tbuckley/cabot-search huggingface dataset:
SAT0496 THE FREQUENCY OF JOINT HYPERMOBILITY IN TURKISH SCHOOLCHILDREN: EFFECTS TO PHYSICAL ACTIVITY, BALANCE, PAIN AND QUALITY OF LIFE
Authors: Zahide Ekici Tekin, Gulcin Otar Yener, Bilge Başakçi Çalik, Selcuk Yuksel
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Recent studies have focused on the joint hypermobility (JH) to show the association with musculoskeletal pain, functional disability, motor development and psychological distress (1). In contrast, in some publications, the negative effects of JH in childhood were not observed (2). <h3>Objectives</h3> The aim of this study was mainly to determine the frequency of JH in Turkish schoolchildren and to investigate whether relationship between JH and pain, physical activity level and the balance. In addition, the study aimed whether JH has an impact on the quality of life. <h3>Methods</h3> This cross-sectional school-based study evaluated 737 children (52.5% girls) from 8 to 14 years of age, and the data were collected in 2018 in the city of Denizli, Turkey. Firstly, each of the participants was individual assessed by a clinician on the Flamingo Balance Test for stability and Beighton for the diagnosis of JH. According to Beighton, children who scored ≥5 were accepted as hypermobile. Secondly, all participants completed the self-reported measures for the screening of physical activity level and quality of life. The Physical Activity Questionnaire (PAQ) and the Pediatric Quality of Life Inventory (PedsQL) tests were used to determine the level of physical activity and the quality of life. Also, pain severity was quantified by the Visual Analogue Scale (VAS) that is ranging from no pain (score: 0 mm) to worst pain (score: 100 mm) in the last month. <h3>Results</h3> The prevalence of JH in schoolchildren was 19.7% in Turkish population (Table 1). The mean pain severity was 1.29±2.024 in all children. Significant differences were found between hipermobile and non-hipermobile groups in social and school functioning (p&lt;0.05), but no significant differences were found in pain, physical activity level (p&gt;0.05) (Table 2). Beighton score was not significant correlated with pain severity, physical activity, quality of life and balance in childhood (p=0.515, p=0.986, p=0.512, p=0.362 respectively). <h3>Conclusion</h3> As a result, the existence of hypermobility in children had an impact on school and social functions. However, it has been observed that hypermobility does not have a negative effect on these children's pain, balance, physical activity level, and physical and emotional functions. <h3>References</h3> [1] Scheper MC, Engelbert RH, Rameckers EA, Verbunt J, Remvig L, Juul-Kristensen B. Children with generalised joint hypermobility and musculoskeletal complaints: state of the art on diagnostics, clinical characteristics, and treatment. Biomed Res Int. 2013;2013:121054. doi: 10.1155/2013/121054. [2] Leone V, Tornese G, Zerial M, et al. Joint hypermobility and its relationship to musculoskeletal pain in schoolchildren: a cross-sectional study. Archives of Disease in Childhood2009;94: 627-632. <h3>Disclosure of Interests</h3> None declared
Genetic variation in human drug-related genes
Authors: Charlotta Pauline Irmgard Schärfe, Roman Tremmel, Matthias Schwab, Oliver Kohlbacher, Debora Susan Marks
Journal: Genome Medicine (2017)

Variability in drug efficacy and adverse effects are observed in clinical practice. While the extent of genetic variability in classic pharmacokinetic genes is rather well understood, the role of genetic variation in drug targets is typically less studied. Based on 60,706 human exomes from the ExAC dataset, we performed an in-depth computational analysis of the prevalence of functional variants in 806 drug-related genes, including 628 known drug targets. We further computed the likelihood of 1236 FDA-approved drugs to be affected by functional variants in their targets in the whole ExAC population as well as different geographic sub-populations. We find that most genetic variants in drug-related genes are very rare (f < 0.1%) and thus will likely not be observed in clinical trials. Furthermore, we show that patient risk varies for many drugs and with respect to geographic ancestry. A focused analysis of oncological drug targets indicates that the probability of a patient carrying germline variants in oncological drug targets is, at 44%, high enough to suggest that not only somatic alterations but also germline variants carried over into the tumor genome could affect the response to antineoplastic agents. This study indicates that even though many variants are very rare and thus likely not observed in clinical trials, four in five patients are likely to carry a variant with possibly functional effects in a target for commonly prescribed drugs. Such variants could potentially alter drug efficacy.
Richard Valery Mouzoko Kiboung: epidemiologist who was killed by armed rebels while leading an Ebola response team in the Congo
Authors: Ned Stafford
Journal: BMJ (2019)

Credit: World Health Organization

In March 2019, Richard Valery Mouzoko Kiboung left his wife and four young children at home in Cameroon to join the World Health Organization’s mission in the Democratic Republic of Congo (DRC) to fight the second deadliest Ebola outbreak in history. An epidemiologist who had worked with WHO for the past five years, Mouzoko had the experience that was needed.

