tbuckley/cabot-search huggingface dataset:
AB1180 ULTRASOUND SEMIOTICS OF DEFEATS OF THE JOINTS IN REACTIVE ARTHRITIS AND OSTEOARTHRITIS
Authors: Volha Sirotka, Uladzimir Sirotka, Alexandr Litvyakov
Journal: Annals of the Rheumatic Diseases (2019)

Background:The most common cause of knee joint damage in people of working age is osteoarthritis.However, in recent years, cases of reactive arthropathy, which often takes a chronic course, have become more frequent [1].Given the current possible ultrasonic equipment, relevant is the study to study the ultrasonic features of defeat of joints with ReA and OA.Objectives: To study the ultrasonic features of joint lesions at osteoarthritis and reactive arthritis.Methods: We studied 55 patients with ReA and 22 patients with OA.Among patients with ReA were 25 women and 20 men, median age was 31 years (18 to 47), the median duration of the current Imple -of 2.86 (0,07-29,0) months.Among patients with OA were examined in 15 women and 7 men, median age was 56.5 years (43-61), the median duration of flow OA -139 months (12-360 months).All patients with ReA at the time of the study or in history had confirmed genital chlamydial infection.All patients were multiplescale dynamic study of the knee by the ultrasonic device expert class using a sensor with a frequency of 12 MHz.Results: As a result of the ultrasound examination of the 110 joints with ReA, we have identified: pronounced synovitis in 69 (62.7%) joints, but the absence of pathological vascularization in the projection of the synovia; narrowing of the joint space 73 (66,4%) joint; heterogeneous structure of the ligament in 82 (75%) joints, tenosynovitis in 20 (18%) joints, thickening entheses in 89 (80.9%) joints, hypoechoic entheses in 72 (65.5%) joints, hyperechogenic inclusions in projection entheses in 39 (36%) joints; local osteolysis of cortical layer of bone in the fixation entheses with the formation of erosive lesions in 77 (70%) joints, osteitis 26 (23,6%) joints; swelling parenthetically in 81 (74%) joint effusion parenthetically 49 (44,5%) joints (Fig. 1 a,b,c).a. b. c.
Abstract 16663: Child Health Promotion in Underserved Communities: Primary Results From the Cluster Randomized FAMILIA Trial
Authors: Rodrigo Fernandez-Jimenez, Risa Jaslow, Sameer Bansilal, Maribel Santana, Raquel Diaz-Munoz, Giselle Trabal, Jacqueline Latina, Ana V Soto, Rajesh Vedanthan, Chiara Giannarelli, Jason Kovacic, Emilia Bagiella, Andrew Kasarskis, Zahi Fayad, Roger J Hajjar, Valentin Fuster
Journal: Circulation (2018)

Introduction: Preschool-based interventions offer promise to instill healthy behaviors in children. However, its efficacy in underserved communities is not well established. Objective: To assess the impact of a preschool-based health promotion education intervention in an underserved community. Methods: We performed the cluster-randomized controlled “Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health” (FAMILIA) trial involving 15 Head Start preschools in Harlem, New York. Schools and their children were 3:2 randomized to either receive the usual curriculum (control); or a 4-month educational intervention for a total of 50 hours to instill healthy behaviors in relation to diet, physical activity, understanding how the human body and heart work, and emotion management. The primary outcome was the change from baseline in the overall knowledge, attitudes, and habits (KAH) score of the child. As secondary outcomes, we evaluated the changes in KAH subcomponents and in the test of emotion comprehension. Linear mixed-effects models were used to test for intervention effects. Results: We enrolled 562 children 3 to 5 years old, 51% female, 54% Hispanic/Latino and 37% African-American. The mean % relative change from baseline in the overall KAH score was 5.5% and 11.8% in control and intervention groups, respectively. The average between-group absolute difference in overall KAH was 2.89 points (95% CI: 0.61 to 5.17; p = 0.013; Figure). Physical activity and understanding of the human body and heart components, and knowledge and attitudes domains, were the main drivers of the effect. Changes in emotion comprehension trended to favor intervened children as compared to controls. Conclusions: The FAMILIA trial demonstrates that a multidimensional school-based education intervention is an effective strategy for instilling healthy behaviors among preschoolers from a diverse and socially/economically disadvantaged community. As part of our long-term vision, we are conducting a long-term follow-up of the children to assess the sustainability of the intervention effects.
