tbuckley/cabot-search huggingface dataset:
PB2093 CLINICAL, PARACLINICAL CHARACTERISTICS AND OUTCOME IN ALGERIAN MYELODYSPLASTIC SYNDROMES: A SINGLE CENTER EXPERIENCE
Authors: T. F. Talbi, M. R. abbadi, S. menouer, S. belakhel, K. djouadi, F. Z. ardjoun
Journal: HemaSphere (2019)

Background: Myelodysplastic syndromes refer to a heterogeneous group of clonal diseases affecting the hematopoietic stem cell resulting in qualitative and quantitative abnormalities of the three myeloid lineages. The overall incidence is 03‐05/105 hbts/year without ethnic difference; it increases with age (03‐15/105 hbts/year between 50‐70 years and 15‐50/105 hbts/year&gt; 70 years). Aims: we analyzed the characteristics of our patients and we investigated the impact of prognostic factors and parculier comorbidities on their future Methods a single‐center descriptive retrospective study, including all MDS diagnosed in the hematology department of military hospital over a 21‐year period (1994‐2014) from patient records. The diagnosis is retained on blood and bone marrow cytology and Perls staining (the karyotype was carried out in a few cases) after exclusion of a vitamin deficiency (ferritin, folate, vitamin B12: dosage or therapeutic test), or associated pathology (thyroid, lever, inflammatory or haemolytic). We have classified our patients according to the WHO classification (2016). Results: n = 85 evaluable pts: the clinical, biological and cytological characteristics of patients are summarized in the following table I, the observed comorbidities: cardiovascular d (40%), diabetes (30%), and respiratory insufficiency (29%): more frequent (HR = 1.65, 95% CI = 0.65‐ 3, 66) in men/women and more severe (≥3 points: 12 patients): HR: 4.5: 95% CI: 1, 88‐5) P = 0.012. Patients 65 years and older have a high prevalence of comorbidities (vs young): HCT‐CI score: HR = 0, 19 (95% CI: 0, 023‐0, 89): p = 0.01, with a very negative impact on survival (p = 0.001). Summary/Conclusion: the presentation of MDS in our series is similar to that of national and international series with a particularly poor prognosis since this pathology preferentially affects the elderly, with in most cases associated defects making the management very difficult. Immunomodulatory agents could improve the evolution of these patients. image
SP0037 USING GENETICS IN PERSONALISED MEDICINE IN RHEUMATIC DISEASES
Authors: Anne Barton
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> For all treatments available for rheumatoid arthritis (RA), none are effective for all patients. For many drugs, patients are given 3-6 months of treatment before a decision is made regarding efficacy and, for those in whom the treatment does not work, that can be a period of on-going disease activity, exposure to the risk of side effects and possible accumulation of joint damage, all of which impact quality of life. Stratified medicine approaches aim to better target treatments to those most likely to respond. However, currently, CRP/ESR are the only biological markers (biomarkers) routinely used to inform whether therapy is required and RF/ACPA status are often considered. <h3>Objectives:</h3> To update in progress of using genomic approaches to inform treatment selection in rheumatoid arthritis <h3>Methods:</h3> National and international precision/stratified medicine programmes are investigating whether genetic and epigenetic biomarkers could help in the selection of therapies and progress will be reviewed. <h3>Results:</h3> Recent studies have developed new outcome measures to assess treatment efficacy for controlling synovitis, confirming previous findings from genetic studies of heritability. Issues around the best tissue to sample, the predictive ability of a test and confounding factors including adherence will be considered and emerging biomarkers reviewed. <h3>Conclusion:</h3> Matching the right treatments to the right patients is the goal of personalised medicine and potential biomarkers are starting to emerge. However, caution is required as none have so far been proven to be clinically useful or cost-effective. <h3>Reference:</h3> [1] Hensor, et al. Rheumatology 2019; Plat et al, Arthritis and Rheumatol 2019. <h3>Disclosure of Interests:</h3> None declared