Mouzoko, 42 years old, was dispatched to Butembo in north east DRC to lead a response team. Within days of arriving, Dr Richard, as he was known, became a popular figure among the members of his team. “Richard was like a big brother,” said Soterine Tsanga, a communications officer in the WHO office in Cameroon who was also deployed to DRC and worked closely with Mouzoko.

Mouzoko had the heavy responsibility of leading an Ebola response team in a foreign country weighing on him, combined with deep concern about his team’s safety. Rebels in north eastern DRC, as well as many community members, believe that Ebola was deliberately imported or does not exist. Ebola treatment centres had been under attack from local militiamen since January. Responders and burial teams had been threatened and assaulted. In late February Medecins Sans Frontieres suspended some of its operations after two attacks on its treatment centres.

Mouzoko was worried, according to a news report from US National Public Radio, which quoted Michel Yao, head of WHO’s on-the-ground operations for the Ebola response, as saying of Mouzoko: “One of …
PS1093 IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED DLBCL, CHANGE WEIGHT AFTER THE FIRST COURSE R-CHOP (-LIKE) CHEMOTHERAPY IS AN ADVERSE PROGNOSTIC FACTOR
Authors: A. Muramatsu, H. Nagata, K. Kuriyama, M. Oshiro, Y. Hirakawa, T. Iwai, H. Uchiyama
Journal: HemaSphere (2019)

Background: T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive form of lymphoma with poor clinical outcomes and lack of a standard treatment regimen. Aims: This study evaluated the safety and efficacy of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) treatment for adult T-LBL and assessed factors affecting survival. Methods: Newly-diagnosed adult T-LBL patients (n = 160) were divided into three groups: chemotherapy (no HSCT) group (68 patients), single auto-HSCT group (46 patients), and tandem auto-HSCT group (46 patients). The measurement of primary outcome was progression-free survival (PFS). The intermediate outcomes were progression/relapse rate and overall survival (OS). Additionally, this study analyzed factors influencing toxicities related to tandem auto-HSCT treatment and patient prognosis. Results: The 3-year progression/relapse rate of the tandem auto-HSCT group was significantly lower than that of the single auto-HSCT group and chemotherapy group (19.6% vs 45.7% and 70.6%, p < 0.05). The 3-year PFS rate and OS rate of the tandem auto-HSCT group (68.3% and 72.5%, respectively) were significantly higher than those of the single auto-HSCT group (41.5% and 55.4%, respectively, p < 0.05) and the chemotherapy group (23.3% and 43.3%, respectively, p < 0.05). In the tandem auto-HSCT group, age and disease status after the first transplantation impacted the OS and PFS. Multivariate analysis identified disease status after the first transplantation as the only independent prognostic factor for outcome in T-LBL treated with tandem-HSCT. Summary/Conclusion: Tandem auto-HSCT improves long-term survival of adult T-LBL patients compared to recipients of chemotherapy alone or chemotherapy plus single auto-HSCT and disease status after the first transplantation is an independent prognostic indicator for these patients.
Abstract 14378: Premature Atrial Contractions Burden is a Strong Predictor of Recurrence Afterwards in Patients With Successful Catheter Ablation for Atrial Fibrillation
Authors: Hiroyuki Inoue, Nobuaki Tanaka, Koichi Inoue, Ryo Kitagaki, Masato Okada, Takafumi Oka, Yuko Hirao, Yuichi Ninomiya, Koji Tanaka, Katsuomi Iwakura, Kenshi Fujii
Journal: Circulation (2018)