FRI0508 OLIVE OIL POLYPHENOLS AS NOVEL NUTRACEUTICALS IN TREATMENT OF OSTEOARTHRITIS
Authors: Mia S. Meiss, Marina Sanchez-Hidalgo, Catalina Alarcón-de-la-Lastra, José M. Fernández-Bolaños, Richard Oc Oreffo, Maria C de Andres
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Osteoarthritis (OA) is a degenerative disease of the joints characterised by the imbalance of anabolic and catabolic processes in articular cartilage. It is one of the most significant causes of disability in the world affecting over 60% of people over the age of 60, causing joint stiffness, pain and a decrease in the quality of life. Currently no successful disease-modifying agent has been found to prevent or treat the condition. To address this unmet need, alternative approaches, including the use of nutraceuticals as a novel therapeutic intervention are under examination. <h3>Objectives</h3> To analyse if nutraceutical are able to reverse the catabolic activity that contribute to cartilage destruction in OA. Here two polyphenols from extra virgin olive oil (EVOO), oleocanthal (OLC) and ligstroside aglycone (LA), plus a chemically modified acetylated ligstroside aglycone (A-LA), and two marine polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were examined as potential anti-inflammatory agents for OA. <h3>Methods</h3> Human chondrocytes and cartilage explants were extracted from OA femoral heads, cultured and incubated with increasing concentrations of select compounds in combination with the pro-inflammatory cytokines IL-1β and oncostatin M (OSM). Gene expression levels were analysed by qPCR; nitric oxide (NO), GAG release and cytokines were measured in supernatants by colorimetric assays and Luminex technology respectively. Safranin-O and Alcian blue/Sirius red staining were done to quantify extracellular matrix components from cartilage. <h3>Results</h3> Acetylated ligstroside showed the most promising results for implementation in treating OA as it reduced the expression of pro-inflammatory genes such as inducible nitric oxide (<i>iNOS</i>), matrix metalloprotease-13 (<i>MMP13</i>) and interleukin-1β (<i>IL1B</i>) at both RNA and protein levels; decreased nitric oxide (NO) levels from cartilage explants and also reduced proteoglycan (PG) losses in human osteoarthritic cartilage explants and chondrocytes (Figure 1). <h3>Conclusion</h3> These results substantiate the role of nutraceuticals in OA with implications for therapeutic intervention and our understanding of OA pathophysiology. <h3>References</h3> [1] Castrogiovanniet al. Nutraceutical supplements in the management and prevention of osteoarthritis. Int. J. Mol. Sci. 17, (2016). [2] Rigacci &amp; Stefani. Nutraceutical Properties of Olive Oil Polyphenols. An Itinerary from Cultured Cells through Animal Models to Humans. Int. J. Mol. Sci. 17, 128 (2016). [2] Aparicio-Soto, et al. Extra virgin olive oil: a key functional food for prevention of immune-inflammatory diseases. Food Funct. 7, 4492–4505 (2016). <h3>Disclosure of Interests</h3> None declared
Isolation, cloning and confirmation as an allergen of the 2S albumin from hazelnut
Authors: L. Zuidmeer, C. Garino, J. Marsh, A. Lovegrove, M. Morati, S. Versteeg, P. Schilte, P. R. Shewry, M. Arlorio, R. Van Ree
Journal: Allergy (2009)
PS1210 DEVELOPMENT OF A NEXT GENERATION ALLOGENEIC CAR‐T CELL PLATFORM WITHOUT GENE EDITING
Authors: P.A. Sotiropoulou, A. Michaux, S. Raitano, S. Bornschein, J. Bolsée, S.R. Lenger, H.B. Machado, J.D. Moore, D.E. Gilham
Journal: HemaSphere (2019)