PS1494 REDUCED ANTIOXIDANT CAPACITY INDUCED PYROPTOSIS IN PLATELETS IN IMMUNE THROMBOCYTOPENIA PATIENTS
Authors: S. Wang, Y. Liu, M. Hou, J. Peng
Journal: HemaSphere (2019)

Background: The pathophysiology of primary immune thrombocytopenia (ITP) is not fully understood. Antioxidant capacitie (AOC) is reduced in ITP platelets. Mitochondrial reactive oxygen species (ROS) generation can lead to NLRP3 inflammasome activation and pyroptosis. However, the process has not been studied in ITP platelets. Aims: To assess whether the reduced AOC of platelets in ITP can affect the NLRP3 inflammasome signaling pathways and to further explore the pathophysiology of ITP. Methods: We measured mitochondrial membrane potential (MMP) of platelets from patients and healthy donors using JC‐1 by flow cytometry. Next, we investigated AOC of platelets by supplementation of 300 μM H 2 O 2 following loading with 50 μM 2 ’ ,7 ’ ‐dichlorodihydrofluorescein diacetate. ROS level as well as expression of NLRP3, ASC, pro‐caspase‐1 and p20 in platelets after stimulation with H 2 O 2 was detected. Besides, co‐localization of NLRP3 and ASC in platelets after stimulation was assessed by immunofluorescence. Blocking experiments were performed using antioxidant N‐Acetyl‐L‐cysteine, NLRP3 inhibitorMCC950 (CP‐456773) and caspase‐1 inhibitorZ‐VAD‐FMK. Furthermore, we studied the pyroptosis of platelets in passive ITP mouse model using NLRP3‐/‐ mice, Caspase‐1‐/‐ mice and wild type mice. Results: The platelets from ITP patients showed significantly reduced antioxidant capacity compared to healthy donors. A significant lower MMP and higher ROS level were detected in ITP platelets. Expression of NLRP3, ASC, pro‐caspase‐1 and p20 was obviously increased and co‐localization of NLRP3 and ASC was more evident in ITP platelets. An increased level of IL‐1β and IL‐18 were observed in culture supernatant. The application of antioxidant N‐Acetyl‐L‐cysteine (NAC), NLRP3 inhibitor MCC950(CP‐456773) and caspase‐1 inhibitor Z‐VAD‐FMK to H 2 O 2 ‐stimulated ITP platelets significantly inhibit pyroptosis. The indicators of pyroptosis were down‐regulated in NLRP3‐/‐ and Caspase‐1‐/‐ mice. Summary/Conclusion: The reduced AOC of platelets in ITP results in accumulation of intracellular ROS, which contributes to the activation of NLRP3 inflammasome signaling pathways and leads to pyroptosis, which accelerates thrombocytopenia in ITP. image
PS1330 VARIABILITY IN THE EXTENT OF DEL(5Q) AND ITS CLINICAL IMPLICATION IN MYELODYSPLASTIC SYNDROMES (MDS)
Authors: Z. Zemanova, J. Brezinova, K. Michalova, K. Svobodova, H. Lhotska, D. Vesela, S. Izakova, I. Sarova, L. Lizcova, S. Ransdorfova, L. Pavlistova, M. Belickova, J. Vesela, M. Siskova, R. Neuwirtova, J. Cermak, T. Stopka, A. Jonasova
Journal: HemaSphere (2019)

Background: The interstitial deletion of the long arm of chromosome 5—del(5q)—is the most common cytogenetic abnormality in MDS occurring either as a sole aberration or as a part of complex karyotypes (CK). MDS with isolated del(5q) are associated with a favorable outcome while MDS with CK relate to poor prognosis. Extent of deleted segment is highly variable. However, it remains unclear whether its size matters for the different MDS phenotypes. Aims: The aim was to compare the extent of deletion in 264 MDS patients [116 with isolated del(5q) and 148 with del(5q) involved in CK] and