tbuckley/cabot-search huggingface dataset:
PB2343 INDIVIDUALIZED TREATMENT AGAINST BACTERIAL INFECTIONS IN STEM CELL RECIPIENTS ‐ SINGLE CENTER EXPERIENCE
Authors: Z. Stojanoski, A. Pivkova, I. Panovska‐Stavridis, L. Cadievski, B. Georgievski, M. Ivanovski, O. Karanfilski, L. Cevreska
Journal: HemaSphere (2019)

Background: Multidrug resistant (MDR) bacteria are increasingly frequent in HSCT recipients, but significant differences in etiology of bacterial infections and prevalence of resistant strains exist between different transplant centers Extended‐spectrum beta‐lactamase producing Escherichia coli, Vancomicyn resistant enterococci, Penicillin‐resistant Pneumococci Methicillin‐resistant Staphylococcus aureus and are major problem to manage. Aims: Aim: to evaluate the frequency of multidrug resistant bacteria in our center. Methods: During a 19 years period we have transplanted 500 patients with different hematological malignant and nonmalignant diseases. All patients were treated in sterile room conditioned with HEPA filters and low bacterial diet. Antibacterial prophylaxis consisted Ciprofloxacine 1,0gr/day. As empirical antibiotics regimen we administered combination of third‐generation cephalosporin + amynoglicoside, while as second line therapy Imipenem + Vancomycin Results: in every patient 3 times a week we monitor: blood culture, central venous catheter culture, sputum, urine culture. From all 288 bacterial isolates the distribution of MDR bacteria were: ESBL positive Escherichia coli 3 (0,10%) VR Enterococcus 2(0,06%) MDR Pseudomonas aer. 1 (0,03%) Klebsiella aerogenes 2 (0,06%) MRSA 17(0,06%) Acinetobacter baumanii 2(0,06%) Stenotrophomonas Maltophilia 2(0,06%). There were fatal outcome due to sepsis in 3 patients (VRE 1, MDR Pseudomonas 1, Stenotrophomonas maltophilia 1). Summary/Conclusion: The monitoring of local microflora is crucial for every transplant center. Empirical first‐line therapy must be individualized and according to ECIL 4 escalation and de‐escalation strategy is necessery for better outcome in this group of immunocompromised patients.
SP0166 ULTRASOUND OF THE HAMSTRING MUSCLE COMPLEX-CLINICAL APPLICATION + DEMO
Authors: David Andrew Bong
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> The hamstring muscle complex (HMC) are the "brakes" of human bipedal ambulation and are susceptible to injury during concentric contraction. Although common in sports medicine practice, a recent systematic review of severe hamstring injuries (grade II-III) suggests that greater than 10% of these severe injuries are non-sports related and disproportionately affect older women. Musculoskeletal ultrasound (MSKUS) is one of the basic imaging techniques utilized to detect and define these injuries and eliminate other potential causes of posterior thigh pain. This presentation will discuss the clinical application of MSKUS of the HMC in rheumatology/musculoskeletal medicine and offer a systematic anatomically-based method of examining this important non-articular region. <h3>Disclosure of Interests:</h3> None declared
THU0670 PATERNAL USE OF METHOTREXATE AND CONGENITAL MALFORMATIONS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Thomas Bo Jensen, Mikkel Bring Christensen, Nicole Tsao, Seoyoung Kim, Jon Tr&ae;rup Andersen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Maternal exposure to methotrexate (MTX) during pregnancy is known to be teratogenic, but less is known about the risk due to paternal MTX exposure. Because of a theoretical teratogenic risk from paternal exposure, treatment recommendations advocate that men should discontinue MTX three months before conception and continue discontinuation during the partners pregnancy. This may lead to suboptimal adherence to treatment, fear among the future parents and pregnancy termination. <h3>Objectives</h3> The aim was to systematically review and meta-analyze the collective data on paternal MTX exposure and the risk of congenital malformations. <h3>Methods</h3> We performed a systematic search in the databases PubMed, Embase, Cochrane Central, and Cinahl on March 1, 2018. We included studies with an English abstract that assessed major or all (both major and minor) malformations following any paternal exposure to MTX. Studies that included a control group were included in the meta-analysis. No time restriction was applied. Review Manager Version 5.3 was used for the meta-analysis. <h3>Results</h3> We identified 36 studies assessing the risk of congenital malformations following paternal exposure to MTX of which 20 contained original data. Five studies met the inclusion criteria for the meta-analysis: Three studies from Denmark had a major overlap in study populations, one study from Norway, and one German study. All studies were cohort studies using national registries except the German that used structured interviews and phone interviews. Because of the overlapping Danish studies, only the largest Danish study for each of the outcomes