tbuckley/cabot-search huggingface dataset:
AB0271 Rs12218 polymorphism in saa1 gene in the russian population of ra patients is associated with secondary amyloidosis. a pilot study
Authors: M. Krylov, Y. Muraviev, A. Alekseeva, E. Samarkina, I. Guseva, N. Konovalova, D. Varlamov
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Secondary amyloidosis (SA) is a serious complication of rheumatoid arthritis (RA), which is often fatal. Identification of associated risk factors, including genetic ones, is an important task. <h3>Objectives</h3> To assess the role of SAA1 gene polymorphism, encoding serum amyloid-A, as a risk factor predisposing to SA in the sample of Russian RA patients. <h3>Methods</h3> The study included 60 patients with RA, fulfiled the American College of rheumatology criteria (ACR) 1987. Of these 35 (mean age 49.5±10.8 y, mean disease duration 18.5±8,9) developed SA manifestations, confirmed histologically: group SA (+). 25 patients (mean age 56,7±11,7 y, mean disease duration 16.3±7,5 y) did not have either clinical or histological SA signs: group SA(-). The control group (C) consisted of 65 healthy employees. SAA1 gene polymorphism rs12218 (−13 T/C), mapped in the 5' flanking region of the gene, was studied in 125 subjects by polymerase chain reaction in real time (RT-PCR) with subsequent melting curves analysis. <h3>Results</h3> Statistically significant differences in the rates of TT, TC and CC genotypes of rs12218 polymorphism were established between SA(+) group and the controls (17.1%, 64.0%, 48.6% and 38.5%, 46.1%, 15.4%, respectively, p=0.029). High rate (58.6%) of the mutant C allele in SA(+) group compared to the control group (38.5%) predetermines high risk of susceptibility to SA in RA patients [(OR 2.26, 95% CI(1.20–4.28), p=0.010]. Significant differences in rs12218 polymorphism rates were found between SA(+) and SA(-) groups [p&lt;0.001]. The frequency of TC +CC genotype was significantly higher in the SA (+) group compared to SA(-) group [82.9% vs 36.0%, p&lt;0.001]. The risk of predisposition to SA development among RA patients was increased when C allele frequencies in the group with SA (58.6%) were compared with the group without SA (22.0%) [OR 5.01, 95% CI (2.07–12.58), p&lt;0.001]. No significant differences were found in the frequencies of genotypes and rs12218 alleles between SA(-) pts and the controls (p&gt;0.05). <h3>Conclusions</h3> Our data confirm that genetic polymorphism rs12218 in SAA1 gene, is associated with the development of secondary amyloidosis in RA patients and mutation in this gene is an important risk factor predisposing to the development of this severe complication in the Russian population. <h3>Disclosure of Interest</h3> None declared
THU0701 Updated incidence and costs of hip fractures in elderly italian population
Authors: P. Piscitelli, M. Feola, C. Neglia, C. Rao, E. Rizzo, U. Tarantino
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> It had already been evaluated the hospitalisation rate of femoral neck fractures in the elderly Italian population over ten years, showing that incidence of hip fractures in Italy are continuously increasing, although women aged 65–74 years old started showing a decreasing trend. <h3>Objectives</h3> To update our previous researches about the burden of hip fractures in elderly Italian population. <h3>Methods</h3> We analysed national hospitalizations records from 2007 to 2014 to compute age- and sex-specific standardised rates. <h3>Results</h3> 7 41 633 hospitalizations were observed in people≥65 (women: 568,203; men: 173,430), with an overall increase of 5.50% over the 8 year period (females:+3.36; males:+12.9%). About 43.75% of total hip fractures were suffered by patients aged ≥85 years old. Women aged ≥85 accounted for 34.49% (n=255,763) of total fractures. The incidence rate per 10 000 inhabitants in people aged 65–74 decreased from 28.65 to 25.31 in women (–13.02%) and from 13.41 to 11.65 in men (–13.12%). Incidence per 10 000 in people 75–84 decreased from 121,6 to 105,2 in women (−13.49%) and