to assess the relationship of del(5q) extent and TP53 gene mutation. Methods: Extent of del(5q) was analyzed using I‐FISH (Abbott, MetaSystems), mBAND (MetaSystems) and array CGH/SNP (CytoChip Cancer SNP 180K, Illumina or SurePrint G3 Cancer CGH+SNP 4x180K, Agilent). CK were analyzed with mFISH (MetaSystems). Sequence analysis of TP53 gene was performed in 84 cases using amplicon deep sequencing (exons 4–11) on a 454 GS Junior system (Roche) or with TruSight Myeloid Panel Kit on MiSeq sequencing instruments (Illumina). Results: In the group with isolated del(5q), the most frequently deleted segment ranged between the bands 5q14 and 5q33.3, with the smallest deletion encompassing the 5q31.1–5q31.3 region (18.527 Mb). The TP53 mutation was proved in 19.4% cases. The size of the deletion did not significantly differ in patients with and without TP53 mutation. In the group with CK, the deletion often involved entire long arm including the telomeric region. In some cases, a part of short arm was also deleted, but we never observed the loss of the entire chromosome 5. The commonly conserved region (CCR) was localized in bands 5p12 to 5p14.1. In this group, the mutation of TP53 and/or LOH17p was detected in 49% of patients. The commonly deleted regions (CDR) were in the band 5q31.1 (5.522 Mb) in cases with isolated del(5q) and between the bands 5q31.1 and 5q31.3 (18.527 Mb) in patients with CK. Summary/Conclusion: Patients with isolated del(5q) had a smaller size of the deleted segment. More extensive 5q deletion was associated with higher karyotype complexity, increased frequency of TP53 aberrations and worse prognosis. Accurate analysis of breakpoints and range of del(5q) points out to the correlation of deletion size with increasing genomic instability in MDS and contributes to a better understanding of the MDS pathogenesis. Supported by RVO‐VFN64165, GACR P302/12/G157, ProgresQ28/LF1, MHCR 00023736.
AB1074 AUTOIMMUNE/INFLAMMATORY SYNDROME INDUCED BY ADJUVANTS—ASIA—RELATED TO BIOMATERIALS: ANALYSIS OF 50 CASES
Authors: Jaume Alijotas-Reig, Enrique Esteve-Valverde
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Systemic autoimmune or granulomatous disorders related to biomaterials of human use have rarely been described <h3>Objectives</h3> The aim of this study was to report cases of autoimmune/inflammatory syndrome induced by adjuvants (ASIA) related to biomaterial injections and prostheses, mainly silicone, hyaluronic acid, acrylamides and methacrylate compounds in a Spanish patient cohort. <h3>Methods</h3> This study is a retrospective analysis of clinical, laboratory, histopathological and follow-up data of 50 cases of patients suffering from late-onset, non-infectious inflammatory/autoimmune disorders related to bioimplants. Late onset was defined as 3 months or more post injection. Data were obtained through a further non-systematic but comprehensive review of the literature. Fifty cases of late-onset adverse reactions related to biomaterial injections or prostheses were reviewed. <h3>Results</h3> All cases had systemic complaints that could be categorised as ASIA. In all but five patients, inflammatory features at the implantation site preceded distant or systemic manifestations. Abnormal blood tests were common. Localised inflammatory nodules and panniculitis in 88.88% evolved into a variety of disorders, viz., primary biliary cirrhosis, Sjögren's syndrome, sarcoidosis, human adjuvant disease, vasculitis, inflammatory bowel syndrome and inflammatory polyradiculopathy. 11.11% cases presented primarily with systemic autoimmune disorders. <h3>Conclusion</h3> Biomaterials and prostheses can provoke late-onset systemic autoimmune disorders fulfilling ASIA criteria, or present primarily local/regional inflammatory reactions that may eventually evolve into systemic autoimmune and/or granulomatous disorders which fall under ASIA <h3>References</h3> [1] Hanke CW, Rohrich RJ, Busso M, Carruthers A, Carruthers J, Fagien S, et al. Facial soft-tissue fillers: assessing the state of the science conference proceedings report. J Am Acad Dermatol. 