were included. We included a total of 265 fathers exposed to MTX and 1,004,834 controls in the meta-analysis investigating risk of major congenital malformations. Among the offspring of the MTX-exposed 7 (2.64%) had a major malformation compared to 33,816 (3.37%) among the unexposed. Pooled odds ratios were 1.02 (95% confidence interval [CI] 0.48-2.20) for major malformations and 1.02 (CI 0.62-1.66) for all malformations. <h3>Conclusion(s)</h3> In this systematic review and meta-analysis, we found no association between preconceptional paternal MTX use and major or all congenital malformations. The current recommendations to avoid paternal MTX use before conception do not appear to be supported by evidence and paternal treatment with MTX could be continued when planning a pregnancy. <h3>Disclosure of Interests</h3> Thomas Bo Jensen: None declared, Mikkel Bring Christensen: None declared, Nicole Tsao: None declared, Seoyoung Kim Grant/research support from: Pfizer, Bristol-Myers Squibb, Roche/Genentech and AbbVie., Jon Trrup Andersen: None declared
PB2242 COMPARISON BETWEEN MANUAL AND AUTOMATED PLATELET COUNTS OF ADULT PATIENTS WITH THROMBOCYTOPENIA AT ST. PAUL'S HOSPITAL ILOILO (SPHI), PHILIPPINES
Authors: J. Castromayor, L. Agreda‐ Cadete
Journal: HemaSphere (2019)

Background: Platelets are more difficult to count compared to other blood cells. Platelet counting is a significant tool used in clinical investigation to prevent bleeding complications. There is a general agreement that automation bring precision and accuracy for platelet counts in healthy individuals. Automation of platelet counting has been embraced in most part of the world, particularly in more developed countries. However, manual platelet counting &amp; estimation is still being done by skilled medical technologist to generate platelet results in most developing countries like ours. The method of platelet counting in thrombocytopenic patients is still controversial. Aims: To compare if there is significant difference between automated and manual platelet counts of adult patients with thrombocytopenia at the clinical laboratory of Saint Paul Hospital Iloilo City, Philippines. Methods: This is a retrospective‐analytical study of 384 samples of complete blood count (CBC) results with thrombocytopenia that contain both automated and manual platelet count values. Results: Out of the 384 adult patients with thrombocytopenia, there was an approximately 1:1 ratio based on sex. Thrombocytopenia was most common between 6 th to 8 th decades of life affecting 36% of patients. The mean of the automated platelet levels was approximately 76 × 10 9 /L with the standard deviation of 45; while the manual platelet count results was 170 × 10 9 /L with the standard deviation of 99. Among adult patients with thrombocytopenia, there was a significant difference between manual and automated platelet count results with p value &lt; 0.05). Summary/Conclusion: Thrombocytopenia affect both male and female sex equally. The higher the age group, the higher is the incidence of thrombocytopenia. Manual platelet counts are highly variable compared to the automated values. There was a significant difference between manual and automated platelet count results.
PS1428 GCSF ALONE STEM CELL MOBILIZATION IN MULTIPLE MYELOMA PATIENTS CANDIDATES TO HIGH DOSE CHEMOTHERAPY: A MONOCENTRIC RETROSPECTIVE EXPERIENCE
Authors: S. Bramanti, F. Magri, L. Giordano, B. Sarina, L. Morabito, J. Mariotti, C. De Philippis, D. Girardi, I. Timofeeva, R. Capizzuto, R. Mazza, C. Carlo‐Stella, A. Santoro, L. Castagna
Journal: HemaSphere (2019)

Background: Despite the introduction of several effective multidrug combination in the treatment landscape of multiple myeloma (MM), high dose chemotherapy (HDC) is still an important phase in the treatment of MM. On the other hand, chemotherapy used to mobilize stem cell (SC) do not contribute in disease control or long term survival Aims: To analyze the efficacy of granulocyte colony stimulating factor (GCSF) alone to mobilize SC, in a consecutive series of multiple myeloma patients candidate to HDC. Methods: From January 2016 to January 2019, 61 consecutive MM patients underwent GCSF alone stem cell mobilization in our institution. Every patients received GCSF at the dose of 10 mcg/kg/day for 5 days. Peripheral blood circulating CD34+/mcl were checked from day +4. Plerixafor was administered on demand when CD34+ cells were less than 20/mcl at day +4 or +5, or when CD34 harvested was less than 2 × 10^6/kg after the first or second apheresis. The stem cell harvest were performed processing 2.5 − 3 times total blood volume. After collection, the patients received single or double course of melphalan 200 mg/m 2 or 1 course of melphalan 140 mg/m 2 according to local guideline. The minimal CD34+ number to perform a single HDC was 2x106/kg. Results: Patient characteristics are listed in Table 1. All patients but 2 (3%) achieved the target to perform the planned