Background: Autologous CAR‐T cell therapy is now a proven breakthrough technology in the treatment of B cell malignancies and holds promise in the therapy of all types of cancer. However, autologous CAR‐T cell therapy does have significant challenges relating to logistics and product consistency. Allogeneic CAR‐T therapeutic products could allow treatment of multiple patients with cells from the same healthy donor, increasing product consistency, likely reducing manufacturing costs and avoiding the time delay required to generate an autologous T cell product. Aims: Allogeneic CAR‐T cell therapy is dependent upon eliminating the activity of the endogenous T Cell Receptor (TCR) within the engineered T cell, thereby preventing the induction of a graft versus host response and resultant potentially life‐threatening toxicity. We have explored RNA interference to modulate the TCR and to assess the potential of short hairpin RNA (shRNA) as a platform technology for Allogeneic CAR T cell therapy. Methods: shRNAs targeting the CD3ε and CD3ζ chains of the TCR complex were expressed in primary T cells where the efficacy of the individual shRNAs to downregulate the CD3 component and subsequent impact upon TCR expression assessed. The optimal shRNAs were tested in a head to head fashion against the state‐of‐the‐art gene editing technology, CRISPR‐Cas9, in vitro for response against mitogenic stimulation and in animal models for control of xenoGvHD. Results: shRNAs specific for CD3ε and CD3ζ reduced the transcriptional expression of their relevant targets, as well as the cell surface expression of the TCR. Downregulation of TCR expression and inhibition of the in vitro mitogenic response when challenged with anti‐CD3 antibodies was similar between shRNAs and CRISP‐Cas9 targeting CD3ζ. Importantly, in vivo experiments with T cells adoptively transferred to NSG mice showed that shRNAs targeting CD3ζ protected animals from GvHD, while T cell persistence was significantly higher compared to T cells genetically engineered with CRISP‐Cas9 targeting CD3ζ. Summary/Conclusion: This work demonstrates that the expression of shRNA in a standard retroviral vector provides a one‐step solution to produce cells suitable for Allogeneic CAR T cell therapy. Our testing continues, involving the examination of the anti‐tumor potency of such shRNA‐Allo CAR‐T cells. Importantly, this approach provides a one vector solution that offers an alternative to strategies such as gene editing to eliminate the TCR, while also requiring no major alteration to current CAR‐T cell manufacturing, that should enable the rapid adoption of the approach into clinical testing.
PB1953 QUALITY OF LIFE AND SYMPTOM BURDEN WITH FIRST AND SECOND GENERATION TYROSINE KINASE INHIBITORS IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA
Authors: T. Toptas, H. Bostan, K. Kut, F. Pepedil Tanrikulu, F. Yilmaz, I. Atagunduz, T. Tuglular
Journal: HemaSphere (2019)

Background: With the advent of tyrosine kinase inhibitors (TKIs), patients with chronic myeloid leukemia (CML) have a life expectancy similar to those of age‐ and sex‐matched healthy population. Nevertheless, patients receiving TKIs report chronic adverse events, some of which may be associated with severe symptoms including fatigue, edema, muscle cramps. Additionally, generic imatinib has license in various countries. In retrospective analyses and post‐marketing safety monitorization, it seems to have a similar efficacy and safety profile. However, quality of life and symptom burden issues in patients receiving TKIs still remains to be elucidated Aims: We aimed to assess the quality of life and symptom burden in patients receiving original imatinib, generic imatinib, dasatinib, and nilotinib. Methods: A total of 121 patients with CML who have been receiving any TKI for at least three months was contacted either by phone or at their routine outpatient clinic visits. All patients accepted to be included in the study. Their demographic data were recruited from chart files. Quality of life was assessed by EORTC‐QLQ‐C30 and its