tbuckley/cabot-search huggingface dataset:
PS1191 PROGNOSTIC SIGNIFICANCE OF REGULATORY T CELLS (TREGS) IN CHRONIC MYELOID LEUKEMIA PATIENTS TREATED WITH GENERIC IMATINIB
Authors: F. Saj
Journal: HemaSphere (2019)

Background: It has been observed that the proportion of regulatory T cells (Tregs) is elevated in untreated Chronic Myeloid Leukemia (CML) patients that curtail tumor‐specific immune response. The degree of imatinib‐related Treg inhibition correlates with CML prognosis. There is limited information on the dynamics of Tregs in CML patients treated with generic imatinib. We studied Treg proportions in newly‐diagnosed CML patients (at baseline and 3 months of treatment with generic imatinib). Aims: To evaluate Tregs in periperal blood of newly diagnosed patients of CML‐Chronic phase and their association with disease progression. Methods: Newly‐diagnosed adult CML patients in chronic phase were prospectively studied from July 2017 to March 2018. At baseline, a peripheral blood sample for Treg analysis was collected from CML patients before starting imatinib and from healthy controls. At 3 months, in addition to quantitative RQPCR for BCR‐ABL, a repeat peripheral blood sample was collected for Treg analysis. Treg percentage in peripheral blood was assessed by flowcytometry (triple laser BD FACS Canto II flow cytometer). Following sample acquisition on flow cytometer, the data was analysed using BD FACSDIVA software (Becton Dickinson, USA). Tregs were calculated as percentage of CD4+ T lymphocytes. Results: Fifty‐seven newly‐diagnosed CML patients and 30 age‐ and sex‐matched healthy controls were prospectively enrolled. The median age of the CML patients was 39 years (range 16 – 64years); 47.3% were males. The BCR‐ABL (IS) % at 3months was &lt;1%, 1–10% and &gt;10% in 15 (26.3%), 26 (45.6%) and 16 (28.1%) patients, respectively. The mean baseline Treg% of CML patients (3.61 ± 0.32%) was significantly higher than the mean Treg % of controls (1.58 ± 0.21%) (p &lt; 0.001). The mean Treg% at 3 months in CML patients (1.73 ± 0.35%) was significantly lower than baseline Treg% (3.61 ± 0.32%) (p &lt; 0.001). Baseline Treg% in CML patients showed significant positive correlation with Sokal score (r = 0.29), Hasford score (r = 0.33) and EUTOS score (r = 0.28) (p &lt; 0.05). The baseline Treg% correlated significantly with the BCR‐ABL% at 3months (p = 0.03). Summary/Conclusion: We found a significantly higher proportion of Tregs in CML patients in chronic phase vis‐a‐vis healthy controls which significantly decreased with generic imatinib treatment at 3 months. The study results add evidence to the hypothesis that imatinib‐related Treg suppression is another novel mechanism through which it targets CML. Our findings lend support to the fact that generic imatinib is reasonably efficacious in restoring immunological milieu in CML patients.
THU0438 DO CORTICOSTEROIDS OR HYALURONIC ACID INTRA-ARTICULAR INJECTIONS IMPACT THE RISK OF TOTAL KNEE REPLACEMENT? REAL-LIFE DATA FROM THE KHOALA COHORT
Authors: Augustin Latourte, Anne-Christine Rat, Willy Ngueyon Sime, Abdou Omorou, Florent Eymard, Jeremie Sellam, Christian Roux, Francis Guillemin, Pascal Richette
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Long-term structural outcomes of corticosteroids (CS) or hyaluronic acid (HA) intra-articular injections in knee osteoarthritis (KOA) are unclear. Whether HA injections delay the need for total knee replacement (TKR) remains controversial, and an increased risk of cartilage damage has been reported with repeated CS injections. <h3>Objectives:</h3> We conducted this study to compare, in real-life setting, the risk of TKR in patients receiving CS or HA vs. in those who did not receive intra-articular injections. <h3>Methods:</h3> Khoala cohort is a French nationwide population-based cohort of 878 patients with symptomatic hip or knee OA (ACR criteria), aged 40-75 years. This study included patients with baseline KOA only. Patients were followed annually by self-reported questionnaires and by clinical examination and radiography at baseline (year 0), years 3 and 5. The risk of incident TKR was compared between patients who had never received intra-articular injections vs. patients who received at least 1 CS or HA injection during follow-up. We used a marginal structural model with inverse probability of treatment weighting to determine the causal relationship between treatment and the risk of incident TKR in the treated knee during the 5-year follow-up. This model allows the adjustment for time-varying confounding factors (i.e. pain, function and mental health scores) in addition to constant confounders (i.e. baseline age, sex, BMI, Kellgren-Lawrence grade). <h3>Results:</h3> This study involved 656 patients (mean age 62.2 ± 8.5 years; 70.3% females) of which 91 (13.9%) underwent TKR during follow-up. CS or HA injections were performed in 143 (21.8%) and 191 (29.1%) patients, respectively, and 92 (14.0%) received both treatments. The 5-year relative risk of incident TKR in treated vs. untreated knee was 0.96 (95%CI 0.35 to 2.66; p=0.94) CS-treated knees and 0.38 (95%CI 0.15 to 1.03; p=0.06) in HA-treated knees. <h3>Conclusion:</h3> In this study, CS injections for symptomatic KOA did not increase the 5-year risk of incident TKR. There was a non-significant trend for a reduced risk of TKR in HA-treated knees. <h3>Acknowledgement:</h3> This work was supported by the French Society of Rheumatology and ART-Viggo Association. <h3>Disclosure of Interests:</h3> Augustin Latourte: None declared, Anne-Christine Rat: None declared, Willy Ngueyon Sime: None declared, Abdou Omorou: None declared, Florent Eymard: None declared, Jeremie Sellam: None declared, Christian Roux: None declared, Francis Guillemin Grant/research support from: Expanscience, Pascal Richette Consultant for: Grunenthal, Horizon, Speakers bureau: AstraZeneca, Grunenthal
An ABC Method for Whole-Genome Sequence Data: Inferring Paleolithic and Neolithic Human Expansions
Authors: Flora Jay, Simon Boitard, Frédéric Austerlitz
Journal: Molecular Biology and Evolution (2019)

Species generally undergo a complex demographic history consisting, in particular, of multiple changes in population size. Genome-wide sequencing data are potentially highly informative for reconstructing this demographic history. A crucial point is to extract the relevant information from these very large data sets. Here, we design an approach for inferring past demographic events from a moderate number of fully sequenced genomes. Our new approach uses Approximate Bayesian Computation, a simulation-based statistical framework that allows 1) identifying the best demographic scenario among several competing scenarios and 2) estimating the best-fitting parameters under the chosen scenario. Approximate Bayesian Computation relies on the computation of summary statistics. Using a cross-validation approach, we show that statistics such as the lengths of haplotypes shared between individuals, or the decay of linkage disequilibrium with distance, can be combined with classical statistics (e.g., heterozygosity and Tajima's D) to accurately infer complex demographic scenarios including bottlenecks and expansion periods. We also demonstrate the importance of simultaneously estimating the genotyping error rate. Applying our method on genome-wide human-sequence databases, we finally show that a model consisting in a bottleneck followed by a Paleolithic and a Neolithic expansion is the most relevant for Eurasian populations.
Antidiabetic Medications and Mortality Risk in Individuals With Pancreatic Cancer–Related Diabetes and Postpancreatitis Diabetes: A Nationwide Cohort Study
Authors: Jaelim Cho, Robert Scragg, Stephen J. Pandol, Mark O. Goodarzi, Maxim S. Petrov
Journal: Diabetes Care (2019)

OBJECTIVE There are no specific treatment guidelines for diabetes of the exocrine pancreas. High-quality studies are warranted to investigate whether the use of antidiabetic medications has survival benefit in individuals with diabetes of the exocrine pancreas. The objective was to determine the risk of mortality associated with the use of antidiabetic medications in individuals with pancreatic cancer–related diabetes (PCRD) and postpancreatitis diabetes mellitus (PPDM). RESEARCH DESIGN AND METHODS Nationwide pharmaceutical dispensing data (2006–2015) linked to hospital discharge data were used to identify 1,862 individuals with PCRD or PPDM. Multivariable Cox regression analysis was conducted, and the risk was expressed as hazard ratios and 95% CIs. A 6-month lag was used to minimize reverse causality. RESULTS In individuals with PCRD, ever users of metformin (adjusted hazard ratio 0.54; 95% CI 0.46–0.63) and ever users of insulin (adjusted hazard ratio 0.46; 95% CI 0.39–0.55) had significantly lower risks of mortality compared with never users of antidiabetic medications. These associations attenuated toward the null with the use of a 6-month lag. In individuals with PPDM, ever users of metformin had a significantly lower risk of mortality (adjusted hazard ratio 0.51; 95% CI 0.36–0.70), whereas ever-users of insulin did not have a significantly changed risk of mortality (adjusted hazard ratio 0.75; 95% CI 0.49–1.14) compared with never users of antidiabetic medications. The former association remained significant with the use of a 6-month lag. CONCLUSIONS Metformin promotes a survival benefit in individuals with PPDM but not PCRD. Reverse causality may play a role in the association between insulin use and mortality in PCRD.