HCD. Median total CD34+ × 10 6 /kg harvested was 8.6. The proportion of patients able to achieve the goal with one apheresis was 50%. Only 1 patient underwent a third apheresis. Nine patients (14%) received plerixafor, 7 on day +4 and 2 on day +5. Median blood CD34+/mcl on day+4 and +5 was 33.5 (15–98), and 63 (10–171), respectively. Median total blood leucocyte counts (10^3/mm^3) on day 4+ and on day +5 was 41310 and 49250, respectively. Median CD34+ × 10 6 /kg in the first and second apheresis was 6.4 (0,8–16) and 4.7 (1.5–8), respectively. Median total leucocyte count (10 6 ) in the graft on first and second apheresis was respectively 71280 and 49250. After HDC, all patients but one experienced engraftment. Summary/Conclusion: GCSF alone stem cell mobilization is an effective and safe approach after induction in MM patients candidate to HDC. The main advantages are the possibility to predict peak CD34+ level (4–5 days), to schedule apheresis in an outpatient program and to avoid unnecessary toxicity with chemotherapy. image
Cadmium-Associated Differential Methylation throughout the Placental Genome: Epigenome-Wide Association Study of Two U.S. Birth Cohorts
Authors: Todd M. Everson, Tracy Punshon, Brian P. Jackson, Ke Hao, Luca Lambertini, Jia Chen, Margaret R. Karagas, Carmen J. Marsit
Journal: Environmental Health Perspectives (2018)

Cadmium (Cd) is a ubiquitous environmental toxicant that can accumulate in the placenta during pregnancy, where it may impair placental function and affect fetal development.We aimed to investigate Cd-associated variations in placental DNA methylation (DNAM) and associations with gene expression; we also aimed to identify novel pathways involved in Cd-associated reproductive toxicity.Using placental DNAM and Cd concentrations in the New Hampshire Birth Cohort Study (NHBCS, n=343) and the Rhode Island Child Health Study (RICHS, n=141), we performed an epigenome-wide association study (EWAS) between Cd and DNAM, adjusting for tissue heterogeneity using a reference-free method. Cohort-specific results were aggregated via inverse variance weighted fixed effects meta-analysis, and variably methylated CpGs were associated with gene expression. We then performed functional enrichment analysis and tests for associations between gene expression and birth size metrics.We identified 17 Cd-associated differentially methylated CpG sites with meta-analysis p-values<1×10−5, two of which were within a 5% false discovery rate (FDR). DNAM levels at 9 of the 17 loci were associated with increased expression of 6 genes (5% FDR): TNFAIP2, EXOC3L4, GAS7, SREBF1, ACOT7, and RORA. Higher placental expression of TNFAIP2 and ACOT7 and lower expression of RORA were associated with lower birth weight z-scores (p-values<0.05).Cd-associated differential DNAM and corresponding DNAM-expression associations were observed at loci involved in inflammatory signaling and cell growth. The expression levels of genes involved in inflammatory signaling (TNFAIP2, ACOT7, and RORA) were also associated with birth weight, suggesting a role for inflammatory processes in Cd-associated reproductive toxicity. https://doi.org/10.1289/EHP2192.
Transposable Elements Are Important Contributors to Standing Variation in Gene Expression in Capsella Grandiflora
Authors: Jasmina Uzunović, Emily B Josephs, John R Stinchcombe, Stephen I Wright
Journal: Molecular Biology and Evolution (2019)

Abstract Transposable elements (TEs) make up a significant portion of eukaryotic genomes and are important drivers of genome evolution. However, the extent to which TEs affect gene expression variation on a genome-wide scale in comparison with other types of variants is still unclear. We characterized TE insertion polymorphisms and their association with gene expression in 124 whole-genome sequences from a single population of Capsella grandiflora, and contrasted this with the effects of single nucleotide polymorphisms (SNPs). Population frequency of insertions was negatively correlated with distance to genes, as well as density of conserved noncoding elements, suggesting that the negative effects of TEs on gene regulation are important in limiting their abundance. Rare TE variants strongly influence gene expression variation, predominantly through downregulation. In contrast, rare SNPs contribute equally to up- and down-regulation, but have a weaker individual effect than TEs. An expression quantitative trait loci (eQTL) analysis shows that a greater proportion of common TEs are eQTLs as opposed to common SNPs, and a third of the genes with TE eQTLs do not have SNP eQTLs. In contrast with rare TE insertions, common insertions are more likely to increase expression, consistent with recent models of cis-regulatory evolution favoring enhancer alleles. Taken together, these results imply that TEs are a significant contributor to gene expression variation and are individually more likely than rare SNPs to cause extreme changes in gene expression.