CML24 module. Symptom burden was assessed by MD Anderson Symptom Inventory (MDASI). Questionnaire scores were calculated per associated protocols. Group comparisons were made by Kruskal Wallis test. Results: Median age of patient population was 53 (28‐90) years. Fifty‐four (44.6%) was female. Eighty‐three patients (81.4%) had Sokal low‐intermediate disease. Most of the patients had good ECOG performance status (&lt;2: 96%) and low hematopoietic cell transplantation‐comorbidity index score (&lt;3: 90.8%). Median duration of TKIs was 31 (3‐154) months. Ninety‐eight patients (86.7%) had major molecular response at the time of questionnaire. Patients receiving different TKIs had comparable quality of life and treatment‐related symptom burden scores (table and figure). Summary/Conclusion: First and second generation TKIs as well as generic imatinib have similar impact on quality of life. Although these molecules have different safety profiles, severity of treatment‐related adverse events are generally mild. image
Novel ginsenoside-based multifunctional liposomal delivery system for combination therapy of gastric cancer
Authors: Chao Hong, Dan Wang, Jianming Liang, Yizhen Guo, Ying Zhu, Jiaxuan Xia, Jing Qin, Huaxing Zhan, Jianxin Wang
Journal: Theranostics (2019)

The clinical treatment of gastric cancer (GC) is hampered by the development of anticancer drug resistance and the unfavorable pharmacokinetics, off-target toxicity, and inadequate intratumoral accumulation of the current chemotherapy treatments. Ginsenosides combined with paclitaxel (PTX) have been shown to exert synergistic inhibition of human GC cell proliferation. In the present study, we developed a novel multifunctional liposome system, in which ginsenosides functioned as the chemotherapy adjuvant and membrane stabilizer. These had long blood circulation times and active targeting abilities, thus creating multifunctionality of the liposomes and facilitating drug administration to the GC cells. Methods: Three ginsenosides with different structures were used to formulate the unique nanocarrier, which was prepared using the thin-film hydration method. The stability of the ginsenoside liposomes was determined by particle size analysis using dynamic light scattering. The long circulation time of ginsenoside liposomes was compared with that of conventional liposome and polyethylene glycosylated liposomes in vivo. The active targeting effect of ginsenoside liposomes was examined with a GC xenograft model using an in vivo imaging system. To examine the antitumor activity of ginsenoside liposomes against GC, MTT, cell cycle, and apoptosis assays were performed on BGC-823 cells in vitro and PTX-loaded ginsenoside liposomes were prepared to evaluate the therapeutic efficacy on GC in vivo. Results: The ginsenosides stabilized the liposomes in a manner similar to cholesterol. We confirmed the successful delivery of the bioactive combination drugs and internalization into GC cells via analysis of the glucose-related transporter recognition and longer blood circulation time. PTX was encapsulated in different liposomal formulations for use as a combination therapy, in which ginsenosides were found to exert their inherent anticancer activity, as well as act synergistically with PTX. The combination therapy using these targeted liposomes significantly suppressed GC tumor growth and outperformed most reported PTX formulations, including Lipusu® and Abraxane®. Conclusion: We established novel ginsenoside-based liposomes as a tumor-targeting therapy, in which ginsenoside functioned not only as a chemotherapy adjuvant, but also as a functional membrane material. Ginsenoside-based liposomes offer a novel platform for anticancer drug delivery and may lead to a new era of nanocarrier treatments for cancer.