PB2382 FOLLOW UP POST ALLOGENIC STEM CELL TRANSPLANTATION IN MOROCCO: ABOUT 28 PATIENTS
Authors: S. Haidouri, K. zine Filali, M. ababou, E. mahtat, M. mikdame, K. doghmi
Journal: HemaSphere (2019)

Background: Allogenic hematpoetic stem cell transplantation is a cure for hematological malignancies and certain of immune system diseases,but is associated with high morbidity due to immunological reaction between donor and recipient:Graft versus host disease Aims: repport our experience in management of post allograft complications Methods: this is a retrospective descriptive study,between 2007 and 2018,including 28patients The follow up was done in the clinical departement of hematology of Rabat,but allograft was performed in Percy military hospital in Paris Results: In this study, spread between 2007 and 2018, all patients included were sent to the Percy military hospital for an allograft of hematopoietic stem cells between 2007 and 2018, the median age was 32 years (15 years and 60 years), 55% were male, 17 patients were followed for acute leukemias including 09 myeloid type, 04 myeloproliferative neoplasms (01 CML, 03PMF), 03 patients for aplastic anemia, 01 MDS, 03 patients for lympho‐proliferative syndrome (01 Hodgkin's lymphoma, T lymphoma and multiple myeloma). The duration between diagnosis and bone marrow transplant was around 12 months (2 months and 6 years), 75% of patients were transplanted from a geno‐identical donor, 17% from a 10/10 pheno‐identical voluntary donor, while one patient received a haplo‐identical transplant and another a transplant of placental blood units. A peripheral stem cell graft was used in 75% of patients, several conditioning regimens were used, including: Busulfan / Endoxan in 30% (acute leukemias) Fludarabine‐Busulfan‐thymoglobulin in 28%. Anti‐GVHD prophylaxis was done by Methotrexate / ciclosporin in 58% of cases, ciclosporin alone in 22% and ciclosporin‐mycophenolate mofetil in 18% of cases. The immediate consequences of the graft were marked by the occurrence of bacterial infections in 71%, the reactivation of CMV in 9 patients, acute GVH was found in 38% of patients, cutaneous type with a good response to corticosteroids. During our follow‐up, 35% of patients showed signs of chronic GVH ‐with 35% of patients who had acute GVH. All types was present:cutaneous and oral (71%), pulmonary (58%), ocular (58%), hepatic (28%), muscular (28%), digestive and gynecologic GVHD. (14%), immunosuppressive treatments (ciclosporin) and corticosteroids were used in the first line in all patients with a response less than 30%. In the second line, Rituximab was used in 71% of patients, ITK (Imatinib) in 28% (pulmonary GVH), and extracorporeal photophoresis in a patient with musculoskeletal GVHD. The median follow‐up was 45 months with an overall survival of 67% and an event‐free survival of 60%. Summary/Conclusion: Allogenic stem cell transplantation is a real challenge in under‐developing countries, The post‐transplant represent a heavy multidisciplinary approach and a very expensive In our series 10% of patients have died from chronic GVH, then we need a better understanding and mastery of this complication.
Abstract MP094: Cardiorespiratory Fitness and Birth Outcomes: the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Abbi D Lane-Cordova, Mercedes R Carnethon, Janet M Catov, Cora E Lewis, Samantha E Montag, Pamela J Schreiner, Annie Dude, Barbara Sternfeld, T H Vu, Sylvia Badon, Philip Greenland, Erica P Gunderson
Journal: Circulation (2017)

Background: High fitness is related to inflammation, blood pressure (BP), and endothelial dysfunction, the pathways believed to be involved in the development of hypertension in pregnancy. High fitness may also protect against preterm birth (PTB) and small for gestational age (SGA) deliveries, birth outcomes frequently associated with maternal vascular dysfunction. Hypothesis: Higher cardiorespiratory fitness in the years preceding pregnancy and childbirth is inversely associated with incident SGA and PTB. Methods: The CARDIA study is a prospective cohort study that encompasses child-bearing years. We studied 840 women who were nulliparous at baseline, reported ≥1 live birth(s) between the baseline and year 25 exam, and underwent a maximal treadmill exercise test at baseline. Number of births, gestational age for each birth, and birth weight were obtained by self-report at each exam. SGA was defined as birth weight &lt;10 th percentile for gestational age, and PTB was any birth that occurred before week 37 of pregnancy. We used Cox regression to determine hazard ratios for incident SGA and/or PTB. We adjusted for demographic and clinical co-variates at the exam immediately preceding the incident SGA/PTB or the 1 st birth for women who did not report SGA or PTB (Model 2). Results: Women who reported SGA (n=118) or PTB (n=185) were younger at baseline, completed fewer years of education, and were more likely to be black compared to women who did not report SGA/PTB (n=537). There was no difference in baseline BP or BMI between groups. Women without SGA/PTB had higher fitness than women with SGA/PTB; treadmill test duration was 541 s (95% CI: 529, 553 s) vs 500 s (95% CI: 483, 518 s). Treadmill test duration was inversely associated with time to SGA/PTB following adjustment (Table). Findings were similar by race. Conclusions: Higher cardiorespiratory fitness in the years preceding pregnancy and childbirth was associated with decreased risk of SGA/PTB. Achieving a higher fitness level in young adulthood may help protect against SGA and PTB.