2011;64(4 Suppl):S53–65. [2] Ellis DA, Makdessian AS, Brown DJ. Survey of future injectables. Facial Plast Surg Clin North Am. 2001;9:405–11. [3] American Society of Plastic Surgery. Statistics of 2010, http://www.surgery.org/site/default/stats2010_1.pdf (2010, Accessed 01 Aug 2011). <h3>Disclosure of Interests</h3> None declared
THU0714-HPR RELATIONSHIP BETWEEN TRUNK POSITION SENSE, TRUNK MUSCLE ENDURANCE AND BALANCE IN WOMEN WITH FIBROMYALGIA SYNDROME
Authors: Özge Çoban, Seyda Toprak Celenay, Oguzhan Mete, Deran Oskay
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Position sense plays a fundamental role in human movement which is crucial for daily activities, exercise and sports [1]. Trunk endurance and balance were also integrated part of normal functional movements. Decreased balance and trunk muscle endurance were reported in women with fibromyalgia syndrome (FMS) [2]. However, to our knowledge, the relationship between trunk position sense, trunk muscle endurance and balance has not been studied in women with FMS. <h3>Objectives</h3> This study aimed to determine the relationship between trunk position sense, trunk muscle endurance and balance in women with FMS. <h3>Methods</h3> Women with FMS (n: 25, age: 42.88±11,66 years, body mass index: 25.69±3.48 kg/m²) were recruited. Trunk position sense was assessed with digital inclinometer by trunk reposition errors in which higher scores indicates poor trunk position sense [3]. Trunk flexor, extensor, dominant and non-dominant lateral side muscle endurance with McGill's trunk muscle endurance tests [4] in seconds and balance with the Mini-Balance Evaluation Systems Test (Mini BEStest) [5] were assessed. Spearman's rank correlation test was used for analysis. <h3>Results</h3> There were significant negative correlations between trunk position sense and trunk flexor, extensor, dominant and non-dominant lateral side muscle endurance (r=-0.61, p=0.001; r=-049, p=0.011; r=-0.048, p=0.014; r=-0,048, p=0.014, respectively). There were also high significant negative correlations between trunk position sense and Mini BEStest score (r=-0.73, p&lt;0.001). <h3>Conclusion</h3> It was found that there were moderate to high correlations between trunk position sense, trunk muscle endurance and balance. Therefore, addition of trunk position sense training to the rehabilitation programs might be effective in improving trunk muscle endurance and balance in women with FMS. <h3>References</h3> [1] Han J, Waddington G, Adams R, Anson J, Liu Y (2016) Assessing proprioception: a critical review of methods. Journal of Sport and Health Science 5 (1):80-90 [2] ÇELENAY ŞT, KÜLÜNKOĞLU BA, KÜÇÜKŞAHİN O Fibromiyalji Sendromu Olan Kadınlarda Denge, Endurans ve Esnekliğin Değerlendirilmesi. Türk Fizyoterapi ve Rehabilitasyon Dergisi 28 (3):125-131 [3] Goldberg A, Hernandez ME, Alexander NB (2005) Trunk repositioning errors are increased in balance-impaired older adults. The journals of gerontology Series A, Biological sciences and medical sciences 60 (10):1310-1314 [4] McGill SM, Childs A, Liebenson C (1999) Endurance times for low back stabilization exercises: clinical targets for testing and training from a normaldatabase. Arch Phys Med Rehabil 80 (8):941-944 [5] Horak FB, Wrisley DM, Frank J (2009) The Balance Evaluation Systems Test (BESTest) to differentiate balance deficits. Physical therapy 89 (5):484-498. doi:10.2522/ptj.20080071 <h3>Disclosure of Interests</h3> None declared
SP0004 MANAGING PATIENTS WITH AXSPA: WHAT ARE THE QUALITY STANDARDS?