AB0618 A SNAPSHOT OF DISEASE ACTIVITY IN PATIENTS WITH BEHCET’S SYNDROME: PREDICTIVE FACTORS AND RELATIONSHIP WITH QUALITY OF LIFE
Authors: Rosaria Talarico, Alice Parma, Eralda Zera, Emanuele Calabresi, Chiara Tani, Chiara Baldini, Marta Mosca
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Behçet's Syndrome (BS) is globally characterized by a variable spectrum of disease profile: while prevalent muco-cutaneous lesions and arthritis represent the only clinical features in patients with a benign disease subset, there are other patients who develop potentially sight or life-threatening manifestations, due to ocular, neurological or major vascular involvement. Beside the organ involvement, demographic factors could considerably influence the long-term and short-term outcomes of BD <h3>Objectives:</h3> The primary aim of the study was to evaluate disease activity in a cohort of BS patients consecutively followed in a BS clinic of a tertiary centre; the secondary aims were to identify potential predictive factors of disease activity and to compare disease activity with quality of life. <h3>Methods:</h3> One-hundred and thirty patients (71 males and 59 females; mean age 42±8 years, mean disease duration 11±4) with a diagnosis of BS according to the ISG criteria were studied. Disease activity has been evaluated by BDCAF and quality of life by the Short form (SF) 36. Patients were also categorized in major or minor involvement of BS according or not to the presence of ocular, neurological and vascular involvement in the course of disease Predictors of long-term outcome were identified by univariate analysis using the log-rank test and by multivariate analysis using Cox proportional hazards regression models. <h3>Results:</h3> At time of the evaluation, 39% of BS patients presented an active disease. Thirty-six patients presented muco-cutaneous involvement, 21 ocular disease, 10 joint involvement, 6 neurological impairment and 4 gastro-enteric involvement. Sixty-two percent of patients presented in the course of the disease a severe BS involvement and, among these, the majority was represented by males HLAB51 positive patients. The major limitations of quality of life related to disease activity were represented by vitality, physical functioning, bodily pain, general health perception. <h3>Conclusion:</h3> Younger men patients affected by BS are more suitable to have a more severe disease, due to an increased frequency both of morbidity and mortality, secondary to ocular, vascular and neurological involvement. The variable prognosis associated to different gender or age, may represent an essential and useful element to tailor the management not only to the type and severity of symptoms, but also to the epidemiological profile of BD patients. <h3>Disclosure of interests:</h3> Rosaria Talarico: None declared, alice Parma: None declared, Eralda Zera: None declared, Emanuele Calabresi: None declared, Chiara Tani: None declared, Chiara Baldini: None declared, Marta Mosca Paid instructor for: GlaxoSmithKline, Lilly, UCB
Abstract 12495: Body Mass Index and In-Hospital Mortality in Acute Heart Failure Patients
Authors: John Parissis, Katerina Fountoulaki, Alexandre Mebazaa, Gerasimos Filippatos, Ignatios Ikonomidis, Maria Anastasiou-Nana, Ferenc Follath
Journal: Circulation (2012)

Objectives: Observational data suggest that there is a potentially protective effect of increased body mass index (BMI) in chronic heart failure (HF) with reduced left ventricular ejection fraction...