AB0125 CXCL17 IN RHEUMATOID ARTHRITIS: INTERFERONE-GAMMA INDUCIBLE EXPRESSION AND INHIBITION OF ANGIOGENESIS
Authors: Anna Kernder, Johanna Mucke, Long Tang-Chieu, Torsten Lowin, Tim Claßen, Oliver Sander, Ellen Bleck, Claudia Heier, Georg Pongratz, Matthias Schneider, Stefan Vordenbäumen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> CXCL17 is the latest chemokine discovered and was reported to influence angiogenesis and monocyte trafficking<sup>1-2</sup>. Its role in rheumatoid arthritis (RA) has not been assessed so far. <h3>Objectives:</h3> To assess the role of CXCL17 and its putative receptor G-protein-coupled receptor 35 (GPR35) in RA. <h3>Methods:</h3> Synovial tissue from joint replacements of RA and osteoarthritis (OA) patients was used for CXCL17 and GPR35 immunohistochemistry and in-situ-hybridization/immunofluorescence double-stainings. CXCL17 concentration in the synovial fluid of RA and CXCL17 production by synovial fibroblasts and smooth muscle cells after stimulation with TNF-α, INF-γ and IL-1β was quantified by qPCR and ELISA. Angiogenesis was assessed by a human umbilical vein endothelial cell culture assay. <h3>Results:</h3> CXCL17 and GPR35 are widely expressed in the synovial membrane of RA compared to OA (p=0.006). Within the synovial membrane CXCL17-mRNA could be located to vascular smooth muscle cells. INF-γ significantly induced CXCL17-mRNA and protein production in RA synovial fibroblasts (1.88-fold, p=0.019 and 2-fold, p=0.0002 respectively) and rat smooth muscle cells (67-fold, p=0.02 and 3.7-fold, p&lt;0.001). CXCL17 was detected in the synovial fluid of RA (mean 310 pg/ml). In vitro angiogenesis was inhibited by CXCL17. This effect was reversed by specific GPR35 antagonists. <h3>Conclusion:</h3> CXCL17 is abundant in RA synovial tissue, localizes to vascular smooth muscle cells and fibroblasts, and is inducible by INF-γ. Antiangiogenic properties are mediated by GPR35. CXCL17 and GPR35 may constitute a hitherto unrecognized regulatory protein in RA pathogenesis and therefore be interesting drug targets. <h3>References</h3> [1] Pisabarro MT, Leung B, Kwong M, Corpuz R, Frantz GD, Chiang N, et al. Cutting edge: novel human dendritic cell- and monocyte-attracting chemokine-like protein identified by fold recognition methods. J Immunol Baltim Md 1950. 2006;176(4):2069–73 [2] Lee W-Y, Wang C-J, Lin T-Y, Hsiao C-L, Luo C-W. CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-inflammatory factor. Am J Physiol Endocrinol Metab. 2013;304(1):E32-40. <h3>Disclosure of Interests:</h3> Anna Kernder Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Johanna Mucke: None declared, Long Tang-Chieu: None declared, Torsten Lowin: None declared, Tim Claßen: None declared, Oliver Sander: None declared, Ellen Bleck: None declared, Claudia Heier: None declared, Georg Pongratz : None declared, Matthias Schneider Grant/research support from: GlaxoSmithKline and UCB Pharma for performing the LuLa-study., Speakers bureau: Chugai, Stefan Vordenbäumen: None declared
THU0300 IMPACT OF VASCULAR ULTRASOUND ON EVALUATION OF GIANT CELL ARTERITIS AMONG 503 PATIENTS IN AN ACADEMIC MEDICAL CENTER
Authors: Julia Ford, Michael Diiorio, William Docken, Piotr Sobieszczyk, Sara Tedeschi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> As vascular ultrasound (VUS) is increasingly used in evaluation of giant cell arteritis (GCA), its impact on clinical care is of great interest. <h3>Objectives</h3> To describe utilization of VUS in GCA evaluation at a large academic medical center and investigate impact of VUS on clinical impression. <h3>Methods</h3> We performed a retrospective cohort study of patients who underwent VUS at a single center in Boston, 2013-2017, to evaluate suspected or known GCA. Trained cardiovascular ultrasound technicians used a standardized protocol to image the temporal, carotid, subclavian, and axillary arteries for presence of