Abstract 16027: Superiority of 3D Strain Over 2D Strain in Single Right Ventricle of Children
Authors: Tomoyuki Sato, Renzo J Calderon-Anyosa, Anirban Banerjee
Journal: Circulation (2017)

Introduction: A myocardial segment is a 3D structure. Measuring deformation of a 3D structure using 2D speckle tracking echocardiography (STE), can be hindered by entrance and exit of speckles in t...
SP0061 GOUT AND ASSOCIATED CO-MORBIDITIES – RELEVANCE TO CLINICAL PRACTICE
Authors: Edward Roddy
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Patients with gout very commonly have multiple co-existent comorbidities. Associations between gout and hypertension, obesity, chronic kidney disease and cardiovascular disease have long been recognised whereas several new comorbid disease associations, such as sleep apnoea and mental health problems, have been described more recently, including lower risk of neurodegenerative diseases. These associations are complex with some comorbidities such as obesity and sleep apnoea predisposing to the development of gout, whereas gout is a risk factor for incident cardiovascular disease and erectile dysfunction. The management of gout is often more complex in the presence of comorbidity and can present a significant therapeutic challenge. This talk will provide an update on the comorbidities that are associated with gout and discuss their implications for the management of gout, in particular for long-term urate-lowering therapy. <h3>Disclosure of Interests:</h3> None declared
FRI0461 GENETIC ANALYSIS OF THE NF-KB PATHWAY CAN BE USEFUL TO DISTINGUISH PATIENTS AT RISK OF PSORIATIC ARTHRITIS WITHIN THE SPECTRUM OF PSORIATIC DISEASE
Authors: Rubén Queiró Silva, Pablo Coto-Segura, Leire González-Lara, Belen Alonso, Juan Gómez, Elías Cuesta-Llavona, Eliecer Coto
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Psoriasis and psoriatic arthritis (PsA) are the main manifestations of what is now known as psoriatic disease. Both entities share common genetic pathways, but they also differ. The NF-κb pathway has been implicated in the genesis of psoriatic disease, but the differential contribution of this genetic pathway to the risk of psoriasis and PsA is not fully understood<sup>1</sup>. <h3>Objectives</h3> Our aim was to study the association of common polymorphisms at genes of the NF-κb pathway in patients with psoriatic disease. <h3>Methods</h3> The study involved a total of 690 psoriatic disease patients (187 of them with PsA) and 550 controls. We genotyped three common polymorphisms in <i>NFKB1</i> (rs230526), <i>NFKBIA</i> (rs7152376) and <i>NFKBIZ</i> (rs3217713 indel) and compared allele and genotype frequencies between cases and controls. <h3>Results</h3> The rare <i>NFKBIA</i> rs7152376 C was significantly more frequent in the PsA group vs. controls (0.42 vs. 0.36; p=0.04, OR=1.29, 95%CI=1.02-1.63). Compared to skin psoriasis, PsA patients showed a significantly higher frequency of the rs7152376 C (0.42 vs. 0.31; p&lt;0.001). In reference to the genotypes, carriers of rs7152376 C (CC+CT) were non-significantly more frequent in PsA compared to controls (0.66 vs. 0.58; p=0.06). However, the frequency of these carriers was significantly higher in PsA vs. skin psoriasis (p=0.004). Thus, our data showed significant association between the rare <i>NFKBIA</i> rs7152376 C allele and PsA, and a trend toward the opposite effect for skin psoriasis. Neither <i>NFKB1</i> rs230526 or <i>NFKBIZ</i> rs3217713 indel were associated with the risk of developing psoriasis or PsA. <h3>Conclusion</h3> We found a significant association between <i>NFKBIA</i> variants and PsA. Our study shows that alterations in the same genetic pathway may have differential effects on different manifestations of psoriatic disease. Additional studies from larger cohorts and different populations are necessary to validate these results. <h3>References</h3> [1] Nair RP, Duffin KC, Helms C, et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet2009; 41: 199-204. <h3>Disclosure of Interests</h3> None declared
SP0111 POTENTIAL CELLULAR AND MOLECULAR TARGETS
Authors: Jörg Distler