from 55.8 to 47.5 in men (–14.87%). Paradoxally, also in people aged ≥85, the incidence per 10 000 declined from 300.99 to 268.72 in women (–10.72%) and from 174.59 to 171.17 in men (−1.96%) because the number of subjects aged ≥85 is growing faster than the number of fractures occurring in this latter age group. Direct hospitalisation costs and rehabilitation costs increased from 433 to 457 million Euros and from 478 to 504 million Euros over the 8 year period, respectively. Overall costs of hip fractures in people aged ≥65 years old raised from 911 to 961 million Euros from 2007 to 2014. <h3>Conclusions</h3> The number of hip fractures and related hospitalizations costs in Italian elderly population is still increasing due to the fractures occurring in people≥85 years old, although incidence rates are decreasing in all the age groups. <h3>Reference</h3> [1] Ten years of hip fractures in Italy: For the first time a decreasing trend in elderly women. Piscitelli P, Feola M, Rao C, Celi M, Gasbarra E, Neglia C, Quarta G, Liuni FM, Parri S, Iolascon G, Brandi ML, Distante A, Tarantino U. World J Orthop2014Jul 18;5(3):386–91. doi:10.5312/wjo.v5.i3.386 <h3>Disclosure of Interest</h3> None declared
Potential roles for the kisspeptin/kisspeptin receptor system in implantation and placentation
Authors: Kai-Lun Hu, Hsun-Ming Chang, Hong-Cui Zhao, Yang Yu, Rong Li, Jie Qiao
Journal: Human Reproduction Update (2018)

Initially identified as suppressors of metastasis in various types of cancer, kisspeptins are a family of neuropeptides that are key regulators of the mammalian reproductive axis. Accumulating evidence has shown that kisspeptin is able to control both the pulsatile and surge GnRH release, playing fundamental roles in female reproduction, which include the secretion of gonadotropins, puberty onset, brain sex differentiation, ovulation and the metabolic regulation of fertility. Furthermore, recent studies have demonstrated the involvement of the kisspeptin system in the processes of implantation and placentation. This review summarizes the current knowledge of the pathophysiological role and utility of these local placental regulatory factors as potential biomarkers during the early human gestation. A successful pregnancy, from the initiation of embryo implantation to parturition, is a complex process that requires the orchestration of a series of events. This review aims to concisely summarize what is known about the role of the kisspeptin system in implantation, placentation, early human pregnancy and pregnancy-related disorders, and to develop strategies for predicting, diagnosing and treating these abnormalities. Using the PubMed and Google Scholar databases, we performed comprehensive literature searches in the English language describing the advancement of kisspeptins and the kisspeptin receptor (KISS1R) in implantation, placentation and early pregnancy in humans, since its initial identification in 1996 and ending in July 2018. Recent studies have shown the coordinated spatial and temporal expression patterns of kisspeptins and KISS1R during human pregnancy. The experimental data gathered recently suggest putative roles of kisspeptin signaling in the regulation of trophoblast invasion, embryo implantation, placentation and early pregnancy. Dysregulation of the kisspeptin system may negatively affect the processes of implantation as well as placentation. Clinical studies indicate that the circulating levels of kisspeptins or the expression levels of kisspeptin/KISS1R in the placental tissues may be used as potential diagnostic markers for women with miscarriage and gestational trophoblastic neoplasia. Comprehensive research on the pathophysiological role of the kisspeptin/KISS1R system in implantation and placentation will provide a dynamic and powerful approach to understanding the processes of early pregnancy, with potential applications in observational and analytic screening as well as the diagnosis, prognosis and treatment of implantation failure and early pregnancy-related disorders.