Background: Atrial tachyarrhythmia recurrence after catheter ablation (CA) for atrial fibrillation (AF) could occur even years after procedure. However, predictive factors which can be obtained during short-term follow up to predict recurrence afterwards still remain unknown. Methods: We retrospectively investigated 380 patients who underwent their initial radiofrequency CA for AF in our institution from March 2012 to March 2014 and didn’t experienced recurrences with 3 months of blanking period until the day of scheduled 24-hour Holter monitoring 6 months after procedure. We analyzed relationship between recurrence afterwards and the number of premature atrial contractions (PAC) during Holter monitoring. We defined initial recurrence after Holter monitoring as late recurrence. Results: Patients were 60.7 +/- 10.2 years old including 81 (21.3%) females and 253 (66.6%) paroxysmal AF (PAF). Average follow-up period was 679 +/- 249 days. Holter monitoring was performed for 22.6 +/- 1.0 hours and detected 53 ...
SP0040 HOT: NOVEL PARADIGMS IN THE MANAGEMENT OF SLE
Authors: Thomas Dörner
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Heterogeneity of systemic lupus erythematosus (SLE) remains challenging and, thus, many unmet needs remain, including the development of safer and more efficacious therapies to better control SLE activity resulting in improved outcomes. To develop innovative therapies, we need a far better understanding of its pathogenesis including delineation of clinical phenotypes. Recently, the the lupus community has developed new classification criteria, T2T principles as well as low lupus disease activity and remission definitions to overcome obstacles created by SLE heterogeneity and improve outcomes. New proposals for the histologic classification of lupus nephritis have also been put forward and undergo evaluation. Recent therapeutic advances and clinical developments hold promise for improved treatments in this challenging disease and will be discussed. <h3>Disclosure of Interests:</h3> Thomas Dörner Grant/research support from: Eli Lilly, Janssen, Roche, UCB Pharma, Consultant for: Eli Lilly, Janssen, Roche, UCB Pharma, Speakers bureau: Eli Lilly, Janssen
AB1393-HPR COMPARISON OF THE QUALITY OF LIFE, FUNCTIONAL AND EMOTIONAL STATUS OF INPATIENTS AND OUTPATIENTS WITH RHEUMATIC DISEASES
Authors: Gamze Arın, Aybüke Seven, Yasemin Özel Aslıyüyce, Aykut Özçadırcı, Fatma Birgül Kumbaroğlu, Şule Apraş Bilgen, Edibe Ünal
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Quality of life, function and emotional status of inpatients with rheumatic diseases may be estimated worse than outpatients. Previous studies had shown that there was a worsening in the emotional state of inpatients (1). <h3>Objectives</h3> The aim of this study is to compare the quality of life, functional and emotional status in inpatients and outpatients with rheumatic diseases. <h3>Methods</h3> The study included 78 patients (inpatient, n = 31; outpatient, n = 47) with rheumatic disease. The Health Assessment Questionnaire (HAQ) (2) and SF-36 (3) were used to evaluate the functionality and quality of life, and the Hospital Anxiety and Depression Scale (HADS) (4) was used to determine their emotional status. The variables were investigated using visual and analytical methods to determine whether or not they are normally disturbed. Since physical function, mental health and general health perception values of SF-36 and HADS-Anxiety were normally distributed, the Students T-test was used to compare these parameters between two groups. Physical role limitation, pain, social status, emotional difficulty, energy viability of SF-36, HAQ and HADS-Depression were not normally distributed. Thus, Mann-Whitney U test was used to compare these scores between two groups. <h3>Results</h3> The mean age of the subjects (n = 78) included in the study was 46.09 13.89 years and the mean BMI was 27.59 15.08. There was a significant difference in depression, anxiety and pain and social functioning sub-parameters of SF-36 (p &lt;0.005) but there was no significant difference in other parameters (p&gt; 0.005). <h3>Conclusion</h3> It was thought that during the period of admission to the hospital, inpatients should be supported in terms of pain management, social functioning and anxiety and, depression as well as taking medication. Besides, caregivers in hospitals should encourage inpatients with regard to maintaining physical activity. <h3>References</h3> [1] Lambert, C. M., Hurst, N. P., Forbes, J. F., Lochhead, A., Macleod, M., &amp; Nuki, G. (1998). Is day care equivalent to inpatient care for active rheumatoid arthritis? Randomised controlled clinical and economic evaluation. Bmj, 316(7136), 965-969. [2] Fries JF, Spitz PW, Young DY: The dimensions of health outcomes: the Health Assessment Questionnaire, Disability and Pain Scales. J Rheumatol 9:789-793, 1982 [3] Brazier, J. E., Harper, R., Jones, N. M., O'cathain, A., Thomas, K. J., Usherwood, T., &amp; Westlake, L. (1992). Validating the SF-36 health survey questionnaire: new outcome measure for primary care. Bmj, 305(6846), 160-164. [4] Zigmond, A. S., &amp; Snaith, R. P. (1983). The hospital anxiety and depression scale. Acta psychiatrica scandinavica, 67(6), 361-370. <h3>Disclosure of Interests</h3> None declared
Abstract 2427: Arrhythmogenic Effects of Transforming Growth Factor-β1 on Hybrid Cardiomyocyte-Myofibroblast Preparations
Authors: Nicolo Salvarani, Christian Rosker, Stephan Rohr
Journal: Circulation (2009)