Authors: Uta Kiltz
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> There is wide variation in the management of patients with axial spondyloarthritis (axSpA) worldwide with significant unmet needs such as delayed diagnosis and inequity in bMARD prescription.<sup>1</sup> Assessing the quality of care provided to patients with axSpA is important not only to patients and physicians, but also to providers and purchasers of health care. There is no agreed methodology to quantify quality of care but several approaches have been proposed aiming to assess quality in a measurable construct, e.g. quality indicators, performance measures or quality standards. Definition of quality standards (QS) enable society to identify resources and processes which may need to be optimized in patients with axSpA. <h3>Objectives:</h3> A major goal of the international organization Assessment of SpondyloArthritis international Society (ASAS) is to improve quality of care and health outcomes in patients with axSpA. Recognized gaps in current care prompted ASAS in 2016 to start developing a quality standard set (ASAS QS) to optimize access, treatment and patient outcomes in axSpA. <h3>Methods:</h3> An ASAS task force developed a set of ASAS QS step-wise. First, key areas for quality improvement were proposed, discussed, rated and agreed on. Thereafter, key areas were prioritized and statements for the most important key areas were phrased on consensus. Appropriate tools were selected and measures developed to be able to assess and quantify the quality of care on the community level. <h3>Results:</h3> The ASAS task force, consisting of 20 rheumatologists, 2 physiotherapists and 2 patients, selected and proposed 34 potential key areas for quality improvement which were commented by 140 ASAS survey participants (86 physicians, 42 patients). Within that process 3 new key areas came up, which led to a reevaluation of all 37 key areas by 120 participants (86 physicians, 29 patients). Five key areas were identified as most important to determine quality of care: referral including rapid access, monitoring, treatment, education including patient information and comorbidities. On that background, 9 QS were agreed on and finally endorsed by ASAS. <h3>Conclusion:</h3> ASAS successfully developed the first QS set for improvement of health care for adult patients with axSpA. All QS are measurable achievable in daily care in an optimized situation and intend to minimize variation in quality of care. <h3>Reference:</h3> [1] Nikiphorou E, et al. Inequity in biological DMARD prescription for spondyloarthritis across the globe: results from the ASAS-COMOSPA study. Ann Rheum Dis 2018;77:405–411. <h3>Disclosure of interests:</h3> Uta Kiltz Grant/research support from: AbbVie, Chugai, Eli Lilly, Grünenthal, Janssen, MSD, Novartis, Pfizer, Roche, and UCB., Consultant for: AbbVie, Chugai, Eli Lilly, Grünenthal, Janssen, MSD, Novartis, Pfizer, Roche, and UCB.
Increased Prevalence of Celiac Disease in School-age Children in Italy
Authors: Simona Gatti, Elena Lionetti, Linda Balanzoni, Anil K. Verma, Tiziana Galeazzi, Rosaria Gesuita, Novella Scattolo, Mauro Cinquetti, Alessio Fasano, Carlo Catassi, Roberta Annibali, Giada Del Baldo, Elisa Franceschini, Alessandra Palpacelli, Chiara Monachesi, Giulia Naspi Catassi, Maria Teresa Trevisan, Genan Anton, Anna Maria Colombari
Journal: Clinical Gastroenterology and Hepatology (2019)
Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights
Authors: Alexander Gusev, Nicholas Mancuso, Hyejung Won, Maria Kousi, Hilary K. Finucane, Yakir Reshef, Lingyun Song, Alexias Safi, Steven McCarroll, Benjamin M. Neale, Roel A. Ophoff, Michael C. O’Donovan, Gregory E. Crawford, Daniel H. Geschwind, Nicholas Katsanis, Patrick F. Sullivan, Bogdan Pasaniuc, Alkes L. Price
Journal: Nature Genetics (2018)
Abstract 20403: Laser Balloon Ablation in Atrial Fibrillation: Clnical Results From a Multicentric Laser Ablation Registry
Authors: Thorsten W Lewalter, Turgut Brodherr, Clemens Jilek, Matthias Hochadel, Jochen Senges, Boris Schmidt
Journal: Circulation (2017)

Background: Pulmonary Vein ablation (PVI) is the cornerstone of an atrial fibrillation (AF) ablation procedure. However, PV reconnection and clinical relapses of AF following the first AF ablation ...
