014 were identified in the Danish Hip Arthroplasty Register/Danish Knee Arthroplasty Register and followed up to 90 days after surgery for the occurrence of VTE, ATE, and infections. Cox models stratified on sex and type of surgery (THA vs TKA) and adjusted for age, calendar period, history of chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM), cancer, VTE and CVD were carried out. Outcome information was obtained through linkage with the Danish National Patient Registry. In DANBIO, we identified RA patients treated with biologics within 90 days preceding surgery and estimated their risk of each outcome compared with non-biologics treated RA patients in a Cox model adjusted for the propensity score (PS) of receiving biologics as a restricted cubic spline covariate. The PS was conditional on age, sex, calendar period, use of methotrexate, other csDMARDs, and/or glucocorticoids, pre-surgical DAS28, HAQ-DI, VAS physician, and COPD, DM, cancer and/or VTE. <h3>Results:</h3> In total, 2899 and 112,571 patients with RA and OA were followed-up (Table). <h3>Conclusion:</h3> In this nationwide cohort study, RA patients were at increased risk of infection after THA/TKA compared to OA patients, but treatment with biologics did not further increase the risk. As seen in other studies RA patients had a lower risk of VTE following TKA when compared with OA patients, but our finding of an increased incidence of VTE in biologics-treated patients warrants further studies. <h3>Disclosure of Interests:</h3> René Cordtz: None declared, Lars Erik Kristensen Grant/research support from: UCB, Biogen, Janssen Pharmaceuticals, and Novartis, Consultant for: Consultant for AbbVie, Amgen, Biogen, BMS, Celgene, Eli Lilly, Janssen Pharmaceuticals, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB Pharma., Speakers bureau: Pfizer, AbbVie, Amgen, UCB, BMS, Biogen, MSD, Novartis, Eli Lilly and Company, and Janssen Pharmaceuticals, Anders Odgaard: None declared, Søren Overgaard: None declared, Lene Dreyer Consultant for: MSD, UCB and Janssen Pharmaceuticals, Speakers bureau: MSD, UCB and Janssen Pharmaceuticals, Speakers bureau: UCB, MSD, Eli Lilly and Janssen Pharmaceuticals.