A Randomized Phase II Study of Azacitidine (AZA) Alone or with Lenalidomide (LEN), Valproic Acid (VPA) or Idarubicin (IDA) in Higher-Risk MDS: Gfm's 'pick a Winner' Trial
Authors: Lionel Ades, Agnès Guerci, Kamel Laribi, Pierre Peterlin, Norbert Vey, Sylvain Thepot, Stefan Wickenhauser, Hacene Zerazhi, Aspasia Stamatoullas, Eric Wattel, Christian Recher, Andrea Toma, Krimo Bouabdallah, Thorsten Braun, Odile Beyne-Rauzy, Berengere Gruson, Stephane Cheze, Sophie Park, Thomas Cluzeau, Stanislas Nimubona, Dominique Bordessoule, Riad Benramdane, Bruno Quesnel, Shanti Ame, Stephane De Botton, Fatiha Chermat, Julie Lejeune, Sylvie Chevret, Pierre Fenaux
Journal: Blood (2018)
FRI0038 Correlation between clinical and ultrasonographic remission? the effect of non-inflammatory patient-based factors on different remission definitions
Authors: Ü. Gazel, S. Yılmaz-Öner, G. Özen, Y. Yalçınkaya, Z. Ertürk, M.P. Atagündüz, H. Direskeneli, N. İnanç
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> In this study, we aimed to investigate the concordance of ultrasonographic remission with other remission criteria and to show the influence of non-inflammatory patient-induced factors such as depression, anxiety, fibromyalgia and fatigue on both clinical and ultrasonographic remission. <h3>Methods</h3> Fifty consecutive patients with clinical remission (DAS-28-ESR&lt;2.6) who were diagnosed according to the 2010 ACR/EULAR criteria were recruited to this study. Patients were also assessed whether they met the Boolean and SDAI remission criteria. 28 joint grey scale (GS) and power Doppler (PD) ultrasonography were performed. Patients' depression and anxiety were assessed by The Hospital Anxiety and Depression Scale (HADS), and their fatigue was assessed by multidimensional Assessment of Fatigue (MAF) scores and patients' fibromyalgia was assessed by widespread pain index (WPI) and symptom severity score (SS). <h3>Results</h3> Patients were divided into 4 groups according to different remission definitions by ultrasonography. (Group1: PD=0 and GS=0, Group2: PD=0 and GS ≥0, Group3: PD=1 or 0 and GS=1 or 0, Group4: PD=1 or 0 and GS ≥0). Although it is not statistically significant, the highest agreement with all the clinical remission criteria was found in the USG remission group 4 (table 1). Patients with ultrasonographic remissions at their first visit in 2011 were reevaluated with clinical remission criteria at the end of 5 years. The highest remission rates were found in patients with USG remission group 3 (DAS28 58%, Boolean 29%, SDAI 47%). There was no significant difference between fatigue, fibromyalgia, depression and anxiety measures between remission and non-remission in all USG remission groups. In contrast, depression (p&lt;0.05) and anxiety (p&lt;0.03) were significantly higher in patients without SDAI remission. Depression (p&lt;0.008) and anxiety (p&lt;0.014) were also significantly higher in patients without Boolean remission. <h3>Conclusions</h3> Clinical and ultrasonographic remission was found to be compatible in half of the patients. The compliance of the USG remission in Group 4 with the clinical remission definitions was good, and clinical remission continuity was higher in the group meeting the definition of group 3. In contrast the ultrasound remission, the high levels of depression and anxiety in patients without SDAI and Boolean remission suggest that non-inflammatory patient-derived measures have less influence on the ultrasound remission. <h3>Disclosure of Interest</h3> None declared
Prognostic implications of cytogenetics in adults with acute lymphoblastic leukemia treated with inotuzumab ozogamicin
Authors: Elias Jabbour, Anjali S. Advani, Matthias Stelljes, Wendy Stock, Michaela Liedtke, Nicola Gökbuget, Giovanni Martinelli, Susan O'Brien, Jane Liang White, Tao Wang, M. Luisa Paccagnella, Barbara Sleight, Erik Vandendries, Daniel J. DeAngelo, Hagop M. Kantarjian
Journal: American Journal of Hematology (2019)

Karyotype is frequently used to predict response and outcome in leukemia. This post hoc exploratory analysis evaluated the relationship between baseline cytogenetics and outcome in patients with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) treated with inotuzumab ozogamicin (InO), a humanized CD22 antibody conjugated to calicheamicin, in the phase 3, open-label, randomized INO-VATE trial. Data as of March 8, 2016, are presented in this analysis. Of the 326 patients randomized, 284 had screening karyotyping data (144 in the InO arm and 140 in the standard care [SC] arm). With InO, complete remission or complete remission with incomplete hematologic recovery (CR/CRi), minimal residual disease negativity rates, and overall survival (OS) were not significantly different between cytogenetic subgroups. CR/CRi rates favored InO over SC in the diploid with ≥20 metaphases, complex, and "other" cytogenetic subgroups. The OS hazard ratio favored InO over SC in the diploid with ≥20 metaphases, complex, and other cytogenetic subgroups. Generally, InO is effective and provides substantial clinical benefit in patients with R/R ALL who have specific baseline karyotypes.