Introduction: Structural remodeling of the heart is typically accompanied by the appearance of myofibroblasts (MFBs) in the working myocardium. In-vitro, MFBs were shown to induce arrhythmogenic sl...
A Mucin 16 bispecific T cell–engaging antibody for the treatment of ovarian cancer
Authors: Alison Crawford, Lauric Haber, Marcus P. Kelly, Kristin Vazzana, Lauren Canova, Priyanka Ram, Arpita Pawashe, Jennifer Finney, Sumreen Jalal, Danica Chiu, Curtis A. Colleton, Elena Garnova, Sosina Makonnen, Carlos Hickey, Pamela Krueger, Frank DelFino, Terra Potocky, Jessica Kuhnert, Stephen Godin, Marc W. Retter, Paurene Duramad, Douglas MacDonald, William C. Olson, Jeanette Fairhurst, Tammy Huang, Joel Martin, John C. Lin, Eric Smith, Gavin Thurston, Jessica R. Kirshner
Journal: Science Translational Medicine (2019)

A CD3 bispecific antibody targeting Mucin 16 shows preclinical efficacy in mouse tumor models and a tolerable safety profile in nonhuman primates.
Impact of Teratoma on the Cumulative Incidence of Disease-Related Death in Patients With Advanced Germ Cell Tumors
Authors: Samuel A. Funt, Sujata Patil, Darren R. Feldman, Robert J. Motzer, Dean F. Bajorin, Joel Sheinfeld, Satish K. Tickoo, Victor E. Reuter, George J. Bosl
Journal: Journal of Clinical Oncology (2019)

In men with metastatic germ cell tumors (GCTs), risk-directed treatment is determined, in part, by a distinction between seminoma and nonseminomatous GCT (NSGCT). The importance of NSGCT cell type is uncertain. We evaluated the long-term impact of teratoma on survival in patients with NSGCT.Prechemotherapy, primary tumors from patients who received platinum-based chemotherapy were studied, and the histology was confirmed by a genitourinary pathologist. The cumulative incidence of disease-related death (CIDD) was the primary end point, and a competing-risk analysis was performed.Tumors were available from 232 patients, including 193 with NSGCT. An element of teratoma was present in 82 NSGCT primary tumors (42%). With a median follow-up of 17 years (range, 0.3 to 35 years), 58 patients with NSGCT died, 47 as a result of GCT and 11 as a result of other causes. Most GCT deaths occurred within the first 5 years and were associated with pretreatment risk status (P < .001). Death as a result of other causes rose steadily after 15 years and was not associated with risk status (P = .66). A higher CIDD was observed in patients who had NSGCT with teratoma than those with NSGCT without teratoma and seminoma (5-year CIDD rate, 27.4%, 17.4%, and 10.3%, respectively; P = .03). A higher CIDD was observed in patients who had NSGCT with mature teratoma compared with those with either NSGCT with immature teratoma or NSGCT without teratoma (5-year CIDD rate, 38.1%, 19.9%, and 17.4%, respectively; P = .01).The presence of teratoma, particularly mature teratoma, in an NSGCT primary tumor is associated with a higher CIDD, consistent with the hypothesis that differentiation is associated with adverse outcomes. Death as a result of non-GCT causes is not associated with risk status and must be separated from GCT death when evaluating long-term survival.
Spatial Heterogeneity and Evolutionary Dynamics Modulate Time to Recurrence in Continuous and Adaptive Cancer Therapies
Authors: Jill A. Gallaher, Pedro M. Enriquez-Navas, Kimberly A. Luddy, Robert A. Gatenby, Alexander R.A. Anderson
Journal: Cancer Research (2018)