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> The pathophysiology of systemic sclerosis (SSc) is characterized by a cascade of microvascular injury with apoptosis of endothelial cells, Th2/M2 biased inflammation and autoimmunity and aberrant fibroblast activation with excessive matrix deposition. We increasingly recognize that physiological wound healing and the initial stages of SSc share many commonalities. However, in contrast to physiological repair, these tissue repair programs are not effectively terminated in SSc resulting in progressive matrix deposition and tissue damage. The mechanisms of fibroblast activation may change during the cause of SSc; Profibrotic mediators released from infiltrating leukocytes, activated endothelial cells and degranulated platelets may drive fibroblast activation and collagen release in particular in early stages, whereas endogenous activation loops with activation of fibroblasts by epigenetic changes and biomechanical or physical factors may be of increasing importance in later stages of SSc. In my presentation, I will discuss novel insights into the pathogenesis of SSc with a particular focus on the interplay of inflammation and fibroblast activation. I will focus on translational aspects and highlight mechanisms with high potential for transfer from bench-to-bedside. <h3>Disclosure of Interests:</h3> None declared
Origin of Gibberellin-Dependent Transcriptional Regulation by Molecular Exploitation of a Transactivation Domain in DELLA Proteins
Authors: Jorge Hernández-García, Asier Briones-Moreno, Renaud Dumas, Miguel A Blázquez
Journal: Molecular Biology and Evolution (2019)

DELLA proteins are plant-specific transcriptional regulators known to interact through their C-terminal GRAS domain with over 150 transcription factors in Arabidopsis thaliana. Besides, DELLAs from vascular plants can interact through the N-terminal domain with the gibberellin receptor encoded by GID1, through which gibberellins promote DELLA degradation. However, this regulation is absent in nonvascular land plants, which lack active gibberellins or a proper GID1 receptor. Current knowledge indicates that DELLAs are important pieces of the signaling machinery of vascular plants, especially angiosperms, but nothing is known about DELLA function during early land plant evolution or if they exist at all in charophytan algae. We have now elucidated the evolutionary origin of DELLA proteins, showing that algal GRAS proteins are monophyletic and evolved independently from those of land plants, which explains why there are no DELLAs outside land plants. DELLA genes have been maintained throughout land plant evolution with only two major duplication events kept among plants. Furthermore, we show that the features needed for DELLA interaction with the receptor were already present in the ancestor of all land plants and propose that these DELLA N-terminal motifs have been tightly conserved in nonvascular land plants for their function in transcriptional coactivation, which allowed subsequent exaptation for the interaction with the GID1 receptor when vascular plants developed gibberellin synthesis and the corresponding perception module.
FRI0697-HPR CONSUMPTION OF DAIRY PRODUCTS AND RISK OF RHEUMATOID ARTHRITIS AMONG WOMEN: A POPULATION-BASED PROSPECTIVE COHORT STUDY
Authors: Björn Sundström, Lotta Ljung, Daniela DI Giuseppe
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Conflicting results have been reported regarding the association between consumption of milk and dairy products and the risk for development of rheumatoid arthritis (RA). <h3>Objectives</h3> The aim of this study was to investigate the association between consumption of milk and dairy products and the development of RA in a large population-based cohort of women. <h3>Methods</h3> In a prospective cohort study 35,600 women aged 48-83 years, from the Swedish Mammography Cohort (SMC), were followed between 2003 and 2015. Consumption of dairy products was assessed in 1997 at a mean age of mean age of 61.5 years (SD 9.1 years) with a 96-item self-administered questionnaire. The risk (hazard ratio; HR) of RA development associated with consumption of dairy products was estimated using Cox proportional hazard regression models with adjustment for age, alcohol intake, smoking, energy intake, meat and fish consumption. <h3>Results</h3> During the follow-up of 12 years, 368 individuals were identified with a new diagnosis of RA. Comparing high consumption with low consumption of dairy products, no association between consumption of dairy products and the development of RA was observed: HR for the fully adjusted model=1.12 (95% CI: 0.78-1.59 (Table 1). Also when evaluating milk and cheese consumption separately, no association with the risk of RA was observed: HR for the highest milk consumption=1.10 (95% CI: 0.82-1.44) and highest cheese consumption HR=1.20 (95% CI: 0.81-1.79), compared with low consumption (fully adjusted models, table 1). <h3>Conclusion</h3> In this large population-based cohort study, consumption of dairy products was not associated with risk to develop RA. <h3>Disclosure of Interests</h3> None declared