Native T1 Mapping in the Diagnosis of Cardiac Allograft Rejection
Authors: Muhammad Imran, Louis Wang, Jane McCrohon, Chung Yu, Cameron Holloway, James Otton, Justyn Huang, Christian Stehning, Kirsten Jane Moffat, Joanne Ross, Valentina O. Puntmann, Vassilios S. Vassiliou, Sanjay Prasad, Eugene Kotlyar, Anne Keogh, Christopher Hayward, Peter Macdonald, Andrew Jabbour
Journal: JACC. Cardiovascular imaging (2019)
SP0077 New insights into strategies to effectively promote physical activity
Authors: K. Knittle
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Physical activity is generally safe and beneficial for people with rheumatic diseases. Despite this, people with rheumatic diseases commonly engage in physical activity at levels which fall below common recommendations. Recent advances in behavioural science and health psychology offer healthcare professionals new tools and methods for promomting physical activity among people with rheumatic conditions. This lecture will present the most recent evidence on the interventions and behaviour change techniques that are most likely to increase motivation for physical activity, help individuals translate their motivation into action, and promote long-term maintenance of physical activity. <h3>Disclosure of Interest</h3> None declared
AB0742 Hand x-ray lesions are frequent in antisynthetase syndrome patients with arthralgia and increase with the radiographic follow-up, whatever the extra-articular features and the serotype of antisynthetase syndrome
Authors: C. Guillochon-Petitcuenot, G. Bierry, F. Maurier, N. Afif, L. Messer, J.-E. Gottenberg, J. Sibilia, A. Meyer
Journal: Annals of the Rheumatic Diseases (2018)

Methods: 17 patients with SSc who met 2013 ACR/EULAR SSc criteria were included in the study.Clinical and laboratory parameters, Rodnan skin scores, Valentini disease activity index, were evaluated in detail.Concurrent peripheral blood Tregs (CD4 +CD25+, CD4 +FOXP3+T reg, CD4 +CD25+FOXP3+T reg) and Th17 (IL-17 producing T cells) were studied.Age and sex matched 11 subjects were included as healthy control (HC) in this study.Results: Fifteen of seventeen patients were female, median age was 52.8±9.36 years, median disease duration was 5.41±4.51years.While skin involvement and Raynaud's phenomenon were determined in all of the patients, esophageal involvement was determined in 13 of the patients (76.5%), digital ulcer in 2 patients (11.7%), and lung involvement in 14 (94.1%)patients.Median ESR level was 31.29±12.7 mm/hour, median CRP level was 0.573±0.474mg/dl, median Valentini disease activity index was 3.23±1.53.The medications of the patients during the follow up period were as; nifedipine n=15 (88.2%), hydroxychloroquine n=14 (82.4%), corticosteroids n=14 (82.4%), azathioprine n=10 (58.6%), mycophenolate mofetil n=1 (5.9%), cyclophosphamide n=7 (41.2%).In comparison of SSc and HC, all the T-reg cell levels were significantly higher in SSc group than HC (p£0.0001,p£0.0001 and p£0.0001, respectively).Although the levels of CD4 +IL-17 cells in SSc group were high compared to HC, it was not significant (p=0.100).A positive correlation between CD4 +IL-17+cell levels and CRP (r=0.613,p=0.009), a negative correlation between CD4 +CD25+T reg cell levels and dosage of corticosteroid (r=À0.513,p=0.035), a negative correlation between CD4 +CD25+T reg cell levels and platelet levels (r=À0.560,p=0.019) and a negative correlation between CD4 +CD25+FOXP3+T reg cell levels and platelet levels (r=À0.500,p=0.041) were determined.Conclusions: In a cross-sectional study, it is rather difficult to explaine the meaning of increased T-reg cell in SSc patients.These results may be due to modification of the cells by immunosuppressive treatment.It might be more meaningful to evaluate T-reg cell before and after the treatment.