Treatment of advanced cancers has benefited from new agents that supplement or bypass conventional therapies. However, even effective therapies fail as cancer cells deploy a wide range of resistance strategies. We propose that evolutionary dynamics ultimately determine survival and proliferation of resistant cells. Therefore, evolutionary strategies should be used with conventional therapies to delay or prevent resistance. Using an agent-based framework to model spatial competition among sensitive and resistant populations, we applied antiproliferative drug treatments to varying ratios of sensitive and resistant cells. We compared a continuous maximum-tolerated dose schedule with an adaptive schedule aimed at tumor control via competition between sensitive and resistant cells. Continuous treatment cured mostly sensitive tumors, but with any resistant cells, recurrence was inevitable. We identified two adaptive strategies that control heterogeneous tumors: dose modulation controls most tumors with less drug, while a more vacation-oriented schedule can control more invasive tumors. These findings offer potential modifications to treatment regimens that may improve outcomes and reduce resistance and recurrence.
Abstract 17898: Cytoprotective Activated Protein C Averts Nlrp3 Inflammasome Induced Ischemia Reperfusion Injury via Mtorc1 Inhibition
Authors: Sumra Nazir, Ihsan Gadi, Moh’d Mohanad Al-Dabet, Khurrum Shahzad, Berend Isermann
Journal: Circulation (2017)

Cytoprotection by activated protein C (aPC) following ischemia-reperfusion injury (IRI) is associated with apoptosis inhibition. However, IRI is hallmarked by inflammation and hence conceptually ce...
PF448 EFFECTIVE STABILIZATION OF VIRAL VECTORS IN LIQUID USING AN ALGORITHM‐BASED DEVELOPMENT APPROACH
Authors: E. Reinauer, K. Kemter, J. Hasler, C. Rodenstein, J. Altrichter, S. Martin
Journal: HemaSphere (2019)

Background: With both the approvals of CD19 CAR‐T cell therapies and promising clinical data of gene therapy trials such as in hemophilia or sickle cell disease, recent years have seen significant progress of gene and cell therapy in the field of hematological malignancies as well as rare hematologic genetic disorders. Hence, replication‐deficient recombinant viral vectors such as adenovirus serotype 5, adeno‐associated virus and members of the poxvirus family represent a rapidly growing field of vaccine development and gene therapy. Viral vectors are known as complex supra‐molecular ensembles of macromolecules produced by living organisms (nucleic acids, proteins, polysaccharides and in the case of lipid enveloped viruses of phospholipids) which are prone to a variety of complex chemical and physical degradation pathways, in particular due to stress induced by manufacturing, storage and distribution. This represents a significant hurdle for the development of stable vector‐based pharmaceuticals such as vaccines or gene therapeutics Aims: Here, we studied whether LEUKOCAREs formulation platform may also efficiently protect viral vectors in thermal stress experiments. As a representative example of viral vectors we used adenovirus serotype 5 (Ad5). Methods: In an algorithm‐based development approach, we used Design of Experiment (DoE) to select the most effectively stabilizing formulations for Ad5. We stored Ad5 at 37 °C and 25 °C as accelerated aging temperature to identify the most effective stabilizing excipients after short term storage as well as at 5 °C for real time storage. Based on these results, the best selected formulations were further iteratively optimized and used in long term storage at 5 °C. Results: By analysis of the infectious virus titers and mathematical combination of these results with the DoE matrix, the linear influence of each amino acid used in the DoE matrix was determined. The accelerated aging conditions were shown to be predictive for real‐time aging. Several of the excipients indicated a neutral influence, whereby we observed the importance of a well‐balanced combination of the components with each other regarding concentration and stabilizing interactions. The predictive potential of this approach was confirmed by two iteratively composed formulations tailored for Ad5 during long‐term storage. Summary/Conclusion: The pre‐selection strategy of effectively stabilizing excipients by means of an algorithm‐based development approach and the applied accelerated aging model is highly efficient and enables the generation of best‐in‐class stability formulations for Ad5 viruses and viral vectors in liquid. Moreover, this approach could have beneficial impact when applied early in downstream processing, which could enable significant reduction of viral vectors manufacturing costs for gene therapy.