Preventing Alzheimer Disease by Deprescribing Anticholinergic Medications
Authors: Noll L. Campbell, Richard Holden, Malaz A. Boustani
Journal: JAMA Internal Medicine (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
THU0455 PHARMACOKINETICS (PK) OF A SINGLE INTRA-ARTICULAR (IA) INJECTION OF CNTX-4975 (TRANS-CAPSAICIN) VS TOPICAL 8% CAPSAICIN PATCH
Authors: Randall Stevens, Kimberly Guedes, Eddie Armas, Valerie Smith, Andrew Volosov
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> CNTX-4975 is in phase 3 trials for treatment of moderate to severe pain associated with knee osteoarthritis (OA). PK data from prior studies of CNTX-4975 in subjects with moderate to severe knee OA pain suggest low systemic and short-term exposure, similar to the FDA-approved topical capsaicin 8% patch. <h3>Objectives:</h3> We compared single-dose systemic exposure to <i>trans</i>- and <i>cis</i>-capsaicin following IA injection of CNTX-4975 (&gt;99.5% <i>trans</i>-capsaicin, &lt;0.5% total impurities) with 8% capsaicin patch in subjects with moderate to severe knee OA pain. <h3>Methods:</h3> This open-label, crossover study enrolled adults aged 50–75 y with moderate to severe knee OA pain in ≥1 knee (most painful knee, index knee; nonindex knee, no to mild pain [0–1; NPRS 0–4 scale]). Subjects were randomized 1:1 to 2 sequences: A (CNTX-4975 1 mg IA, index knee) followed by B (topical capsaicin 8% patch, posterior rib cage for 60 min) or BA sequence, with ≥7-day washout between treatments. Plasma samples for <i>trans</i>- and <i>cis</i>-capsaicin concentration assays were taken before and at specified times after study treatment. PK parameters, including maximum observed plasma concentration (C<sub>max</sub>), area under the plasma concentration-time curve from time 0 to last quantifiable plasma concentration (AUC<sub>0-t</sub>) and to infinity (AUC<sub>0-∞</sub>), time to C<sub>max</sub> (T<sub>max</sub>), and half-life (t<sub>1/2</sub>), were determined. PK parameters were reported using descriptive statistics. Geometric means ratios of ln-transformed AUC<sub>0-t</sub>, AUC<sub>0-∞</sub>, and C<sub>max</sub> were evaluated using ANOVA. <h3>Results:</h3> Sixteen subjects (median age, 62 y; female, 62.5%) were randomized to treatment (PK analysis population). T<sub>max</sub> showed more rapid absorption of <i>trans</i>-capsaicin from IA CNTX-4975 vs the topical patch (<b>Table</b>). AUC<sub>0-t</sub> and C<sub>max</sub> indicated greater <i>trans</i>-capsaicin exposure with CNTX-4975 vs the patch; however, exposure was short term, with mean t<sub>1/2</sub>0.5 h. <i>Cis</i>-capsaicin concentrations were insufficient for calculating PK. <h3>Conclusion:</h3> <i>Trans</i>-capsaicin from CNTX-4975 injection was rapidly absorbed and eliminated. The extent of systemic exposure to <i>trans</i>-capsaicin was significantly higher after CNTX-4975 vs the 8% capsaicin patch. <h3>Disclosure of Interests:</h3> Randall Stevens Shareholder of: Centrexion Therapeutics Corp, Employee of: Centrexion Therapeutics Corp, Kimberly Guedes Employee of: Centrexion Therapeutics Corp, Eddie Armas: None declared, Valerie Smith Consultant for: Premier Research, Andrew Volosov Consultant for: Premier Research