hypoechoic circumferential wall thickening (halo sign), hyperechoic wall thickening, stenosis, and occlusion. VUS images were interpreted by trained cardiovascular medicine physicians as consistent with acute arteritis ("acute"), no evidence of arteritis ("none"), or hyperechoic wall thickening without halo sign ("hyperechoic"). Demographic, laboratory, medication, pathology and clinical data including the treating physician's clinical suspicion for GCA pre- and post-VUS were obtained by electronic medical record review. Fisher's exact test and Wilcoxon rank-sum tests compared baseline characteristics among patients with VUS positive for acute arteritis ("acute") vs. negative for acute arteritis ("none" or "hyperechoic"). We compared the treating physician's pre- and post-VUS clinical suspicion for GCA among patients with no history of GCA or aortitis. <h3>Results</h3> We identified 503 patients with median age 70.4 years; 69.0% were female and 87.5% White. VUS interpretation was acute in 48 patients (9.5%), none in 427 (84.9%), and hyperechoic in 28 (5.6%). Baseline characteristics are presented in Table 1. Weight loss, cranial symptoms, higher ESR, and steroid use were more common in patients with VUS positive for acute arteritis. Change in the treating physician's clinical suspicion for GCA is shown in Figure 1. VUS positive for acute arteritis increased suspicion for GCA in 26/35 (74%) cases, and VUS negative for acute arteritis lowered suspicion for GCA in 303/396 (77%). Of 110 patients with a temporal artery biopsy after VUS, 16 (14.6%) biopsies showed active arteritis; 11 of these were in patients with VUS negative for acute arteritis. <h3>Conclusion</h3> VUS result changed the clinical suspicion for GCA in approximately 75% of patients in this large cohort. Presented as% or median (interquartile range). CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; GCA: giant cell arteritis; PMR: polymyalgia rheumatica; TA: temporal artery; VUS: vascular ultrasound. NS: not significant. *Among 418 patients with CRP and 370 with ESR checked within 3 weeks before VUS **p=0.046 <h3>Disclosure of Interests</h3> None declared
Photo‐Fenton‐like Metal–Protein Self‐Assemblies as Multifunctional Tumor Theranostic Agent
Authors: Tianliang Li, Jia Zhou, Lirui Wang, Hanfu Zhang, Cunfeng Song, Jesús M. de la Fuente, Yunxiang Pan, Jie Song, Chunlei Zhang, Daxiang Cui
Journal: Advanced Healthcare Materials (2019)

Abstract Emerging Fenton‐like activity of copper ions has inspired great exploration for tumor microenvironment‐activated tumor therapy due to the toxic ·OH production for chemodynamic therapy and extra oxygen generation for photodynamic therapy (PDT). Still, the ·OH produced by copper ions is not satisfied even when copper ions are placed in a low pH environment (pH ≈ 5.0). To amplify its Fenton‐like activity, in this work, one kind of Cu 2+ –protein self‐assemblies (C‐m‐ABs) loaded with photosensitizer indocyanine green (ICG) is constructed, which can catalyze H 2 O 2 generating more amounts of ·OH under light irradiation once Cu 2+ is reduced to Cu + by glutathione. Such fantastic phenomena confirms that C‐m‐ABs can act as a photo‐Fenton‐like agent. Furthermore, C‐m‐ABs can dramatically accelerate O 2 generation (catalase activity) to enhance the PDT of ICG. After loading with the anticancer drug doxorubicin, C‐m‐ABs are further self‐assembled into novel nanobelts, which simultaneously exhibit superior photo‐heat conversion effects, enhanced r1 relaxation (21.416 s −1 m m −1 ) and stimuli‐responsive drug release behaviors. High cytotoxicity in vitro, effective tumor accumulation capacity observed by fluorescence/photoacoustic/magnetic resonance imaging, and enhanced chemo‐/photodynamic/photothermal therapeutic performance are achieved. Based on these results, a photo‐Fenton‐like metal–protein self‐assemblies demonstrate great potential for tumor theranostics.