PB2045 EFFICACY &amp; SAFETY OF INTRAVENOUS FERRIC CARBOXYMALTOSE IN IRON DEFICIENCY ANEMIA: A PROSPECTIVE STUDY
Authors: U.K. Nath, R. Chetia
Journal: HemaSphere (2019)

Background: Iron deficiency anemia (IDA) is the most common nutritional anemia globally. Goal of iron replacement therapy are correction of anemia and repletion of body iron stores. Oral iron replacement is the preferred route in general. However, response to oral iron replacement therapy is often suboptimal due to poor compliance to treatment resulting from gastrointestinal intolerance and prolonged duration of oral iron therapy. Ferric carboxymaltose is a relatively recently approved parenteral iron formulation which can be administered in large doses of upto 1000 mg in a single infusion. Aims: The present study describes the efficacy &amp; safety of intravenous ferric carboxymaltose for treatment of iron deficiency anemia in a tertiary institution in India. Methods: This non‐randomised prospective study included 77 patients of age ≥ 12 years with confirmed diagnosis of iron deficiency anemia between January 2018 &amp; January 2019. Detailed history was taken &amp; examination performed for signs &amp; etiology of IDA. The cut‐off serum ferritin level for IDA diagnosis was &lt; 15 ng/ml. Pregnant females and patients with concurrent vitamin B12 deficiency were excluded. All patients were treated with Injection Ferric Carboxymaltose (FCM) by I.V. infusion over 30 minutes in day care. Total dose of parenteral iron was calculated according to Ganzoni Formula: Total iron deficit (mg) = 2.4 x body weight (kg) x [target haemoglobin – actual haemoglobin (g/dl)] + 500 mg (depot iron). The maximum dose of FCM administered in a single infusion was 1000 mg. Patients with total iron dose &gt; 1000 mg received two divided doses one week apart. Patients also received oral folic acid at 5 mg/day dose for at least 3 weeks. Appropriate workup for etiology of IDA was performed in all patients. Therapeutic response was assessed after 3 weeks of first FCM dose &amp; was defined as hemoglobin increase of ≥ 2 g/dl from baseline. Results: The median age of patients was 33 years (range 16 ‐ 75 years) and majority (78%) were females. The median baseline hemoglobin was 5 g/dl (range 2.0 ‐ 8.6 g/dl). Therapeutic response was achieved in 100% patients. Mean increase in haemoglobin at 3 weeks was 4.2 g/dl (range 2.8 ‐ 5.5 g/dl). One patient had mild headache during FCM infusion. There was no infusion‐related toxicity or any other adverse event. Summary/Conclusion: In our study, intravenous ferric carboxymaltose was found to be highly effective &amp; safe alternative to oral iron for treatment of iron deficiency anemia, with excellent patient compliance. It is ideally suited for patients who require rapid replenishment of iron stores.
Targeting IRAK4 disrupts inflammatory pathways and delays tumor development in chronic lymphocytic leukemia
Authors: Neus Giménez, Ralph Schulz, Morihiro Higashi, Marta Aymerich, Neus Villamor, Julio Delgado, Manel Juan, Mònica López-Guerra, Elias Campo, Laia Rosich, Martina Seiffert, Dolors Colomer
Journal: Leukemia (2019)

Abstract Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a critical role in Toll-like receptor (TLR) signal transduction and innate immune responses. Recruitment and subsequent activation of IRAK4 upon TLR stimulation is mediated by the myeloid differentiation primary response 88 (MYD88) adaptor protein. Around 3% of chronic lymphocytic leukemia (CLL) patients have activating mutations of MYD88 , a driver mutation in this disease. Here, we studied the effects of TLR activation and the pharmacological inhibition of IRAK4 with ND2158, an IRAK4 competitive inhibitor, as a therapeutic approach in CLL. Our in vitro studies demonstrated that ND2158 preferentially killed CLL cells in a dose-dependent manner. We further observed a decrease in NF-κB and STAT3 signaling, cytokine secretion, proliferation and migration of primary CLL cells from MYD88- mutated and -unmutated cases. In the Eµ -TCL1 adoptive transfer mouse model of CLL, ND2158 delayed tumor progression and modulated the activity of myeloid and T cells. Our findings show the importance of TLR signaling in CLL development and suggest IRAK4 as a therapeutic target for this disease.
Pericyte loss leads to circulatory failure and pleiotrophin depletion causing neuron loss
Authors: Angeliki M. Nikolakopoulou, Axel Montagne, Kassandra Kisler, Zhonghua Dai, Yaoming Wang, Mikko T. Huuskonen, Abhay P. Sagare, Divna Lazic, Melanie D. Sweeney, Pan Kong, Min Wang, Nelly Chuqui Owens, Erica J. Lawson, Xiaochun Xie, Zhen Zhao, Berislav V. Zlokovic
Journal: Nature Neuroscience (2019)