Molecular and translational advances in meningiomas
Authors: Suganth Suppiah, Farshad Nassiri, Wenya Linda Bi, Ian F Dunn, Clemens Oliver Hanemann, Craig M Horbinski, Rintaro Hashizume, Charles David James, Christian Mawrin, Houtan Noushmehr, Arie Perry, Felix Sahm, Andrew Sloan, Andreas Von Deimling, Patrick Y Wen, Kenneth Aldape, Gelareh Zadeh, Kenneth Aldape, Karolyn Au, Jill Barnhartz-Sloan, Wenya Linda Bi, Priscilla K Brastianos, Nicholas Butowski, Carlos Carlotti, Michael D Cusimano, Francesco DiMeco, Katharine Drummond, Ian F Dunn, Evanthia Galanis, Caterina Giannini, Roland Goldbrunner, Brent Griffith, Rintaro Hashizume, C Oliver Hanemann, Christel Herold-Mende, Craig Horbinski, Raymond Y Huang, David James, Michael D Jenkinson, Christine Jungk, Timothy J Kaufman, Boris Krischek, Daniel Lachance, Christian Lafougère, Ian Lee, Jeff C Liu, Yasin Mamatjan, Alireza Mansouri, Christian Mawrin, Michael McDermott, David Munoz, Farshad Nassiri, Houtan Noushmehr, Ho-Keung Ng, Arie Perry, Farhad Pirouzmand, Laila M Poisson, Bianca Pollo, David Raleigh, Felix Sahm, Andrea Saladino, Thomas Santarius, Christian Schichor, David Schultz, Nils O Schmidt, Warren Selman, Andrew Sloan, Julian Spears, James Snyder, Suganth Suppiah, Ghazaleh Tabatabai, Marcos Tatagiba, Daniela Tirapelli, Joerg C Tonn, Derek Tsang, Michael A Vogelbaum, Andreas von Deimling, Patrick Y Wen, Tobias Walbert, Manfred Westphal, Adriana M Workewych, Gelareh Zadeh
Journal: Neuro-Oncology (2018)

Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treatment options for symptomatic meningiomas are limited to surgical resection where possible and adjuvant radiation therapy for tumors with concerning histopathological features or recurrent disease. At present, alternative adjuvant treatment options are not available in part due to limited historical biological analysis and clinical trial investigation on meningiomas. With advances in molecular and genomic techniques in the last decade, we have witnessed a surge of interest in understanding the genomic and epigenomic landscape of meningiomas. The field is now at the stage to adopt this molecular knowledge to refine meningioma classification and introduce molecular algorithms that can guide prediction and therapeutics for this tumor type. Animal models that recapitulate meningiomas faithfully are in critical need to test new therapeutics to facilitate rapid-cycle translation to clinical trials. Here we review the most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation, and highlight the landscape of available preclinical models in meningiomas.
Naïve T-cell Deficits at Diagnosis and after Chemotherapy Impair Cell Therapy Potential in Pediatric Cancers
Authors: Rajat K. Das, Lauren Vernau, Stephan A. Grupp, David M. Barrett
Journal: Cancer Discovery (2019)

Abstract Translational data on chimeric antigen receptor (CAR) T-cell trials indicate that the presence of naïve T cells in the premanufacture product is important to clinical response and persistence. In anticipation of developing CAR trials for other tumors, we investigated the T-cell distribution from children with solid tumors and lymphomas at diagnosis and after every cycle of chemotherapy. We found that patients with T cells enriched for naïve and stem central memory cells expanded well in vitro, but the majority of tumor types showed chemotherapy-related depletion of early lineage cells with a corresponding decline in successful ex vivo stimulation response. Unexpectedly, many pediatric patients with solid tumors had low numbers of naïve T cells prior to any therapy. These data indicate the ex vivo manufacture of CAR T cells may need to be customized based on the nature of T cells available in each disease type. Significance: Cumulative chemotherapy cycles deplete naïve T cells in many pediatric cancer regimens, reducing expansion potential associated with successful adoptive cellular therapies. Naïve T-cell deficits can be seen at diagnosis as well, implying immune deficits that exist prior to chemotherapy, which may also affect the development of immune-based therapies. See related commentary by Leick and Maus, p. 466. This article is highlighted in the In This Issue feature, p. 453